@article {pmid30551119, year = {2018}, author = {McClave, SA and Martindale, RG}, title = {Why do current strategies for optimal nutritional therapy neglect the microbiome?.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {60}, number = {}, pages = {100-105}, doi = {10.1016/j.nut.2018.09.024}, pmid = {30551119}, issn = {1873-1244}, abstract = {Strategies for providing optimal nutritional therapy have evolved over time, with the emphasis on specific directives (such as route, use of immunonutrition, high protein, organ-specific formulas, etc.), achieving variable degrees of success for improving outcomes in the intensive care unit. As the largest immune organ in the body comprising the largest interface between the host and the external environment, the gut can have an amplifying effect on a pattern of dysbiosis, immune dysregulation, and multiple organ failure seen in the critically ill patient. Conversely, maintenance of gut integrity can serve to restore a pattern of homeostasis, appropriate immune responses, symbiosis, and clinical recovery. Simply providing refined polymeric formulas as enteral nutrition may not take full advantage of the potential for optimal outcome that could be derived by giving therapy designed to directly stimulate gut defenses and support the intestinal microbiota. This article describes a series of strategies (such as use of intact whole food formulas, soluble fiber, fecal microbial transplantation, serum bovine immunoglobulin, or agents to promote commensal behavior) that should modulate the gut microbiome and shift the critically ill patient toward a pattern of health and recovery.}, } @article {pmid30543777, year = {2018}, author = {Hu, J and Ma, L and Nie, Y and Chen, J and Zheng, W and Wang, X and Xie, C and Zheng, Z and Wang, Z and Yang, T and Shi, M and Chen, L and Hou, Q and Niu, Y and Xu, X and Zhu, Y and Zhang, Y and Wei, H and Yan, X}, title = {A Microbiota-Derived Bacteriocin Targets the Host to Confer Diarrhea Resistance in Early-Weaned Piglets.}, journal = {Cell host & microbe}, volume = {24}, number = {6}, pages = {817-832.e8}, doi = {10.1016/j.chom.2018.11.006}, pmid = {30543777}, issn = {1934-6069}, abstract = {Alternatives to antibiotics for preventing diarrhea in early-weaned farm animals are sorely needed. CM piglets (a native Chinese breed) are more resistant to early-weaning stress-induced diarrhea than the commercial crossbred LY piglets. Transferring fecal microbiota, but not saline, from healthy CM into LY piglets by oral administration prior to early weaning conferred diarrhea resistance. By comparing the relative abundance of intestinal microbiota in saline and microbiota transferred LY piglets, we identified and validated Lactobacillus gasseri LA39 and Lactobacillus frumenti as two bacterial species that mediate diarrhea resistance. Diarrhea resistance depended on the bacterial secretory circular peptide gassericin A, a bacteriocin. The binding of gassericin A to Keratin 19 (KRT19) on the plasma membrane of intestinal epithelial cells was essential for enhancement of fluid absorption and decreased secretion. These findings suggest the use of L. gasseri LA39 and L. frumenti as antibiotic alternatives for preventing diarrhea in mammals.}, } @article {pmid30540704, year = {2018}, author = {Davidovics, ZH and Michail, S and Nicholson, MR and Kociolek, LK and Pai, N and Hansen, R and Schwerd, T and Maspons, A and Shamir, R and Szajewska, H and Thapar, N and de Meij, T and Mosca, A and Vandenplas, Y and Kahn, SA and Kellermayer, R and , }, title = {Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection and Other Conditions in Children: A Joint Position Paper From the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1097/MPG.0000000000002205}, pmid = {30540704}, issn = {1536-4801}, abstract = {Fecal microbiota transplantation (FMT) is becoming part of the treatment algorithms against recurrent Clostridium difficile infection (rCDI) both in adult and pediatric gastroenterology practice. With our increasing recognition of the critical role the microbiome plays in human health and disease, FMT is also being considered as a potential therapy for other disorders, including inflammatory bowel disease (Crohn disease, ulcerative colitis), graft versus host disease, neuropsychiatric diseases, and metabolic syndrome. Controlled trials with FMT for rCDI have not been performed in children, and numerous clinical and regulatory considerations have to be considered when using this untraditional therapy. This report is intended to provide guidance for FMT in the treatment of rCDI in pediatric patients.}, } @article {pmid30539026, year = {2018}, author = {Leustean, AM and Ciocoiu, M and Sava, A and Costea, CF and Floria, M and Tarniceriu, CC and Tanase, DM}, title = {Implications of the Intestinal Microbiota in Diagnosing the Progression of Diabetes and the Presence of Cardiovascular Complications.}, journal = {Journal of diabetes research}, volume = {2018}, number = {}, pages = {5205126}, doi = {10.1155/2018/5205126}, pmid = {30539026}, issn = {2314-6753}, abstract = {The prevalence of diabetes is steadily rising, and once it occurs, it can cause multiple complications with a negative impact on the whole organism. Complications of diabetes may be macrovascular: such as stroke and ischemic heart disease as well as peripheral vascular and microvascular diseases-retinopathy, nephropathy, and neuropathy. Key factors that cause cardiovascular disease in people with diabetes include hyperglycemia, dyslipidemia, obesity, insulin resistance, inflammation, hypertension, autonomic dysfunction, and decreased vascular response capacity. Microbes can be considered a complex endocrine system capable of ensuring the proper functioning of the body but are also responsible for the development of numerous pathologies (diabetes, coronary syndromes, peripheral arterial disease, neoplasia, Alzheimer's disease, and hepatic steatosis). Changes in the intestinal microbiota may influence the host's sensitivity to insulin, body weight, and lipid and carbohydrate metabolism. Dysbiosis causes activation of proinflammatory mechanisms, metabolic toxicity, and insulin resistance. Trimethylamine N-oxide (TMAO) is a microbial organic compound generated by the large intestine, and its concentration increases in the blood after ingestion of foods rich in L-carnitine and choline, such as red meat, eggs, and fish. The interest for TMAO in cardiometabolic research has recently emerged, given the preclinical evidence that reveals a link between TMAO, diabetes, and cardiovascular complications. Intestinal microbiota can be modulated by changing one's lifestyle but also by antibiotic, probiotic, prebiotic, and fecal transplantation. The purpose of this article is to highlight issues related to the involvement of microbiota and trimethylamine N-oxide in the pathogenesis of diabetes mellitus and cardiovascular disease. Better appreciation of the interactions between food intake and intestinal floral-mediated metabolism can provide clinical insights into the definition of individuals with diabetic risk and cardiometabolic disease as well as potential therapeutic targets for reducing the risk of progression of the disease.}, } @article {pmid30534963, year = {2018}, author = {Kalla, R and Pitt, M and Sharma, A}, title = {The Role of Autologous Fecal Microbiota Transplantation in Diversion Colitis: A Case Report.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izy270}, pmid = {30534963}, issn = {1536-4844}, } @article {pmid30534859, year = {2018}, author = {Quera, R and Ibáñez, P and Simian, D and Rivera, D and Acuña, G and Espinoza, R}, title = {[Fecal microbiota transplantation through colonoscopy for Clostridium difficile recurrent infection. Report of eight cases].}, journal = {Revista medica de Chile}, volume = {146}, number = {8}, pages = {823-830}, doi = {10.4067/s0034-98872018000800823}, pmid = {30534859}, issn = {0717-6163}, abstract = {BACKGROUND: Most cases of Clostridium difficile infection (CDI) respond to a standard course of antibiotics, however recurrent CDI is becoming common and alternative therapeutic strategies are needed. In this scenario, fecal microbiota transplantation (FMT) has been suggested.

AIM: To describe the efficacy and safety of FMT for the treatment of recurrent CDI.

PATIENTS AND METHODS: Review of medical records of all patients with recurrent CDI treated with FMT between April 2013 and April 2017. Demographic and clinical data were abstracted including details of treatment prior to FMT, rate of FMT treatment success and clinical course during follow-up period. Telephone surveys were conducted to determine patient satisfaction.

RESULTS: Eight patients aged 19 to 82 years (six women) underwent FMT. They experienced a median of four previous episodes of CDI (range 3-8). The mean duration of CDI was 18 days (range 3-36) before FMT. All procedures were performed by colonoscopy. Effectiveness with one session of FMT was 100%. During the follow-up period (median 24 months, range 7-55), two patients developed CDI, one of them after using antibiotics. Adverse events were reported in three patients. Two had bloating and one patient with Crohn's disease and a history of bacteremia had an episode of Escherichia coli bacteremia. All patients would use FMT again if necessary.

CONCLUSIONS: FMT through colonoscopy appears to be a safe, effective and long-lasting therapy in cases of recurrent CDI.}, } @article {pmid30534630, year = {2018}, author = {Lindheim, L and Manti, M and Fornes, R and Bashir, M and Czarnewski, P and Diaz, OE and Seifert, M and Engstrand, L and Villablanca, EJ and Obermayer-Pietsch, B and Stener-Victorin, E}, title = {Reproductive and Behavior Dysfunction Induced by Maternal Androgen Exposure and Obesity Is Likely Not Gut Microbiome-Mediated.}, journal = {Journal of the Endocrine Society}, volume = {2}, number = {12}, pages = {1363-1380}, doi = {10.1210/js.2018-00266}, pmid = {30534630}, issn = {2472-1972}, abstract = {Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder of unclear etiology in women and is characterized by androgen excess, insulin resistance, and mood disorders. The gut microbiome is known to influence conditions closely related with PCOS, and several recent studies have observed changes in the stool microbiome of women with PCOS. The mechanism by which the gut microbiome interacts with PCOS is still unknown. We used a mouse model to investigate if diet-induced maternal obesity and maternal DHT exposure, mimicking the lean and obese PCOS women, cause lasting changes in the gut microbiome of offspring. Fecal microbiome profiles were assessed using Illumina paired-end sequencing of 16S rRNA gene V4 amplicons. We found sex-specific effects of maternal and offspring diet, and maternal DHT exposure on fecal bacterial richness and taxonomic composition. Female offspring exposed to maternal obesity and DHT displayed reproductive dysfunction and anxietylike behavior. Fecal microbiota transplantation from DHT and diet-induced obesity exposed female offspring to wild-type mice did not transfer reproductive dysfunction and did not cause the expected increase in anxietylike behavior in recipients. Maternal obesity and androgen exposure affect the gut microbiome of offspring, but the disrupted estrous cycles and anxietylike behavior are likely not microbiome-mediated.}, } @article {pmid30529583, year = {2018}, author = {Paramsothy, S and Nielsen, S and Kamm, MA and Deshpande, NP and Faith, JJ and Clemente, JC and Paramsothy, R and Walsh, AJ and van den Bogaerde, J and Samuel, D and Leong, RWL and Connor, S and Ng, W and Lin, E and Borody, TJ and Wilkins, MR and Colombel, JF and Mitchell, HM and Kaakoush, NO}, title = {Specific Bacteria and Metabolites Associated with Response to Fecal Microbiota Transplantation in Patients with Ulcerative Colitis.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2018.12.001}, pmid = {30529583}, issn = {1528-0012}, abstract = {BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) can induce remission in patients with ulcerative colitis (UC). In a randomized, controlled trial of FMT in patients with active UC, we aimed to identify bacterial taxonomic and functional factors associated with response to therapy.

METHODS: We performed a double-blind trial of 81 patients with active UC randomly assigned to groups that received an initial colonoscopic infusion and then intensive multi-donor FMT or placebo enemas, 5 days/week for 8 weeks. Patients in the FMT group received blended homogenized stool from 3-7 unrelated donors. Patients in the placebo group were eligible to receive open-label FMT, after the double-blind study period. We collected 314 fecal samples from the patients at screening, every 4 weeks during treatment, and 8 weeks after the blinded or open-label FMT therapy. We also collected 160 colonoscopic large bowel biopsies from the patients at study entry, at completion of 8 weeks of blinded therapy, and at the end of open-label FMT if applicable. We analyzed the 105 fecal samples from the 14 individual donors (n=55), which were combined into 21 multi-donor batches (n=50). Bacteria in colonic and fecal samples were analyzed by both 16S rRNA gene and transcript amplicon sequencing; 285 fecal samples were analyzed by shotgun metagenomics and 60 fecal samples were analyzed for metabolome features.

RESULTS: FMT increased microbial diversity and altered composition, based on analyses of colon and fecal samples collected before vs after FMT. Diversity was greater in fecal and colon samples collected before and after FMT treatment from patients who achieved remission compared to patients who did not. Patients in remission after FMT had enrichment of Eubacterium hallii and Roseburia inulivorans, compared to patients who did not achieve remission after FMT, and had increased levels of short-chain fatty acid biosynthesis and secondary bile acids. Patients who did not achieve remission had enrichment of Fusobacterium gonidiaformans, Sutterella wadsworthensis, and Escherichia and increased levels of heme and lipopolysaccharide biosynthesis. Bacteroides in donor stool were associated with remission in patients receiving FMT, and Streptococcus in donor stool associated with no response to FMT.

CONCLUSIONS: In an analysis of fecal and colonic mucosa samples from patients receiving FMT for active UC and stool samples from donors, we associated specific bacteria and metabolic pathways with induction of remission. These findings may be of value in the design of microbe-based therapies for UC. ClinicalTrials.gov no: NCT01896635.}, } @article {pmid30385177, year = {2018}, author = {Peng, J and Xiao, X and Hu, M and Zhang, X}, title = {Interaction between gut microbiome and cardiovascular disease.}, journal = {Life sciences}, volume = {214}, number = {}, pages = {153-157}, doi = {10.1016/j.lfs.2018.10.063}, pmid = {30385177}, issn = {1879-0631}, mesh = {Cardiovascular Diseases/etiology/*microbiology/therapy ; Fatty Acids, Volatile/*metabolism ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Methylamines/*metabolism ; Probiotics/therapeutic use ; }, abstract = {Traditional cardiovascular risk factors do not underlie all incidence of cardiovascular disease. In recent years, accumulating evidence has demonstrated that gut microbiota and its metabolites also play a pivotal role in the onset and development of cardiovascular disease, including atherosclerosis, hypertension, heart failure, atrial fibrillation and myocardial fibrosis. Trillions of bacteria indwell the gastrointestinal tract and metabolize nutrients into trimethylamine-N-oxide, short-chain fatty acids and so on. Targeting these microorganisms and relevant metabolic pathways has beneficial effects in cardiovascular disease. This review will summarize the role of gut microbiota and its metabolites, mainly trimethylamine-N-oxide, in the pathogenesis of cardiovascular diseases, and discuss the possible mechanisms that drive cardiovascular diseases and highlight potential therapies in this field.}, } @article {pmid29744928, year = {2018}, author = {Chen, YJ and Wu, H and Wu, SD and Lu, N and Wang, YT and Liu, HN and Dong, L and Liu, TT and Shen, XZ}, title = {Parasutterella, in association with irritable bowel syndrome and intestinal chronic inflammation.}, journal = {Journal of gastroenterology and hepatology}, volume = {33}, number = {11}, pages = {1844-1852}, doi = {10.1111/jgh.14281}, pmid = {29744928}, issn = {1440-1746}, support = {81272388//National Natural Science Foundation of China/ ; 81172273//National Natural Science Foundation of China/ ; 81101637//National Natural Science Foundation of China/ ; 81101540//National Natural Science Foundation of China/ ; //Foundation of Shanghai Institute of Liver Diseases/ ; 16YF1401500//Shanghai Sailing Program/ ; 2015ZSQN08//Youth Foundation of Zhongshan Hospital/ ; }, mesh = {Adolescent ; Adult ; Aged ; Animals ; Betaproteobacteria/genetics/isolation & purification/*pathogenicity ; DNA, Bacterial/isolation & purification ; Disease Models, Animal ; Disease Progression ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; High-Throughput Nucleotide Sequencing ; Humans ; Irritable Bowel Syndrome/*etiology/*microbiology ; Male ; Mice, Inbred C57BL ; Middle Aged ; Real-Time Polymerase Chain Reaction ; Young Adult ; }, abstract = {BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is a highly prevalent chronic functional gastrointestinal disorder. Recent studies have showed increasing important role of gut microbiota in the pathophysiological changes of IBS. Our study aims to elaborate the association between intestinal flora with the genesis and the development of IBS.

METHODS: Illumina high-throughput sequencing technology was applied to investigate microbial communities of IBS patients and healthy donors. Stool specimens from the IBS-D patients were equally premixed and implanted into germ free C57B/6 mice to construct IBS animal model, and the normal group was also transplanted with normal premixed feces. The post-transplant defecation and intra-epithelial lymphocyte counts were evaluated. Microbial communities were also checked by the illumina high-throughput sequencing technology.

RESULTS: Fifteen genuses significantly different were found expressed in the gut flora of IBS patients, and six genuses showed significantly different abundances between the stool specimens of mice of IBS group and normal group. Among these differences, Parasutterella expression was remarkably different in both screening and validation experiments and also related to chronic intestinal inflammation; therefore, Parasutterella expression is considered in association with the development and progression of IBS.

CONCLUSION: Parasutterella may be related with the genesis and development of IBS and also associated with chronic intestinal inflammation in IBS patients.}, } @article {pmid30521978, year = {2018}, author = {Huang, C and Yang, X and Zeng, B and Zeng, L and Gong, X and Zhou, C and Xia, J and Lian, B and Qin, Y and Yang, L and Liu, L and Xie, P}, title = {Proteomic analysis of olfactory bulb suggests CACNA1E as a promoter of CREB signaling in microbiota-induced depression.}, journal = {Journal of proteomics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jprot.2018.11.023}, pmid = {30521978}, issn = {1876-7737}, abstract = {Major depressive disorders impact approximately 17% of the population worldwide, whose high morbidity and considerable adversity have resulted in enormous social and economic burden. In addition, clinically depressed patients often show reduced volume of olfactory bulb (OB) and decreased olfactory sensitivity. Although mounting evidence conveyed that the gut microbiota may implicate the pathophysiology of major depressive disorder (MDD) via the microbe-gut-brain axis, knowledge about its distinctive molecular mechanism is rudimentary. Herein, iTRAQ coupled with LC-MS/MS was applied to compare the OB proteome between "pathological microbiota" and "healthy microbiota" germ-free mice. A set of 367 proteins were differentially identified in the OB, including 119 up-regulated and 248 down-regulated proteins compared with the levels in controls. A combined analysis with significantly changed OB proteins from CUMS depression model supported the role of CREB signaling, whose dysregulation is likely to disrupt the axonogenesis of OB under microbiota condition. With that, the down-regulated CACNA1E and its downstream proteins (CALM/ CaMKII/ CREB/ BDNF) in CREB pathway were validated by Western blot. Meanwhile, the canonical pathways involved Nuclear Receptor Signaling highlighted the fecal microbiota transplantation (FMT) model, which would be a new breakthrough for depressive research. These findings enrich the previous research achievements about the gut microbiota in psychiatric disorders, providing a creative insight into the intricate mechanisms of OB dysfunction in depression. SIGNIFICANCE: Emerging evidence has shown that gut microbiota can greatly influence brain functions and even behaviors. As one of the post-developmental neurogenesis areas for the adult brain, the OB is becoming increasingly important in the study of the pathogenesis of depression. Using an iTRAQ-based proteomics, we identified 367 altered proteins in the OB of fecal microbiota transplanted mouse, which provide a novel insight for further research of the "microbiota-gut-brain axis". In addition, combined analyses with the CUMS depression model and the validation of key proteins by Western blot may assist in the investigation of OB dysfunction in mental sickness.}, } @article {pmid30521856, year = {2018}, author = {Al-Amer, M and Abdeen, Y and Kaako, A}, title = {Bezlotoxumab Use as Adjunctive Therapy with the Third Fecal Microbiota Transplant in Refractory Recurrent Clostridium Difficile Colitis; A Case Report and Concise Literature Review.}, journal = {Anaerobe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.anaerobe.2018.11.010}, pmid = {30521856}, issn = {1095-8274}, abstract = {Clostridium difficile is the most commonly reported pathogen to cause nosocomial infections in the United States with a high burden affecting morbidity, mortality and healthcare expenditure. The use of Fecal Microbiota Transplantation (FMT) is one of the current standard therapies for recurrent C. difficile infection (CDIr). One emerging promising approach is the use of monoclonal antibodies that bind to and neutralize C. difficile toxins such as Bezlotoxumab. We present the first case report on combining the third FMT with bezlotoxumab after the failure of standard-of-care antibiotics and two trials of FMT alone, with subsequent success in preventing the recurrence of refractory CDI for 12 weeks following treatment. This case highlight the need for further studies and guidelines to recommend the best combination among different treatment options and modalities.}, } @article {pmid30519847, year = {2018}, author = {Allegretti, JR and Fischer, M and Sagi, SV and Bohm, ME and Fadda, HM and Ranmal, SR and Budree, S and Basit, AW and Glettig, DL and de la Serna, EL and Gentile, A and Gerardin, Y and Timberlake, S and Sadovsky, R and Smith, M and Kassam, Z}, title = {Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Lose Dose.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-018-5396-6}, pmid = {30519847}, issn = {1573-2568}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium. difficile infection (rCDI). FMT capsules have emerged, and it is unknown if delivery location and dose impact efficacy.

METHODS: We compared two cohorts of patients receiving two capsule formulations: gastric release (FMTgr) and targeted colonic release (FMTcr) at two different sites. Cohort A received FMTgr at (1) high dose: 60 capsules and low dose: 30 capsules. Patients in Cohort B received FMTcr at (1) high dose: 30 capsules (2) low dose: 10 capsules. Clinical cure rates and adverse events were monitored through week 8. Paired t-tests were used to compare diversity pre- and post-FMT.

RESULTS: 51 rCDI patients were enrolled. Cohort A contained n = 20 and Cohort B contained n = 31. Overall cure at week 8 for FMTgr was 75% (15/20) compared to 80.6% for FMTcr, (25/31), p = 0.63. Both formulations were safe with no serious adverse events. FMTcr was superior at increasing gut microbial diversity.

DISCUSSION: To our knowledge, this is the first study to compare targeted delivery of FMT capsules. While both capsules were safe and efficacious, microbial engraftment patterns were superior in FMTcr.}, } @article {pmid30519748, year = {2018}, author = {Zhu, Y and He, C and Li, X and Cai, Y and Hu, J and Liao, Y and Zhao, J and Xia, L and He, W and Liu, L and Luo, C and Shu, X and Cai, Q and Chen, Y and Lu, N}, title = {Gut microbiota dysbiosis worsens the severity of acute pancreatitis in patients and mice.}, journal = {Journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00535-018-1529-0}, pmid = {30519748}, issn = {1435-5922}, support = {81760120//National Natural Science Foundation of China/ ; 81460116//National Natural Science Foundation of China/ ; 20171BBG70084//Science and Technology Department of Jiangxi Province/ ; }, abstract = {BACKGROUND: The gut is implicated in the pathogenesis of acute pancreatitis (AP) and the infectious complications of AP are commonly associated with enteric bacteria, yet whether gut microbiota dysbiosis participants in AP severity remains largely unknown.

METHODS: We collected clinical information and fecal samples from 165 adult participants, including 41 with mild AP (MAP), 59 with moderately severe AP (MSAP), 30 with severe AP (SAP) and 35 healthy controls (HC). The serum inflammatory cytokines and gut barrier indexes were detected. Male C57BL/6 mice with AP were established and injuries of pancreas were evaluated in antibiotic-treated mice, germ-free mice as well as those transplanted with fecal microbiota. The gut microbiota was analyzed by 16S rRNA gene sequencing.

RESULTS: The structure of gut microbiota was significantly different between AP and HC, and the disturbed microbiota was closely correlated with systematic inflammation and gut barrier dysfunction. Notably, the microbial composition changed further with the worsening of AP and the abundance of beneficial bacteria such as Blautia was decreased in SAP compared with MAP and MSAP. The increased capacity for the inferred pathway, bacterial invasion of epithelial cells in AP, highly correlated with the abundance of Escherichia-Shigella. Furthermore, the antibiotic-treated mice and germ-free mice exhibited alleviated pancreatic injury after AP induction and subsequent fecal microbiota transplantation in turn exacerbated the disease.

CONCLUSIONS: This study identifies the gut microbiota as an important mediator during AP and its dysbiosis is associated with AP severity, which suggests its role as potential therapeutic target.}, } @article {pmid30518356, year = {2018}, author = {Bin, P and Tang, Z and Liu, S and Chen, S and Xia, Y and Liu, J and Wu, H and Zhu, G}, title = {Intestinal microbiota mediates Enterotoxigenic Escherichia coli-induced diarrhea in piglets.}, journal = {BMC veterinary research}, volume = {14}, number = {1}, pages = {385}, doi = {10.1186/s12917-018-1704-9}, pmid = {30518356}, issn = {1746-6148}, abstract = {BACKGROUND: Enterotoxigenic Escherichia coli (ETEC) causes diarrhea in humans, cows, and pigs. The gut microbiota underlies pathology of several infectious diseases yet the role of the gut microbiota in the pathogenesis of ETEC-induced diarrhea is unknown.

RESULTS: By using an ETEC induced diarrheal model in piglet, we profiled the jejunal and fecal microbiota using metagenomics and 16S rRNA sequencing. A jejunal microbiota transplantation experiment was conducted to determine the role of the gut microbiota in ETEC-induced diarrhea. ETEC-induced diarrhea influenced the structure and function of gut microbiota. Diarrheal piglets had lower Bacteroidetes: Firmicutes ratio and microbiota diversity in the jejunum and feces, and lower percentage of Prevotella in the feces, but higher Lactococcus in the jejunum and higher Escherichia-Shigella in the feces. The transplantation of the jejunal microbiota from diarrheal piglets to uninfected piglets leaded to diarrhea after transplantation. Microbiota transplantation experiments also supported the notion that dysbiosis of gut microbiota is involved in the immune responses in ETEC-induced diarrhea.

CONCLUSION: We conclude that ETEC infection influences the gut microbiota and the dysbiosis of gut microbiota after ETEC infection mediates the immune responses in ETEC infection.}, } @article {pmid30518033, year = {2018}, author = {Huang, E and Kang, S and Park, H and Park, S and Ji, Y and Holzapfel, WH}, title = {Differences in Anxiety Levels of Various Murine Models in Relation to the Gut Microbiota Composition.}, journal = {Biomedicines}, volume = {6}, number = {4}, pages = {}, doi = {10.3390/biomedicines6040113}, pmid = {30518033}, issn = {2227-9059}, abstract = {Psychobiotics are probiotic strains that confer mental health benefits to the host through the modulation of the gut microbial population. Mounting evidence shows that the gut microbiota play an important role in communication within the gut⁻brain axis. However, the relationship between the host genetics and the gut microbiota and their influence on anxiety are still not fully understood. Hence, in our research, we attempted to draw a connection between host genetics, microbiota composition, and anxiety by performing an elevated plus maze (EPM) test on four genetically different mice. Four different breeds of 5-week-old mice were used in this experiment: Balb/c, Orient C57BL/6N, Taconic C57BL/6N, and Taconic C57BL/6J. After 1 week of adaptation, their initial anxiety level was monitored using the EPM test via an EthoVision XT, a standardized software used for behavorial testing. Significant differences in the initial anxiety level and microbial composition were detected. Subsequently, the microbiota of each group was modulated by the administration of either a probiotic, fecal microbiota transplantation, or antibiotics. Changes were observed in host anxiety levels in correlation to the shift of the gut microbiota. Our results suggest that the microbiota, host genetics, and psychological symptoms are strongly related, yet the deeper mechanistic links need further exploration.}, } @article {pmid30508676, year = {2018}, author = {Hu, XF and Zhang, WY and Wen, Q and Chen, WJ and Wang, ZM and Chen, J and Zhu, F and Liu, K and Cheng, LX and Yang, J and Shu, YW}, title = {Fecal Microbiota Transplantation Alleviates Myocardial Damage in Myocarditis by Restoring the Microbiota Composition.}, journal = {Pharmacological research}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.phrs.2018.11.042}, pmid = {30508676}, issn = {1096-1186}, abstract = {Myocarditis can be caused by several infectious and noninfectious causes. Treatment for myocarditis is still a difficult task in clinical practice. The gut microbiota is related to cardiovascular diseases such as atherosclerosis and hypertension. However, little is known about the role of the gut microbiota in myocarditis. In our study, we tested the hypothesis that gut dysbiosis is associated with myocarditis. We focused on whether fecal microbiota transplantation (FMT) can be used as an effective treatment for myocarditis. We used an experimental autoimmune myocarditis (EAM) mouse model. Fecal samples were isolated from the control and EAM groups for bacterial genome analysis. We observed an increase in microbial richness and diversity in the myocarditis mice. These changes were accompanied by an increased Firmicutes/Bacteroidetes ratio. We also evaluated the efficacy of FMT for the treatment of myocarditis. EAM mouse guts were repopulated with fecal contents from an untreated male mouse donor. We found that myocardial injury was improved by diminished inflammatory infiltration, showing that IFN-γ gene expression in the heart tissue and CD4+IFN-γ+ cells in the spleen were decreased after FMT in EAM mice. We also found that FMT was able to rebalance the gut microbiota by restoring the Bacteroidetes population and reshaping the microbiota composition. Myocarditis is associated with gut microbiota dysbiosis and characterized by an increased F/B ratio. FMT treatment can rebalance the gut microbiota and attenuate myocarditis. Thus, FMT may be a potential therapeutic strategy for the treatment of myocarditis.}, } @article {pmid30506900, year = {2018}, author = {Leedahl, DD and Personett, HA and Nagpal, A and Barreto, EF}, title = {Prevention of Clostridium difficile Infection in Critically Ill Adults.}, journal = {Pharmacotherapy}, volume = {}, number = {}, pages = {}, doi = {10.1002/phar.2200}, pmid = {30506900}, issn = {1875-9114}, abstract = {The incidence and severity of Clostridium difficile infection (CDI) remain high across intensive care units in the United States despite national efforts to decrease this escalating health care burden. Most published literature and guidelines address treatment rather than prevention, yet this approach may be too downstream to limit morbidity and mortality from the disease and its complications. Mechanisms to successfully prevent CDI include reducing modifiable risk factors and minimizing horizontal transmission of C. difficile spores between patients and the health care environment. Since CDI prevention is characterized by a bundled approach, it is difficult to quantify the individual impact of any one element; however, there are a number of patient- and facility-level strategies that can be considered for CDI prevention. Robust hygiene strategies, diagnostic and antimicrobial stewardship, and particular prophylaxis maneuvers such as continuation of oral vancomycin or fidaxomicin in the setting of systemic antibiotics have all demonstrated benefit. The preventive roles of deprescribing acid suppressants, routine use of probiotics, or early fecal microbiota transplantation remain unclear. The focus of this review is to summarize the evidence related to primary and secondary CDI prevention in critically ill adults and provide a concise implementation pathway for clinicians and policy makers. This article is protected by copyright. All rights reserved.}, } @article {pmid30506577, year = {2018}, author = {Gong, S and Yan, Z and Liu, Z and Niu, M and Fang, H and Li, N and Huang, C and Li, L and Chen, G and Luo, H and Chen, X and Zhou, H and Hu, J and Yang, W and Huang, Q and Schnabl, B and Chang, P and Billiar, TR and Jiang, Y and Chen, P}, title = {Intestinal microbiota mediates the susceptibility to polymicrobial sepsis-induced liver injury by granisetron generation in mice.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep.30361}, pmid = {30506577}, issn = {1527-3350}, abstract = {Sepsis-induced liver injury is recognized as a key problem in intensive care units (ICUs). The gut microbiota has been touted as an important mediator of liver disease development; however, the precise roles of gut microbiota in regulating sepsis-induced liver injury are unknown. Here, we aimed to investigate the role of the gut microbiota in sepsis-induced liver injury and the underlying mechanism. Cecal ligation and puncture (CLP) was employed to induce polymicrobial sepsis and related liver injury. Fecal microbiota transplantation (FMT) was used to validate the roles of gut microbiota in these pathologies. Metabolomics analysis was performed to characterize the metabolic profile differences between sepsis-resistant (Res, survived to 7 days after CLP) and sepsis-sensitive (Sen, moribund before or approximately 24 h after CLP) mice. Mice gavaged with feces from Sen mice displayed more severe liver damage than did mice gavaged with feces from Res mice. The gut microbial metabolic profile between Sen and Res mice was different. In particular, the microbiota from Res mice generated more granisetron, a 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, than the microbiota from Sen mice. Granisetron protected mice against CLP-induced death and liver injury. Moreover, proinflammatory cytokines expression by macrophages after LPS challenge was markedly reduced in the presence of granisetron. Both treatment with granisetron and genetic knockdown of the 5-HT3A receptor in cells suppressed NF-кB transactivation and p-p38 accumulation in macrophages. Gut microbial granisetron levels showed a significantly negative correlation with plasma ALT/AST levels in septic patients. Conclusion: Our study revealed that gut microbiota plays a key role in the sensitization of sepsis-induced liver injury and identified granisetron as a novel hepatoprotective compound during sepsis development. This article is protected by copyright. All rights reserved.}, } @article {pmid30502914, year = {2018}, author = {Niederwerder, MC}, title = {Fecal microbiota transplantation as a tool to treat and reduce susceptibility to disease in animals.}, journal = {Veterinary immunology and immunopathology}, volume = {206}, number = {}, pages = {65-72}, doi = {10.1016/j.vetimm.2018.11.002}, pmid = {30502914}, issn = {1873-2534}, abstract = {Fecal microbiota transplantation (FMT) is the process by which fecal microbiota are donated from a healthy individual and subsequently transplanted into a diseased or young individual. The mechanism by which FMT is effective is believed to be due to enhanced beneficial microbes, increased microbiome diversity, and restored normal flora. Beneficial gut microorganisms not only play a role in maintaining an intestinal barrier and metabolizing nutrients, but importantly, these microbes help regulate local and systemic immune function. Although FMT has been described for several centuries, only recently has it been utilized as a mainstream therapy in humans and significantly considered for applications in other species. In humans and animals, gastrointestinal diseases are by far the most widely accepted FMT-treatable conditions; however, recent research has shown exceptional promise for FMT being used to treat or prevent other conditions, including those outside of the gastrointestinal tract. Overall, FMT is likely an underutilized, widely-available, and inexpensive tool for improving the health and response to disease in animals. In this review, the effects of FMT on veterinary diseases and potential applications for FMT in animals are discussed.}, } @article {pmid30502308, year = {2018}, author = {Davido, B and Batista, R and Fessi, H and Michelon, H and Escaut, L and Lawrence, C and Denis, M and Perronne, C and Salomon, J and Dinh, A}, title = {Fecal microbiota transplantation to eradicate vancomycin-resistant enterococci colonization in case of an outbreak.}, journal = {Medecine et maladies infectieuses}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.medmal.2018.11.002}, pmid = {30502308}, issn = {1769-6690}, abstract = {OBJECTIVE: A rapid and worrying emergence of vancomycin-resistant enterococci (VRE) gut colonization is occurring worldwide and may be responsible for outbreaks, especially in healthcare facilities. While no efficient decolonization strategies are recommended, we assessed fecal microbiota transplantation (FMT) to eradicate VRE colonization.

PATIENTS AND METHOD: Our main objective was to measure the impact of FMT on decolonization of VRE carriers, confirmed by at least two consecutive negative rectal swabs at one-week interval during a 3-month follow-up period. Patients received no antibiotic prior to the FMT.

RESULTS: After a month only three patients remained colonized with VRE. Decolonization was associated with 87.5% (n=7) of success after three months as only one patient remained colonized.

CONCLUSION: Our first results confirm that the FMT seems to be safe, with an impact on VRE colonization over time that may help control outbreaks.}, } @article {pmid30513674, year = {2018}, author = {Carrera-Quintanar, L and Ortuño-Sahagún, D and Franco-Arroyo, NN and Viveros-Paredes, JM and Zepeda-Morales, AS and Lopez-Roa, RI}, title = {The Human Microbiota and Obesity: A Literature Systematic Review of In Vivo Models and Technical Approaches.}, journal = {International journal of molecular sciences}, volume = {19}, number = {12}, pages = {}, doi = {10.3390/ijms19123827}, pmid = {30513674}, issn = {1422-0067}, support = {CB-2015-256736//Consejo Nacional de Ciencia y Tecnología/ ; CB-2017-A1-S-51026//Consejo Nacional de Ciencia y Tecnología/ ; 620112//Consejo Nacional de Ciencia y Tecnología/ ; UDG-PTC-1313//SEP PRODEP/ ; }, abstract = {Obesity is a noncommunicable disease that affects a considerable part of humanity. Recently, it has been recognized that gut microbiota constitutes a fundamental factor in the triggering and development of a large number of pathologies, among which obesity is one of the most related to the processes of dysbiosis. In this review, different animal model approaches, methodologies, and genome scale metabolic databases were revisited to study the gut microbiota and its relationship with metabolic disease. As a data source, PubMed for English-language published material from 1 January 2013, to 22 August 2018, were screened. Some previous studies were included if they were considered classics or highly relevant. Studies that included innovative technical approaches or different in vivo or in vitro models for the study of the relationship between gut microbiota and obesity were selected after a 16-different-keyword exhaustive search. A clear panorama of the current available options for the study of microbiota's influence on obesity, both for animal model election and technical approaches, is presented to the researcher. All the knowledge generated from the study of the microbiota opens the possibility of considering fecal transplantation as a relevant therapeutic alternative for obesity and other metabolic disease treatment.}, } @article {pmid30498879, year = {2018}, author = {Mathias, F and Curti, C and Montana, M and Bornet, C and Vanelle, P}, title = {Management of adult Clostridium difficile digestive contaminations: a literature review.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10096-018-3419-z}, pmid = {30498879}, issn = {1435-4373}, abstract = {Clostridium difficile infections (CDI) dramatically increased during the last decade and cause a major public health problem. Current treatments are limited by the high disease recurrence rate, severity of clinical forms, disruption of the gut microbiota, and colonization by vancomycin-resistant enterococci (VRE). In this review, we resumed current treatment options from official recommendation to promising alternatives available in the management of adult CDI, with regard to severity and recurring or non-recurring character of the infection. Vancomycin remains the first-line antibiotic in the management of mild to severe CDI. The use of metronidazole is discussed following the latest US recommendations that replaced it by fidaxomicin as first-line treatment of an initial episode of non-severe CDI. Fidaxomicin, the most recent antibiotic approved for CDI in adults, has several advantages compared to vancomycin and metronidazole, but its efficacy seems limited in cases of multiple recurrences. Innovative therapies such as fecal microbiota transplantation (FMT) and antitoxin antibodies were developed to limit the occurrence of recurrence of CDI. Research is therefore very active, and new antibiotics are being studied as surotomycin, cadazolid, and rinidazole.}, } @article {pmid30489686, year = {2018}, author = {Takahashi, M and Ishikawa, D and Sasaki, T and Lu, YJ and Kuwahara-Arai, K and Kamei, M and Shibuya, T and Osada, T and Hiramatsu, K and Nagahara, A}, title = {Fecal Freezing Preservation Period Influences Colonization Ability for Fecal Microbiota Transplantation.}, journal = {Journal of applied microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jam.14167}, pmid = {30489686}, issn = {1365-2672}, abstract = {AIMS: There has been growing interest in fecal microbiota transplantation (FMT) as treatment. Although, frozen donor feces preserved at -20°C has been widely used for practical advantages, freezing at -20°C can affect bacterial viability. Adequacy evaluation of fresh and frozen feces as the transplant is necessary for the methodological improvement of FMT.

METHODS AND RESULTS: The viable bacterial compositions of fecal specimens under fresh and freezing conditions were compared by a microbiome analysis using propidium monoazide (PMA microbiome). In addition, recovery abilities from bacterial reduction by antibiotics were compared between fresh and frozen FMT using a murine model. PMA microbiome results suggested that freezing and freeze-thawing didn't significantly affect in vitro fecal bacterial viability. However, the recovery effect from antimicrobial cleansing in frozen FMT was reduced in a freezing time-dependent manner, especially prominent in Actinobacteria and Bacteroidetes phyla.

CONCLUSIONS: Short-term freezing preservation of feces exhibited maintenance of enteric colonization ability in frozen FMT in comparison to 1 month -20°C-preservation.

SIGNIFICANCE AND IMPACT: Long-term -20°C-preservation of transplanted feces can result in instability of the clinical outcome in FMT therapy. The standardization of practical procedures of FMT therapy according to disease types is desirable. This article is protected by copyright. All rights reserved.}, } @article {pmid30483574, year = {2018}, author = {Shi, YC and Yang, YS}, title = {Fecal microbiota transplantation: Current status and challenges in China.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {2}, number = {4}, pages = {114-116}, doi = {10.1002/jgh3.12071}, pmid = {30483574}, issn = {2397-9070}, } @article {pmid30480772, year = {2018}, author = {Imdad, A and Nicholson, MR and Tanner-Smith, EE and Zackular, JP and Gomez-Duarte, OG and Beaulieu, DB and Acra, S}, title = {Fecal transplantation for treatment of inflammatory bowel disease.}, journal = {The Cochrane database of systematic reviews}, volume = {11}, number = {}, pages = {CD012774}, doi = {10.1002/14651858.CD012774.pub2}, pmid = {30480772}, issn = {1469-493X}, abstract = {BACKGROUND: Inflammatory bowel disease (IBD) is a chronic, relapsing disease of the gastrointestinal tract that is thought to be associated with a complex interplay between microbes and the immune system, leading to an abnormal inflammatory response in genetically susceptible individuals. Dysbiosis, characterized by the alteration of the composition of the resident commensal bacteria in a host compared to healthy individuals, is thought to play a major role in the pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD), two subtypes of IBD. There is growing interest to correct the underlying dysbiosis through the use of fecal microbiota transplantation (FMT) for the treatment of IBD.

OBJECTIVES: The objective of this systematic review was to assess the efficacy and safety of FMT for the treatment of IBD.

SEARCH METHODS: We searched the MEDLINE, Embase, Cochrane Library, and Cochrane IBD Group Specialized Register databases from inception to 19 March 2018. We also searched ClinicalTrials.gov, ISRCTN metaRegister of Controlled Trials, and the Conference Proceedings Citation Index.

SELECTION CRITERIA: Only randomized trials or non-randomized studies with a control arm were considered for inclusion. Adults or pediatric participants with UC or CD were eligible for inclusion. Eligible interventions were FMT defined as the administration of fecal material containing distal gut microbiota from a healthy donor to the gastrointestinal tract of a someone with UC or CD. The comparison group included participants who did not receive FMT and were given placebo, autologous FMT, or no intervention.

DATA COLLECTION AND ANALYSIS: Two authors independently screened the titles and extracted data from the included studies. We used the Cochrane risk of bias tool to assess study bias. The primary outcomes were induction of clinical remission, clinical relapse, and serious adverse events. Secondary outcomes included clinical response, endoscopic remission and endoscopic response, quality of life scores, laboratory measures of inflammation, withdrawals, and microbiome outcomes. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes and the mean difference and 95% CI for continuous outcomes. Random-effects meta-analysis models were used to synthesize effect sizes across trials. The overall certainty of the evidence supporting the primary and selected secondary outcomes was rated using the GRADE criteria.

MAIN RESULTS: Four studies with a total of 277 participants were included. These studies assessed the efficacy of FMT for treatment of UC in adults; no eligible trials were found for the treatment of CD. Most participants had mild to moderate UC. Two studies were conducted in Australia, one study was conducted in Canada, and another in the Netherlands. Three of the included studies administered FMT via the rectal route and one study administered FMT via the nasoduodenal route. Three studies were rated as low risk of bias. One study (abstract publication) was rated as unclear risk of bias. Combined results from four studies (277 participants) suggest that FMT increases rates of clinical remission by two-fold in patients with UC compared to controls. At 8 weeks, 37% (52/140) of FMT participants achieved remission compared to 18% (24/137) of control participants (RR 2.03, 95 % CI, 1.07 to 3.86; I² = 50%; low certainty evidence). One study reported data on relapse at 12 weeks among participants who achieved remission. None of the FMT participants (0/7) relapsed at 12 weeks compared to 20% of control participants (RR 0.28, 95% CI 0.02 to 4.98, 17 participants, very low certainty evidence). It is unclear whether there is a difference in serious adverse event rates between the intervention and control groups. Seven per cent (10/140) of FMT participants had a serious adverse event compared to 5% (7/137) of control participants (RR 1.40, 95% CI 0.55 to 3.58; 4 studies; I² = 0%; low certainty evidence). Serious adverse events included worsening of UC necessitating intravenous steroids or surgery; infection such as Clostridium difficile and cytomegalovirus, small bowel perforation and pneumonia. Adverse events were reported by two studies and the pooled data did not show any difference between the study groups. Seventy-eight per cent (50/64) of FMT participants had an adverse event compared to 75% (49/65) of control participants (RR 1.03, 95% CI 0.81 to 1.31; I² = 31%; moderate certainty evidence). Common adverse events included abdominal pain, nausea, flatulence, bloating, upper respiratory tract infection, headaches, dizziness, and fever. Four studies reported on clinical response at 8 weeks. Forty-nine per cent (68/140) of FMT participants had a clinical response compared to 28% (38/137) of control participants (RR 1.70, 95% CI 0.98 to 2.95, I² = 50%, low certainty evidence). Endoscopic remission at 8 weeks was reported by three studies and the combined results favored FMT over the control group. Thirty per cent (35/117) of FMT participants achieved endoscopic remission compared to 10% (11/112) of control participants (RR 2.96, 95 % CI 1.60 to 5.48, I² = 0%; low certainty evidence).

AUTHORS' CONCLUSIONS: Fecal microbiota transplantation may increase the proportion of participants achieving clinical remission in UC. However, the number of identified studies was small and the quality of evidence was low. There is uncertainty about the rate of serious adverse events. As a result, no solid conclusions can be drawn at this time. Additional high-quality studies are needed to further define the optimal parameters of FMT in terms of route, frequency, volume, preparation, type of donor and the type and disease severity. No studies assessed efficacy of FMT for induction of remission in CD or in pediatric participants. In addition, no studies assessed long-term maintenance of remission in UC or CD. Future studies are needed to address the therapeutic benefit of FMT in CD and the long-term FMT-mediated maintenance of remission in UC or CD.}, } @article {pmid30479380, year = {2018}, author = {Wang, Y and Wiesnoski, DH and Helmink, BA and Gopalakrishnan, V and Choi, K and DuPont, HL and Jiang, ZD and Abu-Sbeih, H and Sanchez, CA and Chang, CC and Parra, ER and Francisco-Cruz, A and Raju, GS and Stroehlein, JR and Campbell, MT and Gao, J and Subudhi, SK and Maru, DM and Blando, JM and Lazar, AJ and Allison, JP and Sharma, P and Tetzlaff, MT and Wargo, JA and Jenq, RR}, title = {Author Correction: Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41591-018-0305-2}, pmid = {30479380}, issn = {1546-170X}, abstract = {In the version of this article originally published, an author was missing from the author list. Alexander J. Lazar should have been included between Jorge M. Blando and James P. Allison. The author has been added to the list, and the author contributions section has been updated to include Alexander J. Lazar's contribution to the study. The error has been corrected in the print, PDF and HTML versions of the manuscript.}, } @article {pmid29980607, year = {2018}, author = {Halkjær, SI and Christensen, AH and Lo, BZS and Browne, PD and Günther, S and Hansen, LH and Petersen, AM}, title = {Faecal microbiota transplantation alters gut microbiota in patients with irritable bowel syndrome: results from a randomised, double-blind placebo-controlled study.}, journal = {Gut}, volume = {67}, number = {12}, pages = {2107-2115}, doi = {10.1136/gutjnl-2018-316434}, pmid = {29980607}, issn = {1468-3288}, mesh = {Adolescent ; Adult ; Double-Blind Method ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/microbiology/*therapy ; Male ; Middle Aged ; Psychometrics ; Quality of Life ; Severity of Illness Index ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: IBS is associated with an intestinal dysbiosis and faecal microbiota transplantation (FMT) has been hypothesised to have a positive effect in patients with IBS. We performed a randomised, double-blind placebo-controlled trial to investigate if FMT resulted in an altered gut microbiota and improvement in clinical outcome in patients with IBS.

DESIGN: We performed this study in 52 adult patients with moderate-to-severe IBS. At the screening visit, clinical history and symptoms were assessed and faecal samples were collected. Patients were randomised to FMT or placebo capsules for 12 days and followed for 6 months. Study visits were performed at baseline, 1, 3 and 6 months, where patients were asked to register their symptoms using the IBS-severity scoring system (IBS-SSS) and IBS-specific quality of life (IBS-QoL). Prior to each visit, faecal samples were collected.

RESULTS: A significant difference in improvement in IBS-SSS score was observed 3 months after treatment (p=0.012) favouring placebo. This was similar for IBS-QoL data after 3 months (p=0.003) favouring placebo. Patients receiving FMT capsules had an increase in faecal microbial biodiversity while placebos did not.

CONCLUSION: In this randomised double-blinded placebo-controlled study, we found that FMT changed gut microbiota in patients with IBS. But patients in the placebo group experienced greater symptom relief compared with the FMT group after 3 months. Altering the gut microbiota is not enough to obtain clinical improvement in IBS. However, different study designs and larger studies are required to examine the role of FMT in IBS.

TRIAL REGISTRATION NUMBER: NCT02788071.}, } @article {pmid30474827, year = {2018}, author = {Mehta, R and Kabrawala, M and Nandwani, S and Kalra, P and Patel, C and Desai, P and Parekh, K}, title = {Preliminary experience with single fecal microbiota transplant for treatment of recurrent overt hepatic encephalopathy-A case series.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12664-018-0906-1}, pmid = {30474827}, issn = {0975-0711}, abstract = {Experimental studies demonstrated that fecal microbiota transplant (FMT) may reverse intestinal microbial dysbiosis. In this retrospective case series, we share our experience of treating recurrent overt hepatic encephalopathy (HE) with single FMT treatment. A total of 10 patients, age ranged from 25 to 65 years, were treated with single FMT through colonoscopy using fecal material received from rigorously screened patient-identified donors. There was sustained clinical response with single FMT treatment in 6 patients at post-treatment week 20. Arterial ammonia concentration decreased considerably (96 [87.25-117.75] vs. 74 [70-82]; p = 0.024) at post-treatment week 20. Moreover, there was statistically significant decrease in Child-Turcotte-Pugh (CTP) score (9.5 [9-10.75] vs. 8 [7-8]; p = 0.005) and model for end-stage liver disease (MELD) score (18 [16.25-19] vs. 15 [14-16]; p = 0.008). Four patients experienced six adverse-events. Overt HE and re-hospitalization were observed in 3 and 2 patients, respectively. One patient (who also experienced overt HE) died within 2 months of the index procedure.}, } @article {pmid30474116, year = {2018}, author = {Dai, Z and Zhang, J and Wu, Q and Chen, J and Liu, J and Wang, L and Chen, C and Xu, J and Zhang, H and Shi, C and Li, Z and Fang, H and Lin, C and Tang, D and Wang, D}, title = {The role of microbiota in the development of colorectal cancer.}, journal = {International journal of cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/ijc.32017}, pmid = {30474116}, issn = {1097-0215}, abstract = {Colorectal cancer is the third largest cancer in worldwide and has been proven to be closely related to the intestinal microbiota. Many reports and clinical studies have shown that intestinal microbial behavior may lead to pathological changes in the host intestines. The changes can be divided into epigenetic changes and carcinogenic changes at the gene level, which ultimately promote the production and development of colorectal cancer. This article reviews the pathways of microbial signaling in the intestinal epithelial barrier, the role of microbiota in inflammatory colorectal tumors, and typical microbial carcinogenesis. Finally, by gaining a deeper understanding of the intestinal microbiota, we hope to achieve the goal of treating colorectal cancer using current microbiota technologies, such as fecal microbiological transplantation.}, } @article {pmid30462253, year = {2018}, author = {Riddle, MS and Connor, BA}, title = {Fecal microbiota transplantation: what is the role in travelers' diarrhea?.}, journal = {Journal of travel medicine}, volume = {}, number = {}, pages = {}, doi = {10.1093/jtm/tay129}, pmid = {30462253}, issn = {1708-8305}, } @article {pmid30172346, year = {2018}, author = {Hum, RM and Deambrosis, D and Lum, SH and Davies, E and Bonney, D and Guiver, M and Turner, A and Wynn, RF and Hiwarkar, P}, title = {Molecular monitoring of adenovirus reactivation in faeces after haematopoietic stem-cell transplantation to predict systemic infection: a retrospective cohort study.}, journal = {The Lancet. Haematology}, volume = {5}, number = {9}, pages = {e422-e429}, doi = {10.1016/S2352-3026(18)30130-3}, pmid = {30172346}, issn = {2352-3026}, mesh = {Adenoviridae/*physiology ; Adenoviridae Infections/*diagnosis ; Child ; Child, Preschool ; Cohort Studies ; Feces/*virology ; Female ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Infant ; Male ; Prognosis ; Retrospective Studies ; *Virus Activation ; }, abstract = {BACKGROUND: Faecal shedding of adenovirus following allogeneic haematopoietic stem-cell transplantation (HSCT) is an early sign of loss of immune control over adenovirus, but there is no consensus on the role of monitoring of faecal adenoviral load by serial testing. We investigated whether serial faecal PCR monitoring could predict the risk of adenoviraemia and survival outcomes after HSCT.

METHODS: We did a retrospective cohort study at the Royal Manchester Children's Hospital, Manchester, UK, of patients who had received their first allogeneic HSCT between Feb 1, 2003, and Sept 1, 2016, and adenovirus infection recorded in their medical records. We excluded patients who had received second or third transplants or autologous HSCT transplants. We obtained characteristics of patients and transplants, including mortality and adenoviral reactivation, from medical records and the hospital database. All patients had blood samples tested weekly for adenovirus by PCR until immunosuppression was stopped and CD3 T-cell count recovered to greater than 0·3 × 109/L. Faecal PCR was done before transplantation in all patients, and after transplantation in patients who had diarrhoea, at the onset of symptoms and weekly thereafter until diarrhoea resolved. We analysed all samples available before and after HSCT. We did subgroup analyses for patients undergoing HSCT for cancer versus non-malignant conditions. We also assessed whether 5 log10 copies per g faeces was a suitable predictive threshold for adenoviraemia.

FINDINGS: We included 341 patients who had undergone a first allogeneic HSCT (median age 4·6 years, IQR 1·5-8·0, range 0-20·0). After HSCT, PCR was done in 4116 faecal samples from 293 (86%) patients who had diarrhoea and in 10 649 blood samples from 341 patients. Follow-up ended on July 14, 2017. 173 (59%) of 293 patients had adenovirus in faecal samples and 63 (18%) of 341 had adenovirus in blood samples. Maximum faecal viral load before adenoviraemia correlated significantly with maximum blood viral load (r=0·51, 95% CI 0·38-0·61, p<0·0001). Faecal adenoviral viral load greater than 5 log10 copies per g faeces was predictive of adenoviraemia (odds ratio 10·2, 95% CI 4·9-21·6, p<0·0001) with sensitivity 75·9% and specificity 74·8%. These values were increased further in patients with cancer, to 86·4% and 87·5%, respectively. Among the 28 patients who had positive faecal and blood samples and who had undergone serial faecal PCR monitoring after HSCT, the median time between reaching the faecal viral load threshold and onset of adenoviraemia was 8·0 days (IQR 2·3-21·8, 95% CI 4·0-16·0). Non-relapse mortality was not associated with adenovirus reactivation in faeces alone (9·2%, 95% CI 5·4-14·3 in patients without reactivation vs 7·8%, 3·8-13·7 in those with positive faeces only), but was significantly increased in patients who developed adenoviraemia (27·0%, 95% CI 16·7-38·4, p<0·0001).

INTERPRETATION: We identified a threshold faecal viral load that can predict the risk of adenoviraemia. Our findings support proliferation of adenovirus in the gastrointestinal tract before viraemia develops. Faecal PCR is suitable for early detection of children and young adults at risk of adenoviraemia, and its use might help reduce non-relapse mortality in allogeneic HSCT recipients.

FUNDING: None.}, } @article {pmid30472293, year = {2018}, author = {Saïdani, N and Lagier, JC and Cassir, N and Million, M and Baron, S and Dubourg, G and Eldin, C and Kerbaj, J and Valles, C and Raoult, D and Brouqui, P}, title = {Fecal microbiota transplantation shortens the colonization period and allows the re-entry of patients carrying carbapenamase-producing bacteria into medical care facilities.}, journal = {International journal of antimicrobial agents}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ijantimicag.2018.11.014}, pmid = {30472293}, issn = {1872-7913}, abstract = {BACKGROUND: Colonization with carbapenemase producing Enterobacteriaceae or Acinetobacter (CPE/A) is associated with complex medical care requiring implementation of specific isolation policies and limitation of patient discharge to other medical facilities. Fecal Microbiota Transplantation (FMT) has been proposed in order to reduce the duration of gut colonization.

OBJECTIVES: We investigated whether a dedicated protocol of FMT could reduce the negativation time of CPE/A intestinal carriage in patients whose medical care has been delayed due to such colonization.

METHOD: We performed a matched case-control retrospective study between patients who received FMT treatment and those who did not among CPE/A colonized patient addressed for initial clustering at our institute. We adjusted two controls per case based on sex, age, bacterial species and carbapenemase type. The primary outcome was the delay in negativation of rectal-swab cultures.

RESULTS: At day 14 post-FMT, 8/10 (80%) treated patients were cleared for intestinal CPE/A carriage. In the control group, 2/20 (10%) had a spontaneous clearance at day 14 after CPE/A diagnostic. FMT led patients to reduce the delay of decolonization (median 3 days post-FMT for treated patients versus 50.5 days after the first documentation of digestive carriage for control patients) and discharge from the hospital (median 19.5 days post-FMT for treated patients versus 41 for control patients).

CONCLUSION: FMT is a safe and time saving procedure to discharge CPE/A-colonized patients from the hospital. A standardized protocol including 5 days of antibiotic treatment, bowel cleansing and systematic indwelling devices removal should improve the effectiveness of the protocol.}, } @article {pmid30470860, year = {2018}, author = {Tillmann, S and Abildgaard, A and Winther, G and Wegener, G}, title = {Altered fecal microbiota composition in the Flinders sensitive line rat model of depression.}, journal = {Psychopharmacology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00213-018-5094-2}, pmid = {30470860}, issn = {1432-2072}, abstract = {RATIONALE: The gut microbiota is increasingly recognized as a potential mediator of psychiatric diseases. Depressed patients have been shown to have a different microbiota composition compared with healthy controls, and several lines of research now aim to restore this dysbiosis. To develop novel treatments, preclinical models may provide novel mechanistic insights.

OBJECTIVE AND METHODS: We characterized the gut microbiota of male adult Flinders sensitive line (FSL) rats, an animal model of depression, and their controls, Flinders resistant line (FRL) rats using 16S rRNA amplicon sequencing. Moreover, we performed fecal microbiota transplantation (using saline or pooled FRL/FSL feces) to study if the potential strain-specific differences could be transferred from one strain to the other, and if these differences were reflected in their depressive-like behavior in the forced swim test.

RESULTS: FSL rats tended to have lower bacterial richness and altered relative abundances of several bacterial phyla, families, and species, including higher Proteobacteria and lower Elusimicrobia and Saccharibacteria. There was a clear separation between FRL and FSL rat strains, but no effect of treatment, i.e., the bacterial composition of FSL rats receiving FRL feces was still more similar to FSL and not FRL rats. Similarly, the transplantation did not reverse behavioral differences in the forced swim test, although FSL feces significantly increased immobility compared with saline.

CONCLUSIONS: Our study showed that the gut microbiota composition of the depressive-like rats markedly differed from their controls, which may be of value for future microbiota-targeted work in this and similar animal models.}, } @article {pmid30463925, year = {2018}, author = {Bulow, C and Langdon, A and Hink, T and Wallace, M and Reske, KA and Patel, S and Sun, X and Seiler, S and Jones, S and Kwon, JH and Burnham, CA and Dantas, G and Dubberke, ER}, title = {Impact of Amoxicillin-Clavulanate followed by Autologous Fecal Microbiota Transplantation on Fecal Microbiome Structure and Metabolic Potential.}, journal = {mSphere}, volume = {3}, number = {6}, pages = {}, doi = {10.1128/mSphereDirect.00588-18}, pmid = {30463925}, issn = {2379-5042}, abstract = {Strategies to prevent multidrug-resistant organism (MDRO) infections are scarce, but autologous fecal microbiota transplantation (autoFMT) may limit gastrointestinal MDRO expansion. AutoFMT involves banking one's feces during a healthy state for later use in restoring gut microbiota following perturbation. This pilot study evaluated the effect of autoFMT on gastrointestinal microbiome taxonomic composition, resistance gene content, and metabolic capacity after exposure to amoxicillin-clavulanic acid (Amox-Clav). Ten healthy participants were enrolled. All received 5 days of Amox-Clav. Half were randomized to autoFMT, derived from stool collected pre-antimicrobial exposure, by enema, and half to saline enema. Participants submitted stool samples pre- and post-Amox-Clav and enema and during a 90-day follow-up period. Shotgun metagenomic sequencing revealed taxonomic composition, resistance gene content, and metabolic capacity. Amox-Clav significantly altered gut taxonomic composition in all participants (n = 10, P < 0.01); however, only three participants exhibited major changes at the phylum level following exposure. In the cohort as a whole, beta-lactamase genes were enriched following Amox-Clav (P < 0.05), and predicted metabolic capacity was significantly altered (P < 0.01). Species composition, metabolic capacity, and beta-lactamase abundance returned to pre-antimicrobial exposure state 7 days after either autoFMT or saline enema (P > 0.05, compared to enrollment). Alterations to microbial metabolic capacity occurred following antimicrobial exposure even in participants without substantial taxonomic disruption, potentially creating open niches for pathogen colonization. Our findings suggest that metabolic potential is an important consideration for complete assessment of antimicrobial impact on the microbiome. AutoFMT was well tolerated and may have contributed to phylogenetic recovery. (This study has been registered at ClinicalTrials.gov under identifier NCT02046525.)IMPORTANCE The spread of multidrug resistance among pathogenic organisms threatens the efficacy of antimicrobial treatment options. The human gut serves as a reservoir for many drug-resistant organisms and their resistance genes, and perturbation of the gut microbiome by antimicrobial exposure can open metabolic niches to resistant pathogens. Once established in the gut, antimicrobial-resistant bacteria can persist even after antimicrobial exposure ceases. Strategies to prevent multidrug-resistant organism (MDRO) infections are scarce, but autologous fecal microbiota transplantation (autoFMT) may limit gastrointestinal MDRO expansion. AutoFMT involves banking one's feces during a healthy state for later use in restoring gut microbiota following perturbation. This pilot study evaluated the effect of amoxicillin-clavulanic acid (Amox-Clav) exposure and autoFMT on gastrointestinal microbiome taxonomic composition, resistance gene content, and metabolic capacity. Importantly, we found that metabolic capacity was perturbed even in cases where gross phylogeny remained unchanged and that autoFMT was safe and well tolerated.}, } @article {pmid30458058, year = {2018}, author = {Chen, D and Wu, J and Jin, D and Wang, B and Cao, H}, title = {Fecal microbiota transplantation in cancer management: Current status and perspectives.}, journal = {International journal of cancer}, volume = {}, number = {}, pages = {}, doi = {10.1002/ijc.32003}, pmid = {30458058}, issn = {1097-0215}, abstract = {The human gut is home to a large and diverse microbial community, comprising about 1000 bacterial species. The gut microbiota exists in a symbiotic relationship with its host, playing a decisive role in the host's nutrition, immunity, and metabolism. Accumulating studies have revealed the associations between gut dysbiosis or some special bacteria and various cancers. Emerging data suggest that gut microbiota can modulate the effectiveness of cancer therapies, especially immunotherapy. Manipulating the microbial populations with therapeutic intent has become a hot topic of cancer research, and the most dramatic manipulation of gut microbiota refers to fecal microbiota transplantation (FMT) from healthy individuals to patients. FMT has demonstrated remarkable clinical efficacy against Clostridium difficile infection (CDI) and it is highly recommended for the treatment of recurrent or refractory CDI. Lately, interest is growing in the therapeutic potential of FMT for other diseases, including cancers. We briefly reviewed the current researches about gut microbiota and its link to cancer, and then summarized the recent pre-clinical and clinical evidence to indicate the potential of FMT in cancer management as well as cancer-treatment associated complications. We also presented the rationale of FMT for cancer management such as reconstruction of intestinal microbiota, amelioration of bile acid metabolism, and modulation of immunotherapy efficacy. This article would help to better understand this new therapeutic approach for cancer patients by targeting gut microbiota. This article is protected by copyright. All rights reserved.}, } @article {pmid30455884, year = {2018}, author = {Ohara, T and Suzutani, T}, title = {Efficacy of fecal microbiota transplantation in a patient with chronic intractable constipation.}, journal = {Clinical case reports}, volume = {6}, number = {11}, pages = {2029-2032}, doi = {10.1002/ccr3.1798}, pmid = {30455884}, issn = {2050-0904}, abstract = {We have presented the first case report of FMT therapy for a patient with chronic intractable constipation. This therapy resulted in good, medium-term outcomes. Follow-up analysis of the intestinal flora suggested that transplanted microbes from the donor, particularly Bifidobacterium and Clostridium cluster IX, may have been incorporated into the recipient.}, } @article {pmid30455339, year = {2018}, author = {Weis, M}, title = {Impact of the gut microbiome in cardiovascular and autoimmune diseases.}, journal = {Clinical science (London, England : 1979)}, volume = {132}, number = {22}, pages = {2387-2389}, doi = {10.1042/CS20180410}, pmid = {30455339}, issn = {1470-8736}, abstract = {The gut microbiome functions like an endocrine organ, generating enzymes and bioactive metabolites, which affect host physiology. In addition metabolism-independent processes like impaired intestinal barrier function may result in bacterial translocation and an increased inflammation. Specific microbe-associated molecular patterns (MAMPs) have been detected that induce immune activation via cognate pattern-recognition receptors on host immune cells, with subsequent consequences on inflammatory-induced endothelial dysfunction. Alterations in intestinal microbial and metabolic composition play an important role in human health and disease, including cardiovascular and autoimmune diseases. Changes in the composition of gut microbiota (dysbiosis) are linked to chronic inflammation, thrombosis, atherogenesis, chronic heart, and kidney disease, as well as to autoimmune diseases like systemic lupus erythematodes. Although non-selective approaches that broadly alter microbial community structure, such as prebiotics, probiotics, and fecal microbial transplantation, may have some promise, targeting defined microbial pathways and adjacent host immune responses may be the ultimate scientific goal.}, } @article {pmid30450088, year = {2018}, author = {Li, X and Gao, X and Hu, H and Xiao, Y and Li, D and Yu, G and Yu, D and Zhang, T and Wang, Y}, title = {Clinical Efficacy and Microbiome Changes Following Fecal Microbiota Transplantation in Children With Recurrent Clostridium Difficile Infection.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2622}, doi = {10.3389/fmicb.2018.02622}, pmid = {30450088}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) has been shown as an effective treatment for recurrent clostridium difficile infection (RCDI) in adults. In this study, we aim to evaluate the clinical efficacy of FMT in treating children with RCDI, and explore fecal microbiota changes during FMT treatment. A total of 11 RCDI subjects with a median age of 3.5 years were enrolled in this single-center prospective pilot study. All patients were cured (11/11, 100%) by FMT either through upper gastrointestinal tract route with a nasointestinal tube (13/16, 81.2%) or lower gastrointestinal tract route with a rectal tube (3/16, 18.8%). The cure rate of single FMT was 63.6% (7/11), and 4 (4/11, 36.4%) cases were performed with 2 or 3 times of FMT. Mild adverse events were reported in 4 children (4/11, 36.4%), including transient diarrhea, mild abdominal pain, transient fever and vomit. Gut microbiota composition analysis of 59 fecal samples collected from 34 participants (9 RCDI children, 9 donors and 16 health controls) showed that the alpha diversity was lower in pediatric RCDI patients before FMT than the healthy controls and donors, and fecal microbial community of pre-FMT samples (beta diversity) was apart from that of healthy controls and donors. No significant differences in alpha diversity, beta diversity or phylogenetic distance were detected between donors and healthy controls. Both the richness and diversity of gut microbiota were improved in the pediatric RCDI patients after FMT, and the bacteria community was shifted closer to the donor and healthy control group. Furthermore, FMT re-directed gut microbiome functions of pediatric RCDI toward a health state. Our results indicate that it is safe and tolerant to use FMT in treating pediatric RCDI. FMT shifted the gut microbiome composition and function in children with RCDI toward a healthy state.}, } @article {pmid30449078, year = {2018}, author = {Sood, A and Mahajan, R and Juyal, G and Midha, V and Grewal, CS and Mehta, V and Singh, A and Joshi, MC and Narang, V and Kaur, K and Sidhu, H}, title = {Efficacy of fecal microbiota therapy in steroid dependent ulcerative colitis: a real world intention-to-treat analysis.}, journal = {Intestinal research}, volume = {}, number = {}, pages = {}, doi = {10.5217/ir.2018.00089}, pmid = {30449078}, issn = {1598-9100}, abstract = {Background/Aims: Four high-quality randomized controlled trials have proven the efficacy of fecal microbiota transplantation (FMT) in active ulcerative colitis (UC). We assessed the efficacy of FMT in a real-world setting involving steroid-dependent patients with UC.

Methods: This was a single-center prospective analysis of data from steroid-dependent patients with UC treated with FMT from September 2015 to September 2017 at the Dayanand Medical College, a tertiary care center in India. Fecal samples from random unrelated donors were administered through colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22. The primary outcome was achievement of steroid-free clinical remission, and the secondary outcomes were clinical response and endoscopic remission at 24 weeks. Modified intention-to-treat analysis was performed, which included subjects who underwent at least 1 FMT.

Results: Of 345 patients with UC treated during the study period, 49 (14.2%) had steroid-dependent UC. Of these 49 patients, 41 underwent FMT: 33 completed 7 sessions over 22 weeks according to the protocol, and 8 discontinued treatment (non-response, 5; lost to follow-up, 2; and fear of adverse effects, 1). At week 24, steroid-free clinical remission was achieved in 19 out of 41 (46.3%) patients, whereas clinical response and endoscopic remission were achieved in 31 out of 41 (75.6%) and 26 out of 41 (63.4%) patients, respectively. All patients with clinical response were able to withdraw steroids. There were no serious adverse events necessitating discontinuation.

Conclusions: A multisession FMT via the colonoscopic route is a promising therapeutic option for patients with steroid-dependent UC, as it can induce clinical remission and aid in steroid withdrawal.}, } @article {pmid30442907, year = {2018}, author = {Zhou, W and Chow, KH and Fleming, E and Oh, J}, title = {Selective colonization ability of human fecal microbes in different mouse gut environments.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41396-018-0312-9}, pmid = {30442907}, issn = {1751-7370}, support = {1 DP2 GM126893-01//U.S. Department of Health & Human Services | National Institutes of Health (NIH)/ ; ACS-RSG-16-255-01-MPC//American Cancer Society (American Cancer Society, Inc.)/ ; }, abstract = {Mammalian hosts constantly interact with diverse exogenous microbes, but only a subset of the microbes manage to colonize due to selective colonization resistance exerted by host genetic factors as well as the native microbiota of the host. An important question in microbial ecology and medical science is if such colonization resistance can discriminate closely related microbial species, or even closely related strains of the same species. Using human-mouse fecal microbiota transplantation and metagenomic shotgun sequencing, we reconstructed colonization patterns of human fecal microbes in mice with different genotypes (C57BL6/J vs. NSG) and with or without an intact gut microbiota. We found that mouse genotypes and the native mouse gut microbiota both exerted different selective pressures on exogenous colonizers: human fecal Bacteroides successfully established in the mice gut, however, different species of Bacteroides selectively enriched under different gut conditions, potentially due to a multitude of functional differences, ranging from versatility in nutrient acquisition to stress responses. Additionally, different clades of Bacteroides cellulosilyticus strains were selectively enriched in different gut conditions, suggesting that the fitness of conspecific microbial strains in a novel host environment could differ.}, } @article {pmid30446486, year = {2018}, author = {Kaito, S and Toya, T and Yoshifuji, K and Kurosawa, S and Inamoto, K and Takeshita, K and Suda, W and Kakihana, K and Honda, K and Hattori, M and Ohashi, K}, title = {Fecal microbiota transplantation with frozen capsules for a patient with refractory acute gut graft-versus-host disease.}, journal = {Blood advances}, volume = {2}, number = {22}, pages = {3097-3101}, doi = {10.1182/bloodadvances.2018024968}, pmid = {30446486}, issn = {2473-9537}, } @article {pmid29743671, year = {2018}, author = {Shepherd, ES and DeLoache, WC and Pruss, KM and Whitaker, WR and Sonnenburg, JL}, title = {An exclusive metabolic niche enables strain engraftment in the gut microbiota.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {434-438}, doi = {10.1038/s41586-018-0092-4}, pmid = {29743671}, issn = {1476-4687}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteroides/growth & development/isolation & purification/physiology ; Colon/*microbiology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Mice ; Sepharose/analogs & derivatives/metabolism ; }, abstract = {The dense microbial ecosystem in the gut is intimately connected to numerous facets of human biology, and manipulation of the gut microbiota has broad implications for human health. In the absence of profound perturbation, the bacterial strains that reside within an individual are mostly stable over time 1 . By contrast, the fate of exogenous commensal and probiotic strains applied to an established microbiota is variable, generally unpredictable and greatly influenced by the background microbiota2,3. Therefore, analysis of the factors that govern strain engraftment and abundance is of critical importance to the emerging field of microbiome reprogramming. Here we generate an exclusive metabolic niche in mice via administration of a marine polysaccharide, porphyran, and an exogenous Bacteroides strain harbouring a rare gene cluster for porphyran utilization. Privileged nutrient access enables reliable engraftment of the exogenous strain at predictable abundances in mice harbouring diverse communities of gut microbes. This targeted dietary support is sufficient to overcome priority exclusion by an isogenic strain 4 , and enables strain replacement. We demonstrate transfer of the 60-kb porphyran utilization locus into a naive strain of Bacteroides, and show finely tuned control of strain abundance in the mouse gut across multiple orders of magnitude by varying porphyran dosage. Finally, we show that this system enables the introduction of a new strain into the colonic crypt ecosystem. These data highlight the influence of nutrient availability in shaping microbiota membership, expand the ability to perform a broad spectrum of investigations in the context of a complex microbiota, and have implications for cell-based therapeutic strategies in the gut.}, } @article {pmid30427836, year = {2018}, author = {Mazzawi, T and Lied, GA and Sangnes, DA and El-Salhy, M and Hov, JR and Gilja, OH and Hatlebakk, JG and Hausken, T}, title = {The kinetics of gut microbial community composition in patients with irritable bowel syndrome following fecal microbiota transplantation.}, journal = {PloS one}, volume = {13}, number = {11}, pages = {e0194904}, doi = {10.1371/journal.pone.0194904}, pmid = {30427836}, issn = {1932-6203}, abstract = {BACKGROUND: Gut microbiota alterations are important in irritable bowel syndrome (IBS). The aim was to investigate the effect of fecal microbiota transplantation (FMT) on gut microbiota and the symptoms in patients with IBS.

MATERIAL AND METHODS: The study included 13 IBS patients according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered to the descending part of the duodenum via a gastroscope. Feces were collected from donors and patients before FMT, and from the patients at 1, 3 and 12 weeks and donors and patients at 20/28 weeks after FMT. Microbiota analysis was performed using GA-map Dysbiosis test (Genetic Analysis AS, Oslo, Norway). The patients completed the following questionnaires before and at the aforementioned weeks after FMT: IBS Symptom Questionnaire (IBS-SQ), IBS-Symptom Severity Scoring system (IBS-SSS), Short Form of Nepean Dyspepsia Index (SF-NDI), Bristol stool form scale, the Eysenck Personality Questionnaire-Neuroticism and Hospital Anxiety and Depression.

RESULTS: Donors and IBS patients had significantly different bacterial strain signals before FMT (Ruminococcus gnavus, Actinobacteria and Bifidobacteria) that became non-significant after 3 weeks following FMT. The changes in gut microbiota were similar between donors and patients at 20/28 weeks after FMT. Thus, patients' microbiota profiles became more-or-less similar to donors. The scores of all the questionnaires were significantly improved at all time points following FMT. No reported adverse effects.

CONCLUSIONS: FMT was associated with a change in gut microbiota and improvement in IBS symptoms and quality of life lasting for up to 28 weeks.

TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03333291.}, } @article {pmid30424806, year = {2018}, author = {Kaliannan, K and Robertson, RC and Murphy, K and Stanton, C and Kang, C and Wang, B and Hao, L and Bhan, AK and Kang, JX}, title = {Estrogen-mediated gut microbiome alterations influence sexual dimorphism in metabolic syndrome in mice.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {205}, doi = {10.1186/s40168-018-0587-0}, pmid = {30424806}, issn = {2049-2618}, abstract = {BACKGROUND: Understanding the mechanism of the sexual dimorphism in susceptibility to obesity and metabolic syndrome (MS) is important for the development of effective interventions for MS.

RESULTS: Here we show that gut microbiome mediates the preventive effect of estrogen (17β-estradiol) on metabolic endotoxemia (ME) and low-grade chronic inflammation (LGCI), the underlying causes of MS and chronic diseases. The characteristic profiles of gut microbiome observed in female and 17β-estradiol-treated male and ovariectomized mice, such as decreased Proteobacteria and lipopolysaccharide biosynthesis, were associated with a lower susceptibility to ME, LGCI, and MS in these animals. Interestingly, fecal microbiota-transplant from male mice transferred the MS phenotype to female mice, while antibiotic treatment eliminated the sexual dimorphism in MS, suggesting a causative role of the gut microbiome in this condition. Moreover, estrogenic compounds such as isoflavones exerted microbiome-modulating effects similar to those of 17β-estradiol and reversed symptoms of MS in the male mice. Finally, both expression and activity of intestinal alkaline phosphatase (IAP), a gut microbiota-modifying non-classical anti-microbial peptide, were upregulated by 17β-estradiol and isoflavones, whereas inhibition of IAP induced ME and LGCI in female mice, indicating a critical role of IAP in mediating the effects of estrogen on these parameters.

CONCLUSIONS: In summary, we have identified a previously uncharacterized microbiome-based mechanism that sheds light upon sexual dimorphism in the incidence of MS and that suggests novel therapeutic targets and strategies for the management of obesity and MS in males and postmenopausal women.}, } @article {pmid30420754, year = {2018}, author = {Wang, Y and Wiesnoski, DH and Helmink, BA and Gopalakrishnan, V and Choi, K and DuPont, HL and Jiang, ZD and Abu-Sbeih, H and Sanchez, CA and Chang, CC and Parra, ER and Francisco-Cruz, A and Raju, GS and Stroehlein, JR and Campbell, MT and Gao, J and Subudhi, SK and Maru, DM and Blando, JM and Allison, JP and Sharma, P and Tetzlaff, MT and Wargo, JA and Jenq, RR}, title = {Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis.}, journal = {Nature medicine}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41591-018-0238-9}, pmid = {30420754}, issn = {1546-170X}, abstract = {We report the first case series of immune checkpoint inhibitors (ICI)-associated colitis successfully treated with fecal microbiota transplantation, with reconstitution of the gut microbiome and a relative increase in the proportion of regulatory T-cells within the colonic mucosa. These preliminary data provide evidence that modulation of the gut microbiome may abrogate ICI-associated colitis.}, } @article {pmid29895922, year = {2018}, author = {Reardon, S}, title = {Faecal transplants could help preserve vulnerable species.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {173-174}, doi = {10.1038/d41586-018-05352-1}, pmid = {29895922}, issn = {1476-4687}, mesh = {Animals ; Animals, Wild/microbiology ; Animals, Zoo/microbiology ; Anura/microbiology ; Conservation of Natural Resources/*methods ; Diet/*veterinary ; *Endangered Species ; Eucalyptus ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Food Preferences ; Gastrointestinal Microbiome/*physiology ; Male ; Mycoses/microbiology/prevention & control/veterinary ; Perissodactyla/*microbiology/physiology ; Phascolarctidae/*microbiology/physiology ; Survival Rate ; }, } @article {pmid29205849, year = {2018}, author = {Kreft, JU}, title = {Editorial: The microbiome as a source of new enterprises and job creation.}, journal = {Microbial biotechnology}, volume = {11}, number = {1}, pages = {145-148}, doi = {10.1111/1751-7915.13026}, pmid = {29205849}, issn = {1751-7915}, support = {NC/K000683/1//National Centre for the Replacement, Refinement and Reduction of Animals in Research/International ; }, mesh = {Biomedical Research/*trends ; Dysbiosis/*prevention & control/*therapy ; Fecal Microbiota Transplantation/methods ; *Microbiota ; Probiotics/administration & dosage ; }, } @article {pmid28430063, year = {2017}, author = {Haw, J and Chuong, K and O'Doherty, KC}, title = {FMT Regulatory Challenges and the Lived Experiences of People With IBD.}, journal = {The American journal of bioethics : AJOB}, volume = {17}, number = {5}, pages = {59-61}, doi = {10.1080/15265161.2017.1299253}, pmid = {28430063}, issn = {1536-0075}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases ; }, } @article {pmid28430058, year = {2017}, author = {Huss, J}, title = {Fecal Transplant Bioethics: Beyond Chicken Little.}, journal = {The American journal of bioethics : AJOB}, volume = {17}, number = {5}, pages = {48-50}, doi = {10.1080/15265161.2017.1299254}, pmid = {28430058}, issn = {1536-0075}, mesh = {Animals ; Bioethics ; *Chickens ; *Fecal Microbiota Transplantation ; Humans ; }, } @article {pmid30415447, year = {2018}, author = {Fang, X}, title = {Microbial treatment: the potential application for Parkinson's disease.}, journal = {Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10072-018-3641-6}, pmid = {30415447}, issn = {1590-3478}, support = {81660203//National Natural Science Foundation of China/ ; 20142BAB205092//Natural Science Foundation of Jiangxi Province (CN)/ ; 20181BAB205030//Natural Science Foundation of Jiangxi Province (CN)/ ; }, abstract = {Alterations in the composition of the intestinal flora are associated with the pathophysiology of Parkinson's disease (PD). More importantly, the possible cause-effect links between gut flora and PD pathogenesis have been identified using PD animal models. Recent studies have found that probiotics improve the symptoms associated with constipation in PD patients. In addition, fecal microbiota transplantation (FMT) was recently shown to provide a protective effect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice. Effective microbial therapy for PD includes probiotics and FMT. Therefore, microbial therapy may be a useful and novel approach for treatment of PD. In this review, I discuss the use of microbial treatment in PD.}, } @article {pmid30414693, year = {2018}, author = {Prado, C and Michels, M and Ávila, P and Burger, H and Milioli, MVM and Dal-Pizzol, F}, title = {The protective effects of fecal microbiota transplantation in an experimental model of necrotizing enterocolitis.}, journal = {Journal of pediatric surgery}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jpedsurg.2018.10.045}, pmid = {30414693}, issn = {1531-5037}, abstract = {BACKGROUND: Necrotizing enterocolitis (NEC) is a serious disease that affects premature neonates, causing high mortality. In the search for new options of treatment it was investigated whether fecal microbiota transplantation (FMT) decreased the inflammatory response during NEC development in experimental model.

METHODS: Wistar rats were used and divided as follows: naïve, control (NEC induction), FMT-before (transplantation of microbiota before insult) and FMT-after (microbiota transplantation after insult). The microbiota transplantation was performed by administering a feces solution obtained from an adult donor rat. The induction of enterocolitis involves feeding by artificial formula, hypothermia, hypoxia and endotoxin administration. MPO activity, TNF-α, IL-1β and IL-6 levels, oxidative and nitrosative damage and the grade of intestinal mucosa lesion were analyzed.

RESULTS: The control group had a significant increase of inflammatory and oxidative parameters when compared to naive animals. Both FMT-before and after decreased all inflammatory and oxidative damage parameters when compared to control group. This was also true to the intestinal mucosa damage.

CONCLUSION: FMT administered just before or after NEC induction improved gut and systemic inflammation, and gut oxidative damage and intestinal injury.}, } @article {pmid30409169, year = {2018}, author = {Ma, C and Sun, Z and Zeng, B and Huang, S and Zhao, J and Zhang, Y and Su, X and Xu, J and Wei, H and Zhang, H}, title = {Cow-to-mouse fecal transplantations suggest intestinal microbiome as one cause of mastitis.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {200}, doi = {10.1186/s40168-018-0578-1}, pmid = {30409169}, issn = {2049-2618}, support = {ID0E61AE8001//National Natural Science Foundation of China/ ; ID0EO2AE8002//Postdoctoral Science Foundation of Jiangsu Province/ ; }, abstract = {BACKGROUND: Mastitis, which affects nearly all lactating mammals including human, is generally thought to be caused by local infection of the mammary glands. For treatment, antibiotics are commonly prescribed, which however are of concern in both treatment efficacy and neonate safety. Here, using bovine mastitis which is the most costly disease in the dairy industry as a model, we showed that intestinal microbiota alone can lead to mastitis.

RESULTS: Fecal microbiota transplantation (FMT) from mastitis, but not healthy cows, to germ-free (GF) mice resulted in mastitis symptoms in mammary gland and inflammations in serum, spleen, and colon. Probiotic intake in parallel with FMT from diseased cows led to relieved mastitis symptoms in mice, by shifting the murine intestinal microbiota to a state that is functionally distinct from either healthy or diseased microbiota yet structurally similar to the latter. Despite conservation in mastitis symptoms, diseased cows and mice shared few mastitis-associated bacterial organismal or functional markers, suggesting striking divergence in mastitis-associated intestinal microbiota among lactating mammals. Moreover, an "amplification effect" of disease-health distinction in both microbiota structure and function was apparent during the cow-to-mouse FMT.

CONCLUSIONS: Hence, dysbiosis of intestinal microbiota may be one cause of mastitis, and probiotics that restore intestinal microbiota function are an effective and safe strategy to treat mastitis.}, } @article {pmid29417924, year = {2018}, author = {Kates, AE and Tischendorf, JS and Schweizer, M and Herwaldt, L and Samore, M and Dukes, KC and Gerding, DN and Diekema, DJ and Safdar, N}, title = {Research Agenda for Microbiome Based Research for Multidrug-resistant Organism Prevention in the Veterans Health Administration System.}, journal = {Infection control and hospital epidemiology}, volume = {39}, number = {2}, pages = {202-209}, doi = {10.1017/ice.2017.311}, pmid = {29417924}, issn = {1559-6834}, mesh = {Congresses as Topic ; Dietary Supplements/microbiology ; Drug Resistance, Multiple, Bacterial ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Humans ; Interprofessional Relations ; Microbiota ; Research ; *Research Design ; United States ; *United States Department of Veterans Affairs ; }, } @article {pmid30408565, year = {2018}, author = {DeFilipp, Z and Hohmann, E and Jenq, RR and Chen, YB}, title = {Fecal microbiota transplantation: restoring the injured microbiome after allogeneic hematopoietic cell transplantation.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbmt.2018.10.022}, pmid = {30408565}, issn = {1523-6536}, abstract = {Disruption of the intestinal microbiome early after allogeneic hematopoietic cell transplantation (allo-HCT) has been linked to adverse outcomes in transplant recipients. To date, it remains unknown as to whether microbiome-directed interventions will be able to impact important clinical endpoints. Fecal microbiota transplantation (FMT) is a compelling intervention to restore healthy diversity to the intestinal microenvironment after allo-HCT, but currently has no established role in transplant recipients. In this review, we examine the utilization of FMT as treatment for Clostridium difficile infections and acute graft-versus-host disease, as well as a restorative intervention early after allo-HCT. Ongoing and planned studies will help determine the ultimate role of FMT in recipients of allo-HCT.}, } @article {pmid30405910, year = {2018}, author = {Niccum, BA and Stein, DJ and Behm, BW and Hays, RA}, title = {Zinc Deficiency and the Recurrence of Clostridium difficile Infection after Fecal Microbiota Transplant: A Retrospective Cohort Study.}, journal = {Journal of nutrition and metabolism}, volume = {2018}, number = {}, pages = {9682975}, doi = {10.1155/2018/9682975}, pmid = {30405910}, issn = {2090-0724}, abstract = {Background: Fecal microbiota transplant (FMT) is an effective therapy for recurrent Clostridium difficile infection (CDI). However, in 12% of patients treated with FMT, CDI recurs within one month. Zinc deficiency predicts increased diarrheal frequency in malnourished children, but little is known about its association with FMT outcome. We hypothesized that zinc levels were an independent predictor of CDI recurrence after FMT.

Methods: We performed a retrospective cohort study of 80 patients (mean age, 66; 59 women) receiving FMT for CDI from 9/2013-9/2016 at a tertiary care center. Zinc levels were measured within 90 days before FMT. The primary outcome was CDI recurrence within 90 days after FMT. We controlled for risk factors for FMT failure using Cox regression. We also analyzed the effect of zinc supplementation in individuals with deficiency.

Results: Forty-nine subjects had a normal zinc level, and 31 had a low level (<0.66 µg/mL). CDI recurred in 3/49 (6%) patients with normal zinc and 5/31 (16%) patients with low zinc (HR = 11.327, 95% CI = 2.162-59.336, p=0.004). Among low zinc subjects, 2 of 25 (8%) that received zinc supplements and 3 of 6 (50%) that did not receive zinc supplements had recurrence of CDI (HR = 0.102, 95% CI = 0.015-0.704, p=0.021).

Conclusion: Zinc deficiency was associated with increased CDI recurrence after FMT. Among zinc-deficient patients, supplementation was associated with reduced recurrence. Further study is needed to determine whether zinc deficiency represents a pathophysiologic mechanism and target for therapy.}, } @article {pmid30404941, year = {2018}, author = {Morand, A and Cornu, F and Dufour, JC and Tsimaratos, M and Lagier, JC and Raoult, D}, title = {Human bacterial repertoire of the urinary tract: a potential paradigm shift.}, journal = {Journal of clinical microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1128/JCM.00675-18}, pmid = {30404941}, issn = {1098-660X}, abstract = {The aim of this article is to review the human repertoire of bacteria already described by culture and metagenomic techniques in urine, and published in the literature. Our study led us to compare this repertoire with other human repertoires available.We followed automatic and manual bibliographical methods and found 562 bacterial species reported in the literature as part of the human urinary microbiota. Of the 562 species, 322 were described only by culture, 101 by both culture and metagenomics, and 139 only by metagenomic. Three hundred and fifty-two species (62.6%) have been associated with at least one case report of human infection, of which 225 (40.0%) have been described as causative agents of urinary tract infection. The urinary tract bacterial repertoire contains 21.4% of the known prokaryotic diversity associated with human beings (464 in common) and share 23.6% species with the human gut microbiota (350 in common, 62.3% of the urine species). Urinary repertoire shares a significant difference in aero-intolerant species compared with gut microbiota (100/562; 17.8% and 505/1484; 34.0% respectively; p<0.001; OR=9.0 [7.0-11.4]). Studies using high-throughput sequencing show a higher proportion of aero-intolerant bacteria in urine (74/240, 30.8%).Most pathogenic bacteria are part of the commensal human urinary tract bacteria and their pathogenicity may occur following any imbalance of this microbiota. The restoration of urinary tract health can occur following a fecal transplantation. The potential gut origin of the human bacterial microbiota has to be explored.}, } @article {pmid30403550, year = {2018}, author = {Ooijevaar, RE and Terveer, EM and Verspaget, HW and Kuijper, EJ and Keller, JJ}, title = {Clinical Application and Potential of Fecal Microbiota Transplantation.}, journal = {Annual review of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-med-111717-122956}, pmid = {30403550}, issn = {1545-326X}, abstract = {Fecal microbiota transplantation (FMT) is a well-established treatment for recurrent Clostridioides difficile infection. FMT has become a more readily available and useful new treatment option as a result of stool banks. The current state of knowledge indicates that dysbiosis of the gut microbiota is implicated in several disorders in addition to C. difficile. Randomized controlled studies have shown FMT to be somewhat effective in treating ulcerative colitis, irritable bowel syndrome, and hepatic encephalopathy. In addition, FMT has been beneficial in treating several other conditions, such as the eradication of multidrug-resistant organisms and graft-versus-host disease. We expect that FMT will soon be implemented as a treatment strategy for several new indications, although further studies are needed. Expected final online publication date for the Annual Review of Medicine Volume 70 is January 27, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.}, } @article {pmid30400734, year = {2018}, author = {Song, JH and Kim, YS}, title = {Recurrent Clostridium difficile Infection: Risk Factors, Treatment, and Prevention.}, journal = {Gut and liver}, volume = {}, number = {}, pages = {}, doi = {10.5009/gnl18071}, pmid = {30400734}, issn = {2005-1212}, abstract = {The most common cause of antibiotic-associated diarrhea is Clostridium difficile infection (CDI). Recurrent C. difficile infection (rCDI) often occurs after successful treatment of CDI. Due to the increased incidence and the difficulty in treating rCDI, it is becoming an important clinical issue. Identifying risk factors is helpful for early detection, treatment, and prevention of rCDI. Advanced age, use of antibiotics, gastric acid suppression, and infection with a hypervirulent strain are currently regarded as the major risk factors for rCDI. Several treatment modalities, including vancomycin, fidaxomicin, and fecal microbiota transplant (FMT), are suggested for rCDI treatment. However, there is currently no definitive treatment method with sufficient evidence for rCDI. Recent studies have focused on FMT and have shown positive results for rCDI. Prevention of rCDI by measures such as hand washing and isolation of patients is very important. However, these preventive measures are often overlooked in clinical practice. Here, we review the risk factors, treatment, and prevention of rCDI.}, } @article {pmid30154172, year = {2018}, author = {Mullish, BH and Quraishi, MN and Segal, JP and McCune, VL and Baxter, M and Marsden, GL and Moore, DJ and Colville, A and Bhala, N and Iqbal, TH and Settle, C and Kontkowski, G and Hart, AL and Hawkey, PM and Goldenberg, SD and Williams, HRT}, title = {The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridium difficile infection and other potential indications: joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.}, journal = {Gut}, volume = {67}, number = {11}, pages = {1920-1941}, doi = {10.1136/gutjnl-2018-316818}, pmid = {30154172}, issn = {1468-3288}, support = {MR/R000875/1//Medical Research Council/United Kingdom ; }, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/*therapy ; Clostridium difficile/drug effects ; Fecal Microbiota Transplantation/*methods ; Gastroenterology/organization & administration ; Gastrointestinal Tract/*microbiology ; Humans ; Recurrence ; Societies, Medical ; Tissue Donors ; United Kingdom ; }, abstract = {Interest in the therapeutic potential of faecal microbiota transplant (FMT) has been increasing globally in recent years, particularly as a result of randomised studies in which it has been used as an intervention. The main focus of these studies has been the treatment of recurrent or refractory Clostridium difficile infection (CDI), but there is also an emerging evidence base regarding potential applications in non-CDI settings. The key clinical stakeholders for the provision and governance of FMT services in the UK have tended to be in two major specialty areas: gastroenterology and microbiology/infectious diseases. While the National Institute for Health and Care Excellence (NICE) guidance (2014) for use of FMT for recurrent or refractory CDI has become accepted in the UK, clear evidence-based UK guidelines for FMT have been lacking. This resulted in discussions between the British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS), and a joint BSG/HIS FMT working group was established. This guideline document is the culmination of that joint dialogue.}, } @article {pmid29870851, year = {2018}, author = {Ruppé, E and Martin-Loeches, I and Rouzé, A and Levast, B and Ferry, T and Timsit, JF}, title = {What's new in restoring the gut microbiota in ICU patients? Potential role of faecal microbiota transplantation.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {24}, number = {8}, pages = {803-805}, doi = {10.1016/j.cmi.2018.05.020}, pmid = {29870851}, issn = {1469-0691}, mesh = {Critical Care/methods ; Critical Illness/*therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Intensive Care Units ; }, } @article {pmid29653191, year = {2018}, author = {Vila, J}, title = {Microbiota transplantation and/or CRISPR/Cas in the battle against antimicrobial resistance.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {24}, number = {7}, pages = {684-686}, doi = {10.1016/j.cmi.2018.03.043}, pmid = {29653191}, issn = {1469-0691}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacteria/*genetics ; Bacterial Infections/*microbiology/*therapy ; *CRISPR-Cas Systems ; *Drug Resistance, Bacterial ; Drug Resistance, Multiple, Bacterial ; Enterobacteriaceae/genetics ; Enterobacteriaceae Infections/microbiology/therapy ; *Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Treatment Outcome ; }, } @article {pmid30388112, year = {2018}, author = {Jiang, ZD and Jenq, RR and Ajami, NJ and Petrosino, JF and Alexander, AA and Ke, S and Iqbal, T and DuPont, AW and Muldrew, K and Shi, Y and Peterson, C and Do, KA and DuPont, HL}, title = {Safety and preliminary efficacy of orally administered lyophilized fecal microbiota product compared with frozen product given by enema for recurrent Clostridium difficile infection: A randomized clinical trial.}, journal = {PloS one}, volume = {13}, number = {11}, pages = {e0205064}, doi = {10.1371/journal.pone.0205064}, pmid = {30388112}, issn = {1932-6203}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) via colonoscopy or enema has become a commonly used treatment of recurrent C. difficile infection (CDI).

AIMS: To compare the safety and preliminary efficacy of orally administered lyophilized microbiota product compared with frozen product by enema.

METHODS: In a single center, adults with ≥ 3 episodes of recurrent CDI were randomized to receive encapsulated lyophilized fecal microbiota from 100-200 g of donor feces (n = 31) or frozen FMT from 100 g of donor feces (n = 34) by enema. Safety during the three months post FMT was the primary study objective. Prevention of CDI recurrence during the 60 days after FMT was a secondary objective. Fecal microbiome changes were examined in first 39 subjects studied.

RESULTS: Adverse experiences were commonly seen in equal frequency in both groups and did not appear to relate to the route of delivery of FMT. CDI recurrence was prevented in 26 of 31 (84%) subjects randomized to capsules and in 30 of 34 (88%) receiving FMT by enema (p = 0.76). Both products normalized fecal microbiota diversity while the lyophilized orally administered product was less effective in repleting Bacteroidia and Verrucomicrobia classes compared to frozen product via enema.

CONCLUSIONS: The route of delivery, oral or rectal, did not influence adverse experiences in FMT. In preliminary evaluation, both routes appeared to show equivalent efficacy, although the dose may need to be higher for lyophilized product. Spore-forming bacteria appear to be the most important engrafting organisms in FMT by the oral route using lyophilized product.

TRIAL REGISTRATION: ClinicalTrials.gov NCT02449174.}, } @article {pmid30384952, year = {2018}, author = {Gopalsamy, SN and Woodworth, MH and Wang, T and Carpentieri, CT and Mehta, N and Friedman-Moraco, RJ and Mehta, AK and Larsen, CP and Kraft, CS}, title = {The Use of Microbiome Restoration Therapeutics to Eliminate Intestinal Colonization With Multidrug-Resistant Organisms.}, journal = {The American journal of the medical sciences}, volume = {356}, number = {5}, pages = {433-440}, doi = {10.1016/j.amjms.2018.08.015}, pmid = {30384952}, issn = {1538-2990}, abstract = {Antibiotic resistance (AR) has been described by the World Health Organization as an increasingly serious threat to global public health. Many mechanisms of AR have become widespread due to global selective pressures such as widespread antibiotic use. The intestinal tract is an important reservoir for many multidrug-resistant organisms (MDROs), and next-generation sequencing has expanded understanding of the resistome, defined as the comprehensive sum of genetic determinants of AR. Intestinal decolonization has been explored as a strategy to eradicate MDROs with selective digestive tract decontamination and probiotics being notable examples with mixed results. This review focuses on fecal microbiota transplantation and the early evidence supporting its efficacy in decolonizing MDROs and potential mechanisms of action to reduce AR genes. Current evidence suggests that fecal microbiota transplantation may have promise in restoring healthy microbial diversity and reducing AR, and clinical trials are underway to better characterize its safety and efficacy.}, } @article {pmid30384951, year = {2018}, author = {Stripling, J and Rodriguez, M}, title = {Current Evidence in Delivery and Therapeutic Uses of Fecal Microbiota Transplantation in Human Diseases-Clostridium difficile Disease and Beyond.}, journal = {The American journal of the medical sciences}, volume = {356}, number = {5}, pages = {424-432}, doi = {10.1016/j.amjms.2018.08.010}, pmid = {30384951}, issn = {1538-2990}, abstract = {The use of fecal microbiota transplantation (FMT) was first described in China in the 4th century by Ge Hong when "yellow soup," a fecal slurry, was administered for the treatment of severe food poisoning and diarrhea, a practice that continued for centuries. Bedouin groups also consumed stools of their camels as a remedy for dysentery. FMT was also applied in veterinary medicine in Europe in the 16th century. Additional therapeutic use of human excretions was described in Europe in the 18th and 19th century and in World War II, when gut bacteria were administered to German soldiers suffering from dysentery in the North African campaign. More scientifically, Eismann, in 1958, utilized fecal transplantation via enema in 4 patients for the treatment of severe pseudomembranous colitis with success. Following this report a number of isolated cases were published describing the use of FMT by different delivery routes for the treatment of a variety of illnesses.}, } @article {pmid29428498, year = {2018}, author = {Samarkos, M and Mastrogianni, E and Kampouropoulou, O}, title = {The role of gut microbiota in Clostridium difficile infection.}, journal = {European journal of internal medicine}, volume = {50}, number = {}, pages = {28-32}, doi = {10.1016/j.ejim.2018.02.006}, pmid = {29428498}, issn = {1879-0828}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/*microbiology/*therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Proton Pump Inhibitors/therapeutic use ; }, abstract = {Clostridium difficile infection has emerged as a major health problem. Because it is a spore-forming microorganism, C. difficile is difficult to eradicate and recurrences of the infection are frequent. The strong association of CDI with prior use of antibiotics led to the recognition that disturbances in the gut microbiota apparently plays a central role in CDI. Except for antibiotics, several other risk factors for CDI have been recognised, such as advanced age and use of proton pump inhibitors. The common characteristic of these factors is that they are associated with changes in the composition of gut microbiota. Data from human studies have shown that the presence of C. difficile, either as a colonizer or as a pathogen, is associated with reduced microbiota diversity. C. difficile infection per se seems to be associated with changes in the representation of specific microbial populations (e.g. taxa) which either may act protectively against C. difficile colonization of the gut or may increase susceptibility for C. difficile infection. Therapeutic gut microbiota manipulation can be achieved by faecal microbiota transplantation, which is highly effective for the treatment of CDI.}, } @article {pmid30376869, year = {2018}, author = {Khoruts, A}, title = {Targeting the microbiome: from probiotics to fecal microbiota transplantation.}, journal = {Genome medicine}, volume = {10}, number = {1}, pages = {80}, doi = {10.1186/s13073-018-0592-8}, pmid = {30376869}, issn = {1756-994X}, abstract = {The modern techniques of microbiome science can be applied to the development and evaluation of all microbiota-directed products, including probiotics and fecal microbiota transplantation.}, } @article {pmid28267142, year = {2017}, author = {Moayyedi, P and Jaeschke, R}, title = {Microbiome: fecal transplant in Clostridium difficile and ulcerative colitis. Dr. Paul Moayyedi in an interview with Dr. Roman Jaeschke: part 2.}, journal = {Polish archives of internal medicine}, volume = {127}, number = {2}, pages = {137-138}, doi = {10.20452/pamw.3963}, pmid = {28267142}, issn = {1897-9483}, mesh = {Clostridium Infections/*therapy ; Colitis, Ulcerative/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Microbiota ; }, } @article {pmid30370307, year = {2018}, author = {Sun, W and Guo, Y and Zhang, S and Chen, Z and Wu, K and Liu, Q and Liu, K and Wen, L and Wei, Y and Wang, B and Chen, D}, title = {Fecal Microbiota Transplantation Can Alleviate Gastrointestinal Transit in Rats with High-Fat Diet-Induced Obesity via Regulation of Serotonin Biosynthesis.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {8308671}, doi = {10.1155/2018/8308671}, pmid = {30370307}, issn = {2314-6141}, abstract = {Aim: We tested the hypothesis that fecal microbiota transplantation (FMT) could regulate the biotransformation of bile acids, such as deoxycholic acid (DCA) and cholic acid (CA), which in turn regulate the biosynthesis of serotonin in the gut and relieve gastrointestinal dysmotility in high-fat diet- (HFD-) induced obesity in rats.

Methods: Male Sprague-Dawley rats were randomly divided into the control diet group, HFD group, and HFD-fed with receiving FMT. HFD was fed for 12 weeks. At the end of two-week HFD, FMT was carried out for two weeks. The gastrointestinal transit, serotonin concentration, the expression of tryptophan hydroxylase 1 (TPH1) and serotonin reuptake transporter (SERT), and the levels of bile acids in intestinal contents were examined.

Results: Compared with the control group, the gastrointestinal transit and small intestinal serotonin concentration of HFD-fed rats were increased. In HFD-fed rats, TPH1 protein expression was increased significantly, while SERT protein expression was decreased, but not significant. The levels of CA and DCA in intestinal contents were also significantly increased in HFD-fed rats compared with the control group. After HFD-fed rats receiving FMT treatment, the gastrointestinal transit, small intestinal serotonin concentration, and TPH1 expression were decreased, while SERT expression was not affected. Moreover, the levels of CA and DCA in intestinal contents were also decreased.

Conclusions: FMT could alleviate small intestinal transit in the HFD-fed rats by regulating the serotonin biosynthesis. In this process, CA and DCA may be related to the regulation of synthesis of serotonin.}, } @article {pmid30367124, year = {2018}, author = {Brunse, A and Martin, L and Rasmussen, TS and Christensen, L and Skovsted Cilieborg, M and Wiese, M and Khakimov, B and Pieper, R and Nielsen, DS and Sangild, PT and Thymann, T}, title = {Effect of fecal microbiota transplantation route of administration on gut colonization and host response in preterm pigs.}, journal = {The ISME journal}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41396-018-0301-z}, pmid = {30367124}, issn = {1751-7370}, abstract = {This study examined gut colonization patterns and host responses to fecal microbiota transplantation (FMT) by different administration routes after preterm birth. In two separate experiments, cesarean-delivered, preterm pigs were administered combined oral + rectal, or exclusively rectal donor feces, and compared with saline controls. After 5 days, stomach and colon bacterial compositions were determined by 16S rRNA gene amplicon sequencing, and organic acid metabolites measured. Further, gut pathology, mucosa bacterial adherence, and goblet cell density were assessed. FMT increased the relative abundance of obligate anaerobes in the colon without affecting total bacterial load. Bacteroides colonized recipients despite low abundance in the donor feces, whereas highly abundant Prevotella and Ruminococcaceae did not. Further, FMT changed carbohydrate metabolism from lactate to propionate production thereby increasing colonic pH. Besides, FMT preserved goblet cell mucin stores and reduced necrotizing enterocolitis incidence. Only rectal FMT increased the stomach-to-colon pH gradient and resistance to mucosa bacterial adhesion. Conversely, oral + rectal FMT increased bacterial adhesion, internal organ colonization, and overall mortality. Our results uncovered distinctions in bacterial colonization patterns along the gastrointestinal tract, as well as host tolerability between oral and rectal FMT administration in preterm newborns. Besides, FMT showed the potential to prevent necrotizing enterocolitis.}, } @article {pmid29528385, year = {2018}, author = {Chen, T and Zhou, Q and Zhang, D and Jiang, F and Wu, J and Zhou, JY and Zheng, X and Chen, YG}, title = {Effect of Faecal Microbiota Transplantation for Treatment of Clostridium difficile Infection in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Cohort Studies.}, journal = {Journal of Crohn's & colitis}, volume = {12}, number = {6}, pages = {710-717}, doi = {10.1093/ecco-jcc/jjy031}, pmid = {29528385}, issn = {1876-4479}, mesh = {*Clostridium difficile ; Colitis, Ulcerative/*complications ; Crohn Disease/*complications ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Symptom Flare Up ; Treatment Outcome ; }, abstract = {Background: Evidence concerning the effect of faecal microbiota transplantation [FMT] in Clostridium difficile infection [CDI] patients with inflammatory bowel disease [IBD] has not been firmly established. Therefore, we performed a systematic review and meta-analysis to evaluate FMT treatment outcomes in patients with IBD treated for CDI.

Methods: An electronic search of four databases was conducted until November 1, 2017. Cohort studies of FMT efficacy and safety in CDI patients with IBD were included. Pooled effect sizes were calculated with 95% confidence intervals [CI] using a random-effects model.

Results: Nine cohort studies comprising a total of 346 CDI patients with IBD were included. The initial cure rate was 81% [95% CI = 76%-85%] and the overall cure rate was up to 89% [95% CI = 83%-93%], both with no significant heterogeneity. The recurrence rate was 19% [95% CI = 13%-27%] with moderate heterogeneity [Cochran's Q, p = 0.19; I2 = 33%]. There was no significant difference in the CDI cure rate after FMT in patients with and without IBD (risk ratio [RR] = 0.92; 95% CI = 0.81-1.05; Cochran's Q, p = 0.06; I2 = 53%). Subgroup analysis revealed a similar CDI treatment effects after FMT in patients with Crohn's disease and in those with ulcerative colitis [p = 0.1804]. Four studies reported adverse events of IBD flares.

Conclusions: FMT is an effective therapy for CDI in patients with IBD. Well-designed randomised controlled trials and well-conducted microbiological studies are needed to validate its efficacy and safety.}, } @article {pmid30359194, year = {2018}, author = {Kiouptsi, K and Ruf, W and Reinhardt, C}, title = {Microbiota-Derived Trimethylamine.}, journal = {Circulation research}, volume = {123}, number = {10}, pages = {1112-1114}, doi = {10.1161/CIRCRESAHA.118.314039}, pmid = {30359194}, issn = {1524-4571}, } @article {pmid30359185, year = {2018}, author = {Skye, SM and Zhu, W and Romano, KA and Guo, CJ and Wang, Z and Jia, X and Kirsop, J and Haag, B and Lang, JM and DiDonato, JA and Tang, WHW and Lusis, AJ and Rey, FE and Fischbach, MA and Hazen, SL}, title = {Microbial Transplantation With Human Gut Commensals Containing CutC Is Sufficient to Transmit Enhanced Platelet Reactivity and Thrombosis Potential.}, journal = {Circulation research}, volume = {123}, number = {10}, pages = {1164-1176}, doi = {10.1161/CIRCRESAHA.118.313142}, pmid = {30359185}, issn = {1524-4571}, abstract = {RATIONALE: Gut microbes influence cardiovascular disease and thrombosis risks through the production of trimethylamine N-oxide (TMAO). Microbiota-dependent generation of trimethylamine (TMA)-the precursor to TMAO-is rate limiting in the metaorganismal TMAO pathway in most humans and is catalyzed by several distinct microbial choline TMA-lyases, including the proteins encoded by the cutC/D (choline utilization C/D) genes in multiple human commensals.

OBJECTIVE: Direct demonstration that the gut microbial cutC gene is sufficient to transmit enhanced platelet reactivity and thrombosis potential in a host via TMA/TMAO generation has not yet been reported.

METHODS AND RESULTS: Herein, we use gnotobiotic mice and a series of microbial colonization studies to show that microbial cutC-dependent TMA/TMAO production is sufficient to transmit heightened platelet reactivity and thrombosis potential in a host. Specifically, we examine in vivo thrombosis potential employing germ-free mice colonized with either high TMA-producing stable human fecal polymcrobial communities or a defined CutC-deficient background microbial community coupled with a CutC-expressing human commensal±genetic disruption of its cutC gene (ie, Clostridium sporogenes Δ cutC).

CONCLUSIONS: Collectively, these studies point to the microbial choline TMA-lyase pathway as a rational molecular target for the treatment of atherothrombotic heart disease.}, } @article {pmid30357440, year = {2018}, author = {Li, P and Zhang, T and Xiao, Y and Tian, L and Cui, B and Ji, G and Liu, YY and Zhang, F}, title = {Timing for the second fecal microbiota transplantation to maintain the long-term benefit from the first treatment for Crohn's disease.}, journal = {Applied microbiology and biotechnology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00253-018-9447-x}, pmid = {30357440}, issn = {1432-0614}, support = {201502026//Special Scientific Research Fund of Public Welfare Profession of National Health and Family Planning Commission/ ; Zhang F//Jiangsu Province Creation Team and Leading Talents project/ ; 81670495//National Natural Science Foundation of China/ ; 81600417//National Natural Science Foundation of China/ ; 2015BAI13B07//National Clinical Research Center for Digestive Diseases/ ; BE2018751//Jiangsu Province Society Development project (CN)/ ; }, abstract = {Increasing evidence has shown that fecal microbiota transplantation (FMT) could be a promising treatment option for Crohn's disease (CD). However, the frequency of FMT for CD treatment remains unclear. This study aimed to evaluate the optimal timing for administering the second course of FMT to maintain the long-term clinical effects from the first FMT for patients with CD. Sixty-nine patients with active CD who underwent FMT twice and benefited from the first FMT were enrolled in this study. Clinical response, stool microbiota, and urine metabolome of patients were assessed during the follow-up. The median time of maintaining clinical response to the first FMT in total 69 patients was 125 days (IQR, 82.5-225.5). The time of maintaining clinical response to the second FMT in 56 of 69 patients was 176.5 days (IQR, 98.5-280). The fecal microbiota composition of each patient post the first FMT was closer to that of his/her donor. Compared to that of the baseline, patients prior to the second course of FMT showed significant differences in urinary metabolic profiles characterized by increased indoxyl sulfate, 4-hydroxyphenylacetate, creatinine, dimethylamine, glycylproline, hippurate, and trimethylamine oxide (TMAO). This study demonstrated that patients with CD could be administered the second course of FMT less than 4 months after the first FMT for maintaining the clinical benefits from the first FMT. This was supported by the host-microbial metabolism changes in patients with active CD. Trial registration: ClinicalTrials.gov , NCT01793831. Registered 18 February 2013. https://clinicaltrials.gov/ct2/show/NCT01793831?term=NCT01793831&rank=1.}, } @article {pmid30355801, year = {2018}, author = {Battaglioli, EJ and Hale, VL and Chen, J and Jeraldo, P and Ruiz-Mojica, C and Schmidt, BA and Rekdal, VM and Till, LM and Huq, L and Smits, SA and Moor, WJ and Jones-Hall, Y and Smyrk, T and Khanna, S and Pardi, DS and Grover, M and Patel, R and Chia, N and Nelson, H and Sonnenburg, JL and Farrugia, G and Kashyap, PC}, title = {Clostridioides difficile uses amino acids associated with gut microbial dysbiosis in a subset of patients with diarrhea.}, journal = {Science translational medicine}, volume = {10}, number = {464}, pages = {}, doi = {10.1126/scitranslmed.aam7019}, pmid = {30355801}, issn = {1946-6242}, abstract = {The gut microbiota plays a critical role in pathogen defense. Studies using antibiotic-treated mice reveal mechanisms that increase susceptibility to Clostridioides difficile infection (CDI), but risk factors associated with CDI in humans extend beyond antibiotic use. Here, we studied the dysbiotic gut microbiota of a subset of patients with diarrhea and modeled the gut microbiota of these patients by fecal transplantation into germ-free mice. When challenged with C. difficile, the germ-free mice transplanted with fecal samples from patients with dysbiotic microbial communities showed increased gut amino acid concentrations and greater susceptibility to CDI. A C. difficile mutant that was unable to use proline as an energy source was unable to robustly infect germ-free mice transplanted with a dysbiotic or healthy human gut microbiota. Prophylactic dietary intervention using a low-proline or low-protein diet in germ-free mice colonized by a dysbiotic human gut microbiota resulted in decreased expansion of wild-type C. difficile after challenge, suggesting that amino acid availability might be important for CDI. Furthermore, a prophylactic fecal microbiota transplant in mice with dysbiosis reduced proline availability and protected the mice from CDI. Last, we identified clinical risk factors that could potentially predict gut microbial dysbiosis and thus greater susceptibility to CDI in a retrospective cohort of patients with diarrhea. Identifying at-risk individuals and reducing their susceptibility to CDI through gut microbiota-targeted therapies could be a new approach to preventing C. difficile infection in susceptible patients.}, } @article {pmid30353027, year = {2018}, author = {Lai, ZL and Tseng, CH and Ho, HJ and Cheung, CKY and Lin, JY and Chen, YJ and Cheng, FC and Hsu, YC and Lin, JT and El-Omar, EM and Wu, CY}, title = {Fecal microbiota transplantation confers beneficial metabolic effects of diet and exercise on diet-induced obese mice.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {15625}, doi = {10.1038/s41598-018-33893-y}, pmid = {30353027}, issn = {2045-2322}, abstract = {Diet and exercise are conventional methods for controlling body weight and are linked to alterations in gut microbiota. However, the associations of diet, exercise, and gut microbiota in the control of obesity remain largely unknown. In the present study, using 16S rRNA amplicon sequencing and fecal microbiota transplantation (FMT), normal fat diet (NFD), exercise and their combination resulted in improved metabolic profiles in comparison to sedentary lifestyle with high fat diet (HFD). Moreover, diet exerted more influence than exercise in shaping the gut microbiota. HFD-fed mice receiving FMT from NFD-exercised donors not only showed remarkably reduced food efficacy, but also mitigated metabolic profiles (p < 0.05). The transmissible beneficial effects of FMT were associated with bacterial genera Helicobacter, Odoribacter and AF12 and overrepresentation of oxidative phosphorylation and glycolysis genes. Our findings demonstrate that the beneficial effects of diet and exercise are transmissible via FMT, suggesting a potential therapeutic treatment for obesity.}, } @article {pmid30153805, year = {2018}, author = {Brown, JR and Flemer, B and Joyce, SA and Zulquernain, A and Sheehan, D and Shanahan, F and O'Toole, PW}, title = {Changes in microbiota composition, bile and fatty acid metabolism, in successful faecal microbiota transplantation for Clostridioides difficile infection.}, journal = {BMC gastroenterology}, volume = {18}, number = {1}, pages = {131}, doi = {10.1186/s12876-018-0860-5}, pmid = {30153805}, issn = {1471-230X}, support = {(SFI/12/RC/2273)//Science Foundation Ireland/Ireland ; SFI/12/RC/2273//Science Foundation Ireland/Ireland ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bile Acids and Salts/metabolism ; Clostridium Infections/metabolism/*microbiology/*therapy ; *Clostridium difficile ; Fatty Acids, Volatile/metabolism ; *Fecal Microbiota Transplantation ; Feces/chemistry ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Recurrence ; Young Adult ; }, abstract = {BACKGROUND: Alteration of the gut microbiota by repeated antibiotic treatment increases susceptibility to Clostridioides difficile infection. Faecal microbiota transplantation from donors with a normal microbiota effectively treats C. difficile infection.

METHODS: The study involved 10 patients with recurrent C. difficile infection, nine of whom received transplants from individual donors and one who received a donor unit from a stool bank (OpenBiome).

RESULTS: All individuals demonstrated enduring post-transplant resolution of C. difficile- associated diarrhoea. Faecal microbiota diversity of recipients significantly increased, and the composition of the microbiota resembled that of the donor. Patients with C. difficile infection exhibited significantly lower faecal levels of secondary/ bile acids and higher levels of primary bile acids. Levels of secondary bile acids were restored in all transplant recipients, but to a lower degree with the OpenBiome transplant. The abundance increased of bacterial genera known from previous studies to confer resistance to growth and germination of C. difficile. These were significantly negatively associated with primary bile acid levels and positively related with secondary bile acid levels. Although reduced levels of the short chain fatty acids, butyrate, propionate and acetate, have been previously reported, here we report elevations in SCFA, pyruvic and lactic fatty acids, saturated, ω-6, monounsaturated, ω-3 and ω-6 polyunsaturated fatty acids (PUFA) in C. difficile infection. This potentially indicates one or a combination of increased dietary FA intake, microbial modification of FAs or epithelial cell damage and inflammatory cell recruitment. No reversion to donor FA profile occurred post-FMT but ω-3 to ω-6 PUFA ratios were altered in the direction of the donor. Archaeal metabolism genes were found in some samples post FMT.

CONCLUSION: A consistent metabolic signature was identified in the post-transplant microbiota, with reduced primary bile acids and substantial restoration of secondary bile acid production capacity. Total FA levels were unchanged but the ratio of inflammatory to non-inflammatory FAs decreased.}, } @article {pmid29685195, year = {2018}, author = {Tirandaz, H and Ebrahim-Habibi, MB and Moradveisi, B and Raoofi, S and Salehi-Najafabadi, A and Mohammadi, E}, title = {Microbiota potential for the treatment of sexual dysfunction.}, journal = {Medical hypotheses}, volume = {115}, number = {}, pages = {46-49}, doi = {10.1016/j.mehy.2018.03.021}, pmid = {29685195}, issn = {1532-2777}, mesh = {Animals ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Male ; Microbiota/*physiology ; Models, Biological ; Prebiotics ; Probiotics/therapeutic use ; Sexual Dysfunction, Physiological/*microbiology/*therapy ; Sexuality/physiology ; }, abstract = {Inability to have a satisfactory sexual intercourse is a serious problem affecting many people. Despite enormous efforts for developing effective treatments for pathologic conditions associated with sexual malfunction, still a lot of patients do not respond well to such treatments. Microbiota has been shown to affect obesity, diabetes, hypertension, stress/anxiety and sex hormonal disturbances. Nevertheless, no research has concentrated on the link between microbiota and human sexuality or sexual dysfunction. We propose another line of enquiry into sexual dysfunction by hypothesizing a relationship between microbiota and factors affecting human sexuality. Hence, it can be assumed that microbiota manipulation may improve sexual behavior and reduce sexual dysfunction. We also discuss the evidence to back up this hypothesis, and present some predictions.}, } @article {pmid28601577, year = {2017}, author = {Davido, B and Batista, R and Fessi, H and Salomon, J and Dinh, A}, title = {Impact of faecal microbiota transplantation to eradicate vancomycin-resistant enterococci (VRE) colonization in humans.}, journal = {The Journal of infection}, volume = {75}, number = {4}, pages = {376-377}, doi = {10.1016/j.jinf.2017.06.001}, pmid = {28601577}, issn = {1532-2742}, mesh = {Anti-Bacterial Agents ; *Fecal Microbiota Transplantation ; Gram-Positive Bacterial Infections ; Humans ; Vancomycin ; *Vancomycin-Resistant Enterococci ; }, } @article {pmid28461230, year = {2017}, author = {Mahieu, R and Cassisa, V and Hilliquin, D and Coron, N and Pailhoriès, H and Kempf, M and Joly-Guillou, ML and Eveillard, M}, title = {Impact of faecal microbiota transplantation on mouse digestive colonization with two extensively resistant bacteria.}, journal = {The Journal of infection}, volume = {75}, number = {1}, pages = {75-77}, doi = {10.1016/j.jinf.2017.04.008}, pmid = {28461230}, issn = {1532-2742}, mesh = {Animals ; Anti-Bacterial Agents ; *Enterococcus faecium ; *Fecal Microbiota Transplantation ; Feces ; Gram-Positive Bacterial Infections ; Mice ; }, } @article {pmid30345252, year = {2018}, author = {Yodoshi, T and Hurt, TL}, title = {Fecal Microbiota Transplantation to Patients with Refractory Very Early Onset Ulcerative Colitis.}, journal = {Pediatric gastroenterology, hepatology & nutrition}, volume = {21}, number = {4}, pages = {355-360}, doi = {10.5223/pghn.2018.21.4.355}, pmid = {30345252}, issn = {2234-8646}, abstract = {Recently, fecal microbiota transplantation (FMT) has been attracting attention as a possible medical treatment of ulcerative colitis (UC). A randomized controlled trial of FMT for children with UC is currently underway. Therapeutic effects of FMT for adults with UC remain controversial. We report two cases of early-onset UC in children. A patient was diagnosed with UC at age 1-year 9-month and underwent FMT at age 2-year 3-month. He attained clinical remission for three weeks after FMT, but then relapsed at four weeks, ultimately undergoing a total colectomy. Another child was diagnosed with UC at 2-year 10-month and she underwent FMT at age 5 years. She has remained in clinical remission following FMT for 24 months and her UC has been maintained without complications with tacrolimus and azathioprine. We report that FMT for early-onset UC appears to be safe and potentially effective.}, } @article {pmid29477634, year = {2018}, author = {Dinh, A and Fessi, H and Duran, C and Batista, R and Michelon, H and Bouchand, F and Lepeule, R and Vittecoq, D and Escaut, L and Sobhani, I and Lawrence, C and Chast, F and Ronco, P and Davido, B}, title = {Clearance of carbapenem-resistant Enterobacteriaceae vs vancomycin-resistant enterococci carriage after faecal microbiota transplant: a prospective comparative study.}, journal = {The Journal of hospital infection}, volume = {99}, number = {4}, pages = {481-486}, doi = {10.1016/j.jhin.2018.02.018}, pmid = {29477634}, issn = {1532-2939}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteriological Techniques ; Carbapenem-Resistant Enterobacteriaceae/*isolation & purification ; Carrier State/microbiology/*therapy ; Drug-Related Side Effects and Adverse Reactions/epidemiology/pathology ; Enterobacteriaceae Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gram-Positive Bacterial Infections/microbiology/*therapy ; Humans ; Male ; Middle Aged ; Polymerase Chain Reaction ; Prospective Studies ; Treatment Outcome ; Vancomycin-Resistant Enterococci/*isolation & purification ; Young Adult ; }, abstract = {BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant enterococci (VRE) carriage are increasing worldwide. Faecal microbiota transplantation (FMT) appears to be an attractive option for decolonization. This study aimed to evaluate CRE vs VRE clearance by FMT among carriers.

METHODS: A multi-centre trial was undertaken on patients with CRE or VRE digestive tract colonization who received FMT between January 2015 and April 2017. Adult patients with CRE or VRE colonization, confirmed by three consecutive rectal swabs at weekly intervals, including one in the week prior to FMT, were included in the study. Patients with immunosuppression or concomitant antibiotic prescription at the time of FMT were excluded. Successful decolonization was determined by at least two consecutive negative rectal swabs [polymerase chain reaction (PCR) and culture] on Days 7, 14, 21 and 28, and monthly for three months following FMT.

RESULTS: Seventeen patients were included, with a median age of 73 years [interquartile range (IQR) 64.3-79.0]. Median duration of carriage of CRE or VRE before FMT was 62.5 days (IQR 57.0-77.5). One week after FMT, three of eight patients were free of CRE colonization and three of nine patients were free of VRE colonization. After three months, four of eight patients were free of CRE colonization and seven of eight patients were free of VRE colonization. Qualitative PCR results were concordant with culture. Six patients received antibiotics during follow-up, three in each group. No adverse events were reported.

CONCLUSION: CRE and VRE clearance rates were not significantly different in this study, possibly due to the small sample size, but a trend was observed. These data should be confirmed by larger cohorts and randomized trials.}, } @article {pmid30342053, year = {2018}, author = {Vallianou, NG and Stratigou, T and Tsagarakis, S}, title = {Microbiome and diabetes: Where are we now?.}, journal = {Diabetes research and clinical practice}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.diabres.2018.10.008}, pmid = {30342053}, issn = {1872-8227}, abstract = {Alterations in the diversity or structure of gut microbiota known as dysbiosis, may affect metabolic activities, resulting in metabolic disorders, such as obesity and diabetes. The development of more sophisticated methods, such as metagenomics sequencing, PCR-denaturing gradient gel electrophoresis, microarrays and fluorescence in situ hybridization, has expanded our knowledge on gut microbiome. Dysbiosis has been related to increased plasma concentrations of gut microbiota-derived lipopolysaccharide (LPS), which triggers the production of a variety of cytokines and the recruitment of inflammatory cells. Metabolomics have demonstrated that butyrate and propionate suppress weight gain in mice with high fat diet-induced obesity, and acetate has been proven to reduce food intake in healthy mice. The role of prebiotics, probiotics, genetically modified bacteria and fecal microbiota transplantation, as potential therapeutic challenges for type 2 diabetes will be discussed in this review.}, } @article {pmid30339501, year = {2018}, author = {Elkrief, A and Derosa, L and Zitvogel, L and Kroemer, G and Routy, B}, title = {The intimate relationship between gut microbiota and cancer immunotherapy.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/19490976.2018.1527167}, pmid = {30339501}, issn = {1949-0984}, abstract = {Immunotherapy is widely used to treat a large variety of malignancies and has revolutionized the therapeutic approach to cancer. Major efforts are ongoing to identify biomarkers that predict response to immunotherapy as well as new strategies to improve ICI efficacy and clinical outcomes. Studies have shown that the gut microbiome determines the extent to which ICIs may invigorate the anticancer immune response. Here, the authors review recent studies that have described the effects of the gut microbiota on the efficacy of CTLA-4 and PD-1 inhibitors and outline potential future clinical directions of these findings.}, } @article {pmid30338410, year = {2018}, author = {Chen, X and Devaraj, S}, title = {Gut Microbiome in Obesity, Metabolic Syndrome, and Diabetes.}, journal = {Current diabetes reports}, volume = {18}, number = {12}, pages = {129}, doi = {10.1007/s11892-018-1104-3}, pmid = {30338410}, issn = {1539-0829}, abstract = {PURPOSE OF REVIEW: Obesity and diabetes are worldwide epidemics. There is also a growing body of evidence relating the gut microbiome composition to insulin resistance. The purpose of this review is to delineate the studies linking gut microbiota to obesity, metabolic syndrome, and diabetes.

RECENT FINDINGS: Animal studies as well as proof of concept studies using fecal transplantation demonstrate the pivotal role of the gut microbiota in regulating insulin resistance states and inflammation. While we still need to standardize methodologies to study the microbiome, there is an abundance of evidence pointing to the link between gut microbiome, inflammation, and insulin resistance, and future studies should be aimed at identifying unifying mechanisms.}, } @article {pmid30337038, year = {2018}, author = {Pesce, M and Borrelli, O and Saliakellis, E and Thapar, N}, title = {Gastrointestinal Neuropathies: New Insights and Emerging Therapies.}, journal = {Gastroenterology clinics of North America}, volume = {47}, number = {4}, pages = {877-894}, doi = {10.1016/j.gtc.2018.07.011}, pmid = {30337038}, issn = {1558-1942}, abstract = {The bewildering complexity of the enteric nervous system makes it susceptible to develop a wide array of motility disorders, collectively called enteric neuropathies. These gastrointestinal conditions are among the most challenging to manage, mainly given poor characterization of their etiopathophysiology and outcomes. Not surprisingly, therefore, targeted or curative therapies for enteric neuropathies are lacking and management is largely symptomatic. Nonetheless, recent advances in neurogastroenterology have witnessed improvements in established strategies, such as intestinal transplantation and the emergence of new treatments including novel drugs, electrical pacing, and manipulation of fecal microbiota, as well as stem cell and gene therapy.}, } @article {pmid30328245, year = {2018}, author = {Lee, P and Yacyshyn, BR and Yacyshyn, MB}, title = {Gut microbiota and obesity: An opportunity to alter obesity through Fecal Microbiota Transplant (FMT).}, journal = {Diabetes, obesity & metabolism}, volume = {}, number = {}, pages = {}, doi = {10.1111/dom.13561}, pmid = {30328245}, issn = {1463-1326}, abstract = {Obesity is a global pandemic with immense health consequences for individuals and societies. Multiple factors including environmental influences and genetic predispositions are known to influence the development of obesity. Despite an increasing understanding of the factors driving the obesity episdemic, therapeutic interventions to prevent or reverse obesity are limited in their impact. Manipulation of the human gut microbiome provides a new potential therapeutic approach in the fight against obesity. Specific gut bacteria and their metabolites are known to affect host metabolism and feeding behavior, and dysbiosis of this biosystem may lead to metabolic syndrome. Potential therapies to alter the gut microbiota to treat obesity include dietary changes, supplementation of the diet with probiotic organisms and prebiotic compounds that influence bacterial growth, and the use of fecal microbiota transplant, in which gut microbiota from healthy indiviudals are introduced into the gut. In this review, we will examine the growing scientific evidence supporting the mechanisms by which the human gut microbiota may influence carbohydrate metabolism and obesity and the various possible therapies that may utilize the gut microbiota to help correct metabolic dysfunction. This article is protected by copyright. All rights reserved.}, } @article {pmid30328062, year = {2018}, author = {Wang, H and Cui, B and Li, Q and Ding, X and Li, P and Zhang, T and Yang, X and Ji, G and Zhang, F}, title = {The Safety of Fecal Microbiota Transplantation for Crohn's Disease: Findings from A Long-Term Study.}, journal = {Advances in therapy}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12325-018-0800-3}, pmid = {30328062}, issn = {1865-8652}, support = {81670495//China National Science Foundation/ ; 81600417//China National Science Foundation/ ; 2015BAI13B07//National Clinical Research Center for Digestive Diseases/ ; }, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) has been used as a potential treatment option for Crohn's disease (CD). However, there is still lack of safety and efficacy evidence based on large samples of CD undergoing FMT. This study aimed to evaluate the risk factors of adverse event (AE) in the long term and the efficacy of FMT in the short term for patients with CD.

METHODS: FMT via mid-gut for mild to severe CD in a single center trial (NCT01793831) was performed from October 2012 to December 2016. The possible factors with AE and efficacy after FMT were prospectively recorded.

RESULTS: A total of 184 frequencies of FMT were performed for 139 patients who received FMT. During 1 month after FMT, 13.6% of mild AEs occurred, including increased frequency of defecation, fever, abdominal pain, flatulence, hematochezia, vomiturition, bloating and herpes zoster. No AE beyond 1 month was observed. Therefore, a 1 month cut-off could be suggested to define short-term and long-term AEs of FMT. Among the possible risk factors, only fecal microbiota purification methods were closely associated with the occurrence of AEs. The rate of AEs in patients undergoing manual methods for the preparation of fecal microbiota was 21.7%, which was significantly higher than the 8.7% in those experiencing an automatic method. The manual or automatic purification of fecal microbiota had no correlation with the efficacy of FMT.

CONCLUSION: This cohort study based on the largest size of cases demonstrated that improved fecal microbiota preparation reduced the rates of AEs, but did not affect the clinical efficacy in patients with CD.}, } @article {pmid30323765, year = {2018}, author = {Li, J and Cui, H and Cai, Y and Lin, J and Song, X and Zhou, Z and Xiong, W and Zhou, H and Bian, Y and Wang, L}, title = {Tong-Xie-Yao-Fang Regulates 5-HT Level in Diarrhea Predominant Irritable Bowel Syndrome Through Gut Microbiota Modulation.}, journal = {Frontiers in pharmacology}, volume = {9}, number = {}, pages = {1110}, doi = {10.3389/fphar.2018.01110}, pmid = {30323765}, issn = {1663-9812}, abstract = {Tong-Xie-Yao-Fang (TXYF) has been widely used for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) in traditional Chinese medicine. However, its mechanism of action in the treatment of IBS-D remains to be fully understood. Recent reports have shown that Clostridium species in the gut can induce 5-HT production in the colon, which then contributes to IBS-D. Due to the wide use of TXYF in the clinical treatment of IBS-D and the close relationship between gut microbiota and IBS-D, we hypothesize that TXYF treats IBS-D by modulating gut microbiota and regulating colonic 5-HT levels. In this study, variation analysis of 16S rRNA was conducted to evaluate changes in the distribution of gut microbiota in IBS-D model rats after TXYF treatment. Moreover, we investigated whether TXYF could affect colonic 5-HT levels in IBS-D model rats. We then performed fecal transplantation experiments to confirm the effects of TXYF on gut microbiota and 5-HT levels. We found that TXYF treatment can ameliorate IBS-D and regulate 5-HT levels in colon tissue homogenates. TXYF treatment also affected the diversity of gut microbiota and altered the relative abundance of Akkermansia and Clostridium sensu stricto 1 in gut flora populations. Finally, we showed that fecal transplantation from TXYF-treated rats could relieve IBS-D and regulate 5-HT levels in colon tissue homogenates. In conclusion, the present study demonstrates that TXYF treatment diminishes colonic 5-HT levels and alleviates the symptoms of IBS-D by favorably affecting microbiota levels in gut flora communities.}, } @article {pmid30320666, year = {2018}, author = {Cho, S and Spencer, E and Hirten, R and Grinspan, A and Dubinsky, MC}, title = {Fecal Microbiota Transplant for Recurrent Clostridium Difficile Infection in Pediatric Inflammatory Bowel Disease.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1097/MPG.0000000000002172}, pmid = {30320666}, issn = {1536-4801}, abstract = {OBJECTIVES: Recurrent Clostridium difficile infection (RCDI) increases morbidity and mortality in patients with inflammatory bowel disease (IBD). Fecal microbiota transplant (FMT) is known to be very effective for RCDI in non-IBD patients with cure rates up to 91%. The same success rates of FMT have not been reported in IBD patients with RCDI, and the data in pediatrics is limited. We aimed to determine the effectiveness of FMT for RCDI in established pediatric IBD patients.

METHODS: We performed a retrospective chart review of pediatric patients with IBD and RCDI (≥3 episodes) who underwent FMT via colonoscopy at a tertiary care IBD center. The primary outcome was the rate of RCDI within 60 days post-FMT. The secondary outcomes were recurrence rate by 6 months, rate of colectomy, and time to recurrence.

RESULTS: Of the 8 eligible patients, 6 had ulcerative colitis, 1 had IBD-unspecified, and 1 had Crohn's disease. Median [interquartile range] age was 13 [11-14] years. All patients were on vancomycin at FMT. Two patients (25%) had RCDI by 60 days post-FMT and another 3 patients had RCDI between 60 days and 6 months. The median time to recurrence was 101 [40-139] days. Two patients (25%) who developed recurrence went to colectomy after FMT.

CONCLUSIONS: With a cure rate of 75% at 60 days, FMT administered for the treatment of RCDI may be an effective treatment option in pediatric IBD. However, there appears to be a significant rate of late recurrence of CDI after 60 days in these patients.}, } @article {pmid30320222, year = {2018}, author = {Cheng, S and Ma, X and Geng, S and Jiang, X and Li, Y and Hu, L and Li, J and Wang, Y and Han, X}, title = {Fecal Microbiota Transplantation Beneficially Regulates Intestinal Mucosal Autophagy and Alleviates Gut Barrier Injury.}, journal = {mSystems}, volume = {3}, number = {5}, pages = {}, doi = {10.1128/mSystems.00137-18}, pmid = {30320222}, issn = {2379-5077}, abstract = {Fecal microbiota transplantation (FMT) is one of the most effective ways to regulate the gut microbiota. Here, we investigated the effect of exogenous fecal microbiota on gut function from the perspective of analysis of the mucosal proteomes in a piglet model. A total of 289 differentially expressed proteins were annotated with 4,068 gene ontology (GO) function entries in the intestinal mucosa, and the levels of autophagy-related proteins in the forkhead box O (FoxO) signaling pathway were increased whereas the levels of proteins related to inflammation response were decreased in the recipient. Then, to assess the alleviation of epithelial injury in the Escherichia coli K88-infected piglets following FMT, intestinal microbiome-metabolome responses were determined. 16S rRNA gene sequencing showed that the abundances of beneficial bacteria, such as Lactobacillus and Succinivibrio, were increased whereas those of Enterobacteriaceae and Proteobacteria bacteria were decreased in the infected piglets following FMT. Metabolomic analysis revealed that levels of 58 metabolites, such as lactic acid and succinic acid, were enhanced in the intestinal lumen and that seven metabolic pathways, such as branched-chain amino acid metabolism pathways, were upregulated in the infected piglets following FMT. In concordance with the metabolome data, results of metagenomics prediction analysis also demonstrated that FMT modulated the metabolic functions of gut microbiota associated with linoleic acid metabolism. In addition, intestinal morphology was improved, a result that coincided with the decrease of intestinal permeability and the enhancement of mucins and mucosal expression of tight junction proteins in the recipient. Taken together, the results showed that FMT triggered intestinal mucosal protective autophagy and alleviated gut barrier injury through alteration of the gut microbial structure. IMPORTANCE The gut microbiota plays a crucial role in human and animal health, and its disorder causes multiple diseases. Over the past decade, FMT has gained increasing attention due to the success in treating Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). Although FMT appears to be effective, how FMT functions in the recipient remains unknown. Whether FMT exerts this beneficial effect through a series of changes in the host organism caused by alteration of gut microbial structure is also not known. In the present study, newborn piglets and E. coli K88-infected piglets were selected as models to explore the interplay between host and gut microbiota following FMT. Our results showed that FMT triggered intestinal mucosal autophagy and alleviated gut barrier injury caused by E. coli K88. This report provides a theoretical basis for the use of FMT as a viable therapeutic method for gut microbial regulation.}, } @article {pmid30319644, year = {2018}, author = {Qi, X and Li, X and Zhao, Y and Wu, X and Chen, F and Ma, X and Zhang, F and Wu, D}, title = {Treating Steroid Refractory Intestinal Acute Graft-vs.-Host Disease With Fecal Microbiota Transplantation: A Pilot Study.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {2195}, doi = {10.3389/fimmu.2018.02195}, pmid = {30319644}, issn = {1664-3224}, abstract = {Patients with steroid refractory gastrointestinal (GI) tract graft- vs.-host disease (GvHD) face a poor prognosis and limited therapeutic options. To accurately assess the efficacy and safety of fecal microbiota transplantation (FMT) in treating steroid refractory GI tract GvHD, we conducted a pilot study involving eight patients. Having received FMTs, all patients' clinical symptoms relieved, bacteria enriched, and microbiota composition reconstructed. Compared to those who did not receive FMT, these eight patients achieved a higher progression-free survival. FMT can serve as a therapeutic option for GI tract aGVHD, but its effectiveness and safety need further evaluations. Clinical Trial Registration: NCT03148743.}, } @article {pmid30319571, year = {2018}, author = {Zuo, T and Ng, SC}, title = {The Gut Microbiota in the Pathogenesis and Therapeutics of Inflammatory Bowel Disease.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2247}, doi = {10.3389/fmicb.2018.02247}, pmid = {30319571}, issn = {1664-302X}, abstract = {In the twenty first century, the changing epidemiology of inflammatory bowel disease (IBD) globally with increasing disease incidence across many countries relates to the altered gut microbiota, due to a combinatorial effect of environmental factors, human immune responses and genetics. IBD is a gastrointestinal disease associated with a gut microbial dysbiosis, including an expansion of facultative anaerobic bacteria of the family Enterobacteriaceae. Advances in high-throughput sequencing enable us to entangle the gut microbiota in human health and IBD beyond the gut bacterial microbiota, expanding insights into the mycobiota, virobiota and helminthes. Caudovirales (viruses) and Basidiomycota, Ascomycota, and Candida albicans (fungi) are revealed to be increased in IBD. The deconvolution of the gut microbiota in IBD lays the basis for unveiling the roles of these various gut microbiota components in IBD pathogenesis and being conductive to instructing on future IBD diagnosis and therapeutics. Here we comprehensively elucidate the alterations in the gut microbiota in IBD, discuss the effect of diets in the gut microbiota in relation to IBD, and illustrate the potential of manipulation of gut microbiota for IBD therapeutics. The therapeutic strategy of antibiotics, prebiotics, probiotics and fecal microbiota transplantation will benefit the effective application of precision microbiome manipulation in IBD.}, } @article {pmid30310254, year = {2018}, author = {Camara-Lemarroy, CR and Metz, LM and Yong, VW}, title = {Focus on the gut-brain axis: Multiple sclerosis, the intestinal barrier and the microbiome.}, journal = {World journal of gastroenterology}, volume = {24}, number = {37}, pages = {4217-4223}, doi = {10.3748/wjg.v24.i37.4217}, pmid = {30310254}, issn = {2219-2840}, abstract = {The brain-gut axis serves as the bidirectional connection between the gut microbiome, the intestinal barrier and the immune system that might be relevant for the pathophysiology of inflammatory demyelinating diseases. People with multiple sclerosis have been shown to have an altered microbiome, increased intestinal permeability and changes in bile acid metabolism. Experimental evidence suggests that these changes can lead to profound alterations of peripheral and central nervous system immune regulation. Besides being of pathophysiological interest, the brain-gut axis could also open new avenues of therapeutic targets. Modification of the microbiome, the use of probiotics, fecal microbiota transplantation, supplementation with bile acids and intestinal barrier enhancers are all promising candidates. Hopefully, pre-clinical studies and clinical trials will soon yield significant results.}, } @article {pmid30302341, year = {2018}, author = {Fang, H and Fu, L and Wang, J}, title = {Protocol for Fecal Microbiota Transplantation in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {8941340}, doi = {10.1155/2018/8941340}, pmid = {30302341}, issn = {2314-6141}, abstract = {Background: Fecal microbiota transplantation (FMT) is an emerging treatment approach for inflammatory bowel disease (IBD). The donor selection, the separation of fecal bacteria, the frequency of FMT, the way of infusion, the long-term safety, and efficacy are still uncertain.

Aim: To further study the efficacy and safety and protocol of FMT for IBD.

Methods: A systematic review and meta-analysis were conducted until February, 2018. Clinical remission was established as the primary outcome.

Results: A total of 596 paediatric and adult IBD patients were enrolled, and 459 patients received FMT therapy. 28.8% (132/459) patients achieved clinical remission during follow-up. 53% (241/459) patients achieved clinical response. The pooled estimated clinical remission for ulcerative colitis (UC) was 21% (95% CI: 8%-37%) and 30% (95% CI: 11%-52%) for Crohn's disease (CD), both with a risk of heterogeneity; 10% (95% CI: 0%-43%) for paediatric UC; 26% (95% CI: 10%-48%) for adult UC; 45% for paediatric CD (95% CI: 24%-66%); 22% (95% CI: 3%-52%) for adult CD. Meta-analysis of cohort studies showed that moderate-severe IBD patients could achieve more significant remission from FMT than mild-moderate patients (P=0.037). Delivery route has no impact on the efficacy of FMT in UC and CD. Based on current available evidence, a trend was observed towards higher clinical remission rate of frozen stool FMT than that of fresh stool for UC, while there was no significant difference between fresh and frozen FMT for CD. The optimal donor stool for FMT is still uncertain. Meta-analysis of RCTs showed that FMT treatment achieved significantly higher clinical remission rate than placebo for UC (28% versus 9%, P=0.0003).

Conclusion: FMT is an effective and safe therapy for both paediatric and adult IBD; fresh or frozen donor stool, delivery route, and antibiotic pretreatment or not have no impact on the efficacy of FMT in IBD. FMT might be a potential rescue therapy and even an initial standardized therapy for IBD. However, few data exist on long-term safety and efficacy and further validation is needed.}, } @article {pmid30301167, year = {2018}, author = {Paule, A and Frezza, D and Edeas, M}, title = {Microbiota and Phage Therapy: Future Challenges in Medicine.}, journal = {Medical sciences (Basel, Switzerland)}, volume = {6}, number = {4}, pages = {}, doi = {10.3390/medsci6040086}, pmid = {30301167}, issn = {2076-3271}, abstract = {An imbalance of bacterial quantity and quality of gut microbiota has been linked to several pathologies. New strategies of microbiota manipulation have been developed such as fecal microbiota transplantation (FMT); the use of pre/probiotics; an appropriate diet; and phage therapy. The presence of bacteriophages has been largely underestimated and their presence is a relevant component for the microbiome equilibrium. As a promising treatment, phage therapy has been extensively used in Eastern Europe to reduce pathogenic bacteria and has arisen as a new method to modulate microbiota diversity. Phages have been selected and "trained" to infect a wide spectrum of bacteria or tailored to infect specific antibiotic resistant bacteria present in patients. The new development of genetically modified phages may be an efficient tool to treat the gut microbiota dysbiosis associated with different pathologies and increased production of bacterial metabolites and subsequently decrease systemic low-grade chronic inflammation associated with chronic diseases. Microbiota quality and mitochondria dynamics can be remodulated and manipulated by phages to restore the equilibrium and homeostasis of the system. Our aim is to highlight the great interest for phages not only to eliminate and control pathogenic bacterial infection but also in the near future to modulate the microbiota by adding new functions to selected bacteria species and rebalance the dynamic among phages and bacteria. The challenge for the medicine of tomorrow is to re-think and redesign strategies differently and far from our traditional thinking.}, } @article {pmid30300561, year = {2018}, author = {Paknikar, R and Pekow, J}, title = {Fecal Microbiota Transplantation for the Management of Clostridium difficile Infection.}, journal = {Surgical infections}, volume = {}, number = {}, pages = {}, doi = {10.1089/sur.2018.221}, pmid = {30300561}, issn = {1557-8674}, abstract = {The clinical burden of Clostridium difficile infection (CDI) continues to grow. Despite the multitude of treatment options that have been developed and tested to combat the morbidity and death associated with CDI, recurrence remains common. As such, treatment modalities such as fecal microbiota transplantation (FMT) have become studied increasingly; FMT serves to transplant stool from carefully selected healthy subjects into C. difficile positive patients through a variety of delivery routes. In doing so, FMT is hypothesized to correct dysbiosis of the recipient gut microbiome addressing the root cause of the pathogenesis of C. difficile infection. A growing body of evidence shows FMT to be efficacious in this setting, and the study of FMT accordingly continues to evolve to identify novel indications for its utilization.}, } @article {pmid30290648, year = {2018}, author = {Wen, W and Zhang, H and Shen, J and Wei, L and Shen, S}, title = {Fecal microbiota transplantation for patients with irritable bowel syndrome: A meta-analysis protocol.}, journal = {Medicine}, volume = {97}, number = {40}, pages = {e12661}, doi = {10.1097/MD.0000000000012661}, pmid = {30290648}, issn = {1536-5964}, abstract = {Irritable bowel syndrome (IBS) is a common functional bowel disease characterized by chronic or recurrent abdominal pain, bloating, constipation, and diarrhea. Many patients with IBS have a poor quality of life due to abdominal discomfort, diarrhea, constipation, and the presence of other diseases. At present, intestinal motility inhibitors, adsorbents, astringents, intestinal mucosal protective agents, and antidepressants have been combined to treat IBS, but the treatment process is long, which results in a large economic burden to patients. Fecal microbiota transplantation (FMT) is a treatment involving the transplantation of functional bacteria from healthy human feces into the gastrointestinal tract of patients; thus, replacing the intestinal flora and modulating intestinal and extra-intestinal diseases. In recent years, the efficacy and economic benefits of FMT in the treatment of IBS have received increasing attention from researchers.A search for randomized controlled trials (RCTs) on treating IBS with FMT will be performed using 9 databases, including PubMed, the Cochrane Library, Embase, ClinicalTrails, China National Knowledge Infrastructure, Sino Med, ScienceDirect, VIP, and Wanfang Data. Two reviewers will independently screen data extraction studies and assess study quality and risk of bias. The risk of bias for each RCT will be assessed against the Cochrane Handbook standards to assess methodological quality. RevMan V.5.3 software will be used to calculate data synthesis when meta-analysis is allowed.This study will provide a high-quality synthesis of existing evidence on the effectiveness and safety of FMT in the treatment of IBS.This study will determine if FMT is an effective and safe intervention for IBS.PROSPERO registration number is PROSPERO CRD42018108080.}, } @article {pmid30283047, year = {2018}, author = {Warner, BB}, title = {The contribution of the gut microbiome to neurodevelopment and neuropsychiatric disorders.}, journal = {Pediatric research}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41390-018-0191-9}, pmid = {30283047}, issn = {1530-0447}, abstract = {Bidirectional communication between the gut and brain is well recognized, with data now accruing for a specific role of the gut microbiota in that link, referred to as the microbiome-gut-brain axis. This review will discuss the emerging role of the gut microbiota in brain development and behavior. Animal studies have clearly demonstrated effects of the gut microbiota on gene expression and neurochemical metabolism impacting behavior and performance. Based on these changes, a modulating role of the gut microbiota has been demonstrated for a variety of neuropsychiatric disorders, including depression, anxiety, and movement including Parkinson's, and importantly for the pediatric population autism. Critical developmental windows that influence early behavioral outcomes have been identified that include both the prenatal environment and early postnatal colonization periods. The clearest data regarding the role of the gut microbiota on neurodevelopment and psychiatric disorders is from animal studies; however, human data have begun to emerge, including an association between early colonization patterns and cognition. The importance of understanding the contribution of the gut microbiota to the development and functioning of the nervous system lies in the potential to intervene using novel microbial-based approaches to treating neurologic conditions. While pathways of communication between the gut and brain are well established, the gut microbiome is a new component of this axis. The way in which organisms that live in the gut influence the central nervous system (CNS) and host behavior is likely to be multifactorial in origin. This includes immunologic, endocrine, and metabolic mechanisms, all of which are pathways used for other microbial-host interactions. Germ-free (GF) mice are an important model system for understanding the impact of gut microbes on development and function of the nervous system. Alternative animal model systems have further clarified the role of the gut microbiota, including antibiotic treatment, fecal transplantation, and selective gut colonization with specific microbial organisms. Recently, researchers have started to examine the human host as well. This review will examine the components of the CNS potentially influenced by the gut microbiota, and the mechanisms mediating these effects. Links between gut microbial colonization patterns and host behavior relevant to a pediatric population will be examined, highlighting important developmental windows in utero or early in development.}, } @article {pmid30282817, year = {2018}, author = {Bromberg, JS and Hittle, L and Xiong, Y and Saxena, V and Smyth, EM and Li, L and Zhang, T and Wagner, C and Fricke, WF and Simon, T and Brinkman, CC and Mongodin, EF}, title = {Gut microbiota-dependent modulation of innate immunity and lymph node remodeling affects cardiac allograft outcomes.}, journal = {JCI insight}, volume = {3}, number = {19}, pages = {}, doi = {10.1172/jci.insight.121045}, pmid = {30282817}, issn = {2379-3708}, abstract = {We hypothesized that the gut microbiota influences survival of murine cardiac allografts through modulation of immunity. Antibiotic pretreated mice received vascularized cardiac allografts and fecal microbiota transfer (FMT), along with tacrolimus immunosuppression. FMT source samples were from normal, pregnant (immune suppressed), or spontaneously colitic (inflammation) mice. Bifidobacterium pseudolongum (B. pseudolongum) in pregnant FMT recipients was associated with prolonged allograft survival and lower inflammation and fibrosis, while normal or colitic FMT resulted in inferior survival and worse histology. Transfer of B. pseudolongum alone resulted in reduced inflammation and fibrosis. Stimulation of DC and macrophage lines with B. pseudolongum induced the antiinflammatory cytokine IL-10 and homeostatic chemokine CCL19 but induced lesser amounts of the proinflammatory cytokines TNFα and IL-6. In contrast, LPS and Desulfovibrio desulfuricans (D. desulfuricans), more abundant in colitic FMT, induced a more inflammatory cytokine response. Analysis of mesenteric and peripheral lymph node structure showed that B. pseudolongum gavage resulted in a higher laminin α4/α5 ratio in the lymph node cortical ridge, indicative of a suppressive environment, while D. desulfuricans resulted in a lower laminin α4/α5 ratio, supportive of inflammation. Discrete gut bacterial species alter immunity and may predict graft outcomes through stimulation of myeloid cells and shifts in lymph node structure and permissiveness.}, } @article {pmid30280023, year = {2018}, author = {Li, X and Li, Z and Chang, Y and Hou, F and Huang, Z and Ni, H and Yang, R and Bi, Y}, title = {Successful transplantation of guinea pig gut microbiota in mice and its effect on pneumonic plague sensitivity.}, journal = {PeerJ}, volume = {6}, number = {}, pages = {e5637}, doi = {10.7717/peerj.5637}, pmid = {30280023}, issn = {2167-8359}, abstract = {Microbiota-driven variations in the inflammatory response are predicted to regulate host responses to infection. Increasing evidence indicates that the gastrointestinal and respiratory tracts have an intimate relationship with each other. Gut microbiota can influence lung immunity whereby gut-derived injurious factors can reach the lungs and systemic circulation via the intestinal lymphatics. The intestinal microbiota's ability to resist colonization can be extended to systemic infections or to pathogens infecting distant sites such as the lungs. Unlike the situation with large mammals, the microtus Yersinia pestis 201 strain exhibits strong virulence in mice, but nearly no virulence to large mammals (such as guinea pigs). Hence, to assess whether the intestinal microbiota from guinea pigs was able to affect the sensitivity of mice to challenge infection with the Y. pestis 201 strain, we fed mice with guinea pig diets for two months, after which they were administered 0.5 ml of guinea pig fecal suspension for 30 days by oral gavage. The stools from each mouse were collected on days 0, 15, and 30, DNA was extracted from them, and 16S rRNA sequencing was performed to assess the diversity and composition of the gut microbiota. We found that the intestinal microbiota transplants from the guinea pigs were able to colonize the mouse intestines. The mice were then infected with Yersinia pestis 201 by lung invasion, but no statistical difference was found in the survival rates of the mice that were colonized with the guinea pig's gut microbiota and the control mice. This indicates that the intestinal microbiota transplantation from the guinea pigs did not affect the sensitivity of the mice to pneumonic plague.}, } @article {pmid30271330, year = {2018}, author = {Liang, S and Wu, X and Jin, F}, title = {Gut-Brain Psychology: Rethinking Psychology From the Microbiota-Gut-Brain Axis.}, journal = {Frontiers in integrative neuroscience}, volume = {12}, number = {}, pages = {33}, doi = {10.3389/fnint.2018.00033}, pmid = {30271330}, issn = {1662-5145}, abstract = {Mental disorders and neurological diseases are becoming a rapidly increasing medical burden. Although extensive studies have been conducted, the progress in developing effective therapies for these diseases has still been slow. The current dilemma reminds us that the human being is a superorganism. Only when we take the human self and its partner microbiota into consideration at the same time, can we better understand these diseases. Over the last few centuries, the partner microbiota has experienced tremendous change, much more than human genes, because of the modern transformations in diet, lifestyle, medical care, and so on, parallel to the modern epidemiological transition. Existing research indicates that gut microbiota plays an important role in this transition. According to gut-brain psychology, the gut microbiota is a crucial part of the gut-brain network, and it communicates with the brain via the microbiota-gut-brain axis. The gut microbiota almost develops synchronously with the gut-brain, brain, and mind. The gut microbiota influences various normal mental processes and mental phenomena, and is involved in the pathophysiology of numerous mental and neurological diseases. Targeting the microbiota in therapy for these diseases is a promising approach that is supported by three theories: the gut microbiota hypothesis, the "old friend" hypothesis, and the leaky gut theory. The effects of gut microbiota on the brain and behavior are fulfilled by the microbiota-gut-brain axis, which is mainly composed of the nervous pathway, endocrine pathway, and immune pathway. Undoubtedly, gut-brain psychology will bring great enhancement to psychology, neuroscience, and psychiatry. Various microbiota-improving methods including fecal microbiota transplantation, probiotics, prebiotics, a healthy diet, and healthy lifestyle have shown the capability to promote the function of the gut-brain, microbiota-gut-brain axis, and brain. It will be possible to harness the gut microbiota to improve brain and mental health and prevent and treat related diseases in the future.}, } @article {pmid30268564, year = {2018}, author = {Krajicek, E and Fischer, M and Allegretti, JR and Kelly, CR}, title = {Nuts and Bolts of Fecal Microbiota Transplantation.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2018.09.029}, pmid = {30268564}, issn = {1542-7714}, } @article {pmid30265170, year = {2018}, author = {Martinez, C and Edwards, J and Hassoun, A}, title = {Commercialized fecal microbiota transplantation provides efficacious treatment of Clostridium difficile infection.}, journal = {Infectious diseases (London, England)}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/23744235.2018.1500709}, pmid = {30265170}, issn = {2374-4243}, } @article {pmid30257956, year = {2018}, author = {Taur, Y and Coyte, K and Schluter, J and Robilotti, E and Figueroa, C and Gjonbalaj, M and Littmann, ER and Ling, L and Miller, L and Gyaltshen, Y and Fontana, E and Morjaria, S and Gyurkocza, B and Perales, MA and Castro-Malaspina, H and Tamari, R and Ponce, D and Koehne, G and Barker, J and Jakubowski, A and Papadopoulos, E and Dahi, P and Sauter, C and Shaffer, B and Young, JW and Peled, J and Meagher, RC and Jenq, RR and van den Brink, MRM and Giralt, SA and Pamer, EG and Xavier, JB}, title = {Reconstitution of the gut microbiota of antibiotic-treated patients by autologous fecal microbiota transplant.}, journal = {Science translational medicine}, volume = {10}, number = {460}, pages = {}, doi = {10.1126/scitranslmed.aap9489}, pmid = {30257956}, issn = {1946-6242}, abstract = {Antibiotic treatment can deplete the commensal bacteria of a patient's gut microbiota and, paradoxically, increase their risk of subsequent infections. In allogeneic hematopoietic stem cell transplantation (allo-HSCT), antibiotic administration is essential for optimal clinical outcomes but significantly disrupts intestinal microbiota diversity, leading to loss of many beneficial microbes. Although gut microbiota diversity loss during allo-HSCT is associated with increased mortality, approaches to reestablish depleted commensal bacteria have yet to be developed. We have initiated a randomized, controlled clinical trial of autologous fecal microbiota transplantation (auto-FMT) versus no intervention and have analyzed the intestinal microbiota profiles of 25 allo-HSCT patients (14 who received auto-FMT treatment and 11 control patients who did not). Changes in gut microbiota diversity and composition revealed that the auto-FMT intervention boosted microbial diversity and reestablished the intestinal microbiota composition that the patient had before antibiotic treatment and allo-HSCT. These results demonstrate the potential for fecal sample banking and posttreatment remediation of a patient's gut microbiota after microbiota-depleting antibiotic treatment during allo-HSCT.}, } @article {pmid30251184, year = {2018}, author = {Hughes, HK and Rose, D and Ashwood, P}, title = {The Gut Microbiota and Dysbiosis in Autism Spectrum Disorders.}, journal = {Current neurology and neuroscience reports}, volume = {18}, number = {11}, pages = {81}, doi = {10.1007/s11910-018-0887-6}, pmid = {30251184}, issn = {1534-6293}, abstract = {PURPOSE OF REVIEW: There is a growing body of evidence indicating the gut microbiota influence neurodevelopment and behavior. The purposes of this review are to provide an overview of studies analyzing the microbiota and their metabolites in autism spectrum disorders (ASD) and to discuss the possible mechanisms of action involved in microbial influence on the brain and behavior.

RECENT FINDINGS: The microbiota-gut-brain (MGB) axis has been extensively studied in animal models, and it is clear that alterations in the composition of microbiota alter neurological and behavioral outcomes. However, findings in human studies are less abundant. Although there are several studies so far showing altered microbiota (dysbiosis) in ASD, the results are heterogeneous and often contradictory. Intervention studies such as fecal microbiota transplant therapies show promise and lend credence to the involvement of the microbiota in ASD. A role for the microbiota in ASD is likely; however, further studies elucidating microbial or metabolomic signatures and mechanisms of action are needed. Future research should focus on intervention studies that can identify specific metabolites and immune mediators that improve with treatment to help identify etiologies and pathological mechanisms of ASD.}, } @article {pmid30250472, year = {2018}, author = {Haak, BW and Prescott, HC and Wiersinga, WJ}, title = {Therapeutic Potential of the Gut Microbiota in the Prevention and Treatment of Sepsis.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {2042}, doi = {10.3389/fimmu.2018.02042}, pmid = {30250472}, issn = {1664-3224}, support = {K08 GM115859/GM/NIGMS NIH HHS/United States ; }, abstract = {Alongside advances in understanding the pathophysiology of sepsis, there have been tremendous strides in understanding the pervasive role of the gut microbiota in systemic host resistance. In pre-clinical models, a diverse and balanced gut microbiota enhances host immunity to both enteric and systemic pathogens. Disturbance of this balance increases susceptibility to sepsis and sepsis-related organ dysfunction, while restoration of the gut microbiome is protective. Patients with sepsis have a profoundly distorted composition of the intestinal microbiota, but the impact and therapeutic potential of the microbiome is not well-established in human sepsis. Modulation of the microbiota consists of either resupplying the pool of beneficial microbes by administration of probiotics, improving the intestinal microenvironment to enhance the growth of beneficial species by dietary interventions and prebiotics, or by totally recolonizing the gut with a fecal microbiota transplantation (FMT). We propose that there are three potential opportunities to utilize these treatment modalities over the course of sepsis: to decrease sepsis incidence, to improve sepsis outcome, and to decrease late mortality after sepsis. Exploring these three avenues will provide insight into how disturbances of the microbiota can predispose to, or even perpetuate the dysregulated immune response associated with this syndrome, which in turn could be associated with improved sepsis management.}, } @article {pmid30249647, year = {2018}, author = {Plantamura, E and Dzutsev, A and Chamaillard, M and Djebali, S and Moudombi, L and Boucinha, L and Grau, M and Macari, C and Bauché, D and Dumitrescu, O and Rasigade, JP and Lippens, S and Plateroti, M and Kress, E and Cesaro, A and Bondu, C and Rothermel, U and Heikenwälder, M and Lina, G and Bentaher-Belaaouaj, A and Marie, JC and Caux, C and Trinchieri, G and Marvel, J and Michallet, MC}, title = {MAVS deficiency induces gut dysbiotic microbiota conferring a proallergic phenotype.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10404-10409}, doi = {10.1073/pnas.1722372115}, pmid = {30249647}, issn = {1091-6490}, abstract = {Prominent changes in the gut microbiota (referred to as "dysbiosis") play a key role in the development of allergic disorders, but the underlying mechanisms remain unknown. Study of the delayed-type hypersensitivity (DTH) response in mice contributed to our knowledge of the pathophysiology of human allergic contact dermatitis. Here we report a negative regulatory role of the RIG-I-like receptor adaptor mitochondrial antiviral signaling (MAVS) on DTH by modulating gut bacterial ecology. Cohousing and fecal transplantation experiments revealed that the dysbiotic microbiota of Mavs-/- mice conferred a proallergic phenotype that is communicable to wild-type mice. DTH sensitization coincided with increased intestinal permeability and bacterial translocation within lymphoid organs that enhanced DTH severity. Collectively, we unveiled an unexpected impact of RIG-I-like signaling on the gut microbiota with consequences on allergic skin disease outcome. Primarily, these data indicate that manipulating the gut microbiota may help in the development of therapeutic strategies for the treatment of human allergic skin pathologies.}, } @article {pmid30246002, year = {2018}, author = {Shogbesan, O and Poudel, DR and Victor, S and Jehangir, A and Fadahunsi, O and Shogbesan, G and Donato, A}, title = {A Systematic Review of the Efficacy and Safety of Fecal Microbiota Transplant for Clostridium difficile Infection in Immunocompromised Patients.}, journal = {Canadian journal of gastroenterology & hepatology}, volume = {2018}, number = {}, pages = {1394379}, doi = {10.1155/2018/1394379}, pmid = {30246002}, issn = {2291-2797}, abstract = {Background: Fecal microbiota transplantation (FMT) has been shown to be effective in recurrent Clostridium difficile (CD) infection, with resolution in 80% to 90% of patients. However, immunosuppressed patients were often excluded from FMT trials, so safety and efficacy in this population are unknown.

Methods: We searched MEDLINE and EMBASE for English language articles published on FMT for treatment of CD infection in immunocompromised patients (including patients on immunosuppressant medications, patients with human immunodeficiency virus (HIV), inherited or primary immunodeficiency syndromes, cancer undergoing chemotherapy, or organ transplant, including-bone marrow transplant) of all ages. We excluded inflammatory bowel disease patients that were not on immunosuppressant medications. Resolution and adverse event rates (including secondary infection, rehospitalization, and death) were calculated.

Results: Forty-four studies were included, none of which were randomized designs. A total of 303 immunocompromised patients were studied. Mean patient age was 57.3 years. Immunosuppressant medication use was the reason for the immunocompromised state in the majority (77.2%), and 19.2% had greater than one immunocompromising condition. Seventy-six percent were given FMT via colonoscopy. Of the 234 patients with reported follow-up outcomes, 207/234 (87%) reported resolution after first treatment, with 93% noting success after multiple treatments. There were 2 reported deaths, 2 colectomies, 5 treatment-related infections, and 10 subsequent hospitalizations.

Conclusion: We found evidence that supports the use of FMT for treatment of CD infection in immunocompromised patients, with similar rates of serious adverse events to immunocompetent patients.}, } @article {pmid30233520, year = {2018}, author = {Fortier, LC}, title = {Bacteriophages Contribute to Shaping Clostridioides (Clostridium) difficile Species.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {2033}, doi = {10.3389/fmicb.2018.02033}, pmid = {30233520}, issn = {1664-302X}, abstract = {Bacteriophages (phages) are bacterial viruses that parasitize bacteria. They are highly prevalent in nature, with an estimated 1031 viral particles in the whole biosphere, and they outnumber bacteria by at least 10-fold. Hence, phages represent important drivers of bacterial evolution, although our knowledge of the role played by phages in the mammalian gut is still embryonic. Several pathogens owe their virulence to the integrated phages (prophages) they harbor, which encode diverse virulence factors such as toxins. Clostridioides (Clostridium) difficile is an important opportunistic pathogen and several phages infecting this species have been described over the last decade. However, their exact contribution to the biology and virulence of this pathogen remains elusive. Current data have shown that C. difficile phages can alter virulence-associated phenotypes, in particular toxin production, by interfering with bacterial regulatory circuits through crosstalk with phage proteins for example. One phage has also been found to encode a complete binary toxin locus. Multiple regulatory genes have also been identified in phage genomes, suggesting that their impact on the host can be complex and often subtle. In this minireview, the current state of knowledge, major findings, and pending questions regarding C. difficile phages will be presented. In addition, with the apparent role played by phages in the success of fecal microbiota transplantation and the perspective of phage therapy for treatment of recurrent C. difficile infection, it has become even more crucial to understand what C. difficile phages do in the gut, how they impact their host, and how they influence the epidemiology and evolution of this clinically important pathogen.}, } @article {pmid30232757, year = {2018}, author = {Lu, M and Wang, Z}, title = {Microbiota and Aging.}, journal = {Advances in experimental medicine and biology}, volume = {1086}, number = {}, pages = {141-156}, doi = {10.1007/978-981-13-1117-8_9}, pmid = {30232757}, issn = {0065-2598}, abstract = {The human gut microbiota is a huge ecosystem that provides lots of functions for host development, immune system, and metabolism. Gut microbiota is linked to lots of diseases, including human metabolic diseases such as obesity, type 2 diabetes (T2D), irritable bowel syndrome, and cardiovascular disease (CVD). Few studies, however, have noted the relationship between aging and microbiota; the connection between aging and microbiota remains largely to be researched. In this review, recent research findings are summarized on the role of gut microbiota in aging processes with emphasis on therapeutic potential of microbiome-targeted interventions in antiaging medicine.}, } @article {pmid30227892, year = {2018}, author = {Staley, C and Kaiser, T and Vaughn, BP and Graiziger, CT and Hamilton, MJ and Rehman, TU and Song, K and Khoruts, A and Sadowsky, MJ}, title = {Predicting recurrence of Clostridium difficile infection following encapsulated fecal microbiota transplantation.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {166}, doi = {10.1186/s40168-018-0549-6}, pmid = {30227892}, issn = {2049-2618}, support = {R21 AI114722/AI/NIAID NIH HHS/United States ; 1R21-AI114722-01//National Institutes of Health/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). The use of freeze-dried, encapsulated donor material for FMT (cap-FMT) allows for an easy route of administration and remains clinically effective in the majority of rCDI patients. We hypothesized that specific shifts in the microbiota in response to cap-FMT could predict clinical outcome. We further evaluated the degree of donor microbiota engraftment to determine the extent that donor transfer contributed to recovery.

RESULTS: In total, 89 patients were treated with 100 separate cap-FMTs, with a success rate (no rCDI 60 days post cap-FMT) of 80%. Among responders, the lower alpha diversity (ANOVA P < 0.05) observed among patient's pre-FMT samples was restored following cap-FMT. At 1 week post-FMT, community composition varied by clinical outcome (ANOSIM P < 0.001), with similar abundances among families (Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae) in responder and donor samples. Families that showed differential abundances by outcome (response vs. recurrence) from samples collected 7 days following cap-FMT were used to construct a regression tree-based model to predict recurrence. Results showed a training accuracy of 100% to predict recurrence and the model was 97% accurate against a test data set of samples collected 8-20 days following cap-FMT. Evaluation of the extent of engraftment using the Bayesian algorithm SourceTracker revealed that approximately 50% of the post-FMT communities of responders were attributable to donor microbiota, while an additional 20-30% of the communities were similar to a composite healthy microbiota consisting of all donor samples.

CONCLUSIONS: Regression tree-based analyses of microbial communities identified taxa significantly related to clinical response after 7 days, which can be targeted to improve microbial therapeutics. Furthermore, reinstatement of a healthy assemblage following cap-FMT was only partially attributable to explicit donor engraftment and continued to develop towards an overall healthy assemblage, independent of donor.}, } @article {pmid30223665, year = {2018}, author = {Drastich, P and Bajer, L and Kverka, M}, title = {Possibilities of therapeutic manipulation of the gut microbiota.}, journal = {Vnitrni lekarstvi}, volume = {64}, number = {6}, pages = {665-671}, pmid = {30223665}, issn = {0042-773X}, abstract = {Human gut microbiota, complex ecosystem of microbes associated with human gut, is essential for the development of the host's immune system and many other physiological functions. Recently, numerous diseases and syndromes were associated with disruption of this ecosystem thus stressing its importance in maintaining the host's health. Growing evidence suggests that by manipulating the gut microbiota, some of these diseases could be treated or even prevented. These manipulations include changes in diet, use of probiotics, prebiotics, antibiotics and fecal microbiota transplantation (FMT). The successes in FMT treatment of recurrent infection of Clostridium difficile led recently to a great interest in extending this treatment modality to other diseases with proven disruption of gut microbiota, such as ulcerative colitis or metabolic syndrome. Key words: Clostridium difficile - dysbiosis - fecal microbial transplantation - microbiota - prebiotics - probiotics.}, } @article {pmid30221898, year = {2018}, author = {Reigadas, E and Olmedo, M and Valerio, M and Vázquez-Cuesta, S and Alcalá, L and Marín, M and Muñoz, P and Bouza, E}, title = {Fecal microbiota transplantation for recurrent Clostridium difficile infection: Experience, protocol, and results.}, journal = {Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia}, volume = {31}, number = {5}, pages = {411-418}, pmid = {30221898}, issn = {1988-9518}, abstract = {OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (R-CDI). Despite its excellent efficacy, it is still not a routine procedure in most European centers. FMT has not been widely used in Spain to date. We describe our experience with FMT, including a novel approach based on oral fecal capsules.

METHODS: We analyzed a prospectively recorded case series of patients with R-CDI treated with FMT at a single center (June 2014-July 2017). Primary outcome was defined as resolution of CDI without recurrence in a two-month period. FMT was administered via colonoscopy, nasojejunal tube, or oral capsules. All stool donors were rigorously screened.

RESULTS: FMT was performed in 13 patients with R-CDI. Median age was 75.0 years and 76.9% were females. Six FMT were performed via nasojejunal tube, 5 via oral capsules, and 2 by colonoscopy. There were no procedure-related adverse events, except for bacteremia in one patient. During follow-up, R- CDI was observed in one patient at one month after FMT. The primary resolution rate was 83.3% and the overall resolution rate was 91.7%. FMT by capsules achieved a 100% resolution rate, colonoscopy 100%, and nasojejunal tube 80.0%.

CONCLUSIONS: In our cohort, FMT proved to be safe and effective, even in high risk patients. Oral administration in capsules also proved to be safe, well-tolerated, and highly effective for R-CDI. In our experience, the FMT capsule formulation seems feasible in the routine of a hospital. This administration method will allow FMT to be more widely used.}, } @article {pmid30220230, year = {2018}, author = {Daniels, LM and Kufel, WD}, title = {Clinical review of Clostridium difficile infection: an update on treatment and prevention.}, journal = {Expert opinion on pharmacotherapy}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/14656566.2018.1524872}, pmid = {30220230}, issn = {1744-7666}, abstract = {INTRODUCTION: Clostridium difficile infection (CDI) has become a significant healthcare-associated infection and is strongly associated with antibiotic use. Practice guidelines have recently been revised incorporating updated recommendations for diagnosis, treatment, and prevention. Areas covered: This review discusses updated aspects of CDI management. New and emerging pharmacologic options for treatment and prevention are reviewed. Expert opinion: Metronidazole is associated with lower rates of treatment success compared to vancomycin and should no longer be used as primary therapy for the first episode of CDI or recurrent disease. Vancomycin or fidaxomicin are now recommended for first-line therapy for most cases of CDI. Fecal microbiota transplant is effective and safe for the treatment of recurrent CDI. Evidence supports the use of fidaxomicin and bezlotoxumab for prevention of recurrent CDI; however, the costs associated with these therapies may limit their use. Validated risk prediction tools are needed to identify patients most likely to benefit from these treatments. Future advancements in microbiota targeting treatments will emerge as promising alternatives to standard CDI treatments. Antibiotic stewardship and infection control measures will remain essential components for CDI management.}, } @article {pmid30218939, year = {2018}, author = {Schmulson, M and Bashashati, M}, title = {Fecal microbiota transfer for bowel disorders: efficacy or hype?.}, journal = {Current opinion in pharmacology}, volume = {43}, number = {}, pages = {72-80}, doi = {10.1016/j.coph.2018.08.012}, pmid = {30218939}, issn = {1471-4973}, abstract = {PURPOSE OF REVIEW: Dysbiosis has been related to the pathophysiology of disorders of - gut-brain interaction (DGBI) including irritable bowel syndrome (IBS) and functional constipation (FC). Accordingly, modulation of gut microbiota has been proposed as a potential treatment for these disorders. Gut microbiota modulation can be effected by probiotics, prebiotics, symbiotics, postbiotics, antibiotics and fecal transplantation (FMT) or bacteriotherapy. The latter is currently used for recurrent or severe Clostridium difficile colitis and has been the focus of recent research in IBS and FC.

RECENT FINDINGS: Several case series reported promising results for FMT in patients with IBS and FC, which prompted the conduction of randomized controlled trials (RCT) in these DGBI.

SUMMARY: Both case series and RCTs are herein discussed. To the best of our knowledge, as of yet, 5 RCTs have been published on IBS and one in FC with slow colonic transit. In IBS, the majority of studies have used the IBS severity scoring system (IBS-SSS) as an outcome measure; however, the selection criteria were different among the trials as well as the route and form of administration of the FMT. Therefore, the results are inconsistent and no conclusion can be drawn. Some studies suggest that the presence of post-infection (PI)-IBS and the baseline microbiota status in the donors could be predictor factors of successful FMT in IBS. In constipation with slow colonic transit, the FMT seems to be more effective, although the data is based on only one RCT. We believe that larger RCTs, controlled with true placebos and considering baseline intestinal microbiota of the study subjects as well as donors' microbiota are still needed before recommending FMT in IBS and/or FC. History of previous GI infection (e.g. PI-IBS) and IBS subtypes should also be taken into account.}, } @article {pmid30216124, year = {2018}, author = {Diorio, C and Robinson, PD and Ammann, RA and Castagnola, E and Erickson, K and Esbenshade, A and Fisher, BT and Haeusler, GM and Kuczynski, S and Lehrnbecher, T and Phillips, R and Cabral, S and Dupuis, LL and Sung, L}, title = {Guideline for the Management of Clostridium Difficile Infection in Children and Adolescents With Cancer and Pediatric Hematopoietic Stem-Cell Transplantation Recipients.}, journal = {Journal of clinical oncology : official journal of the American Society of Clinical Oncology}, volume = {}, number = {}, pages = {JCO1800407}, doi = {10.1200/JCO.18.00407}, pmid = {30216124}, issn = {1527-7755}, abstract = {Purpose The aim of this work was to develop a clinical practice guideline for the prevention and treatment of Clostridium difficile infection (CDI) in children and adolescents with cancer and pediatric hematopoietic stem-cell transplantation (HSCT) patients. Methods An international multidisciplinary panel of experts in pediatric oncology and infectious diseases with patient advocate representation was convened. We performed systematic reviews of randomized controlled trials for the prevention or treatment of CDI in any population and considered the directness of the evidence to children with cancer and pediatric HSCT patients. We used the Grading of Recommendations Assessment, Development, and Evaluation approach to generate recommendations. Results The panel made strong recommendations to administer either oral metronidazole or oral vancomycin for the initial treatment of nonsevere CDI and oral vancomycin for the initial treatment of severe CDI. Fidaxomicin may be considered in the setting of recurrent CDI. The panel suggested that probiotics not be routinely used for the prevention of CDI, and that monoclonal antibodies and probiotics not be routinely used for the treatment of CDI. A strong recommendation to not use fecal microbiota transplantation was made in this population. We identified key knowledge gaps and suggested directions for future research. Conclusion We present a guideline for the prevention and treatment of CDI in children and adolescents with cancer and pediatric HSCT patients. Future research should include randomized controlled trials that involve children with cancer and pediatric HSCT patients to improve the management of CDI in this population.}, } @article {pmid30214266, year = {2018}, author = {Sunkara, T and Rawla, P and Ofosu, A and Gaduputi, V}, title = {Fecal microbiota transplant - a new frontier in inflammatory bowel disease.}, journal = {Journal of inflammation research}, volume = {11}, number = {}, pages = {321-328}, doi = {10.2147/JIR.S176190}, pmid = {30214266}, issn = {1178-7031}, abstract = {Inflammatory bowel disease (IBD) is a chronic multifactorial disease that affects the gastrointestinal tract and results from an aberrant immune response toward luminal antigens in genetically susceptible people. Most of the current therapies for IBD focus on the management of the inflammation by using corticosteroids, immune modulators, and more recently, monoclonal antibodies (biological therapy). Although these therapies provide benefit in most cases, there are still a significant number of patients who do not respond or become refractory over time, suggesting the need for alternative therapeutic options. In the last decade, it has been recognized that "dysbiosis," an imbalanced gut microbiota, is a key element in IBD suggesting microbiome-based therapies as an attractive approach. Recently, fecal microbiota transplant (FMT) has been successfully used for the treatment of Clostridium difficile infection, and it is now under investigation for the treatment of IBD. Clinical trials data are still poor but strongly support a future introduction of FMT in therapy to manage IBD microbiome. More studies are needed to assess the optimal route of administration and the frequency of FMT, the best matched donor for each patient as well as the risks associated with FMT in IBD.}, } @article {pmid30212271, year = {2018}, author = {Ossorio, PN and Zhou, Y}, title = {Regulating stool for microbiota transplantation.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/19490976.2018.1502537}, pmid = {30212271}, issn = {1949-0984}, abstract = {In 2017 Gut Microbes published "A proposed definition of microbiota transplantation for regulatory purposes," in which the authors suggest that regulators should draw a line between microbiota transplants and biologic drugs composed of microbial communities (or other products derived from the human microbiome). They develop a definition of microbiota transplantation (MT) to help regulators draw such a line, and suggest that MT need not be, and cannot be, regulated as a biologic drug (a live biotherapeutic product). However, an agency's regulatory scrutiny of a medical product should be commensurate with that product's degree of risk to patients. Products for MT, such as stool, are likely to be as or more dangerous than more highly manipulated microbial products that scientists and regulators agree should be regulated as biologic drugs. Therefore, we argue that MT, as defined by the authors, should receive the same regulatory oversight as any other biologic product intended to cure, mitigate, treat, or prevent disease. We also suggest that regulators might not be able to operationalize the proposed definition of MT.}, } @article {pmid30210803, year = {2018}, author = {Wang, Z and Lou, H and Wang, Y and Shamir, R and Jiang, R and Chen, T}, title = {GePMI: A statistical model for personal intestinal microbiome identification.}, journal = {NPJ biofilms and microbiomes}, volume = {4}, number = {}, pages = {20}, doi = {10.1038/s41522-018-0065-2}, pmid = {30210803}, issn = {2055-5008}, abstract = {Human gut microbiomes consist of a large number of microbial genomes, which vary by diet and health conditions and from individual to individual. In the present work, we asked whether such variation or similarity could be measured and, if so, whether the results could be used for personal microbiome identification (PMI). To address this question, we herein propose a method to estimate the significance of similarity among human gut metagenomic samples based on reference-free, long k-mer features. Using these features, we find that pairwise similarities between the metagenomes of any two individuals obey a beta distribution and that a p value derived accordingly well characterizes whether two samples are from the same individual or not. We develop a computational framework called GePMI (Generating inter-individual similarity distribution for Personal Microbiome Identification) and apply it to several human gut metagenomic datasets (>300 individuals and >600 samples in total). From the results of GePMI, most of the human gut microbiomes can be identified (auROC = 0.9470, auPRC = 0.8702). Even after antibiotic treatment or fecal microbiota transplantation, the individual k-mer signature still maintains a certain specificity.}, } @article {pmid30202057, year = {2018}, author = {Zuo, T and Wong, SH and Cheung, CP and Lam, K and Lui, R and Cheung, K and Zhang, F and Tang, W and Ching, JYL and Wu, JCY and Chan, PKS and Sung, JJY and Yu, J and Chan, FKL and Ng, SC}, title = {Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in Clostridium difficile infection.}, journal = {Nature communications}, volume = {9}, number = {1}, pages = {3663}, doi = {10.1038/s41467-018-06103-6}, pmid = {30202057}, issn = {2041-1723}, abstract = {Fecal microbiota transplantation (FMT) is effective in treating recurrent Clostridium difficile infection (CDI). Bacterial colonization in recipients after FMT has been studied, but little is known about the role of the gut fungal community, or mycobiota. Here, we show evidence of gut fungal dysbiosis in CDI, and that donor-derived fungal colonization in recipients is associated with FMT response. CDI is accompanied by over-representation of Candida albicans and decreased fungal diversity, richness, and evenness. Cure after FMT is associated with increased colonization of donor-derived fungal taxa in recipients. Recipients of successful FMT ("responders") display, after FMT, a high relative abundance of Saccharomyces and Aspergillus, whereas "nonresponders" and individuals treated with antibiotics display a dominant presence of Candida. High abundance of C. albicans in donor stool also correlates with reduced FMT efficacy. Furthermore, C. albicans reduces FMT efficacy in a mouse model of CDI, while antifungal treatment reestablishes its efficacy, supporting a potential causal relationship between gut fungal dysbiosis and FMT outcome.}, } @article {pmid30197631, year = {2018}, author = {Wei, YL and Chen, YQ and Gong, H and Li, N and Wu, KQ and Hu, W and Wang, B and Liu, KJ and Wen, LZ and Xiao, X and Chen, DF}, title = {Fecal Microbiota Transplantation Ameliorates Experimentally Induced Colitis in Mice by Upregulating AhR.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1921}, doi = {10.3389/fmicb.2018.01921}, pmid = {30197631}, issn = {1664-302X}, abstract = {Ulcerative colitis (UC) is a chronic non-specific inflammatory disease that occurs in the colon and rectum. While fecal microbiota transplantation (FMT) is gaining attention as a clinical treatment of UC, the molecular mechanisms behind this effect have yet to be fully understood. A C57BL/6 mouse model was established to test whether FMT promotes the recovery of colon inflammation. Administration of 2% dextran sulfate sodium (DSS) for 7 days successfully induced acute colitis, as evidenced by diarrhea, hematochezia and colon shortening as well as a decrease in body weight. FMT alleviated the severity of colon mucosa injury and improved histological alterations compared with that of the DSS group. In addition, FMT promoted homeostasis of the intestinal microbiota. Furthermore, FMT upregulated the expression of aryl hydrocarbon receptor (AHR), interleukin-10 (IL-10), and transforming growth factor beta (TGF-β) in colon tissues. These results suggest that the significant anti-inflammatory effect of FMT may be attributed to its promotion of IL-10 and TGF-β production and AHR activation. Based on these results, FMT had a favorable therapeutic effect on DSS-induced colitis.}, } @article {pmid30194287, year = {2018}, author = {Luo, Y and Zeng, B and Zeng, L and Du, X and Li, B and Huo, R and Liu, L and Wang, H and Dong, M and Pan, J and Zheng, P and Zhou, C and Wei, H and Xie, P}, title = {Gut microbiota regulates mouse behaviors through glucocorticoid receptor pathway genes in the hippocampus.}, journal = {Translational psychiatry}, volume = {8}, number = {1}, pages = {187}, doi = {10.1038/s41398-018-0240-5}, pmid = {30194287}, issn = {2158-3188}, support = {81701361//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {Gut microbiota has an important role in the immune system, metabolism, and digestion, and has a significant effect on the nervous system. Recent studies have revealed that abnormal gut microbiota induces abnormal behaviors, which may be associated with the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, we investigated the behavioral changes in germ-free (GF) mice by behavioral tests, quantified the basal serum cortisol levels, and examined glucocorticoid receptor pathway genes in hippocampus using microarray analysis followed by real-time PCR validation, to explore the molecular mechanisms by which the gut microbiota influences the host's behaviors and brain function. Moreover, we quantified the basal serum cortisol levels and validated the differential genes in an Escherichia coli-derived lipopolysaccharide (LPS) treatment mouse model and fecal "depression microbiota" transplantation mouse model by real-time PCR. We found that GF mice showed antianxiety- and antidepressant-like behaviors, whereas E. coli LPS-treated mice showed antidepressant-like behavior, but did not show antianxiety-like behavior. However, "depression microbiota" recipient mice exhibited anxiety- and depressive-like behaviors. In addition, six glucocorticoid receptor pathway genes (Slc22a5, Aqp1, Stat5a, Ampd3, Plekhf1, and Cyb561) were upregulated in GF mice, and of these only two (Stat5a and Ampd3) were upregulated in LPS-treated mice, whereas the shared gene, Stat5a, was downregulated in "depression microbiota" recipient mice. Furthermore, basal serum cortisol levels were decreased in E. coli LPS-treated mice but not in GF mice and "depression microbiota" recipient mice. These results indicated that the gut microbiota may lead to behavioral abnormalities in mice through the downstream pathway of the glucocorticoid receptor. Herein, we proposed a new insight into the molecular mechanisms by which gut microbiota influence depressive-like behavior.}, } @article {pmid30183484, year = {2018}, author = {Monaghan, T and Mullish, BH and Patterson, J and Wong, GK and Marchesi, JR and Xu, H and Jilani, T and Kao, D}, title = {Effective fecal microbiota transplantation for recurrent Clostridioides difficile infection in humans is associated with increased signalling in the bile acid-farnesoid X receptor-fibroblast growth factor pathway.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-7}, doi = {10.1080/19490976.2018.1506667}, pmid = {30183484}, issn = {1949-0984}, abstract = {The mechanisms of efficacy for fecal microbiota transplantation (FMT) in treating recurrent Clostridioides difficile infection (rCDI) remain poorly defined, with restored gut microbiota-bile acid interactions representing one possible explanation. Furthermore, the potential implications for host physiology of these FMT-related changes in gut bile acid metabolism are also not well explored. In this study, we investigated the impact of FMT for rCDI upon signalling through the farnesoid X receptor (FXR)-fibroblast growth factor (FGF) pathway. Herein, we identify that in addition to restoration of gut microbiota and bile acid profiles, FMT for rCDI is accompanied by a significant, sustained increase in circulating levels of FGF19 and reduction in FGF21. These FGF changes were associated with weight gain post-FMT, to a level not exceeding the pre-rCDI baseline. Collectively, these data support the hypothesis that the restoration of gut microbial communities by FMT for rCDI is associated with an upregulated FXR-FGF pathway, and highlight the potential systemic effect of FMT.}, } @article {pmid30181015, year = {2018}, author = {Wang, JW and Kuo, CH and Kuo, FC and Wang, YK and Hsu, WH and Yu, FJ and Hu, HM and Hsu, PI and Wang, JY and Wu, DC}, title = {Fecal microbiota transplantation: Review and update.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jfma.2018.08.011}, pmid = {30181015}, issn = {0929-6646}, abstract = {Fecal microbiota transplantation (FMT) is a method to directly change the recipient's gut microbiota to normalize the composition and gain a therapeutic benefit. The history of FMT has been traced back to the 4th century and has been highly regarded since 2013, when the United States Food and Drug Administration approved FMT for treating recurrent and refractory Clostridium difficile infection. Since then, the range of FMT applications extended rapidly and broadly not only in gastrointestinal disorders, but also in extra-gastrointestinal diseases. Donor selection with questionnaire, interview, blood tests, and stool examinations should be strictly performed before FMT to reduce and prevent occurrence of any adverse events. Step-by-step cautious fecal and recipient preparation along with adequately choosing delivery methods based on individual clinical situations are key points of the FMT process. Although current evidence deems FMT as a generally safe therapeutic method with few adverse effects, the long-term outcomes of FMT have not been completely elucidated. Therefore, establishing periodicity and length of regular follow-up after FMT to monitor the clinical efficacy and long-term adverse events are other essential issues. In the future, we will look forward to personalized FMT for different patients and conditions according to varied hosts and diseases.}, } @article {pmid30178233, year = {2018}, author = {Han, R and Ma, J and Li, H}, title = {Mechanistic and therapeutic advances in non-alcoholic fatty liver disease by targeting the gut microbiota.}, journal = {Frontiers of medicine}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11684-018-0645-9}, pmid = {30178233}, issn = {2095-0225}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is one of the most common metabolic diseases currently in the context of obesity worldwide, which contains a spectrum of chronic liver diseases, including hepatic steatosis, non-alcoholic steatohepatitis and hepatic carcinoma. In addition to the classical "Two-hit" theory, NAFLD has been recognized as a typical gut microbiota-related disease because of the intricate role of gut microbiota in maintaining human health and disease formation. Moreover, gut microbiota is even regarded as a "metabolic organ" that play complementary roles to that of liver in many aspects. The mechanisms underlying gut microbiota-mediated development of NAFLD include modulation of host energy metabolism, insulin sensitivity, and bile acid and choline metabolism. As a result, gut microbiota have been emerging as a novel therapeutic target for NAFLD by manipulating it in various ways, including probiotics, prebiotics, synbiotics, antibiotics, fecal microbiota transplantation, and herbal components. In this review, we summarized the most recent advances in gut microbiota-mediated mechanisms, as well as gut microbiota-targeted therapies on NAFLD.}, } @article {pmid30178042, year = {2018}, author = {Gupta, A and Cifu, AS and Khanna, S}, title = {Diagnosis and Treatment of Clostridium difficile Infection.}, journal = {JAMA}, volume = {320}, number = {10}, pages = {1031-1032}, doi = {10.1001/jama.2018.12194}, pmid = {30178042}, issn = {1538-3598}, mesh = {Adult ; Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; Child ; *Clostridium Infections/diagnosis/drug therapy/therapy ; Clostridium difficile/genetics ; *Fecal Microbiota Transplantation ; Humans ; Nucleic Acid Amplification Techniques ; *Practice Guidelines as Topic ; Recurrence ; Vancomycin/*therapeutic use ; }, } @article {pmid30173572, year = {2018}, author = {Ruiz, L and López, P and Suárez, A and Sánchez, B and Margolles, A}, title = {The role of gut microbiota in lupus: what we know in 2018?.}, journal = {Expert review of clinical immunology}, volume = {14}, number = {10}, pages = {787-792}, doi = {10.1080/1744666X.2018.1519395}, pmid = {30173572}, issn = {1744-8409}, abstract = {INTRODUCTION: The role of the human intestinal microbiota in the maintenance of a healthy physiological condition, as well as its relation to the development of disease, remains to be clarified. Current evidence suggests that intestinal microbes could be involved in the initiation and amplification of autoimmune diseases, including rheumatoid arthritis and systemic lupus erythematosus (SLE). Despite recent progress in understanding how these microbes influence the pathophysiology of lupus, studies are still limited. Areas covered: In this review, we have tried to summarize the most relevant findings that have contributed to our understanding of the links between the human intestinal microbiota and the development of lupus. We also describe the potential role of individual microbial players in the physiology of lupus, and how they can shape relevant immune responses. Expert commentary: Culture-independent techniques based on massive sequencing represent a powerful tool to unravel the biological activity of gut microbes. Current data demonstrates that, depending on the pattern of intestinal microorganisms or the presence of specific bacteria, different responses related to lupus physiology can be triggered. Fecal microbiota transplantation, live biotherapeutics, or dietary interventions targeting the microbiota will likely become a treatment for SLE.}, } @article {pmid30173562, year = {2018}, author = {Delaune, V and Orci, LA and Lacotte, S and Peloso, A and Schrenzel, J and Lazarevic, V and Toso, C}, title = {Fecal microbiota transplantation: a promising strategy in preventing the progression of non-alcoholic steatohepatitis and improving the anti-cancer immune response.}, journal = {Expert opinion on biological therapy}, volume = {18}, number = {10}, pages = {1061-1071}, doi = {10.1080/14712598.2018.1518424}, pmid = {30173562}, issn = {1744-7682}, abstract = {INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) has the potential to progress to hepatocellular carcinoma (HCC). However, limited therapies are currently available for the treatment of advanced HCC, and one must strive to search for novel strategies. Areas covered: We provide insight on current knowledge related to gut microbiota and NAFLD, summarize the sequence linking obesity to HCC and highlight gut dysbiosis in obesity and its consequences on the liver. We detail the impact of the gut microbiota on immune checkpoint inhibitors, and speculate on the role of fecal microbiota transplantation (FMT) in NAFLD and in improving anti-neoplastic immune response. Expert Opinion: Manipulation of the gut microbiota seems promising in the secondary prevention of NAFLD/NASH and/or in potentiating anti-cancer immune response, notably by a global 'resetting' using FMT. However, the composition of a 'harmful' gut microbiome in HCC still needs to be characterized, and the impact of FMT on HCC growth needs to be assessed.}, } @article {pmid30158649, year = {2018}, author = {Wang, S and Huang, M and You, X and Zhao, J and Chen, L and Wang, L and Luo, Y and Chen, Y}, title = {Gut microbiota mediates the anti-obesity effect of calorie restriction in mice.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {13037}, doi = {10.1038/s41598-018-31353-1}, pmid = {30158649}, issn = {2045-2322}, support = {2016YFA0500103//Ministry of Science and Technology of the People&apos;s Republic of China (Chinese Ministry of Science and Technology)/ ; }, abstract = {Calorie restriction (CR) extends lifespan and elicits numerous effects beneficial to health and metabolism in various model organisms, but the underlying mechanisms are not completely understood. Gut microbiota has been reported to be associated with the beneficial effects of CR; however, it is unknown whether these effects of CR are causally mediated by gut microbiota. In this study, we employed an antibiotic-induced microbiota-depleted mouse model to investigate the functional role of gut microbiota in CR. Depletion of gut microbiota rendered mice resistant to CR-induced loss of body weight, accompanied by the increase in fat mass, the reduction in lean mass and the decline in metabolic rate. Depletion of gut microbiota led to increases in fasting blood glucose and cholesterol levels independent of CR. A few metabolism-modulating hormones including leptin and insulin were altered by CR and/or gut microbiota depletion. In addition, CR altered the composition of gut microbiota with significant increases in major probiotic genera such as Lactobacillus and Bifidobacterium, together with the decrease of Helicobacter. In addition, we performed fecal microbiota transplantation in mice fed with high-fat diet. Mice with transferred microbiota from calorie-restricted mice resisted high fat diet-induced obesity and exhibited metabolic improvement such as alleviated hepatic lipid accumulation. Collectively, these data indicate that CR-induced metabolic improvement especially in body weight reduction is mediated by intestinal microbiota to a certain extent.}, } @article {pmid30158252, year = {2018}, author = {Enck, P}, title = {Primum non nocere: is faecal microbiota transplantation doing harm to patients with IBS?.}, journal = {Gut}, volume = {}, number = {}, pages = {}, doi = {10.1136/gutjnl-2018-317277}, pmid = {30158252}, issn = {1468-3288}, } @article {pmid30155958, year = {2018}, author = {Barfuss, S and Knackstedt, ED and Jensen, K and Molina, K and Lal, A}, title = {Cardiac allograft vasculopathy following fecal microbiota transplantation for recurrent C. difficile infection.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {}, number = {}, pages = {e12983}, doi = {10.1111/tid.12983}, pmid = {30155958}, issn = {1399-3062}, abstract = {We report the case of a 3-year-old male who developed recurrent Clostridium difficile infection after receiving an orthotopic heart transplant. Despite multiple courses of antibiotics, C. difficile infection was persistent and he underwent a fecal microbiota transplant. The patient responded with resolution of his diarrhea. However, within 2 months he developed severe mixed rejection with high circulating donor-specific antibodies and significant coronary vasculopathy. Organ dysfunction led to the need for re-transplantation. The patient's postoperative course has since been complicated by pneumatosis intestinalis and recurrent C. difficile infection.}, } @article {pmid30154767, year = {2018}, author = {Kho, ZY and Lal, SK}, title = {The Human Gut Microbiome - A Potential Controller of Wellness and Disease.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1835}, doi = {10.3389/fmicb.2018.01835}, pmid = {30154767}, issn = {1664-302X}, abstract = {Interest toward the human microbiome, particularly gut microbiome has flourished in recent decades owing to the rapidly advancing sequence-based screening and humanized gnotobiotic model in interrogating the dynamic operations of commensal microbiota. Although this field is still at a very preliminary stage, whereby the functional properties of the complex gut microbiome remain less understood, several promising findings have been documented and exhibit great potential toward revolutionizing disease etiology and medical treatments. In this review, the interactions between gut microbiota and the host have been focused on, to provide an overview of the role of gut microbiota and their unique metabolites in conferring host protection against invading pathogen, regulation of diverse host physiological functions including metabolism, development and homeostasis of immunity and the nervous system. We elaborate on how gut microbial imbalance (dysbiosis) may lead to dysfunction of host machineries, thereby contributing to pathogenesis and/or progression toward a broad spectrum of diseases. Some of the most notable diseases namely Clostridium difficile infection (infectious disease), inflammatory bowel disease (intestinal immune-mediated disease), celiac disease (multisystemic autoimmune disorder), obesity (metabolic disease), colorectal cancer, and autism spectrum disorder (neuropsychiatric disorder) have been discussed and delineated along with recent findings. Novel therapies derived from microbiome studies such as fecal microbiota transplantation, probiotic and prebiotics to target associated diseases have been reviewed to introduce the idea of how certain disease symptoms can be ameliorated through dysbiosis correction, thus revealing a new scientific approach toward disease treatment. Toward the end of this review, several research gaps and limitations have been described along with suggested future studies to overcome the current research lacunae. Despite the ongoing debate on whether gut microbiome plays a role in the above-mentioned diseases, we have in this review, gathered evidence showing a potentially far more complex link beyond the unidirectional cause-and-effect relationship between them.}, } @article {pmid30150145, year = {2018}, author = {Zhang, X and Zhao, S and Song, X and Jia, J and Zhang, Z and Zhou, H and Fu, H and Cui, H and Hu, S and Fang, M and Liu, X and Bian, Y}, title = {Inhibition effect of glycyrrhiza polysaccharide (GCP) on tumor growth through regulation of the gut microbiota composition.}, journal = {Journal of pharmacological sciences}, volume = {137}, number = {4}, pages = {324-332}, doi = {10.1016/j.jphs.2018.03.006}, pmid = {30150145}, issn = {1347-8648}, abstract = {Glycyrrhiza Uralensis Polysaccharide (GCP), as a macromolecular polysaccharide extracted from the Traditional Chinese Medicine (TCM) - Licorice has been proved to inhibit tumor growth in vitro and in vivo; however, the specific anti-tumor mechanism of GCP needs to be further investigated. In this study, we explore the anti-tumor mechanism of GCP from the angle of gut microbiota. Colon carcinoma cells (CT-26) were used to set up a tumor-bearing mouse model. After 14 days of GCP treatment, the weights of tumors were significantly reduced. In addition, HE staining of tissue sections reflected that GCP could effectively inhibit tumor metastasis. 16SrRNA high-throughput sequencing of fecal samples showed a significant change between the model group and GCP group in the composition of gut microbiota. Subsequently, gut microbiota depletion and fecal transplantation experiments further confirmed the relationship between the anti-tumor effects of GCP and gut microbiota. Following depletion of gut microbiota, GCP cannot inhibit tumor growth. Fecal transplantation experiments found that transplanting the feces of GCP-treated mice, to a certain extent, could inhibit tumor growth and metastasis. These results indicate that Glycyrrhiza Polysaccharides exert anti-tumor effects by affecting gut microbiota composition.}, } @article {pmid30148975, year = {2018}, author = {Tampaki, EC and Tampakis, A and Posabella, A and Patsouris, E and Kontzoglou, K and Kouraklis, G}, title = {Current clostridium difficile treatments: Lessons that need to be learned from the clinical trials.}, journal = {Human vaccines & immunotherapeutics}, volume = {}, number = {}, pages = {1-2}, doi = {10.1080/21645515.2018.1493327}, pmid = {30148975}, issn = {2164-554X}, abstract = {Clostridium difficile infection (CDI) is the most common infectious disease cause of nosocomial diarrhea in adults in developed countries. Judging from the clinical trials on drugs used in CDIs, no approved treatment for recurrences exists, possibly indicating that a combination of treatment approaches are mandatory especially in severe infections, with current studies not being fully representative. Among the new strategies researched intensively fidaxomicin is presented, which demonstrates reduced CDI recurrences. Moreover, biotherapeutic strategies, mainly fecal microbiota transplantation but also competitive inhibition with non-toxigenic strains of C. difficile, and finally monoclonal antibodies against C. difficile toxins which offer protection against recurrences. Careful interpretation of the results based on lessons learned from previous trials conducted seems crucial. Questions are raised regarding how the results of future studies regarding new strategies researched will be managed and interpreted especially with regard to recurrence management as relevant data must be monitored for at least 30 days after end of treatment.}, } @article {pmid30146033, year = {2018}, author = {Pouch, SM and Friedman-Moraco, RJ}, title = {Prevention and Treatment of Clostridium difficile-Associated Diarrhea in Solid Organ Transplant Recipients.}, journal = {Infectious disease clinics of North America}, volume = {32}, number = {3}, pages = {733-748}, doi = {10.1016/j.idc.2018.05.001}, pmid = {30146033}, issn = {1557-9824}, abstract = {Clostridium difficile infection is a significant cause of morbidity and mortality in solid organ transplant recipients. Risk factors in this population include frequent hospitalizations, receipt of immunosuppressive agents, and intestinal dysbiosis triggered by several factors, including exposure to broad-spectrum antimicrobials. The incidence and potential for significant adverse outcomes among solid organ transplant recipients with C difficile infection highlight the evolving need for strategic C difficile infection risk factor modification and novel approaches to disease management in this patient population. This review focuses on current concepts related to the prevention and treatment of C difficile infection in solid organ transplant recipients.}, } @article {pmid30140609, year = {2018}, author = {Dias, C and Pipa, S and Duarte-Ribeiro, F and Mota, M}, title = {Fecal microbiota transplantation as a potential way to eradicate multiresistant microorganisms.}, journal = {IDCases}, volume = {13}, number = {}, pages = {e00432}, doi = {10.1016/j.idcr.2018.e00432}, pmid = {30140609}, issn = {2214-2509}, abstract = {Multiresistant microorganism infection often can produce a life-threatening situation. We report two cases in which fecal microbiota transplantation used for the treatment of recurrent Clostridium difficile infection were effective in eradicating colonization by carbapenemase-producing Enterobacteriaceae. The presented cases illustrate the potential benefit of fecal microbiota transplantation in resolution of asymptomatic carrier states of multiresistant microorganisms, suggesting the need for further investigations with a view to their applicability in this area.}, } @article {pmid30138161, year = {2018}, author = {Khan, MY and Dirweesh, A and Khurshid, T and Siddiqui, WJ}, title = {Comparing fecal microbiota transplantation to standard-of-care treatment for recurrent Clostridium difficile infection: a systematic review and meta-analysis.}, journal = {European journal of gastroenterology & hepatology}, volume = {30}, number = {11}, pages = {1309-1317}, doi = {10.1097/MEG.0000000000001243}, pmid = {30138161}, issn = {1473-5687}, abstract = {BACKGROUND: The use of fecal microbiota transplantation (FMT) as a treatment option for recurrent Clostridium difficile infection (rCDI) is well established. Various studies have used different forms and administration routes for FMT. We performed a systemic review and meta-analysis to update the clinical knowledge about different FMT modalities for curing rCDI compared with medical treatment (MT).

PATIENTS AND METHODS: We searched PubMed and Medline from inception through 10 May 2018 for randomized control trials (RCTs) comparing FMT (fresh or frozen) versus MT. We used Cochrane Collaboration's Risk of Bias tool to assess bias in the RCTs. We estimated odds ratio (OR) with 95% confidence interval (CI) for each outcome using a random effects model. P values of less than 0.05 were considered significant.

RESULTS: We included seven RCTs comprising a total of 543 patients with recurrent CDI. There was a nonsignificant trend toward resolution of diarrhea following a single fresh FMT infusion compared with frozen FMT and MT (OR=2.45, 95% CI=0.78-7.71, P=0.12, I=69%). Subgroup analysis of fresh FMT vs. frozen FMT showed no difference between the two groups (OR=2.13, 95% CI=0.22-20.41, P=0.51, I=61%). Frozen FMT infusion through upper route versus lower route showed no difference (OR=0.62, 95% CI=0.15-2.54, P=0.51, I=0%). There was a nonsignificant trend favoring multiple treatments with FMT versus multiple courses of MT (OR=3.68, 95% CI=0.74-18.22, P=0.11, I=0%).

CONCLUSION: FMT is a promising treatment modality for rCDI compared with MT alone. Different forms and routes of FMT administration seem to be equally efficacious. In future, more well-designed RCTs directed at homogenous FMT preparation and delivery methods are required to validate these findings.}, } @article {pmid30124831, year = {2018}, author = {Ishikawa, D and Sasaki, T and Takahashi, M and Kuwahara-Arai, K and Haga, K and Ito, S and Okahara, K and Nakajima, A and Shibuya, T and Osada, T and Hiramatsu, K and Watanabe, S and Nagahara, A}, title = {The Microbial Composition of Bacteroidetes Species in Ulcerative Colitis Is Effectively Improved by Combination Therapy With Fecal Microbiota Transplantation and Antibiotics.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izy266}, pmid = {30124831}, issn = {1536-4844}, abstract = {Background: We previously reported that fresh fecal microbiota transplantation (FMT) after triple-antibiotic therapy (amoxicillin, fosfomycin, and metronidazole [AFM]; A-FMT) synergistically contributed to the recovery of phylum Bacteroidetes composition associated with the endoscopic severity and treatment efficacy of ulcerative colitis (UC). Here, we performed further microbial analyses using a higher-resolution method to identify the key bacterial species in UC and determine whether viable Bacteroidetes species from donor feces were successfully colonized by A-FMT.

Methods: The taxonomic composition of Bacteroidetes in 25 healthy donors and 27 UC patients at baseline was compared at the species level using a heat-shock protein (hsp) 60-based microbiome method. Microbiota alterations before and after treatment of UC patients were also analyzed in 24 cases (n = 17 A-FMT; n = 3 mono-AFM; n = 4 mono-FMT).

Results: We found species-level dysbiosis within the phylum Bacteroidetes in UC samples, which was associated with reduced species diversity, resulting from hyperproliferation and hypoproliferation of particular species. Moreover, in responders treated with A-FMT, diversity was significantly recovered at 4 weeks after a fresh round of FMT, after which high degrees of similarity in Bacteroidetes species composition among recipients and donors were observed.

Conclusions: A-FMT alleviated intestinal dysbiosis, which is caused by the loss of Bacteroidetes species diversity in patients with UC. Eradication of dysbiotic indigenous Bacteroidetes species by AFM pretreatment might promote the colonization of viable Bacteroidetes cells, thereby improving the intestinal microbiota dysbiosis induced by UC. Our findings serve as a basis for further investigations into the mechanisms of FMT.}, } @article {pmid30123820, year = {2018}, author = {Williamson, IA and Arnold, JW and Samsa, LA and Gaynor, L and DiSalvo, M and Cocchiaro, JL and Carroll, I and Azcarate-Peril, MA and Rawls, JF and Allbritton, NL and Magness, ST}, title = {A High-Throughput Organoid Microinjection Platform to Study Gastrointestinal Microbiota and Luminal Physiology.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {6}, number = {3}, pages = {301-319}, doi = {10.1016/j.jcmgh.2018.05.004}, pmid = {30123820}, issn = {2352-345X}, support = {UL1 TR001111/TR/NCATS NIH HHS/United States ; R01 DK091427/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; R01 DK081426/DK/NIDDK NIH HHS/United States ; R01 DK109559/DK/NIDDK NIH HHS/United States ; UL1 TR001117/TR/NCATS NIH HHS/United States ; }, abstract = {Background & Aims: The human gut microbiota is becoming increasingly recognized as a key factor in homeostasis and disease. The lack of physiologically relevant in vitro models to investigate host-microbe interactions is considered a substantial bottleneck for microbiota research. Organoids represent an attractive model system because they are derived from primary tissues and embody key properties of the native gut lumen; however, access to the organoid lumen for experimental perturbation is challenging. Here, we report the development and validation of a high-throughput organoid microinjection system for cargo delivery to the organoid lumen and high-content sampling.

Methods: A microinjection platform was engineered using off-the-shelf and 3-dimensional printed components. Microinjection needles were modified for vertical trajectories and reproducible injection volumes. Computer vision (CVis) and microfabricated CellRaft Arrays (Cell Microsystems, Research Triangle Park, NC) were used to increase throughput and enable high-content sampling of mock bacterial communities. Modeling preformed using the COMSOL Multiphysics platform predicted a hypoxic luminal environment that was functionally validated by transplantation of fecal-derived microbial communities and monocultures of a nonsporulating anaerobe.

Results: CVis identified and logged locations of organoids suitable for injection. Reproducible loads of 0.2 nL could be microinjected into the organoid lumen at approximately 90 organoids/h. CVis analyzed and confirmed retention of injected cargos in approximately 500 organoids over 18 hours and showed the requirement to normalize for organoid growth for accurate assessment of barrier function. CVis analyzed growth dynamics of a mock community of green fluorescent protein- or Discosoma sp. red fluorescent protein-expressing bacteria, which grew within the organoid lumen even in the presence of antibiotics to control media contamination. Complex microbiota communities from fecal samples survived and grew in the colonoid lumen without appreciable changes in complexity.

Conclusions: High-throughput microinjection into organoids represents a next-generation in vitro approach to investigate gastrointestinal luminal physiology and the gastrointestinal microbiota.}, } @article {pmid30118620, year = {2018}, author = {Farowski, F and Els, G and Tsakmaklis, A and Higgins, PG and Kahlert, CR and Stein-Thoeringer, CK and Bobardt, JS and Dettmer-Wilde, K and Oefner, PJ and Vehreschild, JJ and Vehreschild, MJGT}, title = {Assessment of urinary 3-indoxyl sulfate as a marker for gut microbiota diversity and abundance of Clostridiales.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-9}, doi = {10.1080/19490976.2018.1502536}, pmid = {30118620}, issn = {1949-0984}, abstract = {OBJECTIVES: After allogeneic hematopoietic stem cell transplantation (allo-HCT), urinary levels of 3-indoxyl sulfate (3-IS) correlate with the relative abundance of bacteria from the class Clostridia (RAC), and antibiotic treatment is considered the major determinant of this outcome. A high RAC has been associated with favorable outcome after allo-HCT and protection from Clostridium difficile infection (CDI). We assessed correlations between alpha diversity, RAC and urinary 3-IS levels in a non-allo-HCT clinical cohort of antibiotic treated patients to further explore 3-IS as a biomarker of reduced diversity and predisposition to CDI.

METHODS: Fecal and urinary specimens were analyzed from 40 non-allo-HCT hospitalized patients before and 9 ± 2 days after initiation of intravenous antibiotic treatment. Fecal microbiota were analyzed by 16s RNA sequencing and urinary 3-IS was analyzed by liquid chromatography-tandem mass spectrometry. Receiver operating characteristic (ROC) analysis was performed to assess the predictive value of 3-IS.

RESULTS: At a RAC cutoff of <30%, the binary logarithm of 3-IS (medium 3-IS: ≤2.5; high 3-IS: >2.5) was predictive with an accuracy of 82% (negative predictive value: 87%, positive predictive value 67%). Accuracy was improved by combing antibiotic history with 3-IS levels (accuracy 89%, npv 88%, ppv 92%).

CONCLUSION: In conjunction with patient antibiotic history, 3-IS is a candidate marker to predict RAC.}, } @article {pmid30109576, year = {2018}, author = {Biehl, LM and Cruz Aguilar, R and Farowski, F and Hahn, W and Nowag, A and Wisplinghoff, H and Vehreschild, MJGT}, title = {Fecal microbiota transplantation in a kidney transplant recipient with recurrent urinary tract infection.}, journal = {Infection}, volume = {}, number = {}, pages = {}, doi = {10.1007/s15010-018-1190-9}, pmid = {30109576}, issn = {1439-0973}, support = {BI 1899/1-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {PURPOSE: We report on a kidney transplant recipient treated with fecal microbiota transplantation (FMT) for recurrent urinary tract infections.

METHODS: FMT was administered via frozen capsulized microbiota. Before and after FMT, urinary, fecal and vaginal microbiota compositions were analyzed.

RESULTS: The patient remained without symptoms after FMT.

CONCLUSIONS: Underlying mechanisms of action need to be addressed in depth by future research.}, } @article {pmid30099108, year = {2018}, author = {Colombel, JF and Shin, A and Gibson, PR}, title = {Functional Gastrointestinal Symptoms in Patients With Inflammatory Bowel Disease.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2018.08.001}, pmid = {30099108}, issn = {1542-7714}, support = {KL2 TR001106/TR/NCATS NIH HHS/United States ; }, abstract = {DESCRIPTION: The purpose of this clinical practice update review is to describe key principles in the diagnosis and management of functional gastrointestinal (GI) symptoms in patients with inflammatory bowel disease (IBD).

METHODS: The evidence and best practices summarized in this manuscript are based on relevant scientific publications, systematic reviews, and expert opinion where applicable. Best practice advice 1: A stepwise approach to rule-out ongoing inflammatory activity should be followed in IBD patients with persistent GI symptoms (measurement of fecal calprotectin, endoscopy with biopsy, cross-sectional imaging). Best practice advice 2: In those patients with indeterminate fecal calprotectin levels and mild symptoms, clinicians may consider serial calprotectin monitoring to facilitate anticipatory management. Best practice advice 3: Anatomic abnormalities or structural complications should be considered in patients with obstructive symptoms including abdominal distention, pain, nausea and vomiting, obstipation or constipation. Best practice advice 4: Alternative pathophysiologic mechanisms should be considered and evaluated (small intestinal bacterial overgrowth, bile acid diarrhea, carbohydrate intolerance, chronic pancreatitis) based on predominant symptom patterns. Best practice advice 5: A low FODMAP diet may be offered for management of functional GI symptoms in IBD with careful attention to nutritional adequacy. Best practice advice 6: Psychological therapies (cognitive behavioural therapy, hypnotherapy, mindfulness therapy) should be considered in IBD patients with functional symptoms. Best practice advice 7: Osmotic and stimulant laxative should be offered to IBD patients with chronic constipation. Best practice advice 8: Hypomotility agents or bile-acid sequestrants may be used for chronic diarrhea in quiescent IBD. Best practice advice 9: Antispasmodics, neuropathic-directed agents, and anti-depressants should be used for functional pain in IBD while use of opiates should be avoided. Best practice advice 10: Probiotics may be considered for treatment of functional symptoms in IBD. Best practice advice 11: Pelvic floor therapy should be offered to IBD patients with evidence of an underlying defecatory disorder. Best practice advice 12: Until further evidence is available, fecal microbiota transplant should not be offered for treatment of functional GI symptoms in IBD. Best practice advice 13: Physical exercise should be encourage in IBD patients with functional GI symptoms. Best practice advice 14: Until further evidence is available, complementary and alternative therapies should not be routinely offered for functional symptoms in IBD.}, } @article {pmid30093802, year = {2018}, author = {Filip, M and Tzaneva, V and Dumitrascu, DL}, title = {Fecal transplantation: digestive and extradigestive clinical applications.}, journal = {Clujul medical (1957)}, volume = {91}, number = {3}, pages = {259-265}, doi = {10.15386/cjmed-946}, pmid = {30093802}, issn = {1222-2119}, abstract = {Background and aim: Fecal transplantation or fecal material transplantation (FMT) became a hot topic in gastroenterology in recent years. Therefore it is important to disseminate the up-to-date information on FMT. The aim of the paper is to review the knowledge on FMT and its clinical applications.

Methods: An extensive review of the literature was carried out. Titles from Pubmed were searched and analyzed. A narrative review has been written with emphasis on indications of FMT in different conditions.

Results: The guidelines recommend FMT in relapsing infection with Clostridium difficile. Several attempts to use FMT in other conditions have been analyzed. Attempts were recorded in other bowel disorders like IBD, IBS, chronic constipation and even colorectal cancer. The attempt to change the microbiota by FMT in diabetes and obesity represent challenges for the future.

Conclusions: Fecal transplantation represents an important therapeutic method, intensively investigated these years. Beside the indication for persistent and recurrent Clostridium difficile infection, several attempts were undertaken in other intestinal diseases and in metabolic conditions. The efficiency of these applications has to be demonstrated.}, } @article {pmid30090049, year = {2018}, author = {Micic, D and Hirsch, A and Setia, N and Rubin, DT}, title = {Enteric infections complicating ulcerative colitis.}, journal = {Intestinal research}, volume = {16}, number = {3}, pages = {489-493}, doi = {10.5217/ir.2018.16.3.489}, pmid = {30090049}, issn = {1598-9100}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; }, abstract = {Enteric infections have previously been postulated to play a role in the pathogenesis of inflammatory bowel disease (IBD), however, little evidence exists in the etiologic role of specific enteric infections in the development of IBD. When encountered in the setting of IBD, enteric infections pose a clinical challenge in management given the competing treatment strategies for infectious conditions and autoimmune disorders. Here we present the case of a young male with enteric infections complicating a new diagnosis of IBD. Our patient's initial clinical presentation included diagnoses of Klebsiella oxytoca isolation and Clostridium difficile infection. Directed therapies to include withdrawal of antibiotics and fecal microbiota transplantation were performed without resolution of clinical symptoms. Given persistence of symptoms and active colitis, the patient was diagnosed with ulcerative colitis (UC), requiring treatments directed at severe UC to include cyclosporine therapy. The finding of multiple enteric infections in a newly presenting patient with IBD is an unexpected finding that has treatment implications.}, } @article {pmid30090033, year = {2018}, author = {Yu, LC and Wei, SC and Ni, YH}, title = {Impact of microbiota in colorectal carcinogenesis: lessons from experimental models.}, journal = {Intestinal research}, volume = {16}, number = {3}, pages = {346-357}, doi = {10.5217/ir.2018.16.3.346}, pmid = {30090033}, issn = {1598-9100}, abstract = {A role of gut microbiota in colorectal cancer (CRC) growth was first suggested in germ-free rats almost 50 years ago, and the existence of disease-associated bacteria (termed pathobionts) had becoming increasingly evident from experimental data of fecal transplantation, and microbial gavage or monoassociation. Altered bacterial compositions in fecal and mucosal specimens were observed in CRC patients compared to healthy subjects. Microbial fluctuations were found at various cancer stages; an increase of bacterial diversity was noted in the adenoma specimens, while a reduction of bacterial richness was documented in CRC samples. The bacterial species enriched in the human cancerous tissues included Escherichia coli, Fusobacterium nucleatum, and enterotoxigenic Bacteroides fragilis. The causal relationship of gut bacteria in tumorigenesis was established by introducing particular bacterial strains in in situ mouse CRC models. Detailed experimental protocols of bacterial gavage and the advantages and caveats of different experimental models are summarized in this review. The microbial genotoxins, enterotoxins, and virulence factors implicated in the mechanisms of bacteria-driven tumorigenesis are described. In conclusion, intestinal microbiota is involved in colon tumorigenesis. Bacteria-targeting intervention would be the next challenge for CRC.}, } @article {pmid30087270, year = {2018}, author = {Gagliardi, A and Totino, V and Cacciotti, F and Iebba, V and Neroni, B and Bonfiglio, G and Trancassini, M and Passariello, C and Pantanella, F and Schippa, S}, title = {Rebuilding the Gut Microbiota Ecosystem.}, journal = {International journal of environmental research and public health}, volume = {15}, number = {8}, pages = {}, doi = {10.3390/ijerph15081679}, pmid = {30087270}, issn = {1660-4601}, abstract = {A microbial ecosystem in which bacteria no longer live in a mutualistic association is called dysbiotic. Gut microbiota dysbiosis is a condition related with the pathogenesis of intestinal illnesses (irritable bowel syndrome, celiac disease, and inflammatory bowel disease) and extra-intestinal illnesses (obesity, metabolic disorder, cardiovascular syndrome, allergy, and asthma). Dysbiosis status has been related to various important pathologies, and many therapeutic strategies aimed at restoring the balance of the intestinal ecosystem have been implemented. These strategies include the administration of probiotics, prebiotics, and synbiotics; phage therapy; fecal transplantation; bacterial consortium transplantation; and a still poorly investigated approach based on predatory bacteria. This review discusses the various aspects of these strategies to counteract intestinal dysbiosis.}, } @article {pmid30085388, year = {2018}, author = {Cheng, YW and Phelps, E and Ganapini, V and Khan, N and Ouyang, F and Xu, H and Khanna, S and Tariq, R and Friedman-Moraco, RJ and Woodworth, MH and Dhere, T and Kraft, CS and Kao, D and Smith, J and Le, L and El-Nachef, N and Kaur, N and Kowsika, S and Ehrlich, A and Smith, M and Safdar, N and Ann Misch, E and Allegretti, JR and Flynn, A and Kassam, Z and Sharfuddin, A and Vuppalanchi, R and Fischer, M}, title = {Fecal microbiota transplantation for the treatment of recurrent and severe Clostridium difficile infection in solid organ transplant recipients: A multicenter experience.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {}, number = {}, pages = {}, doi = {10.1111/ajt.15058}, pmid = {30085388}, issn = {1600-6143}, support = {TL1 TR002382/TR/NCATS NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; }, abstract = {Fecal microbiota transplant (FMT) is recommended for Clostridium difficile infection (CDI) treatment; however, use in solid organ transplantation (SOT) patients has theoretical safety concerns. This multicenter, retrospective study evaluated FMT safety, effectiveness, and risk factors for failure in SOT patients. Primary cure and overall cure were defined as resolution of diarrhea or negative C difficile stool test after a single FMT or after subsequent FMT(s) ± anti-CDI antibiotics, respectively. Ninety-four SOT patients underwent FMT, 78% for recurrent CDI and 22% for severe or fulminant CDI. FMT-related adverse events (AE) occurred in 22.3% of cases, mainly comprising self-limiting conditions including nausea, abdominal pain, and FMT-related diarrhea. Severe AEs occurred in 3.2% of cases, with no FMT-related bacteremia. After FMT, 25% of patients with underlying inflammatory bowel disease had worsening disease activity, while 14% of cytomegalovirus-seropositive patients had reactivation. At 3 months, primary cure was 58.7%, while overall cure was 91.3%. Predictors of failing a single FMT included inpatient status, severe and fulminant CDI, presence of pseudomembranous colitis, and use of non-CDI antibiotics at the time of FMT. These data suggest FMT is safe in SOT patients. However, repeated FMT(s) or additional antibiotics may be needed to optimize rates of cure with FMT.}, } @article {pmid30083142, year = {2018}, author = {Niederwerder, MC and Constance, LA and Rowland, RRR and Abbas, W and Fernando, SC and Potter, ML and Sheahan, MA and Burkey, TE and Hesse, RA and Cino-Ozuna, AG}, title = {Fecal Microbiota Transplantation Is Associated With Reduced Morbidity and Mortality in Porcine Circovirus Associated Disease.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1631}, doi = {10.3389/fmicb.2018.01631}, pmid = {30083142}, issn = {1664-302X}, abstract = {Porcine circovirus associated disease (PCVAD) is a term used to describe the multi-factorial disease syndromes caused by porcine circovirus type 2 (PCV-2), which can be reproduced in an experimental setting through the co-infection of pigs with PCV-2 and porcine reproductive and respiratory syndrome virus (PRRSV). The resulting PCVAD-affected pigs represent a subpopulation within the co-infected group. In co-infection studies, the presence of increased microbiome diversity is linked to a reduction in clinical signs. In this study, fecal microbiota transplantation (FMT) was investigated as a means to prevent PCVAD in pigs co-infected with PRRSV and PCV-2d. The sources of the FMT material were high-parity sows with a documented history of high health status and robust litter characteristics. The analysis of the donated FMT material showed the absence of common pathogens along with the presence of diverse microbial phyla and families. One group of pigs (n = 10) was administered the FMT while a control group (n = 10) was administered a sterile mock-transplant. Over the 42-day post-infection period, the FMT group showed fewer PCVAD-affected pigs, as evidenced by a significant reduction in morbidity and mortality in transplanted pigs, along with increased antibody levels. Overall, this study provides evidence that FMT decreases the severity of clinical signs following co-infection with PRRSV and PCV-2 by reducing the prevalence of PCVAD.}, } @article {pmid30081949, year = {2018}, author = {Montassier, E and Al-Ghalith, GA and Hillmann, B and Viskocil, K and Kabage, AJ and McKinlay, CE and Sadowsky, MJ and Khoruts, A and Knights, D}, title = {CLOUD: a non-parametric detection test for microbiome outliers.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {137}, doi = {10.1186/s40168-018-0514-4}, pmid = {30081949}, issn = {2049-2618}, abstract = {BACKGROUND: Dysbiosis of the human gut microbiome is defined as a maladaptive or clinically relevant deviation of the community profile from the healthy or normal state. Dysbiosis has been implicated in an extensive set of metabolic, auto-immune, and infectious diseases, and yet there is substantial inter-individual variation in microbiome composition even within body sites of healthy humans. An individual's microbiome varies over time in a high-dimensional space to form their personal microbiome cloud. This cloud may or may not be similar to that of other people, both in terms of the average microbiome profile (conformity) and the diameter of the cloud (stability). However, there is currently no robust non-parametric test that determines whether a patient's microbiome cloud is an outlier with respect to a reference group of healthy individuals with widely varying microbiome profiles.

METHODS: Here, we propose a test for outliers' detection in the human gut microbiome that accounts for the wide range of microbiome phenotypes observed in a typical set of healthy individuals and for intra-individual temporal variation. Our robust nonparametric outlier detection test, the CLOUD test, performs two assessments of a patient's microbiome health: conformity, the extent to which the patient's microbiome cloud is ecologically similar to a subset of healthy subjects; and stability, which compares the cloud diameter of a patient to those of healthy subjects. The CLOUD test is based on locally linear embedded ecological distances, allowing it to account for widely varying microbiome compositions among reference individuals. It also leverages temporal variability within patients and reference individuals to increase the robustness of the test.

RESULTS: We describe the CLOUD test, and we apply it to one novel and two previously published cohorts of patients receiving fecal microbiota transplantation for recurrent Clostridium difficile colitis, as well as to two known healthy cohorts, demonstrating high concordance of the CLOUD conformity and stability indices with clinical outcomes.

CONCLUSIONS: Although the CLOUD test is not, on its own, a test for clinical dysbiosis, it nonetheless provides a framework for outlier testing that could be incorporated into evaluation of suspected dysbiosis, which may play a role in diagnosis and prognosis of numerous pediatric and adult diseases.}, } @article {pmid30078058, year = {2018}, author = {Singh, S}, title = {Evolution of Clinical Trials in Inflammatory Bowel Diseases.}, journal = {Current gastroenterology reports}, volume = {20}, number = {9}, pages = {41}, doi = {10.1007/s11894-018-0648-3}, pmid = {30078058}, issn = {1534-312X}, abstract = {PURPOSE OF REVIEW: Since the first clinical trial of cortisone in ulcerative colitis in 1955, remarkable progress has been made in the design and conduct of clinical trials in inflammatory bowel diseases (IBD). In this review article, we will discuss evolution of clinical trials in IBD over the last 3-5 years.

RECENT FINDINGS: Recognizing limitations intrinsic to clinical disease activity indices in IBD, regulatory authorities have recommended evaluating co-primary endpoints of patient-reported outcomes and endoscopic disease activity in clinical trials. Biomarker-enriched trial enrolment and central endoscopy reading have emerged as critical events in trial recruitment and outcome assessment and have driven placebo response rates down. While trials of novel biologic therapies and advanced small molecules continue at an accelerated pace, pragmatic comparative efficacy trials of treatment strategy aimed at optimizing current therapies (such as early combined immunosuppression [REACT], tight disease control [CALM], therapeutic drug monitoring [TAXIT, TAILORIX]) have directly informed clinical practice. With emphasis on value-based care and population health management, multi-pronged remote monitoring, self-management, and telemedicine approaches in the era of smartphones have re-emerged with promise. Non-conventional therapies such as fecal microbiota transplantation, though still experimental, have provided insight into disease pathogenesis and offered hope for microbial manipulation strategies for treating these complex diseases. Clinical trials have rapidly evolved over the last 5 years not only focusing on novel therapies but also optimizing existing treatment approaches and population health management. Over the next decade, these trials will continue to advance the field, and be readily translatable into clinical practice.}, } @article {pmid30077182, year = {2018}, author = {Ye, Z and Zhang, N and Wu, C and Zhang, X and Wang, Q and Huang, X and Du, L and Cao, Q and Tang, J and Zhou, C and Hou, S and He, Y and Xu, Q and Xiong, X and Kijlstra, A and Qin, N and Yang, P}, title = {A metagenomic study of the gut microbiome in Behcet's disease.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {135}, doi = {10.1186/s40168-018-0520-6}, pmid = {30077182}, issn = {2049-2618}, abstract = {BACKGROUND: Behcet's disease (BD) is a recalcitrant, multisystemic inflammatory disease that can lead to irreversible blindness. Microbial agents have been considered to contribute to the pathogenesis of this disease, but the underlying mechanisms remain unclear. In this study, we investigated the association of gut microbiome composition with BD as well as its possible roles in the development of this disease.

METHODS: Fecal and saliva samples were collected from 32 active BD patients and 74 healthy controls. DNA extracted from fecal samples was subjected to metagenomic analysis, whereas DNA extracted from saliva samples was subjected to 16S rRNA gene sequencing analysis. The results were used to compare the composition and biological function of the microbiome between patients and healthy controls. Lastly, transplantation of pooled fecal samples from active BD patients into B10RIII mice undergoing experimental autoimmune uveitis (EAU) was performed to determine the causal relationship between the gut microbiome and BD.

RESULTS: Fecal samples from active BD patients were shown to be enriched in Bilophila spp., a sulfate-reducing bacteria (SRB) and several opportunistic pathogens (e.g., Parabacteroides spp. and Paraprevotella spp.) along with a lower level of butyrate-producing bacteria (BPB) Clostridium spp. and methanogens (Methanoculleus spp. Methanomethylophilus spp.). Analysis of microbial functions revealed that capsular polysaccharide transport system, oxidation-reduction process, type III, and type IV secretion systems were also increased in active BD patients. Network analysis showed that the BD-enriched SRB and opportunistic pathogens were positively correlated with each other, but they were negatively associated with the BPB and methanogens. Animal experiments revealed that fecal microbiota transplantation with feces from BD patients significantly exacerbated EAU activity and increased the production of inflammatory cytokines including IL-17 and IFN-γ.

CONCLUSIONS: Our findings revealed that BD is associated with considerable gut microbiome changes, which is corroborated by a mouse study of fecal microbiota transplants. A model explaining the association of the gut microbiome composition with BD pathogenesis is proposed.}, } @article {pmid30075573, year = {2018}, author = {Chehri, M and Christensen, AH and Halkjær, SI and Günther, S and Petersen, AM and Helms, M}, title = {Case series of successful treatment with fecal microbiota transplant (FMT) oral capsules mixed from multiple donors even in patients previously treated with FMT enemas for recurrent Clostridium difficile infection.}, journal = {Medicine}, volume = {97}, number = {31}, pages = {e11706}, doi = {10.1097/MD.0000000000011706}, pmid = {30075573}, issn = {1536-5964}, mesh = {Adult ; Aged ; Aged, 80 and over ; Capsules ; Clostridium Infections/*therapy ; Denmark ; Drug Administration Routes ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Middle Aged ; Recurrence ; }, abstract = {RATIONALE: Studies have shown that fecal microbiota transplantation (FMT) is a safe and highly efficient treatment for recurrent Clostridium difficile infection (rCDI). However, it is still unknown if one versus multiple donors or enemas versus capsule FMT are most efficient.

PATIENT CONCERNS: 10 patients with at least 3 previous episodes of CDI were offered treatment with FMT capsules. 9 patients decided to participate.

DIAGNOSES: In this study, we treated 9 patients (25-86 years) with rCDI.

INTERVENTIONS: From October to November 2016, a total of 9 patients with recurrent CDI were treated with oral fecal microbiota capsules, with mixed donor feces from 4 donors with high microbiota diversity. All patients received treatment with vancomycin prior to the capsule regime.

OUTCOME: Patients had previous recurrences ranging from 2 to 10 recurrences. All 9 patients were successfully treated without recurrence after 180 days follow-up, even 2 patients previously treated with FMT enemas.

LESSONS: FMT capsules based on multiple donors are highly efficient in patients with rCDI.}, } @article {pmid30055267, year = {2018}, author = {Vaughn, BP and Rank, KM and Khoruts, A}, title = {Fecal Microbiota Transplantation: Current Status in Treatment of GI and Liver Disease.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2018.07.026}, pmid = {30055267}, issn = {1542-7714}, abstract = {Fecal microbiota transplantation was originally introduced as a method to repair intestinal microbiota following failure of multiple treatments of recurrent Clostridiumdifficile infection with antibiotics. However, it is hypothesized that intestinal dysbiosis may contribute to the pathogenesis of many diseases, especially those involving the gastrointestinal tract. Therefore, fecal microbiota transplantation is increasingly being explored as a potential treatment that aims to optimize microbiota composition and functionality. Here, we review the current state of fecal microbiota transplantation development and applications in conditions of greatest interest to a gastroenterologist.}, } @article {pmid30054112, year = {2018}, author = {Su, HJ and Chiu, YT and Chiu, CT and Lin, YC and Wang, CY and Hsieh, JY and Wei, SC}, title = {Inflammatory bowel disease and its treatment in 2018: Global and Taiwanese status updates.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jfma.2018.07.005}, pmid = {30054112}, issn = {0929-6646}, abstract = {The global incidence and prevalence of inflammatory bowel disease (IBD) has increased over the last 2-4 decades, likely because of the adoption of a more "western" lifestyle as well as improved detection and awareness, and Taiwan is no exception. To characterize the increasing burden of IBD, we conducted a comprehensive review of IBD in the existing literature. The following parameters were reviewed: background knowledge and current standard care for IBD, including natural history, epidemiology, pathogenesis, diagnosis, monitoring, and treatment. In addition, new imaging modalities and treatment options such as combined positron emission tomography and magnetic resonance enterography, new biologic agents, small-molecule therapy, biosimilar therapeutics, mesenchymal stem cell transplantation, and fecal microbiota transplantation, all of which have been introduced for IBD management, were reviewed. We also used the hospital-based as well as population-based Taiwan National Health Insurance Research Database to assess Taiwan-specific trends for comparison with global trends.}, } @article {pmid30048534, year = {2018}, author = {Jiang, M and Leung, NH and Ip, M and You, JHS}, title = {Cost-effectiveness analysis of ribotype-guided fecal microbiota transplantation in Chinese patients with severe Clostridium difficile infection.}, journal = {PloS one}, volume = {13}, number = {7}, pages = {e0201539}, doi = {10.1371/journal.pone.0201539}, pmid = {30048534}, issn = {1932-6203}, abstract = {BACKGROUND: Clostridium difficile infection (CDI) caused by ribotype 002 strain is associated with poor outcomes in Chinese patients. Fecal microbiota transplantation (FMT) is an effective but costly treatment for CDI. We aimed to examine potential cost-effectiveness of ribotype-guided FMT in Chinese patients with severe CDI.

METHODS: A decision-analytic model was designed to simulate outcomes of ribotype 002-guided FMT versus vancomycin treatment in Chinese patients with severe CDI in the hospital setting. Outcome measures included mortality rate; direct medical cost; and quality-adjusted life year (QALY) loss for CDI. Sensitivity analysis was performed to examine robustness of base-case results.

RESULTS: Comparing to vancomycin treatment, ribotype-guided FMT group reduced mortality (11.6% versus 17.1%), cost (USD8,807 versus USD9,790), and saved 0.472 QALYs in base-case analysis. One-way sensitivity analysis found the ribotype-guided FMT group to remain cost-effective when patient acceptance rate of FMT was >0.6% and ribotype 002 prevalence was >0.07%. In probabilistic sensitivity analysis, ribotype-guided FMT gained higher QALYs at 100% of simulations with mean QALY gain of 0.405 QALYs (95%CI: 0.400-0.410; p<0.001). The ribotype-guided group was less costly in 97.9% of time, and mean cost-saving was USA679 (95%CI: 670-688; p<0.001).

CONCLUSIONS: In the present model, ribotype-guided FMT appears to be a potential option to save QALYs and cost when comparing with vancomycin. The cost-effectiveness of ribotype-guided FMT is subject to the patient acceptance to FMT and prevalence of ribotype 002.}, } @article {pmid30047327, year = {2018}, author = {Mogilnicka, I and Ufnal, M}, title = {Gut Mycobiota and Fungal Metabolites in Human Homeostasis.}, journal = {Current drug targets}, volume = {}, number = {}, pages = {}, doi = {10.2174/1389450119666180724125020}, pmid = {30047327}, issn = {1873-5592}, abstract = {BACKGROUND: Accumulating evidence suggests that microbiota plays an important role in host's homeostasis. Thus far researchers have mostly focused on the role of bacterial microbiota. However, human gut is a habitat for several fungal species, which produce numerous metabolites. Furthermore, various types of food and beverages are rich in a wide spectrum of fungi and their metabolites.

METHODS: We searched PUBMED and Google Scholar databases to identify clinical and pre-clinical studies on fungal metabolites, composition of human mycobiota and fungal dysbiosis.

RESULTS: Fungal metabolites may serve as signaling molecules and exert significant biological effects including trophic, anti-inflammatory or antibacterial actions. Finally, research suggests an association between shifts in gut fungi composition and human health. Changes in mycobiota composition have been found in obesity, hepatitis and inflammatory bowel diseases.

CONCLUSION: The influence of mycobiota and dietary fungi on homeostasis in mammals suggests a pharmacotherapeutic potential of modulating the mycobiota which may include treatment with probiotics and fecal transplantation. Furthermore, antibacterial action of fungi-derived molecules may be considered as a substitution for currently used antibacterial agents and preservatives in food industry.}, } @article {pmid30031625, year = {2018}, author = {Leclercq, S and Stärkel, P and Delzenne, NM and de Timary, P}, title = {The gut microbiota: A new target in the management of alcohol dependence?.}, journal = {Alcohol (Fayetteville, N.Y.)}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.alcohol.2018.03.005}, pmid = {30031625}, issn = {1873-6823}, abstract = {The gastrointestinal tract is the natural habitat for a huge community of microorganisms, comprising bacteria, viruses, fungi and yeast. This microbial ecosystem codevelops with the host throughout life and is subject to a complex interplay that depends on multiple factors including host genetics, nutrition, life-style, stress, diseases and antibiotics use. The gut microbiota, that refers to intestinal bacteria, has profound influence on the host immune system, metabolism and nervous system. Indeed, intestinal bacteria supply the host with essential nutrients such as vitamins, metabolize bile acids and undigested compounds, defend against pathogen invasion, participate to the development of the intestinal architecture and the intestinal immune system and play an important role in the maintenance of the gut barrier function. More recently, the gut microbiota has been shown to influence brain functions, such as myelin synthesis, the blood-brain barrier permeability and neuroinflammatory responses but also mood and behavior. The cross-talk between microbes and the host implicates a vast array of signaling pathways that involve many different classes of molecules like metabolites produced by the bacteria from dietary or endogenous sources of carbohydrates and proteins (i.e. short-chain fatty acids (SCFAs), indole), neurotransmitters and inflammatory cytokines. This review will focus on the involvement of the gut microbiota in the pathophysiological aspects of alcohol dependence related to the gut barrier function, liver damage and psychological disturbances. We will also discuss the possibility to create new and realistic humanized animal models of alcohol dependence by the use of fecal transplantation.}, } @article {pmid30025704, year = {2018}, author = {McDonald, JAK and Mullish, BH and Pechlivanis, A and Liu, Z and Brignardello, J and Kao, D and Holmes, E and Li, JV and Clarke, TB and Thursz, MR and Marchesi, JR}, title = {Inhibiting Growth of Clostridioides difficile by Restoring Valerate, Produced by the Intestinal Microbiota.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2018.07.014}, pmid = {30025704}, issn = {1528-0012}, support = {MR/R000875/1//Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is effective for treating recurrent Clostridioides difficile infection (CDI), but there are concerns about its long-term safety. Understanding the mechanisms of the effects of FMT could help us design safer, targeted therapies. We aimed to identify microbial metabolites that are important for C difficile growth.

METHODS: We used a CDI chemostat model as a tool to study the effects of FMT in vitro. The following analyses were performed: C difficile plate counts, 16S rRNA gene sequencing, proton nuclear magnetic resonance spectroscopy, and ultra-performance liquid chromatography and mass spectrometry bile acid profiling. FMT mixtures were prepared using fresh fecal samples provided by donors enrolled in an FMT program in the United Kingdom. Results from chemostat experiments were validated using human stool samples, C difficile batch cultures, and C57BL/6 mice with CDI. Human stool samples were collected from 16 patients with recurrent CDI and healthy donors (n = 5) participating in an FMT trial in Canada.

RESULTS: In the CDI chemostat model, clindamycin decreased valerate and deoxycholic acid concentrations and increased C difficile total viable counts and valerate precursors, taurocholic acid, and succinate concentrations. After we stopped adding clindamycin, levels of bile acids and succinate recovered, whereas levels of valerate and valerate precursors did not. In the CDI chemostat model, FMT increased valerate concentrations and decreased C difficile total viable counts (94% decrease), spore counts (86% decrease), and valerate precursor concentrations; concentrations of bile acids were unchanged. In stool samples from patients with CDI, valerate was depleted before FMT but restored after FMT. Clostridioides difficile batch cultures confirmed that valerate decreased vegetative growth, and that taurocholic acid was required for germination but had no effect on vegetative growth. Clostridioides difficile total viable counts were decreased by 95% in mice with CDI given glycerol trivalerate compared with phosphate buffered saline.

CONCLUSIONS: We identified valerate as a metabolite that is depleted with clindamycin and only recovered with FMT. Valerate is a target for a rationally designed recurrent CDI therapy.}, } @article {pmid30011107, year = {2018}, author = {Lin, SC and Alonso, CD and Moss, AC}, title = {Fecal microbiota transplantation for recurrent Clostridium difficile infection in patients with solid organ transplants: an institutional experience and review of the literature.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {}, number = {}, pages = {e12967}, doi = {10.1111/tid.12967}, pmid = {30011107}, issn = {1399-3062}, abstract = {Clostridium difficile, an anaerobic gram-positive, spore-forming bacillus, has become the most common cause of nosocomial infectious diarrhea, and is associated with increased mortality in all populations. Patients who have received solid organ transplants (SOT) are at increased risk of Clostridium difficile infection (CDI) and CDI recurrence (rCDI). This may be related to chronic immunosuppression, frequent antibiotic exposure, and increased or prolonged hospitalizations. Increased morbidity and mortality from CDI is well-described in SOT patients. Conventional treatments for index and recurrent CDI include vancomycin and fidaxomicin. Fecal microbiota transplantation has emerged as an effective and safe alternative for treating rCDI in the general population. Reports of its safety in certain immunocompromised populations, such as those with inflammatory bowel disease, appear reassuring, but outcomes among SOT patients are less well known. Here, we summarize the experiences published to date on the treatment of rCDI with FMT in SOT patient, and also describe our detailed FMT protocol and experience in treating a series of SOT patients with rCDI. In addition to reporting the safety and efficacy of our FMT experience, we also discuss the diagnostic challenges and considerations in this population of solid organ transplant recipients.}, } @article {pmid30010747, year = {2018}, author = {Nusbaum, DJ and Sun, F and Ren, J and Zhu, Z and Ramsy, N and Pervolarakis, N and Kunde, S and England, W and Gao, B and Fiehn, O and Michail, S and Whiteson, K}, title = {Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy133}, pmid = {30010747}, issn = {1574-6941}, abstract = {Ulcerative colitis is a chronic inflammatory disease of the colon that carries a significant disease burden in children. Therefore, new therapeutic approaches are being explored to help children living with this disease. Fecal microbiota transplantation (FMT) has been successful in some children with ulcerative colitis. However, the mechanism of its therapeutic effect in this patient population is not well understood. To characterize changes in gut microbial and metabolomic profiles after FMT, we performed 16S rRNA gene sequencing, shotgun metagenomic sequencing, virome analysis and untargeted metabolomics by gas chromatography-time of flight-mass spectrometry on stool samples collected before and after FMT from four children with ulcerative colitis who responded to this treatment. Alpha diversity of the gut microbiota increased after intervention, with species richness rising from 251 (S.D. 125) to 358 (S.D. 27). In responders, the mean relative abundance of bacteria in the class Clostridia shifted toward donor levels, increasing from 33% (S.D. 11%) to 54% (S.D. 16%). Patient metabolomic and viromic profiles exhibited a similar but less pronounced shift toward donor profiles after FMT. The fecal concentrations of several metabolites were altered after FMT, correlating with clinical improvement. Larger studies using a similar multi-omics approach may suggest novel strategies for the treatment of pediatric ulcerative colitis.}, } @article {pmid30010734, year = {2018}, author = {Geng, S and Cheng, S and Li, Y and Wen, Z and Ma, X and Jiang, X and Wang, Y and Han, X}, title = {Fecal Microbiota Transplantation Reduces Susceptibility to Epithelial Injury and Modulates Tryptophan Metabolism of Microbial Community in a Piglet Model.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjy103}, pmid = {30010734}, issn = {1876-4479}, abstract = {Background and Aims: Fecal microbiota transplantation [FMT] has shown promise as a treatment for inflammatory bowel disease [IBD]. Using a piglet model, our previous study indicated that exogenous fecal microbiota can enhance gastrointestinal health through enhancing intestinal barrier. However, specific connections between FMT-induced microbial changes and modulation of intestinal barrier still remain to be fully illustrated. Here, we aimed to determine the potential role of metabolic function of gut microbiota in the beneficial effects of FMT.

Methods: The influence of FMT on the maintenance of intestinal homeostasis was assessed by early-life gut microbiota intervention on newborn piglets and subsequent lipopolysaccharide [LPS] challenge. Analysis of the gut microbiome and metabolome was carried out by 16S rRNA sequencing and multiple mass spectrometry platforms.

Results: FMT modulated the diversity and composition of colonic microbiota and reduced the susceptibility to LPS-induced destruction of epithelial integrity and severe inflammatory response. Metabolomic analysis revealed functional changes of the gut metabolome along with significant increase of typical microbiota-derived tryptophan catabolite indole-3-acetic acid in the colonic lumen. Further, metagenomics prediction analysis based on 16S rRNA sequencing also demonstrated that FMT modulated the metabolic functions of gut microbiota associated with tryptophan metabolism and intestinal homeostasis, which coincided with up-regulation of cytokine interleukin-22 and enhanced activation of aryl hydrocarbon receptor in the recipient colon.

Conclusions: Our data reveal a regulatory effect of FMT on tryptophan metabolism of gut microbiota in the recipient colon, which may play a potential role in the maintenance of intestinal barrier.}, } @article {pmid30009869, year = {2018}, author = {Cheminet, G and Kapel, N and Bleibtreu, A and Sadou-Yaye, H and Bellanger, A and Duval, X and Joly, F and Fantin, B and de Lastours, V and , }, title = {Faecal microbiota transplantation with frozen capsules for relapsing Clostridium difficile infections: the first experience from 15 consecutive patients in France.}, journal = {The Journal of hospital infection}, volume = {100}, number = {2}, pages = {148-151}, doi = {10.1016/j.jhin.2018.07.005}, pmid = {30009869}, issn = {1532-2939}, } @article {pmid30004130, year = {2018}, author = {Inserra, A and Rogers, GB and Licinio, J and Wong, ML}, title = {The Microbiota-Inflammasome Hypothesis of Major Depression.}, journal = {BioEssays : news and reviews in molecular, cellular and developmental biology}, volume = {40}, number = {9}, pages = {e1800027}, doi = {10.1002/bies.201800027}, pmid = {30004130}, issn = {1521-1878}, abstract = {We propose the "microbiota-inflammasome" hypothesis of major depressive disorder (MDD, a mental illness affecting the way a person feels and thinks, characterized by long-lasting feelings of sadness). We hypothesize that pathological shifts in gut microbiota composition (dysbiosis) caused by stress and gut conditions result in the upregulation of pro-inflammatory pathways mediated by the Nod-like receptors family pyrin domain containing 3 (NLRP3) inflammasome (an intracellular platform involved in the activation of inflammatory processes). This upregulation exacerbates depressive symptomatology and further compounds gut dysbiosis. In this review we describe MDD/chronic stress-induced changes in: 1) NLRP3 inflammasome; 2) gut microbiota; and 3) metabolic pathways; and how inflammasome signaling may affect depressive-like behavior and gut microbiota composition. The implication is that novel therapeutic strategies could emerge for MDD and co-morbid conditions. A number of testable predictions surface from this microbiota-gut-inflammasome-brain hypothesis of MDD, using approaches that modulate gut microbiota composition via inflammasome modulation, fecal microbiota transplantation, psychobiotics supplementation, or dietary change.}, } @article {pmid29997912, year = {2018}, author = {Heimesaat, MM and Escher, U and Grunau, A and Fiebiger, U and Bereswill, S}, title = {Peroral Low-Dose Toxoplasma gondii Infection of Human Microbiota-Associated Mice - A Subacute Ileitis Model to Unravel Pathogen-Host Interactions.}, journal = {European journal of microbiology & immunology}, volume = {8}, number = {2}, pages = {53-61}, doi = {10.1556/1886.2018.00005}, pmid = {29997912}, issn = {2062-509X}, abstract = {Within 1 week following high-dose Toxoplasma gondii infection, mice develop lethal necrotizing ileitis. However, data from a subacute T. gondii-induced ileitis model are scarce. Therefore, mice harboring a human gut microbiota were perorally infected with one cyst of T. gondii. Within 9 days post-infection, the intestinal microbiota composition shifted towards higher loads of commensal enterobacteria and enterococci. Following T. gondii infection, mice were clinically only mildly affected, whereas ≈60% of mice displayed fecal blood and mild-to-moderate ileal histopathological changes. Intestinal inflammation was further characterized by increased apoptotic intestinal epithelial cells, which were accompanied by elevated proliferating gut epithelial cell numbers. As compared to naive controls, infected mice displayed elevated numbers of intestinal T lymphocytes and regulatory T-cells and increased pro-inflammatory mediator secretion. Remarkably, T. gondii-induced apoptotic and pro-inflammatory immune responses were not restricted to the gut, but could also be observed in extra-intestinal compartments including kidney, liver, and lung. Strikingly, low-dose T. gondii infection resulted in increased serum levels of pro- and anti-inflammatory cytokines. In conclusion, the here presented subacute ileitis model following peroral low-dose T. gondii infection of humanized mice allows for detailed investigations of the molecular mechanism underlying the "ménage à trois" of pathogens, human gut microbiota, and immunity.}, } @article {pmid29997909, year = {2018}, author = {Escher, U and Giladi, E and Dunay, IR and Bereswill, S and Gozes, I and Heimesaat, MM}, title = {Anti-inflammatory Effects of the Octapeptide NAP in Human Microbiota-Associated Mice Suffering from Subacute Ileitis.}, journal = {European journal of microbiology & immunology}, volume = {8}, number = {2}, pages = {34-40}, doi = {10.1556/1886.2018.00006}, pmid = {29997909}, issn = {2062-509X}, abstract = {The octapeptide NAP is well known for its neuroprotective properties. We here investigated whether NAP treatment could alleviate pro-inflammatory immune responses during experimental subacute ileitis. To address this, mice with a human gut microbiota were perorally infected with one cyst of Toxoplasma gondii (day 0) and subjected to intraperitoneal synthetic NAP treatment from day 1 until day 8 postinfection (p.i.). Whereas placebo (PLC) control animals displayed subacute ileitis at day 9 p.i., NAP-treated mice exhibited less pronounced pro-inflammatory immune responses as indicated by lower numbers of intestinal mucosal T and B lymphocytes and lower interferon (IFN)-γ concentrations in mesenteric lymph nodes. The NAP-induced anti-inflammatory effects were not restricted to the intestinal tract but could also be observed in extra-intestinal including systemic compartments, given that pro-inflammatory cytokines were lower in liver, kidney, and lung following NAP as compared to PLC application, whereas at day 9 p.i., colonic and serum interleukin (IL)-10 concentrations were higher in the former as compared to the latter. Remarkably, probiotic commensal bifidobacterial loads were higher in the ileal lumen of NAP as compared to PLC-treated mice with ileitis. Our findings thus further support that NAP might be regarded as future treatment option directed against intestinal inflammation.}, } @article {pmid29992140, year = {2018}, author = {Bai, T and Zhang, L and Wang, H and Qian, W and Song, J and Hou, X}, title = {Fecal Microbiota Transplantation Is Effective in Relieving Visceral Hypersensitivity in a Postinfectious Model.}, journal = {BioMed research international}, volume = {2018}, number = {}, pages = {3860743}, doi = {10.1155/2018/3860743}, pmid = {29992140}, issn = {2314-6141}, abstract = {Aim: To investigate the effect of fecal microbiota transplantation on visceral hypersensitivity compared with Bifidobacterium longum.

Methods: Mice visceral hypersensitivity was induced by Trichinella spiralis. After 8 weeks, they were divided into three groups (controls, Bifidobacterium longum, and fecal microbiota transplantation) and were daily treated by gavage with 0.2 ml PBS, Bifidobacterium longum HB55020, or fecal microbiota for 7 days. Visceral hypersensitivity was tested with abdominal withdrawal reflex. Permeability of colon epithelium was assessed with Ussing chamber.

Results: After administration of Bifidobacterium longum, compared with mice in postinfectious group, mice had higher pain threshold (p < 0.05). After administration of fecal microbiota, compared with mice in postinfectious group, mice had higher pain threshold (p < 0.05). Fecal microbiota transplantation was as effective as Bifidobacterium in relieving visceral hypersensitivity. Administration of Bifidobacterium longum or fecal microbiota transplantation improved colon epithelium permeability. Expression of occluding-1 was increased.

Conclusion: Manipulation of microbiota is effective in relieving visceral hypersensitivity. Fecal microbiota transplantation is as effective as Bifidobacterium longum administration.}, } @article {pmid29991941, year = {2018}, author = {Moayyedi, P}, title = {Update on Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Disease.}, journal = {Gastroenterology & hepatology}, volume = {14}, number = {5}, pages = {319-322}, pmid = {29991941}, issn = {1554-7914}, } @article {pmid29981382, year = {2018}, author = {Imangaliyev, S and Prodan, A and Nieuwdorp, M and Groen, AK and van Riel, NAW and Levin, E}, title = {Domain intelligible models.}, journal = {Methods (San Diego, Calif.)}, volume = {149}, number = {}, pages = {69-73}, doi = {10.1016/j.ymeth.2018.06.011}, pmid = {29981382}, issn = {1095-9130}, abstract = {Mining biological information from rich "-omics" datasets is facilitated by organizing features into groups that are related to a biological phenomenon or clinical outcome. For example, microorganisms can be grouped based on a phylogenetic tree that depicts their similarities regarding genetic or physical characteristics. Here, we describe algorithms that incorporate auxiliary information in terms of groups of predictors and the relationships between them into the metagenome learning task to build intelligible models. In particular, our cost function guides the feature selection process using auxiliary information by requiring related groups of predictors to provide similar contributions to the final response. We apply the developed algorithms to a recently published dataset analyzing the effects of fecal microbiota transplantation (FMT) in order to identify factors that are associated with improved peripheral insulin sensitivity, leading to accurate predictions of the response to the FMT.}, } @article {pmid29976114, year = {2018}, author = {Wang, J and Wang, P and Tian, H and Tian, F and Zhang, Y and Zhang, L and Gao, X and Wang, X}, title = {Aryl hydrocarbon receptor/IL-22/Stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota in mice.}, journal = {Innate immunity}, volume = {24}, number = {5}, pages = {297-306}, doi = {10.1177/1753425918785016}, pmid = {29976114}, issn = {1753-4267}, abstract = {Compelling evidence demonstrates the crucial role of the commensal microbiota in host physiology and the detrimental effects of its perturbations following antibiotic treatment. However, the effects of commensal microbiota on intestinal mucosa antimicrobial molecules have not been elucidated systematically. Here, we investigate the impacts of antibiotic-induced depletion and subsequent restoration of the intestinal microbiota on the murine antimicrobial molecules in intestinal mucosa. Our results demonstrate that depletion of commensal microbiota leads to intestinal mucosa atrophy and reduction of antimicrobial molecules, including lysozyme, regenerating islet-derived protein 3 gamma (RegIIIγ), and cryptdin 5 mRNA, whereas subsequent reconstitution of intestinal microbiota by fecal microbiota transplantation (FMT) rescues mucosa morphology and antimicrobials. Importantly, our study shows that down-regulation of aryl hydrocarbon receptor (AhR), interleukin-22 (IL-22), and phosphorylated Stat3 (p-Stat3) is associated with decreased antimicrobials, which might mediate the antibiotic-associated intestinal mucosa injury. Last, exogenous activation of the AhR/IL-22/Stat3 signaling pathway with the AhR agonist 6-formylindolo(3,2-b)carbazole (Ficz) rescued antimicrobial molecule levels markedly after antibiotic treatment to levels similar to those following reconstitution of intestinal microbiota by FMT. Together, our results demonstrate that the AhR/IL-22/Stat3 signaling pathway is involved in the modulation of intestinal mucosa antimicrobial molecules by commensal microbiota and suggest this pathway as a promising target in the treatment of antibiotic-associated gut barrier damage.}, } @article {pmid29972839, year = {2018}, author = {Klag, T and Wehkamp, J}, title = {[Crohn's Disease - New Therapies].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {113}, number = {13}, pages = {953-959}, doi = {10.1055/a-0538-3671}, pmid = {29972839}, issn = {1439-4413}, mesh = {Anti-Bacterial Agents/therapeutic use ; Antibodies, Monoclonal/adverse effects/therapeutic use ; Antibodies, Monoclonal, Humanized/adverse effects/therapeutic use ; Clinical Trials as Topic ; Colitis, Ulcerative/immunology/*therapy ; Crohn Disease/immunology/*therapy ; Defensins/adverse effects/therapeutic use ; Fecal Microbiota Transplantation ; Humans ; Immunosuppressive Agents/adverse effects/therapeutic use ; Integrins/antagonists & inhibitors ; Lecithins/therapeutic use ; Probiotics/adverse effects/therapeutic use ; Ustekinumab/therapeutic use ; }, abstract = {New promising treatment options for chronic inflammatory bowel diseases, confirm the expanded pathophysiological understanding in terms of the interactions of the gastrointestinal microbiome with the adaptive and innate immune response and barrier protection. Therefore, these interrelations are focus of research and therapeutic strategies. The following review will give insights into the pathomechanisms, current treatment options and future developments.}, } @article {pmid29971061, year = {2018}, author = {Hu, J and Chen, L and Tang, Y and Xie, C and Xu, B and Shi, M and Zheng, W and Zhou, S and Wang, X and Liu, L and Yan, Y and Yang, T and Niu, Y and Hou, Q and Xu, X and Yan, X}, title = {Standardized Preparation for Fecal Microbiota Transplantation in Pigs.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1328}, doi = {10.3389/fmicb.2018.01328}, pmid = {29971061}, issn = {1664-302X}, abstract = {The intestine of pigs harbors a mass of microorganisms which are essential for intestinal homeostasis and host health. Intestinal microbial disorders induce enteric inflammation and metabolic dysfunction, thereby causing adverse effects on the growth and health of pigs. In the human medicine, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, has shown efficacy in intestinal microbiota restoration. In addition, it has been used widely in therapy for human gastrointestinal diseases, including Clostridium difficile infection, inflammatory bowel diseases, and irritable bowel syndrome. Given that pigs share many similarities with humans, in terms of anatomy, nutritional physiology, and intestinal microbial compositions, FMT may also be used to restore the normal intestinal microbiota of pigs. However, feasible procedures for performing FMT in pigs remains unclear. Here, we summarize a standardized preparation for FMT in pigs by combining the standard methodology for human FMT with pig production. The key issues include the donor selection, fecal material preparation, fecal material transfer, stool bank establishment, and the safety for porcine FMT. Optimal donors should be selected to ensure the efficacy of porcine FMT and reduce the risks of transmitting infectious diseases to recipients during FMT. Preparing for fresh fecal material is highly recommended. Alternatively, frozen fecal suspension can also be prepared as an optimal choice because it is convenient and has similar efficacy. Oral administration of fecal suspension could be an optimal method for porcine fecal material transfer. Furthermore, the dilution ratio of fecal materials and the frequency of fecal material transfer could be adjusted according to practical situations in the pig industry. To meet the potential large-scale requirement in the pig industry, it is important to establish a stool bank to make porcine FMT readily available. Future studies should also focus on providing more robust safety data on FMT to improve the safety and tolerability of the recipient pigs. This standardized preparation for porcine FMT can facilitate the development of microbial targeted therapies and improve the intestinal health of pigs.}, } @article {pmid29966323, year = {2018}, author = {Chai, J and Lee, CH}, title = {Management of Primary and Recurrent Clostridium difficile Infection: An Update.}, journal = {Antibiotics (Basel, Switzerland)}, volume = {7}, number = {3}, pages = {}, doi = {10.3390/antibiotics7030054}, pmid = {29966323}, issn = {2079-6382}, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections (HAI) in the United States and Canada, and incidence rates have increased worldwide in recent decades. Currently, antibiotics are the mainstay treatments for both primary and recurrent CDI, but their efficacy is limited, prompting further therapies to be developed. Aim: This review summarizes current and emerging therapies in CDI management including antibiotics, fecal microbiota transplantation, monoclonal antibodies, spore-based therapies, and vaccinations.}, } @article {pmid29953876, year = {2018}, author = {van der Beek, CM and Canfora, EE and Kip, AM and Gorissen, SHM and Olde Damink, SWM and van Eijk, HM and Holst, JJ and Blaak, EE and Dejong, CHC and Lenaerts, K}, title = {The prebiotic inulin improves substrate metabolism and promotes short-chain fatty acid production in overweight to obese men.}, journal = {Metabolism: clinical and experimental}, volume = {87}, number = {}, pages = {25-35}, doi = {10.1016/j.metabol.2018.06.009}, pmid = {29953876}, issn = {1532-8600}, abstract = {BACKGROUND AND AIMS: Human gut microbiota play an important role in maintaining human health. Dietary fibers, i.e. prebiotics, are fermented by human gut microbiota into the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate. SCFAs promote fat oxidation and improve metabolic health. Therefore, the prebiotic inulin might be an effective dietary strategy to improve human metabolism. We aimed to investigate the acute metabolic effects of ingesting inulin compared with digestible carbohydrates and to trace inulin-derived SCFAs using stable isotope tracer methodology.

METHODS: In a double-blind, randomized, placebo-controlled crossover design, 14 healthy, overweight to obese men consumed a high-fat milkshake containing A) 24 g inulin of which 0.5 g was U-13C-inulin (INU) or B) 24 g maltodextrin placebo (PLA), with a wash-out period of at least five days. Fat oxidation was measured via an open-circuit ventilated hood and blood samples were collected up to 7 h after ingestion. Plasma, breath, and fecal samples were collected, and appetite and satiety scores were assessed.

RESULTS: Fat oxidation increased in the early postprandial phase (0-3 h), and both plasma glucose and insulin were lower after INU ingestion compared with PLA (all P < 0.05). Plasma free fatty acids were higher in the early, and lower in the late postprandial period after INU ingestion. Inulin was fermented into SCFAs as indicated by higher plasma acetate concentrations after INU compared with PLA (P < 0.05). In addition, we found continuous increases in plasma 13C-SCFA enrichments (P < 0.05 from t = 120 onwards) and breath 13CO2 enrichments after INU intake. There were no effects on plasma triglycerides, free glycerol, satiety hormones GLP-1 and PYY, and appetite and satiety scores.

CONCLUSIONS: Ingestion of the prebiotic inulin improves fat oxidation and promotes SCFA production in overweight to obese men. Overall, replacing digestible carbohydrates with the fermentable inulin may favor human substrate metabolism.

CLINICAL TRIAL REGISTRY: The trial was registered at clinicaltrials.gov under number NCT02009670.}, } @article {pmid29946308, year = {2018}, author = {Baktash, A and Terveer, EM and Zwittink, RD and Hornung, BVH and Corver, J and Kuijper, EJ and Smits, WK}, title = {Mechanistic Insights in the Success of Fecal Microbiota Transplants for the Treatment of Clostridium difficile Infections.}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1242}, doi = {10.3389/fmicb.2018.01242}, pmid = {29946308}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation has proven to be an effective treatment for infections with the gram-positive enteropathogen Clostridium difficile. Despite its effectiveness, the exact mechanisms that underlie its success are largely unclear. In this review, we highlight the pleiotropic effectors that are transferred during fecal microbiota transfer and relate this to the C. difficile lifecycle. In doing so, we show that it is likely that multiple factors contribute to the elimination of symptoms of C. difficile infections after fecal microbiota transplantation.}, } @article {pmid29943234, year = {2018}, author = {Bellocchi, C and Volkmann, ER}, title = {Update on the Gastrointestinal Microbiome in Systemic Sclerosis.}, journal = {Current rheumatology reports}, volume = {20}, number = {8}, pages = {49}, doi = {10.1007/s11926-018-0758-9}, pmid = {29943234}, issn = {1534-6307}, abstract = {PURPOSE OF REVIEW: Accumulating evidence suggests that gut microbiota affect the development and function of the immune system and may play a role in the pathogenesis of autoimmune diseases. The purpose of this review is to summarize recent studies reporting gastrointestinal microbiota aberrations associated with the systemic sclerosis disease state.

RECENT FINDINGS: The studies described herein have identified common changes in gut microbial composition. Specifically, patients with SSc have decreased abundance of beneficial commensal genera (e.g., Faecalibacterium, Clostridium, and Bacteroides) and increased abundance of pathobiont genera (e.g., Fusobacterium, Prevotella, Erwinia). In addition, some studies have linked specific genera with the severity of gastrointestinal symptoms in systemic sclerosis. More research is needed to further characterize the gastrointestinal microbiota in systemic sclerosis and understand how microbiota perturbations can affect inflammation, fibrosis, and clinical outcomes. Interventional studies aimed at addressing/correcting these perturbations, either through dietary modification, pro/pre-biotic supplementation, or fecal transplantation, may lead to improved outcomes for patients with systemic sclerosis.}, } @article {pmid29941542, year = {2018}, author = {Zhao, M and Xiong, X and Ren, K and Xu, B and Cheng, M and Sahu, C and Wu, K and Nie, Y and Huang, Z and Blumberg, RS and Han, X and Ruan, HB}, title = {Deficiency in intestinal epithelial O-GlcNAcylation predisposes to gut inflammation.}, journal = {EMBO molecular medicine}, volume = {10}, number = {8}, pages = {}, doi = {10.15252/emmm.201708736}, pmid = {29941542}, issn = {1757-4684}, support = {R01 DK088199/DK/NIDDK NIH HHS/United States ; }, abstract = {Post-translational modifications in intestinal epithelial cells (IECs) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease. The O-linked β-N-acetylglucosamine (O-GlcNAc) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored. Here, we found that levels of protein O-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients. Deletion of OGT specifically in IECs resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice. Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical-induced colitis. Paneth cell-specific deletion of OGT led to Paneth cell dysfunction, which might predispose mice to chemical-induced colitis. On the other hand, the augmentation of O-GlcNAc signaling by inhibiting O-GlcNAcase, the enzyme removing O-GlcNAcylation, alleviated chemical-induced colitis. Our data reveal that protein O-GlcNAcylation in IECs controls key regulatory mechanisms to maintain mucosal homeostasis.}, } @article {pmid29939968, year = {2018}, author = {Bouri, S and Hart, A}, title = {Fecal microbial transplantation: an update.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {21}, number = {5}, pages = {405-410}, doi = {10.1097/MCO.0000000000000488}, pmid = {29939968}, issn = {1473-6519}, abstract = {PURPOSE OF REVIEW: The purpose of this article is to provide an update on recent developments in fecal microbiota transplantation (FMT) in the last year.

RECENT FINDINGS: Although FMT is an accepted treatment for recurrent Clostridium difficile infection (CDI), recently it is also gaining acceptance for the treatment of refractory CDI. FMT is showing promise in ulcerative colitis and is experimental in many other conditions. The optimal practical aspects to enhance the success of FMT are still being established.

SUMMARY: The implication of current research is that the indications of FMT may be extended to other conditions in the future.}, } @article {pmid29933742, year = {2018}, author = {Cui, B and Su, D and Li, W and She, X and Zhang, M and Wang, R and Zhai, Q}, title = {Effects of chronic noise exposure on the microbiome-gut-brain axis in senescence-accelerated prone mice: implications for Alzheimer's disease.}, journal = {Journal of neuroinflammation}, volume = {15}, number = {1}, pages = {190}, doi = {10.1186/s12974-018-1223-4}, pmid = {29933742}, issn = {1742-2094}, abstract = {BACKGROUND: Chronic noise exposure is associated with neuroinflammation and gut microbiota dysregulation and increases the risk of Alzheimer's disease (AD). Environmental hazards are also thought to be associated with genetic susceptibility factors that increase AD pathogenesis. However, there is limited experimental evidence regarding the link between chronic noise stress and microbiome-gut-brain axis alterations, which may be closely related to AD development.

METHODS: The aim of the present study was to systematically investigate the effects of chronic noise exposure on the microbiome-gut-brain axis in the senescence-accelerated mouse prone 8 (SAMP8) strain. We established SAMP8 mouse models to examine the consequences of noise exposure on the microbiome-gut-brain axis. Hippocampal amyloid-β (Aβ) assessment and the Morris water maze were used to evaluate AD-like changes, 16S ribosomal RNA sequencing analyses were used for intestinal flora measurements, and assessment of endothelial tight junctions and serum neurotransmitter and inflammatory mediator levels, as well as fecal microbiota transplant, was conducted to explore the underlying pathological mechanisms.

RESULTS: Chronic noise exposure led to cognitive impairment and Aβ accumulation in young SAMP8 mice, similar to that observed in aging SAMP8 mice. Noise exposure was also associated with decreased gut microbiota diversity and compositional alterations. Axis-series studies showed that endothelial tight junction proteins were decreased in both the intestine and brain, whereas serum neurotransmitter and inflammatory mediator levels were elevated in young SAMP8 mice exposed to chronic noise, similar to the observations made in the aging group. The importance of intestinal bacteria in noise exposure-induced epithelial integrity impairment and Aβ accumulation was further confirmed through microbiota transplantation experiments. Moreover, the effects of chronic noise were generally intensity-dependent.

CONCLUSION: Chronic noise exposure altered the gut microbiota, accelerated age-related neurochemical and inflammatory dysregulation, and facilitated AD-like changes in the brain of SAMP8 mice.}, } @article {pmid29931479, year = {2018}, author = {Philips, CA and Phadke, N and Ganesan, K and Ranade, S and Augustine, P}, title = {Corticosteroids, nutrition, pentoxifylline, or fecal microbiota transplantation for severe alcoholic hepatitis.}, journal = {Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12664-018-0859-4}, pmid = {29931479}, issn = {0975-0711}, abstract = {INTRODUCTION: Alcohol-induced intestinal dysbiosis is central to the development of the severe alcoholic liver disease. We present the first study to compare outcomes in patients of severe alcoholic hepatitis (SAH) on nutritional therapy, corticosteroids, pentoxifylline, and healthy donor fecal transplantation (FMT) and discuss distinct microbial community and microbiome metabolic functional changes after FMT.

METHODS: Out of 1271 liver disease patients, 809 (63.7%) were diagnosed to have the alcoholic liver disease, of which 51 patients (8 treated with corticosteroids, 17 with nutritional support only, 10 with pentoxifylline, 16 receiving FMT) were included. Clinical, biochemical parameters, liver disease, and alcoholic hepatitis severity scores at baseline and mortality at the end of 1 and 3 months were analyzed between groups. Stool microbiota (SM) analysis was performed for healthy controls (HC) and respective recipients after FMT.

RESULTS: All the patients were male. The proportions of patients surviving at the end of 1 and 3 months in the steroids, nutrition, pentoxifylline, and FMT group were 63%, 47%, 40% and 75% [p = 0.179] and 38%, 29%, 30%, and 75% [p = 0.036], respectively. When compared with FMT, relative risk and hazard ratios for death were higher in all the other groups. Following FMT, distinct and beneficial modulation of SM and pathways of dysregulated metabolism, infections, inflammation, and oxidative stress in SAH patients were noted in tandem with improved clinical outcomes.

CONCLUSIONS: Healthy donor FMT for SAH improves survival beyond what is offered by current therapies and can function as a cost-effective bridge to liver transplant (LT) or for improving transplant-free survival. Larger studies and randomized trials are unmet needs.}, } @article {pmid29929472, year = {2018}, author = {Kumar, A and Vlasova, AN and Deblais, L and Huang, HC and Wijeratne, A and Kandasamy, S and Fischer, DD and Langel, SN and Paim, FC and Alhamo, MA and Shao, L and Saif, LJ and Rajashekara, G}, title = {Impact of nutrition and rotavirus infection on the infant gut microbiota in a humanized pig model.}, journal = {BMC gastroenterology}, volume = {18}, number = {1}, pages = {93}, doi = {10.1186/s12876-018-0810-2}, pmid = {29929472}, issn = {1471-230X}, support = {R01 AI099451/AI/NIAID NIH HHS/United States ; AI099451//National Institutes of Health/ ; }, mesh = {Animals ; Diarrhea/microbiology/virology ; Disease Susceptibility ; Feces/microbiology ; Gastroenteritis/*complications/*microbiology/virology ; *Gastrointestinal Microbiome ; Humans ; Infant ; Intestines/microbiology ; Malnutrition/*complications/*microbiology/virology ; RNA, Ribosomal, 16S ; Rotavirus Infections/*complications/*microbiology/virology ; Sequence Analysis, RNA ; Swine ; Virus Shedding ; Weight Gain ; }, abstract = {BACKGROUND: Human rotavirus (HRV) is a major cause of viral gastroenteritis in infants; particularly in developing countries where malnutrition is prevalent. Malnutrition perturbs the infant gut microbiota leading to sub-optimal functioning of the immune system and further predisposing infants to enteric infections. Therefore, we hypothesized that malnutrition exacerbates rotavirus disease severity in infants.

METHODS: In the present study, we used a neonatal germ free (GF) piglets transplanted with a two-month-old human infant's fecal microbiota (HIFM) on protein deficient and sufficient diets. We report the effects of malnourishment on the HRV infection and the HIFM pig microbiota in feces, intestinal and systemic tissues, using MiSeq 16S gene sequencing (V4-V5 region).

RESULTS: Microbiota analysis indicated that the HIFM transplantation resulted in a microbial composition in pigs similar to that of the original infant feces. This model was then used to understand the interconnections between microbiota diversity, diet, and HRV infection. Post HRV infection, HIFM pigs on the deficient diet had lower body weights, developed more severe diarrhea and increased virus shedding compared to HIFM pigs on sufficient diet. However, HRV induced diarrhea and shedding was more pronounced in non-colonized GF pigs compared to HIFM pigs on either sufficient or deficient diet, suggesting that the microbiota alone moderated HRV infection. HRV infected pigs on sufficient diet showed increased microbiota diversity in intestinal tissues; whereas, greater diversity was observed in systemic tissues of HRV infected pigs fed with deficient diet.

CONCLUSIONS: These results suggest that proper nourishment improves the microbiota quality in the intestines, alleviates HRV disease and lower probability of systemic translocation of potential opportunistic pathogens/pathobionts. In conclusion, our findings further support the role for microbiota and proper nutrition in limiting enteric diseases.}, } @article {pmid29920927, year = {2018}, author = {Lee, JR and Magruder, M and Zhang, L and Westblade, LF and Satlin, MJ and Robertson, A and Edusei, E and Crawford, C and Ling, L and Taur, Y and Schluter, J and Lubetzky, M and Dadhania, D and Pamer, E and Suthanthiran, M}, title = {Gut microbiota dysbiosis and diarrhea in kidney transplant recipients.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {}, number = {}, pages = {}, doi = {10.1111/ajt.14974}, pmid = {29920927}, issn = {1600-6143}, support = {K23 AI124464/AI/NIAID NIH HHS/United States ; R37 AI051652/AI/NIAID NIH HHS/United States ; }, abstract = {Posttransplant diarrhea is associated with kidney allograft failure and death, but its etiology remains unknown in the majority of cases. Because altered gut microbial ecology is a potential basis for diarrhea, we investigated whether posttransplant diarrhea is associated with gut dysbiosis. We enrolled 71 kidney allograft recipients for serial fecal specimen collections in the first 3 months of transplantation and profiled the gut microbiota using 16S ribosomal RNA (rRNA) gene V4-V5 deep sequencing. The Shannon diversity index was significantly lower in 28 diarrheal fecal specimens from 25 recipients with posttransplant diarrhea than in 112 fecal specimens from 46 recipients without posttransplant diarrhea. We found a lower relative abundance of 13 commensal genera (Benjamini-Hochberg adjusted P ≤ .15) in the diarrheal fecal specimens including the same 4 genera identified in our prior study. The 28 diarrheal fecal specimens were also evaluated by a multiplexed polymerase chain reaction (PCR) assay for 22 bacterial, viral, and protozoan gastrointestinal pathogens, and 26 specimens were negative for infectious etiologies. Using PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) to predict metagenomic functions, we found that diarrheal fecal specimens had a lower abundance of metabolic genes. Our findings suggest that posttransplant diarrhea is not associated with common infectious diarrheal pathogens but with a gut dysbiosis.}, } @article {pmid29914912, year = {2018}, author = {Hota, SS and Poutanen, SM}, title = {Fecal microbiota transplantation for recurrent Clostridium difficile infection.}, journal = {CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne}, volume = {190}, number = {24}, pages = {E746}, doi = {10.1503/cmaj.171454}, pmid = {29914912}, issn = {1488-2329}, } @article {pmid29912755, year = {2018}, author = {Rizzatti, G and Ianiro, G and Gasbarrini, A}, title = {Antibiotic and Modulation of Microbiota: A New Paradigm?.}, journal = {Journal of clinical gastroenterology}, volume = {52 Suppl 1, Proceedings from the 9th Probiotics, Prebiotics and New Foods, Nutraceuticals and Botanicals for Nutrition & Human and Microbiota Health Meeting, held in Rome, Italy from September 10 to 12, 2017}, number = {}, pages = {S74-S77}, doi = {10.1097/MCG.0000000000001069}, pmid = {29912755}, issn = {1539-2031}, abstract = {Recently new insights on gut microbiota have revolutionized many concepts of the modern medicine. The alteration of microbiota, which is called dysbiosis, has been associated with an expanding list of diseases and conditions. The development of next-generation sequencing techniques allowed comprehensive analysis of gut microbiota composition without the limitations of classic culture methods. Furthermore, introduction of functional techniques such as metabolomics and proteomics allowed for integrated analysis thus obtaining more robust insights on microbiota functions in health and disease. These tools allow to address the role of factors able to modify the gut microbiota, the so called "microbiota influencers." These data are useful to explain the physiopathology of several disease and thus to identify new potential therapeutic targets. Among microbiota influencers, many studies focused on the impact of antibiotic administration on the gut microbiota, because of their widespread use. Notably, beside the known beneficial effect of antibiotic in treating infectious diseases, these drugs have shown detrimental effects on gut microbiota which, in turn, might have long-term consequences on the host. Finally, therapeutic modulation of gut microbiota, by means of selected antibiotics with eubiotic effects, probiotics and with fecal microbiota transplantation seems of great interest as it might be able to prevent or even revert antibiotic-induced dysbiosis.}, } @article {pmid29910564, year = {2018}, author = {Duarte-Chavez, R and Wojda, TR and Zanders, TB and Geme, B and Fioravanti, G and Stawicki, SP}, title = {Early Results of Fecal Microbial Transplantation Protocol Implementation at a Community-based University Hospital.}, journal = {Journal of global infectious diseases}, volume = {10}, number = {2}, pages = {47-57}, doi = {10.4103/jgid.jgid_145_17}, pmid = {29910564}, issn = {0974-777X}, abstract = {Introduction: Clostridium difficile (CD) is a serious and increasingly prevalent healthcare-associated infection. The pathogenesis of CD infection (CDI) involves the acquisition of CD with a concurrent disruption of the native gut flora. Antibiotics are a major risk although other contributing factors have also been identified. Clinical management combines discontinuation of the offending antibiotic, initiation of CD-specific antibiotic therapy, probiotic agent use, fecal microbiota transplantation (FMT), and surgery as the "last resort" option. The aim of this study is to review short-term clinical results following the implementation of FMT protocol (FMTP) at our community-based university hospital.

Methods: After obtaining Institutional Review Board and Infection Control Committee approvals, we implemented an institution-wide FMTP for patients diagnosed with CDI. Prospective tracking of all patients receiving FMT between July 1, 2015, and February 1, 2017, was conducted using REDCap™ electronic data capture system. According to the FMTP, indications for FMT included (a) three or more CDI recurrences, (b) two or more hospital admissions with severe CDI, or (c) first episode of complicated CDI (CCDI). Risk factors for initial infection and for treatment failure were assessed. Patients were followed for at least 3 months to monitor for cure/failure, relapse, and side effects. Frozen 250 mL FMT samples were acquired from OpenBiome (Somerville, MA, USA). After 4 h of thawing, the liquid suspension was applied using colonoscopy, beginning with terminal ileum and proceeding distally toward mid-transverse colon. Monitored clinical parameters included disease severity (Hines VA CDI Severity Score or HVCSS), concomitant medications, number of FMT treatments, non-FMT therapies, cure rates, and mortality. Descriptive statistics were utilized to outline the study results.

Results: A total of 35 patients (mean age 58.5 years, 69% female) were analyzed, with FMT-attributable primary cure achieved in 30/35 (86%) cases. Within this subgroup, 2/30 (6.7%) patients recurred and were subsequently cured with long-term oral vancomycin. Among five primary FMT failures (14% total sample), 3 (60%) achieved medical cure with long-term oral vancomycin therapy and 2 (40%) required colectomy. For the seven patients who either failed FMT or recurred, long-term vancomycin therapy was curative in all but two cases. For patients with severe CDI (HVCSS ≥3), primary and overall cure rates were 6/10 (60%) and 8/10 (80%), respectively. Patients with CCDI (n = 4) had higher HVCSS (4 vs. 3) and a mortality of 25%. Characteristics of patients who failed initial FMT included older age (70 vs. 57 years), female sex (80% vs. 67%), severe CDI (80% vs. 13%), and active opioid use during the initial infection (60% vs. 37%) and at the time of FMT (60% vs. 27%). The most commonly reported side effect of FMT was loose stools.

Conclusions: This pilot study supports the efficacy and safety of FMT administration for CDI in the setting of a community-based university hospital. Following FMTP implementation, primary (86%) and overall (94%) nonsurgical cure rates were similar to those reported in other studies. The potential role of opioids as a modulator of CDI warrants further clinical investigation.}, } @article {pmid29904348, year = {2018}, author = {Cui, H and Cai, Y and Wang, L and Jia, B and Li, J and Zhao, S and Chu, X and Lin, J and Zhang, X and Bian, Y and Zhuang, P}, title = {Berberine Regulates Treg/Th17 Balance to Treat Ulcerative Colitis Through Modulating the Gut Microbiota in the Colon.}, journal = {Frontiers in pharmacology}, volume = {9}, number = {}, pages = {571}, doi = {10.3389/fphar.2018.00571}, pmid = {29904348}, issn = {1663-9812}, abstract = {Berberine (BBR), an alkaloid isolated from Rhizoma Coptidis, Cortex Phellode, and Berberis, has been widely used in the treatment of ulcerative colitis (UC). However, the mechanism of BBR on UC is unknown. In this study, we investigated the activities of T regulatory cell (Treg) and T helper 17 cell (Th17) in a dextran sulfate sodium (DSS)-induced UC mouse model after BBR administration. We also investigated the changes of gut microbiota composition using 16S rRNA analysis. We also examined whether BBR could regulate the Treg/Th17 balance by modifying gut microbiota. The mechanism was further confirmed by depleting gut microbiota through a combination of antibiotic treatment and fecal transplantations. Results showed that BBR treatment could improve the Treg/Th17 balance in the DSS-induced UC model. BBR also reduced diversity of the gut microbiota and interfered with the relative abundance of Desulfovibrio, Eubacterium, and Bacteroides. Moreover, BBR treatment did not influence the Treg/Th17 balance after the depletion of gut microbiota. Our results also revealed that fecal transplantation from BBR-treated mice could relieve UC and regulate the Treg/Th17 balance. In conclusion, our study provides evidence that BBR prevents UC by modifying gut microbiota and regulating the balance of Treg/Th17.}, } @article {pmid29901551, year = {2018}, author = {Bulik-Sullivan, EC and Roy, S and Elliott, RJ and Kassam, Z and Lichtman, SN and Carroll, IM and Gulati, AS}, title = {Intestinal Microbial and Metabolic Alterations Following Successful Fecal Microbiota Transplant for D-Lactic Acidosis.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {67}, number = {4}, pages = {483-487}, doi = {10.1097/MPG.0000000000002043}, pmid = {29901551}, issn = {1536-4801}, abstract = {Fecal microbiota transplantation (FMT) involves the transfer of stool from a healthy individual into the intestinal tract of a diseased recipient. Although used primarily for recurrent Clostridium difficile infection, FMT is increasingly being attempted as an experimental therapy for other illnesses, including metabolic disorders. D-lactic acidosis (D-LA) is a metabolic disorder that may occur in individuals with short bowel syndrome when lactate-producing bacteria in the colon overproduce D-lactate. This results in elevated systemic levels of D-lactate, metabolic acidosis, and encephalopathy. In this study, we report the successful use of FMT for the treatment of recurrent D-LA in a child who was unresponsive to conventional therapies. Importantly, we also present profiles of the enteric microbiota, as well as fecal D-/L-lactic acid metabolites, before and longitudinally after FMT. These data provide valuable insight into the putative mechanisms of D-LA pathogenesis and its treatment.}, } @article {pmid29896165, year = {2018}, author = {Valenzuela, MJ and Caruffo, M and Herrera, Y and Medina, DA and Coronado, M and Feijóo, CG and Muñoz, S and Garrido, D and Troncoso, M and Figueroa, G and Toro, M and Reyes-Jara, A and Magne, F and Navarrete, P}, title = {Evaluating the Capacity of Human Gut Microorganisms to Colonize the Zebrafish Larvae (Danio rerio).}, journal = {Frontiers in microbiology}, volume = {9}, number = {}, pages = {1032}, doi = {10.3389/fmicb.2018.01032}, pmid = {29896165}, issn = {1664-302X}, support = {T37 MD001425/MD/NIMHD NIH HHS/United States ; }, abstract = {In this study we evaluated if zebrafish larvae can be colonized by human gut microorganisms. We tested two strategies: (1) through transplantation of a human fecal microbiota and (2) by successively transplanting aerotolerant anaerobic microorganisms, similar to the colonization in the human intestine during early life. We used conventionally raised zebrafish larvae harboring their own aerobic microbiota to improve the colonization of anaerobic microorganisms. The results showed with the fecal transplant, that some members of the human gut microbiota were transferred to larvae. Bacillus, Roseburia, Prevotella, Oscillospira, one unclassified genus of the family Ruminococcaceae and Enterobacteriaceae were detected in 3 days post fertilization (dpf) larvae; however only Bacillus persisted to 7 dpf. Successive inoculation of Lactobacillus, Bifidobacterium and Clostridioides did not improve their colonization, compared to individual inoculation of each bacterial species. Interestingly, the sporulating bacteria Bacillus clausii and Clostridioides difficile were the most persistent microorganisms. Their endospores persisted at least 5 days after inoculating 3 dpf larvae. However, when 5 dpf larvae were inoculated, the proportion of vegetative cells in larvae increased, revealing proliferation of the inoculated bacteria and better colonization of the host. In conclusion, these results suggest that it is feasible to colonize zebrafish larvae with some human bacteria, such as C. difficile and Bacillus and open an interesting area to study interactions between these microorganisms and the host.}, } @article {pmid29895255, year = {2018}, author = {Katsi, V and Didagelos, M and Skevofilax, S and Armenis, I and Kartalis, A and Vlachopoulos, C and Karvounis, H and Tousoulis, D}, title = {Gut Microbiome - Gut Dysbiosis - Arterial Hypertension: New Horizons.}, journal = {Current hypertension reviews}, volume = {}, number = {}, pages = {}, doi = {10.2174/1573402114666180613080439}, pmid = {29895255}, issn = {1875-6506}, abstract = {Arterial hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. The human microbiome refers to the community of microorganisms that live in or on the human body. They influence human physiology by interfering in several processes such as providing nutrients and vitamins and in Phase I and Phase II drug metabolism. The human gut microbiota is represented mainly by Firmicutes and Bacteroidetes and to a lesser degree by Actinobacteria and Proteobacteria, with each individual harbouring at least 160 such species. Gut microbiota contributes to blood pressure homeostasis and the pathogenesis of arterial hypertension through production, modification and degradation of a variety of microbial-derived bioactive metabolites. Animal studies and to a lesser degree human research has unmasked relative mechanisms, mainly through the effect of certain microbiome metabolites and their receptors, outlining this relationship. Interventions to utilize these pathways, with probiotics, prebiotics, antibiotics and fecal microbiome transplantation have shown promising results. Personalized microbiome-based disease prediction and treatment responsiveness seems futuristic. Undoubtedly, a long way of experimental and clinical research should be pursued to elucidate this novel, intriguing and very promising horizon.}, } @article {pmid29890556, year = {2018}, author = {Bruensing, J and Buendgens, L and Jochum, C and Herbers, U and Canbay, A and Braun, G and Trautwein, C and Huber, W and Koch, A and Tacke, F}, title = {[Management of Clostridium difficile infections at German intensive care units - results from a survey among intensivists].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {56}, number = {6}, pages = {551-560}, doi = {10.1055/s-0044-102103}, pmid = {29890556}, issn = {1439-7803}, abstract = {BACKGROUND: Clostridium difficile associated colitis is a frequent cause of nosocomial diarrhea at the intensive care unit (ICU) and is associated with poor prognosis in critically ill patients. Few studies have evaluated the efficacy of treatment options or adherence to guideline recommendations of Clostridium difficile infections at the ICU.

METHODS: Therefore, on behalf of the Gastroenterology Intensive Care Medicine working group of the DGVS, we have conducted an online-based survey among leading intensivists in Germany.

RESULTS: Out of the 351 invited, 85 (24.2 %), primarily leading executive physicians at primary to tertiary care hospitals, completed the survey. They reported standardized diagnostic algorithms of 79.3 %, in line with current guideline recommendations (i. e., toxin testing in stool, possibly GDH screening, and endoscopy). First-line therapy of Clostridium difficile infections at the ICU was reported to be oral vancomycin in 48.3 % and oral metronidazole in 34.5 %. The success of first-line therapy was estimated at 67 % for clinical cure, 15 % persisting colitis, 5 % sepsis or megacolon, 10 % recurrence, and 3 % death. Hospitals of primary/secondary care more often used metronidazole compared to university hospitals. Standard treatments for recurrent infection were vancomycin orally (40 % alone, 29.1 % combined with metronidazole) or, more rarely, fidaxomicin (25.5 %). Fidaxomicin has been used at least once at the ICU in 79 % of the respondents. Eleven percent have used fecal microbiota transplant (FMT) in selected cases at the ICU.

CONCLUSION: Our survey indicated a high awareness of German intensivists for Clostridium difficile infections, but also marked differences in local therapeutic algorithms, especially in first-line treatment.}, } @article {pmid29886561, year = {2018}, author = {Bhutiani, N and Schucht, JE and Miller, KR and McClave, SA}, title = {Technical Aspects of Fecal Microbial Transplantation (FMT).}, journal = {Current gastroenterology reports}, volume = {20}, number = {7}, pages = {30}, doi = {10.1007/s11894-018-0636-7}, pmid = {29886561}, issn = {1534-312X}, mesh = {Donor Selection ; Enterocolitis, Pseudomembranous/therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Patient Selection ; }, abstract = {PURPOSE OF REVIEW: Fecal microbial transplantation (FMT) has become established as an effective therapeutic modality in the treatment of antibiotic-refractory recurrent Clostridium difficile colitis. A number of formulations and methods of delivery of FMT are currently available, each with distinct advantages. This review aims to review donor and patient selection for FMT as well as procedural aspects of FMT to help guide clinical practice.

RECENT FINDINGS: FMT can be obtained in fresh, frozen, lyophilized, and capsule-based formulations for delivery by oral ingestion, nasoenteric tube, colonoscopy, or enema (depending on the formulation used). Choosing the optimal method relies heavily on patient-related factors, including underlying pathology and severity of illness. As potential applications for FMT expand, careful donor screening and patient selection are critical to minimizing risk to patients and physicians. FMT represents an excellent therapeutic option for treatment of recurrent Clostridium difficile colitis and holds promise as a possible treatment modality in a variety of other conditions. The wide array of delivery methods allows for its application in various disease states in both the inpatient and outpatient setting.}, } @article {pmid29884929, year = {2018}, author = {Panchal, P and Budree, S and Scheeler, A and Medina, G and Seng, M and Wong, WF and Elliott, R and Mitchell, T and Kassam, Z and Allegretti, JR and Osman, M}, title = {Correction to: Scaling Safe Access to Fecal Microbiota Transplantation: Past, Present, and Future.}, journal = {Current gastroenterology reports}, volume = {20}, number = {7}, pages = {28}, doi = {10.1007/s11894-018-0634-9}, pmid = {29884929}, issn = {1534-312X}, support = {P30 DK034854/DK/NIDDK NIH HHS/United States ; }, abstract = {In the original version of this article, author Ryan Elliott's name was misspelled as Ryan Eliott. The correct spelling of the name is Ryan Elliott.}, } @article {pmid29880966, year = {2018}, author = {Golfeyz, S}, title = {Celiac Disease and Fecal Microbiota Transplantation: A New Beginning?.}, journal = {The American journal of gastroenterology}, volume = {113}, number = {8}, pages = {1256}, doi = {10.1038/s41395-018-0094-8}, pmid = {29880966}, issn = {1572-0241}, } @article {pmid29880353, year = {2018}, author = {Gu, B and Bo, GZ and Ke, C}, title = {Exploration of Fecal Microbiota Transplantation in the Treatment of Refractory Diarrhea After Renal Transplantation.}, journal = {Transplantation proceedings}, volume = {50}, number = {5}, pages = {1326-1331}, doi = {10.1016/j.transproceed.2018.03.013}, pmid = {29880353}, issn = {1873-2623}, mesh = {Adult ; Aged ; Diarrhea/etiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Immunosuppressive Agents/therapeutic use ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Postoperative Complications/etiology/*therapy ; Prognosis ; Tacrolimus/therapeutic use ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: Exploration of fecal microbiota transplantation in the treatment of refractory diarrhea after renal transplantation.

METHODS: Summarize the etiology of 120 cases with diarrhea after renal transplantation from 2014 to 2017 in our hospital. There were 4 recipients of refractory diarrhea who accepted fecal microbiota transplantation with informed consent, and we collected clinical data of stool and bacterial culture, gut microbiota analysis, graft function, electrolytes, immunosuppressant concentrations of prognostic evaluation of patients with fecal transplantation.

RESULTS: The absorption of electrolyte is slightly higher and concentration of tacrolimus and creatinine were not significantly changed compared with before.

CONCLUSION: Fecal microbiota transplantation provides a new choice to refractory diarrhea after renal transplantation as an innovative treatment, but the effectiveness of fecal microbiota transplantation needs long-term observation and further evaluation through large sample data.}, } @article {pmid29877649, year = {2018}, author = {Mareschal, J and Schrenzel, J and Lazarevic, V and Genton, L}, title = {[Microbiota and malnutrition: an overview].}, journal = {Revue medicale suisse}, volume = {14}, number = {610}, pages = {1194-1199}, pmid = {29877649}, issn = {1660-9379}, abstract = {Currently, there is an increased interest in the role of gut microbiota in health issues. Evidence shows that an imbalance of gut microbiota or dysbiosis is involved in the mechanisms of weight changes. This review aims at summarizing the present knowledge between gut microbiota and malnutrition. Intestinal bacterial diversity and richness are altered in malnourished people compared to healthy people. The first studies on the modulation of the gut microbiota by probiotics, prebiotics, symbiotics, fecal transplantation and antibiotics for weight gain are encouraging. However, further studies are needed to develop and implement effective treatment for malnutrition.}, } @article {pmid29877092, year = {2018}, author = {Kang, Y and Cai, Y}, title = {Altered Gut Microbiota in HIV Infection: Future Perspective of Fecal Microbiota Transplantation Therapy.}, journal = {AIDS research and human retroviruses}, volume = {}, number = {}, pages = {}, doi = {10.1089/AID.2017.0268}, pmid = {29877092}, issn = {1931-8405}, abstract = {HIV infection progressively destroys CD4+ mononuclear cells, leading to profound cellular immune deficiency that manifests as life-threatening opportunistic infections and malignancies (i.e., AIDS). Gut microbiota plays key roles in the modulation of host metabolism and gene expression, maintenance of epithelial integrity, and mediation of inflammatory and immunity. Hence, the normal intestinal microbiota plays a major role in the maintenance of health and disease prevention. In fact, a large number of studies have shown that the alteration of the gut microbiota contributes to the pathogenesis of several diseases, such as inflammatory bowel diseases, irritable bowel syndrome, metabolic diseases, anorexia nervosa, autoimmune diseases, multiple sclerosis, cancer, neuropsychiatric disorders, and cardiovascular diseases. Recently, accumulating evidence has shed light on the association of dysbiosis of gut microbiota with HIV infection. Hence, the modification of gut microbiota may be a potential therapeutic tool. Fecal microbiota transplantation may improve the conditions of patients with HIV infection by manipulating the human intestinal bacteria. However, the relevant research is very limited, and a large amount of scientific research work needs to be done in the near future.}, } @article {pmid29874567, year = {2018}, author = {Cignarella, F and Cantoni, C and Ghezzi, L and Salter, A and Dorsett, Y and Chen, L and Phillips, D and Weinstock, GM and Fontana, L and Cross, AH and Zhou, Y and Piccio, L}, title = {Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota.}, journal = {Cell metabolism}, volume = {27}, number = {6}, pages = {1222-1235.e6}, doi = {10.1016/j.cmet.2018.05.006}, pmid = {29874567}, issn = {1932-7420}, abstract = {Multiple sclerosis (MS) is more common in western countries with diet being a potential contributing factor. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS model, experimental autoimmune encephalomyelitis (EAE). IF led to increased gut bacteria richness, enrichment of the Lactobacillaceae, Bacteroidaceae, and Prevotellaceae families and enhanced antioxidative microbial metabolic pathways. IF altered T cells in the gut with a reduction of IL-17 producing T cells and an increase in regulatory T cells. Fecal microbiome transplantation from mice on IF ameliorated EAE in immunized recipient mice on a normal diet, suggesting that IF effects are at least partially mediated by the gut flora. In a pilot clinical trial in MS patients, intermittent energy restriction altered blood adipokines and the gut flora resembling protective changes observed in mice. In conclusion, IF has potent immunomodulatory effects that are at least partially mediated by the gut microbiome.}, } @article {pmid29870270, year = {2018}, author = {Larroya-García, A and Navas-Carrillo, D and Orenes-Piñero, E}, title = {Impact of gut microbiota on neurological diseases: Diet composition and novel treatments.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/10408398.2018.1484340}, pmid = {29870270}, issn = {1549-7852}, abstract = {Gut microbiota has significant effects on the structure and function of the enteric and central nervous system including human behaviour and brain regulation. Herein, we analyze the role of this intestinal ecosystem, the effects of dietary changes and the administration of nutritional supplements, such as probiotics, prebiotics, or fecal transplantation in neuropsychiatric disorders. Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth delivery and environment. However, diet composition and nutritional status has been repeatedly shown to be one of the most critical modifiable factors of this ecosystem. A comprehensively analysis of the microbiome-intestine-brain axis has been performed, including the impact of intestinal bacteria in alterations in the nervous, immune and endocrine systems and their metabolites. Finally, we discuss the latest literature examining the effects of diet composition, nutritional status and microbiota alterations in several neuropsychiatric disorders, such as autism, anxiety, depression, Alzheimer's disease and anorexia nervosa.}, } @article {pmid29868248, year = {2018}, author = {Fareed, S and Sarode, N and Stewart, FJ and Malik, A and Laghaie, E and Khizer, S and Yan, F and Pratte, Z and Lewis, J and Immergluck, LC}, title = {Applying fecal microbiota transplantation (FMT) to treat recurrent Clostridium difficile infections (rCDI) in children.}, journal = {PeerJ}, volume = {6}, number = {}, pages = {e4663}, doi = {10.7717/peerj.4663}, pmid = {29868248}, issn = {2167-8359}, abstract = {Background: Fecal Microbiota Transplantation (FMT) is an innovative means of treating recurrent Clostridium difficile infection (rCDI), through restoration of gut floral balance. However, there is a lack of data concerning the efficacy of FMT and its impact on the gut microbiome among pediatric patients. This study analyzes clinical outcomes and microbial community composition among 15 pediatric patients treated for rCDI via FMT.

Methods: This is a prospective, observational, pilot study of 15 children ≤18 years, who presented for rCDI and who met inclusion criteria for FMT at a pediatric hospital and pediatric gastroenterology clinic. Past medical history and demographics were recorded at enrollment and subsequent follow-up. Specimens of the donors' and the patients' pre-FMT and post-FMT fecal specimen were collected and used to assess microbiome composition via 16S rRNA gene sequencing.

Results: FMT successfully prevented rCDI episodes for minimum of 3 months post-FMT in all patients, with no major adverse effects. Three patients reported continued GI bleeding; however, all three also had underlying Inflammatory Bowel Disease (IBD). Our analyses confirm a significant difference between pre-and post-FMT gut microbiome profiles (Shannon diversity index), whereas no significant difference was observed between post-FMT and donor microbiome profiles. At the phyla level, post-FMT profiles showed significantly increased levels of Bacteroidetes and significantly decreased levels of Proteobacteria. Subjects with underlying IBD showed no difference in their pre-and post-FMT profiles.

Conclusion: The low rate of recurrence or re-infection by C. difficile, coupled with minimal adverse effects post-FMT, suggests that FMT is a viable therapeutic means to treat pediatric rCDI. Post-FMT microbiomes are different from pre-FMT microbiomes, and similar to those of healthy donors, suggesting successful establishment of a healthier microbiome.}, } @article {pmid29860912, year = {2018}, author = {Juul, FE and Garborg, K and Bretthauer, M and Skudal, H and Øines, MN and Wiig, H and Rose, Ø and Seip, B and Lamont, JT and Midtvedt, T and Valeur, J and Kalager, M and Holme, Ø and Helsingen, L and Løberg, M and Adami, HO}, title = {Fecal Microbiota Transplantation for Primary Clostridium difficile Infection.}, journal = {The New England journal of medicine}, volume = {378}, number = {26}, pages = {2535-2536}, doi = {10.1056/NEJMc1803103}, pmid = {29860912}, issn = {1533-4406}, mesh = {Anti-Infective Agents/*therapeutic use ; Clostridium Infections/drug therapy/*therapy ; Clostridium difficile ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Metronidazole/*therapeutic use ; Recurrence ; Treatment Outcome ; }, } @article {pmid29851248, year = {2018}, author = {Toral, M and Romero, M and Rodríguez-Nogales, A and Jiménez, R and Robles-Vera, I and Algieri, F and Chueca-Porcuna, N and Sánchez, M and de la Visitación, N and Olivares, M and García, F and Pérez-Vizcaíno, F and Gálvez, J and Duarte, J}, title = {Lactobacillus fermentum Improves Tacrolimus-Induced Hypertension by Restoring Vascular Redox State and Improving eNOS Coupling.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e1800033}, doi = {10.1002/mnfr.201800033}, pmid = {29851248}, issn = {1613-4133}, abstract = {SCOPE: The aim is to analyze whether the probiotic Lactobacillus fermentum CECT5716 (LC40) can prevent endothelial dysfunction and hypertension induced by tacrolimus in mice.

METHODS AND RESULTS: Tacrolimus increases systolic blood pressure (SBP) and impairs endothelium-dependent relaxation to acetylcholine and these effects are partially prevented by LC40. Endothelial dysfunction induced by tacrolimus is related to both increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX2) and uncoupled endothelial nitric oxide synthase (eNOS)-driven superoxide production and Rho-kinase-mediated eNOS inhibition. LC40 treatment prevents all the aortic changes induced by tacrolimus. LC40 restores the imbalance between T-helper 17 (Th17)/regulatory T (Treg) cells induced by tacrolimus in mesenteric lymph nodes and the spleen. Tacrolimus-induced gut dysbiosis, that is, it decreases microbial diversity, increases the Firmicutes/Bacteroidetes (F/B) ratio and decreases acetate- and butyrate-producing bacteria, and these effects are prevented by LC40. Fecal microbiota transplantation (FMT) from LC40-treated mice to control mice prevents the increase in SBP and the impaired relaxation to acetylcholine induced by tacrolimus.

CONCLUSION: LC40 treatment prevents hypertension and endothelial dysfunction induced by tacrolimus by inhibiting gut dysbiosis. These effects are associated with a reduction in vascular oxidative stress, mainly through NOX2 downregulation and prevention of eNOS uncoupling, and inflammation possibly because of decreased Th17 and increased Treg cells polarization in mesenteric lymph nodes.}, } @article {pmid29849592, year = {2018}, author = {Cao, Y and Zhang, B and Wu, Y and Wang, Q and Wang, J and Shen, F}, title = {The Value of Fecal Microbiota Transplantation in the Treatment of Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis.}, journal = {Gastroenterology research and practice}, volume = {2018}, number = {}, pages = {5480961}, doi = {10.1155/2018/5480961}, pmid = {29849592}, issn = {1687-6121}, abstract = {Background and Aims: Fecal microbiota transplantation (FMT) has challenged the traditional management of ulcerative colitis (UC) in recent years, while it remained controversial. We aimed to provide a systematic protocol of FMT treatment on UC.

Methods: Studies reporting on FMT treatment in UC patients were performed. A fixed-effect model was used to assess the efficacy of FMT.

Results: Eighteen studies were enrolled (n = 446). A pooled proportion of patients who received FMT had a significant efficacy compared to the placebo group (odds ratio (OR): 2.73, P = 0.002) with a low risk of heterogeneity (P = 0.59, I2 = 0%). The Mayo score decreased to 5 points in a state of mild-moderate activity after FMT treatment, and the optimal range of the Mayo score baseline was 6-9 for FMT administration. Then, the baseline of the Shannon diversity index (SDI) had a negative correlation with the clinical response rate (R = -0.992, P = 0.08) or remission rate (R = -0.998, P = 0.036), and the optimal diversity of bacteria was at 7 days to one month. Moreover, the colonoscopy delivery and unrelated fecal donor had slight superiorities of FMT treatment.

Conclusion: FMT treatment had a higher efficacy and shorter time-point of early assessment of effectiveness on UC patients compared to traditional therapies. And the optimal FMT delivery and donor were colonoscopy delivery and unrelated donor in clinical practice.}, } @article {pmid29846464, year = {2018}, author = {Messias, BA and Franchi, BF and Pontes, PH and Barbosa, DÁAM and Viana, CAS}, title = {Fecal microbiota transplantation in the treatment of Clostridium difficile infection: state of the art and literature review.}, journal = {Revista do Colegio Brasileiro de Cirurgioes}, volume = {45}, number = {2}, pages = {e1609}, doi = {10.1590/0100-6991e-20181609}, pmid = {29846464}, issn = {1809-4546}, abstract = {Clostridium difficile infection is a common complication following intestinal dysbiosis caused by abusive antibiotic use. It presents medical importance due to the high rates of recurrence and morbidity. Fecal microbiota transplantation is an effective alternative for the treatment of recurrent and refractory C. difficile infection and consists of introducing the intestinal microbiota from a healthy donor into a patient with this infection. The exact physiological mechanism by which fecal microbiota transplantation alters the intestinal microbiota is not well established, but it is clear that it restores the diversity and structure of the microbiota by promoting increased resistance to colonization by C. difficile. Several routes of transplant administration are being studied and used according to the advantages presented. All forms of application had a high cure rate, and the colonoscopic route was the most used. No relevant complications and adverse events have been documented, and the cost-effectiveness over conventional treatment has proven advantageous. Despite its efficacy, it is not commonly used as initial therapy, and more studies are needed to establish this therapy as the first option in case of refractory and recurrent Clostridium difficileinfection.}, } @article {pmid29843959, year = {2018}, author = {Adolph, TE and Grander, C and Moschen, AR and Tilg, H}, title = {Liver-Microbiome Axis in Health and Disease.}, journal = {Trends in immunology}, volume = {39}, number = {9}, pages = {712-723}, doi = {10.1016/j.it.2018.05.002}, pmid = {29843959}, issn = {1471-4981}, abstract = {The intestinal and hepatobiliary tract exhibits host-specific commensal colonization. The resident microbiota has emerged as a key player in intestinal and hepatic diseases. Alcoholic and nonalcoholic fatty liver diseases (ALD/NAFLD), primary sclerosing cholangitis (PSC), liver cirrhosis, and some of their clinical complications, such as hepatic encephalopathy (HE), have been linked to a microbial signature, as also observed for severe liver inflammation in alcoholic hepatitis. In turn, the liver impacts, and communicates with, the microbiota through hepatic mediators, such as bile acids or inflammatory signals. Therefore, a liver-microbiome bidirectional crosstalk appears to be critical in health and various liver diseases and could be therapeutically targeted, such as by fecal microbiota transplantation.}, } @article {pmid29807377, year = {2018}, author = {Lübbert, C and Lippmann, N and von Braun, A}, title = {[New Guidelines and Data to Clostridium difficile - What's New?].}, journal = {Deutsche medizinische Wochenschrift (1946)}, volume = {143}, number = {11}, pages = {787-792}, doi = {10.1055/a-0585-9595}, pmid = {29807377}, issn = {1439-4413}, mesh = {Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; *Clostridium Infections/epidemiology/therapy ; *Clostridium difficile ; Fecal Microbiota Transplantation ; Germany ; Humans ; Practice Guidelines as Topic ; }, abstract = {The incidence of Clostridium difficile infections (CDI) remains on a high level globally. In Germany, the burden of disease and especially the number of severe or even lethal cases continue to increase. The main risk factor for the development of CDI is the exposure to broad-spectrum antibiotics, which disturb the intestinal microbiota and therefore enable the colonization with C. difficile. According to IDSA's and SHEA's updated US guidelines, vancomycin is the treatment of choice. Fidaxomicin is as effective as vancomycin, but its advantage is the lower rate of recurrence. For the treatment of multiple relapsing CDI, there are assured treatment successes of ≥ 90 % through a fecal microbiome transfer (FMT), whereby FMT in Germany currently only has the status of an individual therapeutic attempt. Thus, an evidence-based general recommendation for clinical practice is not possible. Currently, new antibiotics with narrow-spectrum activity and low intestinal resorption have been developed for the treatment of CDI, including surotomycin, cadazolid, and ridinilazol. Furthermore, recent clinical studies demonstrated that significantly fewer recurrences occurred in patients who additionally received the monoclonal antibody bezlotoxumab. Novel toxoid vaccines are expected to become an efficacious tool in the prevention of CDI. However, pivotal clinical trials have so far not been completed.}, } @article {pmid29804272, year = {2018}, author = {Jeon, SR and Chai, J and Kim, C and Lee, CH}, title = {Current Evidence for the Management of Inflammatory Bowel Diseases Using Fecal Microbiota Transplantation.}, journal = {Current infectious disease reports}, volume = {20}, number = {8}, pages = {21}, doi = {10.1007/s11908-018-0627-8}, pmid = {29804272}, issn = {1523-3847}, abstract = {PURPOSE OF REVIEW: Fecal microbiota transplantation (FMT) has been investigated as a potential treatment for inflammatory bowel disease (IBD). This review examines current evidence around the efficacy and safety of FMT for patients with IBD.

RECENT FINDINGS: Randomized controlled trials (RCTs) and meta-analyses have suggested that FMT may facilitate clinical and endoscopic remission in patients with active ulcerative colitis (UC). Although the evidence for FMT in Crohn's disease (CD) is more limited, positive outcomes have been observed in small cohort studies. Most adverse events (AEs) were mild and included transient gastrointestinal symptoms. Serious adverse events (SAEs) did not differ significantly between the FMT and control groups, and a marginal increased rate of IBD flares following FMT was observed. Microbiota analysis following FMT showed increased intestinal bacterial diversity and a shift towards the donor microbial profile in recipients' stools. FMT for patients with IBD is promising as RCTs have shown the benefit of FMT for UC, although the efficacy of FMT for CD is less clear. Further large and well-designed trials are necessary to resolve critical issues such as the donor selection, the ideal route of administration, duration, frequency of FMT, and the long-term sustained efficacy and safety.}, } @article {pmid29793999, year = {2018}, author = {Bidu, C and Escoula, Q and Bellenger, S and Spor, A and Galan, M and Geissler, A and Bouchot, A and Dardevet, D and Morio-Liondor, B and Cani, PD and Lagrost, L and Narce, M and Bellenger, J}, title = {The Transplantation of ω3 PUFA-Altered Gut Microbiota of fat-1 Mice to Wild-Type Littermates Prevents Obesity and Associated Metabolic Disorders.}, journal = {Diabetes}, volume = {67}, number = {8}, pages = {1512-1523}, doi = {10.2337/db17-1488}, pmid = {29793999}, issn = {1939-327X}, mesh = {Animals ; Cadherins/genetics/metabolism ; Diet, Carbohydrate Loading/adverse effects ; Diet, High-Fat/adverse effects ; Dietary Sucrose/adverse effects ; Dysbiosis/microbiology/physiopathology/therapy ; Endotoxemia/etiology/prevention & control ; Fatty Acids, Omega-3/*metabolism ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Glucose Intolerance/microbiology/pathology/physiopathology/*prevention & control ; *Insulin Resistance ; Intestinal Mucosa/metabolism/microbiology/pathology/physiopathology ; Intestines/metabolism/microbiology/pathology/physiopathology ; Liver/metabolism/pathology ; Male ; Mice, Transgenic ; Muscle, Skeletal/metabolism ; Non-alcoholic Fatty Liver Disease/microbiology/pathology/physiopathology/*prevention & control ; Obesity/microbiology/pathology/physiopathology/*prevention & control ; Permeability ; Phylogeny ; }, abstract = {Altering the gut microbiome may be beneficial to the host and recently arose as a promising strategy to manage obesity. Here, we investigated the relative contribution of ω3 polyunsaturated fatty acid (PUFA)-mediated alterations in the microbiota to metabolic parameter changes in mice. Four groups were compared: male fat-1 transgenic mice (with constitutive production of ω3 PUFAs) and male wild-type (WT) littermates fed an obesogenic (high fat/high sucrose [HFHS]) or a control diet. Unlike WT mice, HFHS-fed fat-1 mice were protected against obesity, glucose intolerance, and hepatic steatosis. Unlike WT mice, fat-1 mice maintained a normal barrier function, resulting in a significantly lower metabolic endotoxemia. The fat-1 mice displayed greater phylogenic diversity in the cecum, and fecal microbiota transplantation from fat-1 to WT mice was able to reverse weight gain and to normalize glucose tolerance and intestinal permeability. We concluded that the ω3 PUFA-mediated alteration of gut microbiota contributed to the prevention of metabolic syndrome in fat-1 mice. It occurred independently of changes in the PUFA content of host tissues and may represent a promising strategy to prevent metabolic disease and preserve a lean phenotype.}, } @article {pmid29793539, year = {2018}, author = {McIntosh, CM and Chen, L and Shaiber, A and Eren, AM and Alegre, ML}, title = {Gut microbes contribute to variation in solid organ transplant outcomes in mice.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {96}, doi = {10.1186/s40168-018-0474-8}, pmid = {29793539}, issn = {2049-2618}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 AI115716/AI/NIAID NIH HHS/United States ; R01 AI115716//National Institute of Allergy and Infectious Diseases/ ; }, abstract = {BACKGROUND: Solid organ transplant recipients show heterogeneity in the occurrence and timing of acute rejection episodes. Understanding the factors responsible for such variability in patient outcomes may lead to improved diagnostic and therapeutic approaches. Rejection kinetics of transplanted organs mainly depends on the extent of genetic disparities between donor and recipient, but a role for environmental factors is emerging. We have recently shown that major alterations of the microbiota following broad-spectrum antibiotics, or use of germ-free animals, promoted longer skin graft survival in mice. Here, we tested whether spontaneous differences in microbial colonization between genetically similar individuals can contribute to variability in graft rejection kinetics.

RESULTS: We compared rejection kinetics of minor mismatched skin grafts in C57BL/6 mice from Jackson Laboratory (Jax) and Taconic Farms (Tac), genetically similar animals colonized by different commensal microbes. Female Tac mice rejected skin grafts from vendor-matched males more quickly than Jax mice. We observed prolonged graft survival in Tac mice when they were exposed to Jax mice microbiome through co-housing or fecal microbiota transplantation (FMT) by gastric gavage. In contrast, exposure to Tac mice did not change graft rejection kinetics in Jax mice, suggesting a dominant suppressive effect of Jax microbiota. High-throughput sequencing of 16S rRNA gene amplicons from Jax and Tac mice fecal samples confirmed a convergence of microbiota composition after cohousing or fecal transfer. Our analysis of amplicon data associated members of a single bacterial genus, Alistipes, with prolonged graft survival. Consistent with this finding, members of the genus Alistipes were absent in a separate Tac cohort, in which fecal transfer from Jax mice failed to prolong graft survival.

CONCLUSIONS: These results demonstrate that differences in resident microbiome in healthy individuals may translate into distinct kinetics of graft rejection, and contribute to interpersonal variability in graft outcomes. The association between Alistipes and prolonged skin graft survival in mice suggests that members of this genus might affect host physiology, including at sites distal to the gastrointestinal tract. Overall, these findings allude to a potential therapeutic role for specific gut microbes to promote graft survival through the administration of probiotics, or FMT.}, } @article {pmid29781761, year = {2018}, author = {Eliakim-Raz, N and Bishara, J}, title = {Prevention and treatment of Clostridium difficile associated diarrhea by reconstitution of the microbiota.}, journal = {Human vaccines & immunotherapeutics}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/21645515.2018.1472184}, pmid = {29781761}, issn = {2164-554X}, abstract = {This review summarizes the latest advances in treating and preventing Clostridium difficile infection (CDI), the most common infectious disease cause of nosocomial diarrhea in adults in developed countries. As customary antibiotic therapies against C. difficile, metronidazole and vancomycin, are broad spectrum, they affect greatly the gut microbiota, which result in very high recurrence rates. Therefore, new strategies are researched intensively. New therapies focus on limiting further destruction of the gut microbiota or restoring the microbiota to its pre-destructed state. These include new antibiotics, such as fidaxomicin, which demonstrates reduced CDI recurrences, among other new drugs, biotherapeutic strategies, mainly fecal microbiota transplantation but also competitive inhibition with non-toxigenic strains of C. difficile, and finally, monoclonal antibodies against C. difficile toxins which offer protection against recurrences.}, } @article {pmid29780597, year = {2018}, author = {Ding, C and Fan, W and Gu, L and Tian, H and Ge, X and Gong, J and Nie, Y and Li, N}, title = {Outcomes and prognostic factors of fecal microbiota transplantation in patients with slow transit constipation: results from a prospective study with long-term follow-up.}, journal = {Gastroenterology report}, volume = {6}, number = {2}, pages = {101-107}, doi = {10.1093/gastro/gox036}, pmid = {29780597}, issn = {2052-0034}, abstract = {Background and aim: Gut microbiota may contribute to regulate colonic motility, which is involved in the etiology of constipation. Fecal microbiota transplantation (FMT) has been demonstrated to restore intestinal homeostasis. The aim of this study was to evaluate the clinical outcomes and prognostic factors of FMT for the treatment of slow transit constipation (STC).

Methods: Fifty-two patients with STC received standardized FMT and were followed up for 6 months. Bowel habit, colonic transit time, constipation-related symptoms (PAC-SYM score), quality of life (PAC-QOL score), treatment satisfaction scores and adverse events were monitored. The primary efficacy endpoint was the proportion of patients having on average three or more complete spontaneous bowel movements (CSBMs) per week.

Results: The primary efficacy endpoint was achieved in 50.0%, 38.5% and 32.7% of patients over week intervals 3-4, 9-12 and 21-24, respectively (P < 0.01 for all comparisons). Significant improvements were also observed in other bowel movement assessments, colonic transit time, constipation-related symptoms and quality of life; but all improvements diminished at weeks 12 and 24. Incompleteness of evacuation served as the only factor associated with efficacy. No serious treatment-related adverse events were observed.

Conclusion: This study suggested FMT was effective and safe for STC, while a late loss of efficacy was also observed. A lower degree of sensation of incompleteness predicted a better outcome.}, } @article {pmid29773467, year = {2018}, author = {Daliri, EB and Tango, CN and Lee, BH and Oh, DH}, title = {Human microbiome restoration and safety.}, journal = {International journal of medical microbiology : IJMM}, volume = {308}, number = {5}, pages = {487-497}, doi = {10.1016/j.ijmm.2018.05.002}, pmid = {29773467}, issn = {1618-0607}, mesh = {Anti-Bacterial Agents ; Bacteria/classification/isolation & purification ; Diet ; Dysbiosis/*therapy ; Fecal Microbiota Transplantation/*adverse effects/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Probiotics/*administration & dosage ; }, abstract = {The human gut microbiome consists of many bacteria which are in symbiotic relationship with human beings. The gut microbial metabolism, as well as the microbial-host co-metabolism, has been found to greatly influence health and disease. Factors such as diet, antibiotic use and lifestyle have been associated with alterations in the gut microbial community and may result in several pathological conditions. For this reason, several strategies including fecal microbiota transplant and probiotic administration have been applied and proven to be feasible and effective in restoring the gut microbiota in humans. Yet, safety concerns such as potential health risks that may arise from such interventions and how these strategies are regulated need to be addressed. Also, it will be important to know if these microbiome restoration strategies can have a profound impact on health. This review provides an overview of our current knowledge of the microbiome restoration strategies and safety issues on how these strategies are regulated.}, } @article {pmid29750050, year = {2018}, author = {Segal, JP and Abbasi, F and Kanagasundaram, C and Hart, A}, title = {Does the Internet promote the unregulated use of fecal microbiota transplantation: a potential public health issue?.}, journal = {Clinical and experimental gastroenterology}, volume = {11}, number = {}, pages = {179-183}, doi = {10.2147/CEG.S159609}, pmid = {29750050}, issn = {1178-7023}, abstract = {Introduction: The Internet has become an increasingly popular resource for medical information. Fecal microbiota transplantation (FMT) has changed the treatment of Clostridium difficile with cure rates of 81% following one infusion of FMT, further studies have since validated these findings. The Medicines and Health care Products Regulatory Agency has classified FMT as a medicine and hence should be only utilized in strict clinical settings.

Methods: We searched Facebook, Twitter, Google, and YouTube using the words "Faecal Microbiota Transplantation" and "FMT". We utilized the first 50 hits on each site. We analyzed the percentage of articles that fell outside regulated medical practice. We searched how many clinics in the UK advertised practice that falls outside suggested guidelines.

Results: Google, YouTube, and Facebook had a variety of information regarding FMT available. Nine out of 50 (18%) of the top 50 google searches can be considered articles that fall outside regulated practice. YouTube highlighted four videos describing how to self-administer FMT, one of these was for ulcerative colitis. Fourteen percent of the top 50 YouTube videos fall outside regulated practice and 8% of the top 50 Facebook searches fall outside regulated clinical practice. There were two clinics in the UK advertising FMT for uses that fall outside regulated practice.

Conclusion: Clinicians and patients need to be aware of the resources available through social media and the Internet. It should be appreciated that some websites fall outside regulated clinical practice. Private clinics offering FMT need to ensure that they are offering FMT within a regulated framework.}, } @article {pmid29748817, year = {2018}, author = {Mohajeri, MH and Brummer, RJM and Rastall, RA and Weersma, RK and Harmsen, HJM and Faas, M and Eggersdorfer, M}, title = {The role of the microbiome for human health: from basic science to clinical applications.}, journal = {European journal of nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00394-018-1703-4}, pmid = {29748817}, issn = {1436-6215}, abstract = {The 2017 annual symposium organized by the University Medical Center Groningen in The Netherlands focused on the role of the gut microbiome in human health and disease. Experts from academia and industry examined interactions of prebiotics, probiotics, or vitamins with the gut microbiome in health and disease, the development of the microbiome in early-life and the role of the microbiome on the gut-brain axis. The gut microbiota changes dramatically during pregnancy and intrinsic factors (such as stress), in addition to extrinsic factors (such as diet, and drugs) influence the composition and activity of the gut microbiome throughout life. Microbial metabolites, e.g. short-chain fatty acids affect gut-brain signaling and the immune response. The gut microbiota has a regulatory role on anxiety, mood, cognition and pain which is exerted via the gut-brain axis. Ingestion of prebiotics or probiotics has been used to treat a range of conditions including constipation, allergic reactions and infections in infancy, and IBS. Fecal microbiota transplantation (FMT) highly effective for treating recurrent Clostridium difficile infections. The gut microbiome affects virtually all aspects of human health, but the degree of scientific evidence, the models and technologies and the understanding of mechanisms of action vary considerably from one benefit area to the other. For a clinical practice to be broadly accepted, the mode of action, the therapeutic window, and potential side effects need to thoroughly be investigated. This calls for further coordinated state-of-the art research to better understand and document the human gut microbiome's effects on human health.}, } @article {pmid29745777, year = {2018}, author = {Hvas, CL and Bendix, M and Dige, A and Dahlerup, JF and Agnholt, J}, title = {Current, experimental, and future treatments in inflammatory bowel disease: a clinical review.}, journal = {Immunopharmacology and immunotoxicology}, volume = {}, number = {}, pages = {1-15}, doi = {10.1080/08923973.2018.1469144}, pmid = {29745777}, issn = {1532-2513}, abstract = {Inflammatory bowel diseases (IBDs) may result from dysregulated mucosal immune responses directed toward the resident intestinal microbiota. This review describes the hallmark immunobiology of Crohn's disease and ulcerative colitis as well as therapeutic targets and mechanisms of action for current, experimental, and future treatments in IBD. Conventional therapies include 5-aminosalicylic acid, glucocorticosteroids, thiopurines, and methotrexate. Since 1997, monoclonal antibodies have gained widespread use. These consist of antibodies directed against pro-inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-12, and IL-23, or anti-homing antibodies directed against α4β7 integrin. Emerging oral therapies include modulators of intracellular signal transduction such as Janus kinase inhibitors. Vitamin D may help to regulate innate and adaptive immune responses. Modulation of the intestinal microbiota, using live microorganisms (probiotics), substrates for the colonic microbiota (prebiotics), or fecal microbiota transplantation (FMT), is in development. Dietary supplements are in widespread use, but providing evidence for their benefit is challenging. Stem cell treatment and nervous stimulation are promising future treatments.}, } @article {pmid29743833, year = {2018}, author = {Fairhurst, NG and Travis, SPL}, title = {Why is it so difficult to evaluate faecal microbiota transplantation as a treatment for ulcerative colitis?.}, journal = {Intestinal research}, volume = {16}, number = {2}, pages = {209-215}, doi = {10.5217/ir.2018.16.2.209}, pmid = {29743833}, issn = {1598-9100}, abstract = {Faecal microbiota transplantation (FMT) has recently re-emerged as a viable therapeutic option for colonic disorders. Its efficacy has been proved in the treatment of Clostridium difficile infection which has encouraged research into the use of FMT for other disorders involving gut dysbiosis, such as ulcerative colitis (UC), a chronic inflammatory disease characterized by relapsing and remitting colonic inflammation. Although the FMT protocol for C. difficile treatment is well established, there are numerous additional factors to consider when applying FMT to treat inflammatory diseases. Various studies have attempted to address these factors but technical inconsistency between reports has resulted in a failure to achieve clinically significant findings. Case reports of FMT in UC have shown favorable outcomes yet demonstrating these effects on a larger scale has proved difficult. The following review aims to explore these issues and to analyze why they may be hindering the progression of FMT therapy in UC.}, } @article {pmid29743453, year = {2018}, author = {Mizuno, S and Nanki, K and Kanai, T}, title = {[Future perspectives on fecal microbiota transplantation].}, journal = {Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology}, volume = {115}, number = {5}, pages = {449-459}, doi = {10.11405/nisshoshi.115.449}, pmid = {29743453}, issn = {0446-6586}, } @article {pmid29742710, year = {2018}, author = {Wang, HG and Liu, SP and Ma, TH and Yan, W and Zhou, JF and Shi, YT and Shen, P and Yang, XZ and Wu, SN}, title = {Fecal microbiota transplantation treatment for refractory ulcerative colitis with allergy to 5-aminosalicylic acid: A case report.}, journal = {Medicine}, volume = {97}, number = {19}, pages = {e0675}, doi = {10.1097/MD.0000000000010675}, pmid = {29742710}, issn = {1536-5964}, mesh = {*Anti-Inflammatory Agents, Non-Steroidal ; Colitis, Ulcerative/*therapy ; *Drug Hypersensitivity ; *Fecal Microbiota Transplantation ; Humans ; Male ; *Mesalamine ; Middle Aged ; Remission Induction ; }, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT) is currently being explored as a potential therapy for ulcerative colitis (UC). Here, we report the first case of a UC patient with allergy to 5-aminosalicylic acid (5-ASA) who underwent FMT and achieved clinical remission.

CASE PRESENTATION: This patient had a 9-year history of UC and was allergic to 5-ASA. He suffered from gradually aggravated abdominal pain and frequent bloody diarrhea. There was a continuous distribution of superficial erosion and ulceration by colonoscopy. After steroid therapy failed, he underwent FMT. The donated fecal microbes were purified in laboratory and then transplanted into the terminal ileum and right colon of the patient by colonoscopy. During the 9 months' follow-up, FMT has proved its efficacy in inducing and maintaining clinical and endoscopic remission of the patient.

CONCLUSION: The choice of treatment for refractory UC patients who are allergic to 5-ASA is relatively limited. In our case, we highlight the specific role of FMT for refractory UC with absence of 5-ASA through intestinal microbiota reconstruction.}, } @article {pmid29738579, year = {2018}, author = {Solbach, P and Chhatwal, P and Woltemate, S and Tacconelli, E and Buhl, M and Gerhard, M and Thoeringer, CK and Vehreschild, MJGT and Jazmati, N and Rupp, J and Manns, MP and Bachmann, O and Suerbaum, S}, title = {BaiCD gene cluster abundance is negatively correlated with Clostridium difficile infection.}, journal = {PloS one}, volume = {13}, number = {5}, pages = {e0196977}, doi = {10.1371/journal.pone.0196977}, pmid = {29738579}, issn = {1932-6203}, mesh = {Anti-Bacterial Agents/therapeutic use ; Bacterial Proteins/*genetics ; Bacterial Toxins ; Bile/microbiology ; Bile Acids and Salts/biosynthesis/*genetics ; Clostridium Infections/*genetics/microbiology/transmission ; Clostridium difficile/*genetics/pathogenicity ; Diarrhea/*genetics/microbiology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; Male ; Microbiota/genetics ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is a major cause of hospital-acquired diarrhea. Secondary bile acids were shown to confer resistance to colonization by C. difficile. 7α-dehydroxylation is a key step in transformation of primary to secondary bile acids and required genes have been located in a single bile acid-inducible (bai) operon in C. scindens as well as in C. hiranonis, two Clostridium sp. recently reported to protect against C. difficile colonization.

AIM: To analyze baiCD gene abundance in C. difficile positive and negative fecal samples.

MATERIAL & METHODS: A species-specific qPCR for detecting baiCD genes was established. Fecal samples of patients with CDI, asymptomatic toxigenic C. difficile colonization (TCD), non-toxigenic C. difficile colonization (NTCD), of C. difficile negative (NC) patients, and of two patients before and after fecal microbiota transplantation (FMT) for recurrent CDI (rCDI) were tested for the presence of the baiCD genes.

RESULTS: The prevalence of the baiCD gene cluster was significantly higher in C. difficile negative fecal samples than in samples of patients diagnosed with CDI (72.5% (100/138) vs. 35.9% (23/64; p<0.0001). No differences in baiCD gene cluster prevalence were seen between NC and NTCD or NC and TCD samples. Both rCDI patients were baiCD-negative at baseline, but one of the two patients turned positive after successful FMT from a baiCD-positive donor.

CONCLUSION: Fecal samples of CDI patients are less frequently baiCD-positive than samples from asymptomatic carriers or C. difficile-negative individuals. Furthermore, we present a case of baiCD positivity observed after successful FMT for rCDI.}, } @article {pmid29728643, year = {2018}, author = {Couturier-Maillard, A and Froux, N and Piotet-Morin, J and Michaudel, C and Brault, L and Le Bérichel, J and Sénéchal, A and Robinet, P and Chenuet, P and Jejou, S and Dumoutier, L and Renauld, JC and Iovanna, J and Huber, S and Quesniaux, V and Sokol, H and Ryffel, B}, title = {Interleukin-22-deficiency and microbiota contribute to the exacerbation of Toxoplasma gondii-induced intestinal inflammation.}, journal = {Mucosal immunology}, volume = {11}, number = {4}, pages = {1181-1190}, doi = {10.1038/s41385-018-0005-8}, pmid = {29728643}, issn = {1935-3456}, abstract = {Upon oral infection with Toxoplasma gondii cysts (76 K strain) tachyzoites are released into the intestinal lumen and cross the epithelial barrier causing damage and acute intestinal inflammation in C57BL/6 (B6) mice. Here we investigated the role of microbiota and IL-22 in T.gondii-induced small intestinal inflammation. Oral T.gondii infection in B6 mice causes inflammation with IFNγ and IL-22 production. In IL-22-deficient mice, T.gondii infection augments the Th1 driven inflammation. Deficiency in either IL-22bp, the soluble IL-22 receptor or Reg3γ, an IL-22-dependent antimicrobial lectin/peptide, did not reduce inflammation. Under germ-free conditions, T.gondii-induced inflammation was reduced in correlation with parasite load. But intestinal inflammation is still present in germ-free mice, at low level, in the lamina propria, independently of IL-22 expression. Exacerbated intestinal inflammation driven by absence of IL-22 appears to be independent of IL-22 deficiency associated-dysbiosis as similar inflammation was observed after fecal transplantation of IL-22-/- or WT microbiota to germ-free-WT mice. Our results suggest cooperation between parasite and intestinal microbiota in small intestine inflammation development and endogenous IL-22 seems to exert a protective role independently of its effect on the microbiota. In conclusion, IL-22 participates in T.gondii induced acute small intestinal inflammation independently of microbiota and Reg3γ.}, } @article {pmid29728388, year = {2018}, author = {Yan, ZX and Gao, XJ and Li, T and Wei, B and Wang, PP and Yang, Y and Yan, R}, title = {Fecal Microbiota Transplantation in Experimental Ulcerative Colitis Reveals Associated Gut Microbial and Host Metabolic Reprogramming.}, journal = {Applied and environmental microbiology}, volume = {84}, number = {14}, pages = {}, doi = {10.1128/AEM.00434-18}, pmid = {29728388}, issn = {1098-5336}, abstract = {Fecal microbiota transplantation (FMT) is gaining attention for the treatment of ulcerative colitis (UC). Data from individual case studies have suggested that FMT may be beneficial for UC, but the detailed microbial and molecular basis remains unknown. Here, we employ 16S rRNA gene sequencing and metabolomics to investigate the influence of FMT on gut microbial community composition and host metabolism in the dextran sulfate sodium-induced UC rat model. The findings from this pilot study suggest that FMT from normal donors to UC recipients could alleviate UC symptoms without close resemblance of donor's gut microbial and metabolic pattern. Meanwhile, FMT from UC donors to normal recipient rats triggered UC symptoms, UC-prone microbial shift, and host metabolic adaption. Gut microbiota under normal conditions could maintain stable species richness and diversity upon FMT intervention, but the disturbed gut microbiota under UC conditions could not maintain such homeostasis. Significant correlations between altered bacterial composition and host metabolism could be assigned to the pathological effects of UC (accounting for 8.0 to 16.2% of total variance) and/or the FMT intervention effects (3.9 to 7.0% of total variance). Overall, our study reveals diverse gut microbial shifts in UC related FMT and their association with host metabolic reprogramming.IMPORTANCE This study combined clinical symptoms measurement, 16S rRNA gene microbial profiling and metabolomics to comprehensively investigate the gut bacterial and host metabolic association and reprogramming in FMT-treated experimental UC. These data can advance our understanding of the effect of FMT on UC and the involvement of gut microbial dysbiosis in the development of UC.}, } @article {pmid29717179, year = {2018}, author = {Wrzosek, L and Ciocan, D and Borentain, P and Spatz, M and Puchois, V and Hugot, C and Ferrere, G and Mayeur, C and Perlemuter, G and Cassard, AM}, title = {Transplantation of human microbiota into conventional mice durably reshapes the gut microbiota.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {6854}, doi = {10.1038/s41598-018-25300-3}, pmid = {29717179}, issn = {2045-2322}, abstract = {Human microbiota-associated (HMA) mice are an important model to study the relationship between liver diseases and intestinal microbiota. We describe a new method to humanize conventional mice based on bowel cleansing with polyethylene glycol followed by fecal microbiota transplantation (FMT) from a human donor. Four successive bowel cleansings were sufficient to empty the intestine and decrease the microbiota by 90%. We then compared four different strategies based on the frequency of FMT over four weeks: (1) twice a week; (2) once a week; (3) two FMTs; (4) one FMT. We were able to transfer human bacteria to mice, irrespective of the strategy used. We detected human bacteria after four weeks, even if only one FMT was performed, but there was a shift of the microbiota over time. FMT twice a week for four weeks was too frequent and perturbed the stability of the newly formed ecosystem. FMT once a week appears to be the best compromise as it allowed engraftment of Faecalibacterium, and a higher diversity of bacteria belonging to the Bacteroidales order. Our easy to establish HMA mouse model could be used as an alternative to classical HMA mice to study the relationship between the liver and the microbiota.}, } @article {pmid29712976, year = {2018}, author = {Hoel, H and Hove-Skovsgaard, M and Hov, JR and Gaardbo, JC and Holm, K and Kummen, M and Rudi, K and Nwosu, F and Valeur, J and Gelpi, M and Seljeflot, I and Ueland, PM and Gerstoft, J and Ullum, H and Aukrust, P and Nielsen, SD and Trøseid, M}, title = {Impact of HIV and Type 2 diabetes on Gut Microbiota Diversity, Tryptophan Catabolism and Endothelial Dysfunction.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {6725}, doi = {10.1038/s41598-018-25168-3}, pmid = {29712976}, issn = {2045-2322}, abstract = {HIV infection and type 2 diabetes are associated with altered gut microbiota, chronic inflammation, and increased cardiovascular risk. We aimed to investigate the combined effect of these diseases on gut microbiota composition and related metabolites, and a potential relation to endothelial dysfunction in individuals with HIV-infection only (n = 23), diabetes only (n = 16) or both conditions (n = 21), as well as controls (n = 24). Fecal microbiota was analyzed by Illumina sequencing of the 16 S rRNA gene. Markers of endothelial dysfunction (asymmetric dimethylarginine [ADMA]), tryptophan catabolism (kynurenine/tryptophan [KT]-ratio), and inflammation (neopterin) were measured by liquid chromatography-tandem mass spectrometry. The combination of HIV and type 2 diabetes was associated with reduced gut microbiota diversity, increased plasma KT-ratio and neopterin. Microbial genes related to tryptophan metabolism correlated with KT-ratio and low alpha diversity, in particular in HIV-infected with T2D. In multivariate analyses, KT-ratio associated with ADMA (β = 4.58 [95% CI 2.53-6.63], p < 0.001), whereas microbiota composition per se was not associated with endothelial dysfunction. Our results indicate that tryptophan catabolism may be related to endothelial dysfunction, with a potentially detrimental interaction between HIV and diabetes. The potential contribution of gut microbiota and the impact for cardiovascular risk should be further explored in prospective studies powered for clinical end points.}, } @article {pmid29709869, year = {2018}, author = {Gardiner, BJ and Thorpe, CM and Pinkham, NV and McDermott, LA and Walk, ST and Snydman, DR}, title = {A repeat offender: Recurrent extraintestinal Clostridium difficile infection following fecal microbiota transplantation.}, journal = {Anaerobe}, volume = {51}, number = {}, pages = {68-72}, doi = {10.1016/j.anaerobe.2018.04.007}, pmid = {29709869}, issn = {1095-8274}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/*epidemiology ; Clostridium difficile/classification/genetics/*isolation & purification ; Fecal Microbiota Transplantation/*adverse effects ; Humans ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; Whole Genome Sequencing ; }, abstract = {Extraintestinal infection with Clostridium difficile has been reported but remains uncommon. Treatment of this unusual complication is complex given the limitations of current therapeutic options. Here we report a novel case of recurrent extraintestinal C. difficile infection that occurred following fecal microbiota transplantation. Using whole genome sequencing, we confirmed recrudescence rather than reinfection was responsible. The patient ultimately responded to prolonged, targeted antimicrobial therapy informed by susceptibility testing.}, } @article {pmid29705917, year = {2018}, author = {Nardelli, S and Ridola, L and Gioia, S and Riggio, O}, title = {Management of Hepatic Encephalopathy Not Responsive to First-Line Treatments.}, journal = {Current treatment options in gastroenterology}, volume = {16}, number = {2}, pages = {253-259}, doi = {10.1007/s11938-018-0183-1}, pmid = {29705917}, issn = {1092-8472}, abstract = {PURPOSE OF REVIEW: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that occurs in up to 30% of patients with cirrhosis. HE may be a consequence of pure liver failure, as in patients with fulminant hepatitis, or of the combination of liver failure and portal-systemic shunting, as in patients with liver cirrhosis. Episodes of HE are usually related to precipitating events, such as infections or gastrointestinal bleeding; a minority of cirrhotic patients experienced a chronic HE, refractory to standard medical treatment. The prevention of HE recurrence, after the first episode of HE, could be obtained by the administration of prophylactic therapy with lactulose, rifaximin or a combination of both. The aim of this review is to clarify some key points in the management of cirrhotic patients with HE, not responsive to first line treatment.

RECENT FINDINGS: Recent studies investigated the role of fecal microbiota transplantation in the treatment of HE with promising results, but further investigations are needed. In a cirrhotic patient with acute cognitive impairment, the correct diagnosis of HE, after excluding other causes of neurological diseases, is mandatory for the correct management of the precipitating factors and for the treatment. In patients not responsive to standard treatment, the probable precipitating factors have not been correctly identified, multiple precipitating events are coexisting or a new precipitating event is superimposed. In some patients with recurrent HE, characterized by persistent alterations in neurological symptoms, without specific precipitants events, the presence of spontaneous or iatrogenic shunts should be investigated.}, } @article {pmid29705121, year = {2018}, author = {Sun, MF and Shen, YQ}, title = {Dysbiosis of gut microbiota and microbial metabolites in Parkinson's Disease.}, journal = {Ageing research reviews}, volume = {45}, number = {}, pages = {53-61}, doi = {10.1016/j.arr.2018.04.004}, pmid = {29705121}, issn = {1872-9649}, abstract = {Gut microbial dysbiosis and alteration of microbial metabolites in Parkinson's disease (PD) have been increasingly reported. Dysbiosis in the composition and abundance of gut microbiota can affect both the enteric nervous system and the central nervous system (CNS), indicating the existence of a microbiota-gut-brain axis and thereby causing CNS diseases. Disturbance of the microbiota-gut-brain axis has been linked to specific microbial products that are related to gut inflammation and neuroinflammation. Future directions should therefore focus on the exploration of specific gut microbes or microbial metabolites that contribute to the development of PD. Microbiota-targeted interventions, such as antibiotics, probiotics and fecal microbiota transplantation, have been shown to favorably affect host health. In this review, recent findings regarding alterations and the role of gut microbiota and microbial metabolites in PD are summarized, and potential molecular mechanisms and microbiota-targeted interventions in PD are discussed.}, } @article {pmid29703246, year = {2018}, author = {Dow, DE and Seed, PC}, title = {Clostridium difficile cure with fecal microbiota transplantation in a child with Pompe disease: a case report.}, journal = {Journal of medical case reports}, volume = {12}, number = {1}, pages = {112}, doi = {10.1186/s13256-018-1659-2}, pmid = {29703246}, issn = {1752-1947}, mesh = {Anti-Bacterial Agents/administration & dosage ; Clostridium difficile/isolation & purification ; Diarrhea/therapy ; Enterocolitis, Pseudomembranous/diagnosis/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Glycogen Storage Disease Type II/*complications ; Humans ; Immunocompetence ; Infant ; Metronidazole/administration & dosage ; Polymerase Chain Reaction ; Treatment Outcome ; Vancomycin/administration & dosage ; }, abstract = {BACKGROUND: Recurrent Clostridium difficile infection is a growing problem among children due to both the increasing survival of medically fragile children with complicated chronic medical conditions resulting in prolonged antibiotic exposure and hospitalization and the emergence of strains of Clostridium difficile that are hypervirulent and associated with high rates of relapse.

CASE PRESENTATION: This case describes a medically complex 21-month-old Hispanic girl with Pompe disease and B cell immunodeficiency with recurrent Clostridium difficile infection refractory to antimicrobial management. She presented with nine recurrent episodes of Clostridium difficile infection including fever, foul smelling diarrhea, and respiratory distress with failed sustained responses to compliant treatment using metronidazole and pulsed vancomycin therapy. Maternal donor fecal microbiota transplantation was performed with complete symptom resolution and produced a sustained cure, now 5 years in duration.

CONCLUSIONS: This patient presented with symptomatic Clostridium difficile at an early age causing significant morbidity and reduced quality of life. After nearly one year of failed medical management, fecal microbiota transplantation provided a cure. Further evidence-based research is necessary to test the safety and efficacy of this low technology, low cost, and morbidity-sparing therapy in children.}, } @article {pmid29696802, year = {2018}, author = {D'Odorico, I and Di Bella, S and Monticelli, J and Giacobbe, DR and Boldock, E and Luzzati, R}, title = {Role of fecal microbiota transplantation in inflammatory bowel disease.}, journal = {Journal of digestive diseases}, volume = {19}, number = {6}, pages = {322-334}, doi = {10.1111/1751-2980.12603}, pmid = {29696802}, issn = {1751-2980}, abstract = {There is increasing evidence of the key role played by altered intestinal microbiota in the pathogenesis of inflammatory bowel disease (IBD). Management strategies involving immune modulation are effective and widely used, but treatment failures and side effects occur. Fecal microbiota transplantation (FMT) provides a novel, perhaps complementary, strategy to restore the normal gut microbiota in patients with IBD. This review summarizes the available efficacy and safety data on the use of FMT in patients with IBD. Several aspects remain to be clarified about the clinical predictors of the response to FMT, its most appropriate route of administration, and the most appropriate quantity and quality of microbiota to be transplanted. Further studies focusing on long-term outcomes and safety are also warranted.}, } @article {pmid29694952, year = {2018}, author = {Enck, P and Mazurak, N}, title = {Dysbiosis in Functional Bowel Disorders.}, journal = {Annals of nutrition & metabolism}, volume = {72}, number = {4}, pages = {296-306}, doi = {10.1159/000488773}, pmid = {29694952}, issn = {1421-9697}, abstract = {Functional bowel disorders (FBD) resemble a group of diseases of the gastrointestinal (GI) tract that are without a clear pathogenesis; the best known is probably the "irritable bowel syndrome" (IBS). Only recently we have been able to explore the role of the gut microbiota in FBD due to progress in microbiological analytic techniques. There are different ways to explore the role of the gut microbiota and its dysbiosis in FBD. Comparison of the microbial composition in a group of patients with FBD, for example, with IBS to a group of healthy volunteers is one way. Studies have shown that the microbiota in FBD is different from that of healthy controls, but the recorded differences are not necessarily specific for FBD, they may also occur in other diseases. Another approach to explore the role of the gut microbiota in FBD is to challenge the existing "flora" with novel bacteria (probiotics) or with nutritional substrates that stimulate bacterial growth (prebiotics). More than 60 such trials including several thousand patients have been performed in IBS. These studies have produced mixed outcome: some probiotics appear to be better than others, and some appear to work only for a part of the IBS symptoms and not for all. An extreme form of this approach is the transfer of an entire microbiota from 1 healthy person to another, called fecal microbiota transplantation. This has rarely been tested in FBD but is not without risk in benign disorders.}, } @article {pmid29691757, year = {2018}, author = {Zhang, F and Cui, B and He, X and Nie, Y and Wu, K and Fan, D and , }, title = {Microbiota transplantation: concept, methodology and strategy for its modernization.}, journal = {Protein & cell}, volume = {9}, number = {5}, pages = {462-473}, doi = {10.1007/s13238-018-0541-8}, pmid = {29691757}, issn = {1674-8018}, abstract = {Fecal microbiota transplantation (FMT) has become a research focus of biomedicine and clinical medicine in recent years. The clinical response from FMT for different diseases provided evidence for microbiota-host interactions associated with various disorders, including Clostridium difficile infection, inflammatory bowel disease, diabetes mellitus, cancer, liver cirrhosis, gut-brain disease and others. To discuss the experiences of using microbes to treat human diseases from ancient China to current era should be important in moving standardized FMT forward and achieving a better future. Here, we review the changing concept of microbiota transplantation from FMT to selective microbiota transplantation, methodology development of FMT and step-up FMT strategy based on literature and state experts' perspectives.}, } @article {pmid29688915, year = {2018}, author = {Francavilla, R and Piccolo, M and Francavilla, A and Polimeno, L and Semeraro, F and Cristofori, F and Castellaneta, S and Barone, M and Indrio, F and Gobbetti, M and De Angelis, M}, title = {Clinical and Microbiological Effect of a Multispecies Probiotic Supplementation in Celiac Patients With Persistent IBS-type Symptoms: A Randomized, Double-Blind, Placebo-controlled, Multicenter Trial.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001023}, pmid = {29688915}, issn = {1539-2031}, abstract = {GOALS: The goals of this study were to evaluate the efficacy and safety of a probiotic mixture in patients with celiac disease (CD) with irritable bowel syndrome (IBS)-type symptoms despite a strict gluten-free diet (GFD).

BACKGROUND: About 30% of patients with CD adherent to a GFD suffer from IBS-type symptoms; a possible cause resides in the imbalances of the intestinal microbiota in CD. Probiotics may represent a potential treatment.

STUDY: CD patients with IBS-type symptoms entered a prospective, double-blind, randomized placebo-controlled study. A 6-week treatment period was preceded by a 2-week run-in and followed by a 6-week follow-up phase. Clinical data were monitored throughout the study by validated questionnaires: IBS Severity Scoring System (IBS-SSS); Gastrointestinal Symptom Rating Scale (GSRS); Bristol Stool Form Scale (BSFS); and IBS Quality of Life Questionnaire (IBS-QOL). The fecal microbiota were assayed using plate counts and 16S rRNA gene-based analysis.

RESULTS: In total, 109 patients were randomized to probiotics (n=54) or placebo (n=55). IBS-SSS and GSRS decreased significantly in probiotics, as compared with placebo [(-15.9%±14.8% vs. 8.2%±25.9%; P<0.001) and (-19.8%±16.6% vs. 12.9%±31.6%; P<0.001)], respectively. Treatment success was significantly higher in patients receiving probiotics, as compared with placebo (15.3% vs. 3.8%; P<0.04). Presumptive lactic acid bacteria, Staphylococcus and Bifidobacterium, increased in patients receiving probiotic treatment. No adverse events were reported.

CONCLUSIONS: A 6-week probiotic treatment is effective in improving the severity of IBS-type symptoms, in CD patients on strict GFD, and is associated with a modification of gut microbiota, characterized by an increase of bifidobacteria.}, } @article {pmid29688901, year = {2018}, author = {Iqbal, U and Anwar, H and Karim, MA}, title = {Safety and efficacy of encapsulated fecal microbiota transplantation for recurrent Clostridium difficile infection: a systematic review.}, journal = {European journal of gastroenterology & hepatology}, volume = {30}, number = {7}, pages = {730-734}, doi = {10.1097/MEG.0000000000001147}, pmid = {29688901}, issn = {1473-5687}, abstract = {BACKGROUND AND AIMS: Fecal microbial transplantation (FMT) has been shown to be effective for the treatment of recurrent clostridium difficile infection (CDI). The efficacy and safety of freeze-dried encapsulated FMT for the treatment of recurrent CDI is unclear. We performed a systematic review to evaluate and analyze the current evidence in this respect.

MATERIALS AND METHODS: A systematic literature search was performed using the PubMed, Embase, and Medline databases until December 2017 to identify all original studies that investigated the role of administration of encapsulated FMT in recurrent CDI. The study included patients of all ages. Two independent reviewers extracted data and assessed the quality of publications; a third investigator resolved any discrepancies.

RESULTS: A total of six studies, five case series and one randomized-controlled trial, were included in this review. Overall, 341 patients completed treatment with encapsulated FMT. Only three major adverse events were reported and no deaths occurred directly related to FMT. In all, 285 patients responded to the first treatment, with no recurrence during the specified follow-up period set to meet the primary endpoint. Forty-two patients underwent a second treatment, with resolution of symptoms in 28 patients. At least five patients were reported to undergo a third treatment, with resolution in three of them. Only one patient was reported to have received four treatments without long-term resolution of symptoms.

CONCLUSION: Low-quality to moderate-quality evidence showed that encapsulated FMT is safe and cost-effective for the treatment and prevention of recurrent CDI. Its efficacy is not inferior to FMT performed through the nonoral route. Randomized-controlled trials are necessary to compare its efficacy with oral antimicrobial drugs and also to evaluate the potential adverse effects associated with the treatment.}, } @article {pmid29684976, year = {2018}, author = {Giron, F and Quigley, EMM}, title = {Pharmabiotic Manipulation of the Microbiota in Gastrointestinal Disorders: A Clinical Perspective.}, journal = {Journal of neurogastroenterology and motility}, volume = {24}, number = {3}, pages = {355-366}, doi = {10.5056/jnm18004}, pmid = {29684976}, issn = {2093-0879}, abstract = {The advent and widespread availability of high-throughput technology has revolutionized the assessment of the communities of microorganisms that inhabit the gastrointestinal tract-the gut microbiota. As our understanding of the role of the microbiota in health and human disease increases, so also do efforts to prevent and treat disease through the modulation of the microbiota. Several strategies are available to us and range from time honored approaches, such as antibiotics and probiotics, to changes in diet, the administration of prebiotics as food supplements, and fecal microbiota transplantation. Of these, diet is perhaps the most pervasive but often ignored modulator of the microbiota, and a failure to recognize its impact complicates the interpretation of many microbiota studies. The impacts of antibiotics on the microbiota are more complex than originally thought and, though antibiotics can be life-saving, their effects on commensal bacterial populations can be clinically significant. Though there have been many studies of, and even more claims made for, probiotics, the majority of available studies suffer from significant deficits in study design and execution and many claims remain to be substantiated. Though holding much promise, the study of prebiotics in human disease is still in its infancy. Possibilities other than the administration of live organisms have been identified through efforts to mine the microbiota for novel therapeutics and include: dead organisms, bacterial components, small molecules elaborated by bacteria, and even bacterial DNA. Accordingly, the term pharmabiotic has been introduced to encompass the full range of therapeutic possibilities that the microbiota offers.}, } @article {pmid29684865, year = {2018}, author = {Kurokawa, S and Kishimoto, T and Mizuno, S and Masaoka, T and Naganuma, M and Liang, KC and Kitazawa, M and Nakashima, M and Shindo, C and Suda, W and Hattori, M and Kanai, T and Mimura, M}, title = {The effect of fecal microbiota transplantation on psychiatric symptoms among patients with irritable bowel syndrome, functional diarrhea and functional constipation: An open-label observational study.}, journal = {Journal of affective disorders}, volume = {235}, number = {}, pages = {506-512}, doi = {10.1016/j.jad.2018.04.038}, pmid = {29684865}, issn = {1573-2517}, abstract = {BACKGROUNDS: The intestinal microbiota is considered as a potential common underpinning pathophysiology of Functional Gastrointestinal Disorders (FGIDs) and psychiatric disorders such as depression and anxiety. Fecal Microbiota Transplantation (FMT) has been reported to have therapeutic effects on diseases related to dysbiosis, but few studies have evaluated its effect on psychiatric symptoms.

METHODS: We followed 17 patients with either Irritable Bowel Syndrome (IBS), Functional Diarrhea (FDr) or Functional Constipation (FC) who underwent FMT for the treatment of gastrointestinal symptoms and observation of psychiatric symptoms. Changes in Hamilton Rating Scale for Depression (HAM-D) and subscale of sleep-related items, Hamilton Rating Scale for Anxiety (HAM-A) and Quick Inventory for Depressive Symptoms (QIDS) between baseline and 4 weeks after FMT, and relationship with the intestinal microbiota were measured.

RESULTS: At baseline, 12 out of 17 patients were rated with HAM-D ≥ 8. Significant improvement in HAM-D total and sleep subscale score, HAM-A and QIDS were observed (p = 0.007, p = 0.007, p = 0.01, p = 0.007, respectively). Baseline Shannon index indicated that microbiota showed lower diversity in patients with HAM-D ≥ 8 compared to those of healthy donors and patients with HAM-D < 8. There was a significant correlation between baseline Shannon index and HAM-D score, and a correlation between Shannon index change and HAM-D improvement after FMT.

LIMITATIONS: The small sample size with no control group.

CONCLUSIONS: Our results suggest that depression and anxiety symptoms may be improved by FMT regardless of gastrointestinal symptom change in patients with IBS, FDr and FC, and the increase of microbiota diversity may help to improve patient's mood.}, } @article {pmid29676108, year = {2018}, author = {Du, H and Xu, T and Li, HJ and Li, Q and GangHuan, CL and Fan, G and Zhang, Y}, title = {[Fecal Tibetan medicines].}, journal = {Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica}, volume = {43}, number = {5}, pages = {1054-1061}, pmid = {29676108}, issn = {1001-5302}, abstract = {Fecal Tibetan medicines have a long history of application in China, with a good clinical efficacy. In order to promote the development and modernization of these medicines, we consulted ancient and modern Tibetan medicine literatures to collect and summarize the names, original species, natures, flavor, functions and processing methods of fecal Tibetan medicines. A total of 35 fecal Tibetan medicines were collected, such as Jiufen, Heibingpian, Langfen, Mafen, Goufen, Gezifen. The most commonly used medicines were Jiufen and Heibingpian. Both were mainly used for the treatment of indigestion, food abdominal distension, gastric ulcer, and other gastrointestinal diseases. At present, there are only a few studies on the active ingredients, pharmacodynamics and mechanism of action of these medicines. Therefore, further study shall be conducted. The regulation of gut microbiota may be a new way to evaluate the effectiveness of fecal Tibetan medicines and their mechanism of action.}, } @article {pmid29674425, year = {2018}, author = {Haak, BW and Littmann, ER and Chaubard, JL and Pickard, AJ and Fontana, E and Adhi, F and Gyaltshen, Y and Ling, L and Morjaria, SM and Peled, JU and van den Brink, MR and Geyer, AI and Cross, JR and Pamer, EG and Taur, Y}, title = {Impact of gut colonization with butyrate-producing microbiota on respiratory viral infection following allo-HCT.}, journal = {Blood}, volume = {131}, number = {26}, pages = {2978-2986}, doi = {10.1182/blood-2018-01-828996}, pmid = {29674425}, issn = {1528-0020}, support = {P01 CA023766/CA/NCI NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI095706/AI/NIAID NIH HHS/United States ; R01 AI042135/AI/NIAID NIH HHS/United States ; }, abstract = {Respiratory viral infections are frequent in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) and can potentially progress to lower respiratory tract infection (LRTI). The intestinal microbiota contributes to resistance against viral and bacterial pathogens in the lung. However, whether intestinal microbiota composition and associated changes in microbe-derived metabolites contribute to the risk of LRTI following upper respiratory tract viral infection remains unexplored in the setting of allo-HCT. Fecal samples from 360 allo-HCT patients were collected at the time of stem cell engraftment and subjected to deep, 16S ribosomal RNA gene sequencing to determine microbiota composition, and short-chain fatty acid levels were determined in a nested subset of fecal samples. The development of respiratory viral infections and LRTI was determined for 180 days following allo-HCT. Clinical and microbiota risk factors for LRTI were subsequently evaluated using survival analysis. Respiratory viral infection occurred in 149 (41.4%) patients. Of those, 47 (31.5%) developed LRTI. Patients with higher abundances of butyrate-producing bacteria were fivefold less likely to develop viral LRTI, independent of other factors (adjusted hazard ratio = 0.22, 95% confidence interval 0.04-0.69). Higher representation of butyrate-producing bacteria in the fecal microbiota is associated with increased resistance against respiratory viral infection with LRTI in allo-HCT patients.}, } @article {pmid29674329, year = {2018}, author = {Hota, SS and Surangiwala, S and Paterson, AS and Coburn, B and Poutanen, SM and , }, title = {Regional variability in fecal microbiota transplantation practices: a survey of the Southern Ontario Fecal Microbiota Transplantation Movement.}, journal = {CMAJ open}, volume = {6}, number = {2}, pages = {E184-E190}, doi = {10.9778/cmajo.20170109}, pmid = {29674329}, issn = {2291-0026}, abstract = {BACKGROUND: There is growing evidence that fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection, but little guidance exists for implementation of FMT programs. The objective of this study is to describe the program characteristics and protocols of 9 planned or operating FMT programs in the Southern Ontario Fecal Microbiota Transplantation (SOFT) Movement, to help guide future FMT program implementation.

METHODS: A 59-item survey was administered electronically to clinical leads of the SOFT Movement on June 2, 2016. The survey evaluated 7 domains: FMT program characteristics, FMT recipients, donor screening/selection, transplant manufacturing, FMT administration, good manufacturing procedures/biosafety procedures and infection-control procedures. We used descriptive statistics to analyze quantitative data.

RESULTS: All 9 programs responded to the survey: 6 were active, 1 had FMT standard operating procedures developed but did not have clinical experience, and 2 were in the process of forming FMT programs. All 6 active programs performed FMT in adult patients with C. difficile infection. About 1300 FMT procedures were performed between 2003 and 2016. Five of the 6 operating programs administered the preparation via enema. Programs were driven primarily by physicians. All programs used universal FMT donors and followed Health Canada's screening guidelines, with considerable variability in screening frequency (every 3-6 mo) and modality. Locations for transplant preparation and manufacturing protocols varied across programs. Stool mass for FMT ranged from 20 g to 150 g, and transplant volume ranged from 25 mL to 300 mL.

INTERPRETATION: The experience of this high-volume regional FMT network highlights current challenges in FMT program development, including a high reliance on physicians and the costly nature of donor screening. Standardization and optimization through development of regional centres of excellence for FMT donor recruitment and administration should be explored.}, } @article {pmid29673295, year = {2018}, author = {Groen, RN and de Clercq, NC and Nieuwdorp, M and Hoenders, HJR and Groen, AK}, title = {Gut microbiota, metabolism and psychopathology: A critical review and novel perspectives.}, journal = {Critical reviews in clinical laboratory sciences}, volume = {55}, number = {4}, pages = {283-293}, doi = {10.1080/10408363.2018.1463507}, pmid = {29673295}, issn = {1549-781X}, abstract = {Psychiatric disorders are often associated with metabolic comorbidities. However, the mechanisms through which metabolic and psychiatric disorders are connected remain unclear. Pre-clinical studies in rodents indicate that the bidirectional signaling between the intestine and the brain, the so-called microbiome-gut-brain axis, plays an important role in the regulation of both metabolism and behavior. The gut microbiome produces a vast number of metabolites that may be transported into the host and play a part in homeostatic control of metabolism as well as brain function. In addition to short chain fatty acids, many of these metabolites have been identified in recent years. To what extent both microbiota and their products control human metabolism and behavior is a subject of intense investigation. In this review, we will discuss the most recent findings concerning alterations in the gut microbiota as a possible pathophysiological factor for the co-occurrence of metabolic comorbidities in psychiatric disorders.}, } @article {pmid29670863, year = {2018}, author = {Anonye, BO}, title = {Commentary: Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome.}, journal = {Frontiers in cellular and infection microbiology}, volume = {8}, number = {}, pages = {104}, doi = {10.3389/fcimb.2018.00104}, pmid = {29670863}, issn = {2235-2988}, support = {BB/M017982/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, } @article {pmid29670798, year = {2018}, author = {Amlani, A and Bromley, A and Fifi-Mah, A}, title = {ANCA Vasculitis and Hemophagocytic Lymphohistiocytosis following a Fecal Microbiota Transplant.}, journal = {Case reports in rheumatology}, volume = {2018}, number = {}, pages = {9263537}, doi = {10.1155/2018/9263537}, pmid = {29670798}, issn = {2090-6889}, abstract = {A 69-year-old female with antisynthetase syndrome, a history of multiple recurrent infections, and documented previous negative titres for anti-neutrophil cystoplasmic antibody (ANCA) suddenly developed a de novo MPO-ANCA-associated glomerulonephritis three weeks after a fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infections. Six months following her FMT and less than two weeks following treatment for urosepsis, she developed severe cholestasis, a markedly elevated ferritin and hypertriglyceridemia. An initial liver biopsy was suggestive of drug-induced liver injury and thus she was treated with supportive care. After she failed to improve, a second liver biopsy supported the diagnosis of hemophagocytic lymphohistiocytosis (HLH). This case highlights difficulties surrounding the early diagnosis of HLH and also questions the role of FMT and/or recurrent infections as a trigger for ANCA-associated vasculitis.}, } @article {pmid29670191, year = {2018}, author = {Le Bastard, Q and Ward, T and Sidiropoulos, D and Hillmann, BM and Chun, CL and Sadowsky, MJ and Knights, D and Montassier, E}, title = {Fecal microbiota transplantation reverses antibiotic and chemotherapy-induced gut dysbiosis in mice.}, journal = {Scientific reports}, volume = {8}, number = {1}, pages = {6219}, doi = {10.1038/s41598-018-24342-x}, pmid = {29670191}, issn = {2045-2322}, abstract = {Fecal microbiota transplantation (FMT) is now widely used to treat recurrent Clostridium difficile infection, but has been less studied as a means to restore microbiome diversity and composition following antibiotic or chemotherapy treatments. The purpose of our study was to assess the efficacy of FMT to reverse antibiotic- and chemotherapy-induced gut dysbiosis in a mouse model. C57BL/6J mice were treated with ampicillin for 1 week and/or received a single intraperitoneal injection of 5-Fluorouracil. Fresh stool was collected and analyzed using shotgun metagenomics and the Illumina sequencing platform. Ampicillin caused a significant and immediate decrease in bacterial species richness and diversity that persisted for one week. In mice that received FMT, disruption of the intestinal microbiota was reversed immediately. Antibiotic and chemotherapy administration caused significant alteration in species distribution, including a decrease in the relative proportions of Clostridium scindens and Faecalibacterium prausnitzii, and an increase in known pathogenic species. In mice receiving FMT, we observed a significant increase in species known to exhibit anti-inflammatory properties. Moreover, chemotherapy led to a critical decrease in key 'health-promoting' species and to an altered functional profile, especially when chemotherapy was administered in tandem with antibiotics, and that FMT can ameliorate these effects.}, } @article {pmid29667487, year = {2018}, author = {Markey, L and Shaban, L and Green, ER and Lemon, KP and Mecsas, J and Kumamoto, CA}, title = {Pre-colonization with the commensal fungus Candida albicans reduces murine susceptibility to Clostridium difficile infection.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/19490976.2018.1465158}, pmid = {29667487}, issn = {1949-0984}, support = {R01 AI101018/AI/NIAID NIH HHS/United States ; R01 AI118898/AI/NIAID NIH HHS/United States ; }, abstract = {Clostridium difficile is a major nosocomial pathogen responsible for close to half a million infections and 27,000 deaths annually in the U.S. Preceding antibiotic treatment is a major risk factor for C. difficile infection (CDI) leading to recognition that commensal microbes play a key role in resistance to CDI. Current antibiotic treatment of CDI is only partially successful due to a high rate of relapse. As a result, there is interest in understanding the effects of microbes on CDI susceptibility to support treatment of patients with probiotic microbes or entire microbial communities (e.g., fecal microbiota transplantation). The results reported here demonstrate that colonization with the human commensal fungus Candida albicans protects against lethal CDI in a murine model. Colonization with C. albicans did not increase the colonization resistance of the host. Rather, our findings showed that one effect of C. albicans colonization was to enhance a protective immune response. Mice pre-colonized with C. albicans expressed higher levels of IL-17A in infected tissue following C. difficile challenge compared to mice that were not colonized with C. albicans. Administration of cytokine IL-17A was demonstrated to be protective against lethal murine CDI in mice not colonized with C. albicans. C. albicans colonization was associated with changes in the abundance of some bacterial components of the gut microbiota. Therefore, C. albicans colonization altered the gut ecosystem, enhancing survival after C. difficile challenge. These findings demonstrate a new, beneficial role for C. albicans gut colonization.}, } @article {pmid29667436, year = {2018}, author = {Khoruts, A}, title = {Is fecal microbiota transplantation a temporary patch for treatment of Clostridium difficile infection or a new frontier of therapeutics?.}, journal = {Expert review of gastroenterology & hepatology}, volume = {12}, number = {5}, pages = {435-438}, doi = {10.1080/17474124.2018.1465818}, pmid = {29667436}, issn = {1747-4132}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/diagnosis/microbiology/*therapy ; Clostridium difficile/drug effects/*pathogenicity ; Drug Resistance, Bacterial ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome/drug effects ; Host-Pathogen Interactions ; Humans ; Treatment Outcome ; }, } @article {pmid29665135, year = {2018}, author = {Ponziani, FR and Bhoori, S and Castelli, C and Putignani, L and Rivoltini, L and Del Chierico, F and Sanguinetti, M and Morelli, D and Paroni Sterbini, F and Petito, V and Reddel, S and Calvani, R and Camisaschi, C and Picca, A and Tuccitto, A and Gasbarrini, A and Pompili, M and Mazzaferro, V}, title = {Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep.30036}, pmid = {29665135}, issn = {1527-3350}, abstract = {The gut-liver axis plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), which is the third leading cause of hepatocellular carcinoma (HCC) worldwide. However, the link between gut microbiota and hepatocarcinogenesis remains to be clarified. The aim of this study was to explore what features of the gut microbiota are associated with HCC in patients with cirrhosis and NAFLD. A consecutive series of patients with NAFLD-related cirrhosis and HCC (group 1, 21 patients), NAFLD-related cirrhosis without HCC (group 2, 20 patients), and healthy controls (group 3, 20 patients) was studied for gut microbiota profile, intestinal permeability, inflammatory status, and circulating mononuclear cells. We finally constructed a model depicting the most relevant correlations among these features, possibly involved in hepatocarcinogenesis. Patients with HCC showed increased levels of fecal calprotectin, while intestinal permeability was similar to patients with cirrhosis but without HCC. Plasma levels of interleukin 8 (IL8), IL13, chemokine (C-C motif) ligand (CCL) 3, CCL4, and CCL5 were higher in the HCC group and associated with an activated status of circulating monocytes. The fecal microbiota of the whole group of patients with cirrhosis showed higher abundance of Enterobacteriaceae and Streptococcus and a reduction in Akkermansia. Bacteroides and Ruminococcaceae were increased in the HCC group, while Bifidobacterium was reduced. Akkermansia and Bifidobacterium were inversely correlated with calprotectin concentration, which in turn was associated with humoral and cellular inflammatory markers. A similar behavior was also observed for Bacteroides.

CONCLUSION: Our results suggest that in patients with cirrhosis and NAFLD the gut microbiota profile and systemic inflammation are significantly correlated and can concur in the process of hepatocarcinogenesis. (Hepatology 2018).}, } @article {pmid29654837, year = {2018}, author = {Seekatz, AM and Theriot, CM and Rao, K and Chang, YM and Freeman, AE and Kao, JY and Young, VB}, title = {Restoration of short chain fatty acid and bile acid metabolism following fecal microbiota transplantation in patients with recurrent Clostridium difficile infection.}, journal = {Anaerobe}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.anaerobe.2018.04.001}, pmid = {29654837}, issn = {1095-8274}, support = {K01 GM109236/GM/NIGMS NIH HHS/United States ; R35 GM119438/GM/NIGMS NIH HHS/United States ; U01 AI124255/AI/NIAID NIH HHS/United States ; U19 AI090871/AI/NIAID NIH HHS/United States ; }, abstract = {A significant proportion of individuals develop recurrent Clostridium difficile infection (CDI) following initial disease. Fecal microbiota transplantation (FMT), a highly effective treatment method for recurrent CDI, has been demonstrated to induce microbiota recovery. One of the proposed functions associated with restoration of colonization resistance against C. difficile has been recovery of bile acid metabolism. In this study, we aimed to assess recovery of short chain fatty acids (SCFAs) in addition to bile acids alongside microbial community structure in six patients with recurrent CDI following treatment with FMT over time. Using 16S rRNA gene-based sequencing, we observed marked similarity of the microbiota between recipients following FMT (n = 6, sampling up to 6 months post-FMT) and their respective donors. Sustained increases in the levels of the SCFAs butyrate, acetate, and propionate were observed post-FMT, and variable recovery over time was observed in the secondary bile acids deoxycholate and lithocholate. To correlate these changes with specific microbial taxa at an individual level, we applied a generalized estimating equation approach to model metabolite concentrations with the presence of specific members of the microbiota. Metabolites that increased following FMT were associated with bacteria classified within the Lachnospiraceae, Ruminococcaceae, and unclassified Clostridiales families. In contrast, members of these taxa were inversely associated with primary bile acids. The longitudinal aspect of this study allowed us to characterize individualized patterns of recovery, revealing variability between and within patients following FMT.}, } @article {pmid29651860, year = {2018}, author = {Vigvári, S and Sipos, D and Kappéter, Á and Feiszt, Z and Kovács, B and Péterfi, Z}, title = {Risk factors for Clostridium difficile infections in Baranya County, Southern Hungary.}, journal = {Acta microbiologica et immunologica Hungarica}, volume = {65}, number = {2}, pages = {183-192}, doi = {10.1556/030.65.2018.023}, pmid = {29651860}, issn = {1217-8950}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Case-Control Studies ; Clostridium Infections/*drug therapy/epidemiology/*microbiology ; *Clostridium difficile ; Female ; Humans ; Hungary/epidemiology ; Male ; Middle Aged ; Odds Ratio ; Risk Factors ; Time Factors ; }, abstract = {In the past decade, Clostridium difficile infections (CDIs) have become a major public health challenge. Their epidemiology has radically changed with a significant rise in the number of cases and an increase in severe episodes. Recurrence and failure of conventional treatments are very common. Furthermore, a spread of CDI has emerged in general population without the usual risk factors (unexposed to antibiotic treatment, young people, etc.). The conventional treatments (metronidazole and vancomycin) are still effective and are the first-line antibiotics with new recommendations. New therapeutic strategies are now available. Recent studies show a better efficacy of vancomycin compared with metronidazole for severe episodes. Fidaxomicin is a novel antibiotic drug with an efficacy similar to vancomycin and a lower risk of recurrence. Finally, for relapsing forms, fecal microbiota transplantation (FMT) seems to be the best option. We determined risk factors for CDI among patients treated at the infectious diseases ward of our hospital in Pécs. The study included 886 patients with CDI from 2009 to 2014. The average number of recurrent episodes was 2.16 and the proportion of severe cases was 66%. Among our patients, 726 (82%) had taken antibiotics and 769 (86.8%) had been hospitalized in the prior 3 months before developing CDI. We have found that prior statin use could be a significant risk factor of CDI (OR: 1.7765, 95% CI: 1.3966-2.2597, p < 0.0001). Finally, we present the comparative efficacy of different types of treatment (metronidazole, vancomycin, fidaxomicin, and FMT).}, } @article {pmid29644492, year = {2018}, author = {Kornerup, LS and Gluud, LL and Vilstrup, H and Dam, G}, title = {Update on the Therapeutic Management of Hepatic Encephalopathy.}, journal = {Current gastroenterology reports}, volume = {20}, number = {5}, pages = {21}, doi = {10.1007/s11894-018-0627-8}, pmid = {29644492}, issn = {1534-312X}, mesh = {Amino Acids, Branched-Chain/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Disease Management ; Fecal Microbiota Transplantation ; Gastrointestinal Agents/*therapeutic use ; Hepatic Encephalopathy/*drug therapy/therapy ; Humans ; Lactulose/therapeutic use ; Probiotics/therapeutic use ; Rifamycins/therapeutic use ; }, abstract = {PURPOSE OF REVIEW: Hepatic encephalopathy (HE) is a common and devastating complication to chronic liver disease. In this paper, we summarize the latest research and evidence of both conventional and up-coming treatments.

RECENT FINDINGS: Meta-analyses report beneficial effects of lactulose, branched-chain amino acids, rifaximin, and to some degree L-ornithine L-aspartate on the manifestations of HE in patients with cirrhosis, and generally the numbers needed to treat are low. Recent studies on newer HE treatments including ornithine phenylacetate, spherical carbon, and fecal microbiota transplant also report potentially beneficial effects on HE manifestations. The conventional treatments benefit patients with HE. Newer treatments are under study and more research is needed for their validation.}, } @article {pmid29637938, year = {2018}, author = {Holleran, G and Scaldaferri, F and Ianiro, G and Lopetuso, L and Mc Namara, D and Mele, MC and Gasbarrini, A and Cammarota, G}, title = {Fecal microbiota transplantation for the treatment of patients with ulcerative colitis and other gastrointestinal conditions beyond Clostridium difficile infection: an update.}, journal = {Drugs of today (Barcelona, Spain : 1998)}, volume = {54}, number = {2}, pages = {123-136}, doi = {10.1358/dot.2018.54.2.2760765}, pmid = {29637938}, issn = {1699-3993}, mesh = {Clostridium Infections/microbiology/therapy ; Colitis, Ulcerative/microbiology/*therapy ; Dysbiosis/microbiology/therapy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; Inflammatory Bowel Diseases/microbiology/therapy ; Intestinal Diseases/microbiology/*therapy ; }, abstract = {Fecal microbiota transplantation (FMT) is the transplantation of microbial gut contents from a healthy individual into the gastrointestinal tract of a person with a disease, with a view to increasing the recipient's gut microbial diversity and bacterial richness and restoring microbial homeostasis. FMT has been proven to be a safe and effective treatment for Clostridium difficile infection (CDI) and it is now a recommended treatment for recurrent or refractory infection. FMT is not currently recommended for use outside of CDI due to concerns regarding outcome and safety; however, several case series and randomized controlled trials have described its use in a research environment for a few gastrointestinal conditions related to intestinal dysbiosis including ulcerative colitis (UC), Crohn's disease (CD) and irritable bowel syndrome (IBS). The most successful reports of the clinical efficacy of FMT in gastrointestinal conditions outside of CDI have been in treating UC. We summarize the current literature regarding the use of FMT in UC, including methodology, clinical efficacy and safety concerns, and identify pitfalls and areas for future development. We also describe the available evidence to date on the use of FMT in CD, IBS and other conditions related to intestinal dysbiosi.}, } @article {pmid29626003, year = {2018}, author = {Axtell, S and Shokoya, A and Yocum, C}, title = {Probable fidaxomicin-induced pancytopenia.}, journal = {American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists}, volume = {75}, number = {8}, pages = {532-535}, doi = {10.2146/ajhp170239}, pmid = {29626003}, issn = {1535-2900}, abstract = {PURPOSE: A case of pancytopenia in a patient receiving treatment with fidaxomicin for Clostridium difficile infection (CDI) is described.

SUMMARY: A 33-year-old Caucasian woman was admitted to the hospital with a chief complaint of loose stools occurring approximately 7 times a day; she also reported fever, nausea, diffuse abdominal pain, and fatigue. The patient had a history of recurrent CDI, recurrent urinary tract infections, nephrolithiasis, chronic hepatitis C, and endometriosis. Her previous therapies for CDI included metronidazole, vancomycin, rifaximin, and fecal microbiota transplantation. On admission, she had a platelet count of 172,000 platelets/mm3, hemoglobin concentration of 11.1 g/dL, and white blood cell (WBC) count of 3,100 cells/mm3. Within 24 hours of the first dose of fidaxomicin and before the second dose, the patient's platelet count fell to 156,000 platelets/mm3, her hemoglobin concentration decreased to 9.9 g/dL, and her WBC count fell to 2,600 cells/mm3. Values for all 3 tests continued to decrease during the first few days of fidaxomicin therapy. One dose of filgrastim 300 μg was administered subcutaneously on day 6 in response to the pancytopenia, after which the platelet, hemoglobin, and WBC values stabilized for a day and then generally declined. Platelet, hemoglobin, and WBC values returned to normal within 3 days of the patient's last dose of fidaxomicin. Use of the Naranjo et al. adverse drug reaction probability scale indicated a probable association (score of 6) between fidaxomicin and the patient's pancytopenia.

CONCLUSION: A 33-year-old woman developed pancytopenia during a course of fidaxomicin therapy for CDI. Platelet, hemoglobin, and WBC values returned to normal within 3 days of the final fidaxomicin dose.}, } @article {pmid29620765, year = {2018}, author = {Willyard, C}, title = {Squeaky clean mice could be ruining research.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {16-18}, doi = {10.1038/d41586-018-03916-9}, pmid = {29620765}, issn = {1476-4687}, mesh = {Adult ; Animals ; Animals, Laboratory/genetics/*immunology/microbiology/virology ; Animals, Wild/*immunology/*microbiology/virology ; Biomedical Research/*methods ; *Disease Models, Animal ; Fecal Microbiota Transplantation/veterinary ; Female ; Gene Expression Profiling ; Germ-Free Life/immunology ; *Housing, Animal ; Humans ; Immunologic Memory/immunology ; Infant ; Listeria monocytogenes/immunology ; Listeriosis/immunology/microbiology/veterinary ; Mice ; Microbiota/immunology ; Pregnancy ; T-Lymphocytes/cytology/immunology ; Yellow Fever Vaccine/administration & dosage/immunology ; }, } @article {pmid29619403, year = {2018}, author = {Makkawi, S and Camara-Lemarroy, C and Metz, L}, title = {Fecal microbiota transplantation associated with 10 years of stability in a patient with SPMS.}, journal = {Neurology(R) neuroimmunology & neuroinflammation}, volume = {5}, number = {4}, pages = {e459}, doi = {10.1212/NXI.0000000000000459}, pmid = {29619403}, issn = {2332-7812}, } @article {pmid29617463, year = {2018}, author = {Chassaing, B and Gewirtz, AT}, title = {Mice harboring pathobiont-free microbiota do not develop intestinal inflammation that normally results from an innate immune deficiency.}, journal = {PloS one}, volume = {13}, number = {4}, pages = {e0195310}, doi = {10.1371/journal.pone.0195310}, pmid = {29617463}, issn = {1932-6203}, support = {DK099071/NH/NIH HHS/United States ; DK083890/NH/NIH HHS/United States ; }, mesh = {Animals ; Escherichia coli ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Flagellin/metabolism ; Gastroenteritis/*immunology/*microbiology ; Gastrointestinal Microbiome/*immunology ; Immunity, Innate ; Immunologic Deficiency Syndromes/*metabolism/*microbiology ; Intestines/*immunology/*microbiology ; Lipopolysaccharides/metabolism ; Male ; Metabolic Syndrome/immunology/microbiology ; Mice, Inbred C57BL ; Mice, Knockout ; Toll-Like Receptor 5/deficiency/genetics ; }, abstract = {BACKGROUND: Inability to maintain a stable and beneficial microbiota is associated with chronic gut inflammation, which classically manifests as colitis but may more commonly exist as low-grade inflammation that promotes metabolic syndrome. Alterations in microbiota, and associated inflammation, can originate from dysfunction in host proteins that manage the microbiota, such as the flagellin receptor TLR5. That the complete absence of a microbiota (i.e. germfree conditions) eliminates all evidence of inflammation in TLR5-deficient mice demonstrates that this model of gut inflammation is microbiota-dependent. We hypothesize that such microbiota dependency reflects an inability to manage pathobionts, such as Adherent-Invasive E. coli (AIEC). Herein, we examined the extent to which microbiota mismanagement and associated inflammation in TLR5-deficient mice would manifest in a limited and pathobiont-free microbiota. For this purpose, WT and TLR5-deficient mice were generated and maintained with the 8-member consortium of bacteria referred to as "Altered Schaedler Flora" (ASF). Such ASF animals were subsequently inoculated with AIEC reference strain LF82. Feces were assayed for bacterial loads, fecal lipopolysaccharide and flagellin loads, fecal inflammatory marker lipocalin-2 and microbiota composition.

RESULTS: Relative to similarly maintained WT mice, mice lacking TLR5 (T5KO) did not display low-grade intestinal inflammation nor metabolic syndrome under ASF conditions. Concomitantly, the ASF microbial community was similar between WT and T5KO mice, while inoculation with AIEC strain LF82 resulted in alteration of the ASF community in T5KO mice compared to WT control animals. AIEC LF82 inoculation in ASF T5KO mice resulted in microbiota components having elevated levels of bioactive lipopolysaccharide and flagellin, a modest level of low-grade inflammation and increased adiposity.

CONCLUSIONS: In a limited-complexity pathobiont-free microbiota, loss of the flagellin receptor TLR5 does not impact microbiota composition nor its ability to promote inflammation. Addition of AIEC to this ecosystem perturbs microbiota composition, increases levels of lipopolysaccharide and flagellin, but only modestly promotes gut inflammation and adiposity, suggesting that the phenotypes previously associated with loss of this innate immune receptor require disruption of complex microbiota.}, } @article {pmid29617178, year = {2018}, author = {Jørgensen, SMD and Erikstrup, C and Dinh, KM and Lemming, LE and Dahlerup, JF and Hvas, CL}, title = {Recruitment of feces donors among blood donors: Results from an observational cohort study.}, journal = {Gut microbes}, volume = {}, number = {}, pages = {1-11}, doi = {10.1080/19490976.2018.1458179}, pmid = {29617178}, issn = {1949-0984}, abstract = {As the use of fecal microbiota transplantation (FMT) has gained momentum, an increasing need for continuous access to healthy feces donors has developed. Blood donors constitute a healthy subset of the general population and may serve as an appropriate group for recruitment. In this study, we investigated the suitability of blood donors as feces donors. In a prospective cohort study, we recruited blood donors onsite at a public Danish blood bank. Following their consent, the blood donors underwent a stepwise screening process: First, blood donors completed an electronic pre-screening questionnaire to rule out predisposing risk factors. Second, eligible blood donors had blood and fecal samples examined. Of 155 blood donors asked to participate, 137 (88%) completed the electronic pre-screening questionnaire, 16 declined, and 2 were excluded. Of the 137 donors who completed the questionnaire, 79 (58%) were excluded mainly due to having an allergy, being overweight, or presenting gastrointestinal complaints. Among the remaining 58 (37%) donors, complete blood and feces screenings were obtained from 46 (79%). Of these 46 donors, 15 (33%) were excluded primarily due to abnormal blood results or the presence of apathogenic intestinal parasites. Overall, 31 (20%; 95% confidence interval 14-27%) of the 155 blood donors qualified as feces donors. In conclusion, blood donors constitute a suitable and motivated population for a continuous recruitment of voluntary feces donors. We found that a stepwise recruitment procedure was feasible and that 20% of the blood donors were eligible for feces donation.}, } @article {pmid29607440, year = {2018}, author = {Heath, RD and Cockerell, C and Mankoo, R and Ibdah, JA and Tahan, V}, title = {Fecal microbiota transplantation and its potential therapeutic uses in gastrointestinal disorders.}, journal = {Northern clinics of Istanbul}, volume = {5}, number = {1}, pages = {79-88}, doi = {10.14744/nci.2017.10692}, pmid = {29607440}, issn = {2536-4553}, abstract = {Typical human gut flora has been well characterized in previous studies and has been noted to have significant differences when compared with the typical microbiome of various disease states involving the gastrointestinal tract. Such diseases include Clostridium difficile colitis, inflammatory bowel disease, functional bowel syndromes, and various states of liver disease. A growing number of studies have investigated the use of a fecal microbiota transplant as a potential therapy for these disease states.}, } @article {pmid29606940, year = {2018}, author = {Schneider, KM and Wirtz, TH and Kroy, D and Albers, S and Neumann, UP and Strowig, T and Sellge, G and Trautwein, C}, title = {Successful Fecal Microbiota Transplantation in a Patient with Severe Complicated Clostridium difficile Infection after Liver Transplantation.}, journal = {Case reports in gastroenterology}, volume = {12}, number = {1}, pages = {76-84}, doi = {10.1159/000481937}, pmid = {29606940}, issn = {1662-0631}, abstract = {Clostridium difficile infection (CDI) represents one of the most common healthcare-associated infections. Due to increasing numbers of recurrences and therapy failures, CDI has become a major disease burden. Studies have shown that fecal microbiota transplantation (FMT) can both be a safe and highly efficacious therapy for patients with therapy-refractory CDI. However, patients undergoing solid organ transplantation are at high risk for CDI due to long-term immunosuppression, previous antibiotic therapy, and proton pump inhibitor use. Additionally, these patients may be especially prone to adverse events related to FMT. Here, we report a successful FMT in a patient with severe therapy-refractory CDI after liver transplantation.}, } @article {pmid29605414, year = {2018}, author = {Syal, G and Kashani, A and Shih, DQ}, title = {Fecal Microbiota Transplantation in Inflammatory Bowel Disease: A Primer for Internists.}, journal = {The American journal of medicine}, volume = {131}, number = {9}, pages = {1017-1024}, doi = {10.1016/j.amjmed.2018.03.010}, pmid = {29605414}, issn = {1555-7162}, abstract = {Inflammatory bowel disease consists of disorders characterized by chronic idiopathic bowel inflammation. The concept of host-gut-microbiome interaction in the pathogenesis of various complex immune-mediated chronic diseases, including inflammatory bowel disease, has recently generated immense interest. Mounting evidence confirms alteration of intestinal microflora in patients with inflammatory bowel disease. Thus, restoration of normal gut microbiota has become a focus of basic and clinical research in recent years. Fecal microbiota transplantation is being explored as one such therapeutic strategy and has shown encouraging results in the management of patients with inflammatory bowel disease.}, } @article {pmid29601470, year = {2018}, author = {Wang, G and Feuerbacher, LA and Hardwidge, PR}, title = {Influence of Intestinal Microbiota Transplantation and NleH Expression on Citrobacter rodentium Colonization of Mice.}, journal = {Pathogens (Basel, Switzerland)}, volume = {7}, number = {2}, pages = {}, doi = {10.3390/pathogens7020035}, pmid = {29601470}, issn = {2076-0817}, abstract = {The intestinal microbiota plays an important role in regulating host resistance to enteric pathogens. The relative abundance of the microbiota is dependent upon both genetic and environmental factors. The attaching and effacing pathogens enteropathogenic Escherichia coli, enterohemorrhagic E. coli, and Citrobacter rodentium cause diarrheal disease and translocate type III secretion system effector proteins into host cells to inhibit pro-inflammatory host responses. Here we determined the influence of both the intestinal microbiota and the expression of the C. rodentium NleH effector on C. rodentium colonization in different mouse models. We performed fecal transplantation experiments between C57BL/6J and C57BL/10ScNJ mice and found that such microbiota transfers altered both the host resistance to C. rodentium infection as well as the benefit or detriment of expressing NleH to C. rodentium intestinal colonization.}, } @article {pmid29601446, year = {2018}, author = {Aldrich, AM and Argo, T and Koehler, TJ and Olivero, R}, title = {Analysis of Treatment Outcomes for Recurrent Clostridium difficile Infections and Fecal Microbiota Transplantation in a Pediatric Hospital.}, journal = {The Pediatric infectious disease journal}, volume = {}, number = {}, pages = {}, doi = {10.1097/INF.0000000000002053}, pmid = {29601446}, issn = {1532-0987}, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is one of the most common nosocomial infections in the United States, with an increasing incidence in children. Approximately 20% of pediatric patients develop recurrent infections. It's imperative to further analyze the incidence of recurrent CDI in the pediatric population and determine the most effective treatments. The primary goal of this study is to characterize children with recurrent CDI at our institution, including both hospital-acquired (HA-CDI) and community-acquired (CA-CDI) cases, summarize the various treatments utilized, including fecal microbiota transplant (FMT), and compare their success rates.

METHODS: A retrospective cohort study of pediatric patients aged 1-21 years treated for CDI at a single institution from January 2010 - December 2014 was performed.

RESULTS: There were 175 subjects with 215 separate episodes of CDI. Oral metronidazole was the most common initial treatment (145/207, 70%) followed by oral vancomycin (30/207, 15%), with recurrence rates of 30% (42/145) and 37% (11/30), respectively. Twenty-nine percent (63/215) of all initial CDI cases had at least one documented recurrence. Using multivariate analysis, subjects with HA-CDI were 2.6 times less likely to recur than those with CA-CDI (OR: 0.39; 95% CI: 0.18-0.85; p=0.018). The overall success rate for FMT at our institution was 10/12 (83%).

CONCLUSIONS: Our data show cases of HA-CDI were less likely to recur compared with CA-CDI. Though currently reserved for multiply-recurrent cases, FMT was highly successful in our small cohort. More studies on FMT should be conducted to further evaluate its usefulness in the treatment of recurrent CDI in children.}, } @article {pmid29600698, year = {2018}, author = {Campion, D and Ponzo, P and Alessandria, C and Saracco, GM and Balzola, F}, title = {Role of microbiota in the autism spectrum disorders.}, journal = {Minerva gastroenterologica e dietologica}, volume = {}, number = {}, pages = {}, doi = {10.23736/S1121-421X.18.02493-5}, pmid = {29600698}, issn = {1827-1642}, abstract = {Autism Spectrum Disorder (ASD) defines a set of neurodevelopmental disorders characterized by persistent deficits in social communication and interaction, along with repetitive patterns of behavior. Symptoms generally appear in the early developmental period and cause significant impairment in individual and social functioning. In recent years the increased prevalence of ASD, along with the evidence of a significant link between autism and gastrointestinal (GI) disturbances, raised a special interest in exploringì the reciprocal influences between gut and brain. Investigators highlighted the existence of a so-called "gut-brain axis", empowering the hypothesis that GI abnormalities could trigger neuropsychiatric symptoms in ASD. Intestinal microbiota is thought to play a pivotal role in gut and systemic homeostasis, in CNS development, as well as in behavioral modulation and recurrent microbial imbalances have been shown in gut microbiota of autistic people. In this review we analyze current knowledge about intestinal microbiota and the relevance and role of dysbiosis in ASD. The most accredited theories about gut-brain interaction will be reviewed, along with current scientific evidence supporting the relationship between microbial imbalances and impairment of neurodevelopment. Finally, we will focus on the results of different therapeutic approaches in this context: administration of pre- and probiotics, antibiotics, fecal microbiota transplantation and special diets and dietary supplements.}, } @article {pmid29600252, year = {2018}, author = {Hota, SS and Poutanen, SM}, title = {Is a Single Fecal Microbiota Transplant a Promising Treatment for Recurrent Clostridium difficile Infection?.}, journal = {Open forum infectious diseases}, volume = {5}, number = {3}, pages = {ofy045}, doi = {10.1093/ofid/ofy045}, pmid = {29600252}, issn = {2328-8957}, abstract = {Clostridium difficile infection, a common hospital-associated infection, is a gastrointestinal illness that becomes recurrent in about 25% of infected patients. Fecal microbiota transplantation (FMT) is increasingly supported by clinical trials as an effective treatment for recurrent Clostridium difficile infection, but a number of questions remain about how it can be optimally performed. In this Perspective, we discuss controversies in FMT methodologies and reporting within randomized controlled trials, all of which may influence clinical outcomes in treated patients. Finally, we focus on the question of whether single vs multiple FMTs are necessary to achieve favorable outcomes for the treatment of recurrent Clostridium difficile infection, postulating on why there may be an association between number of FMTs and clinical effectiveness.}, } @article {pmid29599513, year = {2018}, author = {Stoll, ML and Pierce, MK and Watkins, JA and Zhang, M and Weiss, PF and Weiss, JE and Elson, CO and Cron, RQ and Kumar, R and Morrow, CD and Schoeb, TR}, title = {Akkermansia muciniphila is permissive to arthritis in the K/BxN mouse model of arthritis.}, journal = {Genes and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41435-018-0024-1}, pmid = {29599513}, issn = {1476-5470}, support = {P30 AR050948/AR/NIAMS NIH HHS/United States ; P60 AR064172/AR/NIAMS NIH HHS/United States ; R21 ES024413/ES/NIEHS NIH HHS/United States ; UL1 TR001417/TR/NCATS NIH HHS/United States ; }, abstract = {Studies have identified abnormalities in the microbiota of patients with arthritis. To evaluate the pathogenicity of human microbiota, we performed fecal microbial transplantation from children with spondyloarthritis and controls to germ-free KRN/B6xNOD mice. Ankle swelling was equivalent in those that received patient vs. control microbiota. Principal coordinates analysis revealed incomplete uptake of the human microbiota with over-representation of two genera (Bacteroides and Akkermansia) among the transplanted mice. The microbiota predicted the extent of ankle swelling (R2 = 0.185, p = 0.018). The abundances of Bacteroides (r = -0.510, p = 0.010) inversely and Akkermansia (r = 0.367, p = 0.078) directly correlated with ankle swelling. Addition of Akkermansia muciniphila to Altered Schaedler's Flora (ASF) resulted in small but statistically significant increased ankle swelling as compared to mice that received ASF alone (4.0 mm, 3.9-4.1 vs. 3.9 mm, IQR 3.6-4.0, p = 0.041), as did addition of A. muciniphila cultures to transplanted human microbiota as compared to mice that received transplanted human microbiota alone (4.5 mm, IQR 4.3-5.5 vs. 4.1 mm, IQR 3.9-4.3, p = 0.019). This study supports previous findings of an association between A. muciniphila and arthritis.}, } @article {pmid29594746, year = {2018}, author = {Panchal, P and Budree, S and Scheeler, A and Medina, G and Seng, M and Wong, WF and Eliott, R and Mitchell, T and Kassam, Z and Allegretti, JR and Osman, M}, title = {Scaling Safe Access to Fecal Microbiota Transplantation: Past, Present, and Future.}, journal = {Current gastroenterology reports}, volume = {20}, number = {4}, pages = {14}, doi = {10.1007/s11894-018-0619-8}, pmid = {29594746}, issn = {1534-312X}, mesh = {Clostridium Infections/therapy ; Donor Selection/methods ; Fecal Microbiota Transplantation/methods/*trends ; Gastrointestinal Microbiome ; Health Services Accessibility/organization & administration/*trends ; Humans ; Tissue Banks/organization & administration/*trends ; }, abstract = {PURPOSE OF REVIEW: Universal stool banks (USBs) have emerged as a potential model for scaling access to fecal microbiota transplantation (FMT) for Clostridium difficile infection (CDI). In this review, we outline the historical barriers constraining access to FMT, the evidence on methods and outcomes of USBs, and potential future directions for expanding access.

RECENT FINDINGS: Key historical barriers to FMT access include regulatory uncertainty, operational complexity of sourcing screened donor material, and logistical challenges of delivering fresh treatment preparations. USBs have demonstrated that FMT can be delivered safely at scale by centralizing donor selection, material processing, and safety monitoring. More evidence is needed to optimize USB methods, including for donor screening, material processing, and novel delivery modalities. USBs have catalyzed broad access to FMT in North America and Europe. Future directions include developing evidence regarding oral preparations, harmonizing guidelines, disseminating best practice protocols, establishing long-term safety profiles, and expanding access to geographic areas of unmet need.}, } @article {pmid29592876, year = {2018}, author = {DeFilipp, Z and Peled, JU and Li, S and Mahabamunuge, J and Dagher, Z and Slingerland, AE and Del Rio, C and Valles, B and Kempner, ME and Smith, M and Brown, J and Dey, BR and El-Jawahri, A and McAfee, SL and Spitzer, TR and Ballen, KK and Sung, AD and Dalton, TE and Messina, JA and Dettmer, K and Liebisch, G and Oefner, P and Taur, Y and Pamer, EG and Holler, E and Mansour, MK and van den Brink, MRM and Hohmann, E and Jenq, RR and Chen, YB}, title = {Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity.}, journal = {Blood advances}, volume = {2}, number = {7}, pages = {745-753}, doi = {10.1182/bloodadvances.2018017731}, pmid = {29592876}, issn = {2473-9537}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; S10 OD018164/OD/NIH HHS/United States ; }, abstract = {We hypothesized that third-party fecal microbiota transplantation (FMT) may restore intestinal microbiome diversity after allogeneic hematopoietic cell transplantation (allo-HCT). In this open-label single-group pilot study, 18 subjects were enrolled before allo-HCT and planned to receive third-party FMT capsules. FMT capsules were administered no later than 4 weeks after neutrophil engraftment, and antibiotics were not allowed within 48 hours before FMT. Five patients did not receive FMT because of the development of early acute gastrointestinal (GI) graft-versus-host disease (GVHD) before FMT (n = 3), persistent HCT-associated GI toxicity (n = 1), or patient decision (n = 1). Thirteen patients received FMT at a median of 27 days (range, 19-45 days) after HCT. Participants were able to swallow and tolerate all FMT capsules, meeting the primary study endpoint of feasibility. FMT was tolerated well, with 1 treatment-related significant adverse event (abdominal pain). Two patients subsequently developed acute GI GVHD, with 1 patient also having concurrent bacteremia. No additional cases of bacteremia occurred. Median follow-up for survivors is 15 months (range, 13-20 months). The Kaplan-Meier estimates for 12-month overall survival and progression-free survival after FMT were 85% (95% confidence interval, 51%-96%) and 85% (95% confidence interval, 51%-96%), respectively. There was 1 nonrelapse death resulting from acute GI GVHD (12-month nonrelapse mortality, 8%; 95% confidence interval, 0%-30%). Analysis of stool composition and urine 3-indoxyl sulfate concentration indicated improvement in intestinal microbiome diversity after FMT that was associated with expansion of stool-donor taxa. These results indicate that empiric third-party FMT after allo-HCT appears to be feasible, safe, and associated with expansion of recipient microbiome diversity. This trial was registered at www.clinicaltrials.gov as #NCT02733744.}, } @article {pmid29581220, year = {2018}, author = {Smits, LP and Kootte, RS and Levin, E and Prodan, A and Fuentes, S and Zoetendal, EG and Wang, Z and Levison, BS and Cleophas, MCP and Kemper, EM and Dallinga-Thie, GM and Groen, AK and Joosten, LAB and Netea, MG and Stroes, ESG and de Vos, WM and Hazen, SL and Nieuwdorp, M}, title = {Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome.}, journal = {Journal of the American Heart Association}, volume = {7}, number = {7}, pages = {}, doi = {10.1161/JAHA.117.008342}, pmid = {29581220}, issn = {2047-9980}, support = {R01 DK106000/DK/NIDDK NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; R01 HL126827/HL/NHLBI NIH HHS/United States ; P20 HL113452/HL/NHLBI NIH HHS/United States ; R01 HL135920/HL/NHLBI NIH HHS/United States ; 250172//European Research Council/International ; 310372//European Research Council/International ; R01 HL130819/HL/NHLBI NIH HHS/United States ; }, abstract = {BACKGROUND: Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge.

METHODS AND RESULTS: We performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d6-choline and d3-carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250 mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18F-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18F-fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells.

CONCLUSIONS: Single lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation.

CLINICAL TRIAL REGISTRATION: URL: http://www.trialregister.nl. Unique identifier: NTR 4338.}, } @article {pmid29577087, year = {2018}, author = {McCormack, UM and Curião, T and Wilkinson, T and Metzler-Zebeli, BU and Reyer, H and Ryan, T and Calderon-Diaz, JA and Crispie, F and Cotter, PD and Creevey, CJ and Gardiner, GE and Lawlor, PG}, title = {Fecal Microbiota Transplantation in Gestating Sows and Neonatal Offspring Alters Lifetime Intestinal Microbiota and Growth in Offspring.}, journal = {mSystems}, volume = {3}, number = {3}, pages = {}, doi = {10.1128/mSystems.00134-17}, pmid = {29577087}, issn = {2379-5077}, abstract = {Previous studies suggest a link between intestinal microbiota and porcine feed efficiency (FE). Therefore, we investigated whether fecal microbiota transplantation (FMT) in sows and/or neonatal offspring, using inocula derived from highly feed-efficient pigs, could improve offspring FE. Pregnant sows were assigned to control or FMT treatments and the subsequent offspring to control treatment, FMT once (at birth), or FMT four times (between birth and weaning). FMT altered sow fecal and colostrum microbiota compositions and resulted in lighter offspring body weight at 70 and 155 days of age when administered to sows and/or offspring. This was accompanied by FMT-associated changes within the offspring's intestinal microbiota, mostly in the ileum. These included transiently higher fecal bacterial diversity and load and numerous compositional differences at the phylum and genus levels (e.g., Spirochaetes and Bacteroidetes at high relative abundances and mostly members of Clostridia, respectively), as well as differences in the abundances of predicted bacterial pathways. In addition, intestinal morphology was negatively impacted, duodenal gene expression altered, and serum protein and cholesterol concentrations reduced due to FMT in sows and/or offspring. Taken together, the results suggest poorer absorptive capacity and intestinal health, most likely explaining the reduced body weight. An additive effect of FMT in sows and offspring also occurred for some parameters. Although these findings have negative implications for the practical use of the FMT regime used here for improving FE in pigs, they nonetheless demonstrate the enormous impact of early-life intestinal microbiota on the host phenotype. IMPORTANCE Here, for the first time, we investigate FMT as a novel strategy to modulate the porcine intestinal microbiota in an attempt to improve FE in pigs. However, reprogramming the maternal and/or offspring microbiome by using fecal transplants derived from highly feed-efficient pigs did not recapitulate the highly efficient phenotype in the offspring and, in fact, had detrimental effects on lifetime growth. Although these findings may not be wholly attributable to microbiota transplantation, as antibiotic and purgative were also part of the regime in sows, similar effects were also seen in offspring, in which these interventions were not used. Nonetheless, additional work is needed to unravel the effects of each component of the FMT regime and to provide additional mechanistic insights. This may lead to the development of an FMT procedure with practical applications for the improvement of FE in pigs, which could in turn improve the profitability of pig production.}, } @article {pmid29566738, year = {2018}, author = {Singh, R and de Groot, PF and Geerlings, SE and Hodiamont, CJ and Belzer, C and Berge, IJMT and de Vos, WM and Bemelman, FJ and Nieuwdorp, M}, title = {Fecal microbiota transplantation against intestinal colonization by extended spectrum beta-lactamase producing Enterobacteriaceae: a proof of principle study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {190}, doi = {10.1186/s13104-018-3293-x}, pmid = {29566738}, issn = {1756-0500}, support = {016.146.327//zonmw vidi/ ; 024.002.002//nwo gravitation grant/ ; }, mesh = {Adult ; Aged ; Enterobacteriaceae/enzymology/*physiology ; Enterobacteriaceae Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Male ; Middle Aged ; Time Factors ; Treatment Outcome ; Young Adult ; beta-Lactamases/*metabolism ; }, abstract = {OBJECTIVE: Infections with multidrug-resistant microorganisms are associated with increased hospitalization, medication costs and mortality. Based on our fecal microbiota transplantation (FMT) experience for Clostridium difficile infection, we treated 15 patients carrying ESBL-producing Enterobacteriaceae (ESBL-EB) with FMT. Seven patients underwent a second FMT after 4 weeks when ESBL-EB remained, amounting to a total number of 22 transplants. The objective was decolonization of ESBL-EB.

RESULTS: Three out of fifteen (20%) patients were ESBL-negative at 1, 2 and 4 weeks after the first transplant, while six out of 15 (40%) were negative after the second transplant. Comparison of fecal microbiota at baseline and 4 weeks after FMT revealed restoration of microbial diversity after FMT and a microbial shift towards donor composition. Finally, we suggest several possible factors of response to therapy, such as donor-recipient microbiota match and number of FMTs. Therefore, FMT can be an effective treatment in patients carrying ESBL-EB. Response may be determined by microbiota composition and number of FMT procedures. Trial registration ISRCTN ISRCTN48328635 Registered 11 October 2017, retrospectively registered.}, } @article {pmid29564854, year = {2018}, author = {Chuang, YT and Hwu, YJ}, title = {[Nursing Care of Older People With Clostridium Difficile Infection].}, journal = {Hu li za zhi The journal of nursing}, volume = {65}, number = {2}, pages = {27-31}, pmid = {29564854}, issn = {0047-262X}, mesh = {Aged ; Clostridium Infections/*nursing ; Fecal Microbiota Transplantation ; Humans ; }, abstract = {The global incidence of Clostridium difficile infection (CDI) has increased in recent decades. The etiology of CDI includes aging as well as the misuse of antibiotics. This highly infectious disease requires that healthcare workers be vigilant and take isolation precautions, particularly in long-term facilities. CDI contributes to the development of severe diarrhea, which may cause imbalance of electrolytes, malabsorption of nutrients, physical disabilities, and psychosocial impacts in older patients. This article explores the pathophysiology, impacts, treatments (e.g., fecal microbiota transplantation [FMT]), and daily care regimens related to CDI with the goal of helping healthcare workers understand this disease and take action during the early stages of CDI.}, } @article {pmid29538686, year = {2018}, author = {Gerding, DN and Kelly, CP and Rahav, G and Lee, C and Dubberke, ER and Kumar, PN and Yacyshyn, B and Kao, D and Eves, K and Ellison, MC and Hanson, ME and Guris, D and Dorr, MB}, title = {Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {67}, number = {5}, pages = {649-656}, doi = {10.1093/cid/ciy171}, pmid = {29538686}, issn = {1537-6591}, abstract = {Background: Bezlotoxumab is a human monoclonal antibody against Clostridium difficile toxin B indicated to prevent C. difficile infection (CDI) recurrence (rCDI) in adults at high risk for rCDI. This post hoc analysis of pooled monocolonal antibodies for C.difficile therapy (MODIFY) I/II data assessed bezlotoxumab efficacy in participants with characteristics associated with increased risk for rCDI.

Methods: The analysis population was the modified intent-to-treat population who received bezlotoxumab or placebo (n = 1554) by risk factors for rCDI that were prespecified in the statistical analysis plan: age ≥65 years, history of CDI, compromised immunity, severe CDI, and ribotype 027/078/244. The proportion of participants with rCDI in 12 weeks, fecal microbiota transplant procedures, 30-day all cause and CDI-associated hospital readmissions, and mortality at 30 and 90 days after randomization were presented.

Results: The majority of enrolled participants (75.6%) had ≥1 risk factor; these participants were older and a higher proportion had comorbidities compared with participants with no risk factors. The proportion of placebo participants who experienced rCDI exceeded 30% for each risk factor compared with 20.9% among those without a risk factor, and the rCDI rate increased with the number of risk factors (1 risk factor: 31.3%; ≥3 risk factors: 46.1%). Bezlotoxumab reduced rCDI, fecal microbiota transplants, and CDI-associated 30-day readmissions in participants with risk factors for rCDI.

Conclusions: The risk factors prespecified in the MODIFY statistical analysis plan are appropriate to identify patients at high risk for rCDI. While participants with ≥3 risk factors had the greatest reduction of rCDI with bezlotoxumab, those with 1 or 2 risk factors may also benefit.

Clinical Trials Registration: NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II).}, } @article {pmid29537705, year = {2018}, author = {Perales-Puchalt, A and Perez-Sanz, J and Payne, KK and Svoronos, N and Allegrezza, MJ and Chaurio, RA and Anadon, C and Calmette, J and Biswas, S and Mine, JA and Costich, TL and Nickels, L and Wickramasinghe, J and Rutkowski, MR and Conejo-Garcia, JR}, title = {Frontline Science: Microbiota reconstitution restores intestinal integrity after cisplatin therapy.}, journal = {Journal of leukocyte biology}, volume = {103}, number = {5}, pages = {799-805}, doi = {10.1002/JLB.5HI1117-446RR}, pmid = {29537705}, issn = {1938-3673}, support = {P30 CA010815/CA/NCI NIH HHS/United States ; T32 CA009140/CA/NCI NIH HHS/United States ; P30 CA076292/CA/NCI NIH HHS/United States ; R01 CA124515/CA/NCI NIH HHS/United States ; T32 CA009171/CA/NCI NIH HHS/United States ; R01 CA157664/CA/NCI NIH HHS/United States ; R01 CA178687/CA/NCI NIH HHS/United States ; }, abstract = {Due to their cytotoxic activities, many anticancer drugs cause extensive damage to the intestinal mucosa and have antibiotic activities. Here, we show that cisplatin induces significant changes in the repertoire of intestinal commensal bacteria that exacerbate mucosal damage. Restoration of the microbiota through fecal-pellet gavage drives healing of cisplatin-induced intestinal damage. Bacterial translocation to the blood stream is correspondingly abrogated, resulting in a significant reduction in systemic inflammation, as evidenced by decreased serum IL-6 and reduced mobilization of granulocytes. Mechanistically, reversal of dysbiosis in response to fecal gavage results in the production of protective mucins and mobilization of CD11b+ myeloid cells to the intestinal mucosa, which promotes angiogenesis. Administration of Ruminococcus gnavus, a bacterial strain selectively depleted by cisplatin treatment, could only partially restore the integrity of the intestinal mucosa and reduce systemic inflammation, without measurable increases in the accumulation of mucin proteins. Together, our results indicate that reconstitution of the full repertoire of intestinal bacteria altered by cisplatin treatment accelerates healing of the intestinal epithelium and ameliorates systemic inflammation. Therefore, fecal microbiota transplant could paradoxically prevent life-threatening bacteremia in cancer patients treated with chemotherapy.}, } @article {pmid29536125, year = {2018}, author = {von Braun, A and Lübbert, C}, title = {[Treatment of acute and recurrent Clostridium difficile infections : What is new?].}, journal = {Der Internist}, volume = {59}, number = {5}, pages = {505-513}, doi = {10.1007/s00108-018-0401-x}, pmid = {29536125}, issn = {1432-1289}, abstract = {The incidence of clostridium difficile infections (CDI) remains on a high level globally. In Germany, the number of severe or even lethal cases continues to increase. The main risk factor for the development of CDI is exposure to broad spectrum antibiotics, which disturb the physiological microbiome and therefore enable colonization with C. difficile. According to the updated US and European guidelines, orally administered vancomycin is the treatment of choice. Fidaxomicin is as effective as vancomycin but has the advantage of a lower rate of recurrence. Furthermore, recent clinical studies were able to demonstrate that significantly fewer recurrences occurred in patients who additionally received the monoclonal antibody bezlotoxumab. In recent years, several new antibiotics with narrow-spectrum acitivity and low intestinal resorption have been developed for the treatment of CDI, including surotomycin, cadazolid, and ridinilazol. Novel toxoid vaccines are expected to become an efficacious tool in the prevention of CDI; however, pivotal clinical trials have so far not been completed.}, } @article {pmid29535482, year = {2017}, author = {Diamond, C and McNeilly, T}, title = {Faecal Microbiota Transplantation for Clostridium Difficile - a local perspective.}, journal = {The Ulster medical journal}, volume = {86}, number = {2}, pages = {108-110}, pmid = {29535482}, issn = {0041-6193}, mesh = {Aged ; Anti-Bacterial Agents/therapeutic use ; Catheter-Related Infections/microbiology/physiopathology/*therapy ; Clostridium Infections/diagnosis/*therapy ; Clostridium difficile/*pathogenicity ; Fecal Microbiota Transplantation/*methods ; Female ; Follow-Up Studies ; Humans ; Northern Ireland ; Recurrence ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome ; Urinary Catheterization/*adverse effects/methods ; }, abstract = {Clostridium Difficile represents one of the major challenges of the antimicrobial era with associated significant morbidity. Treatment options are limited to a number of specific antibiotics with significant failure rates. Faecal Microbiota Transplantation has been recognised as a possible treatment option when standard therapy fails. We report a local case of Clostridium Difficile Infection ultimately requiring Faecal Microbiota Transplantation with good success. While no formal service providing the treatment is available within Northern Ireland it is a feasible treatment option for Clostridium Difficile Infection.}, } @article {pmid29534703, year = {2018}, author = {Long, C and Yu, Y and Cui, B and Jagessar, SAR and Zhang, J and Ji, G and Huang, G and Zhang, F}, title = {A novel quick transendoscopic enteral tubing in mid-gut: technique and training with video.}, journal = {BMC gastroenterology}, volume = {18}, number = {1}, pages = {37}, doi = {10.1186/s12876-018-0766-2}, pmid = {29534703}, issn = {1471-230X}, support = {81670495//National Natural Science Foundation of China (CN)/ ; 81600417//National Natural Science Foundation of China (CN)/ ; 2015BAI13B07//National Clinical Research Center for Digestive Diseases, Xi'an, China/ ; }, mesh = {Adult ; Endoscopy, Gastrointestinal/adverse effects/*methods ; Enteral Nutrition/methods ; Feasibility Studies ; Fecal Microbiota Transplantation/methods ; Female ; Humans ; Intubation, Gastrointestinal/adverse effects/*methods ; Male ; Patient Satisfaction ; Prospective Studies ; Surgical Instruments ; }, abstract = {BACKGROUND: This study aimed to evaluate the feasibility, safety, and value of a quick technique for transendoscopic enteral tubing (TET) through mid-gut.

METHODS: A prospective interventional study was performed in a single center. A TET tube was inserted into mid-gut through the nasal orifice and fixed on the pylorus wall by one tiny titanium endoscopic clip under anesthesia. The feasibility, safety, success rate, and satisfaction with TET placement were evaluated for enteral nutrition or fecal microbiota transplantation.

RESULTS: A total of 86 patients underwent mid-gut TET. The success rate of the TET procedure was 98.8% (85/86). Mean tubing time of the TET procedure was 4.2 ± 1.9 min. 10 cases of procedure was enough for training of general endoscopist to shorten the procedure time (7.0 min vs 4.0 min, p < 0.05). 97.7% (84/86) of patients were satisfied with the TET placement. Procedure-related and tube-related adverse events were observed in 8.1% (7/86) and 7.0% (6/86) of patients respectively. There were no moderate to severe adverse events during tube extubation.

CONCLUSIONS: TET through mid-gut is a novel, convenient, reliable and safe procedure for mid-gut administration with a high degree of patient satisfaction.

TRIAL REGISTRATION: This research was retrospectively registered with clinicaltrials.gov. Trial registration date: 29th November 2017.

TRIAL REGISTRATION NUMBER: NCT03335982 .}, } @article {pmid29533199, year = {2018}, author = {Walker, MM and Potter, M and Talley, NJ}, title = {Eosinophilic gastroenteritis and other eosinophilic gut diseases distal to the oesophagus.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {3}, number = {4}, pages = {271-280}, doi = {10.1016/S2468-1253(18)30005-0}, pmid = {29533199}, issn = {2468-1253}, mesh = {Adrenal Cortex Hormones/therapeutic use ; Diagnosis, Differential ; Diet Therapy ; *Enteritis/classification/diagnosis/etiology/therapy ; *Eosinophilia/classification/diagnosis/etiology/therapy ; Fecal Microbiota Transplantation ; *Gastritis/classification/diagnosis/etiology/therapy ; Gastrointestinal Agents/therapeutic use ; Humans ; }, abstract = {Under normal physiological conditions, eosinophils are present throughout the gastrointestinal tract distal to the squamous oesophagus. Increases in their numbers signify primary and secondary eosinophilic conditions. The rare primary eosinophilic diseases eosinophilic gastroenteritis and eosinophilic colitis affect fewer than ten in 100 000 people, and are characterised by numerous mucosal eosinophils, distributed in sheets and sometimes extending from the mucosa into the submucosa. Pathogenesis of these diseases is poorly understood, but food allergies and intestinal dysbiosis have been implicated. Presentation ranges from vague abdominal symptoms and systemic complaints to, rarely, an acute abdomen with intestinal obstruction. Diagnosis is made from mucosal biopsy samples taken at endoscopy or from surgically resected specimens that demonstrate substantially increased numbers of eosinophils. Eosinophilia secondary to other conditions, such as pathogenic infections, must be excluded. Subtle eosinophilia has also been identified in the duodenum in functional dyspepsia and in the colon in spirochaetosis. Treatment of eosinophilic gastroenteritis and eosinophilic colitis is based on evidence from case reports and small case series, and first-line therapy includes empirical food-elimination diets and single courses of steroids, whereas relapsing or refractory disease might respond to steroid-sparing immunosuppressive agents and biological agents. The progression of disease in eosinophilic gastroenteritis and eosinophilic colitis is variable: a considerable number of patients have just one episode without relapse, whereas others have relapsing-remitting or chronic disease. Primary and secondary eosinophilia in the gastrointestinal tract is increasingly recognised as a clinical conundrum waiting to be solved.}, } @article {pmid29521664, year = {2018}, author = {Goyal, H and Perisetti, A and Rehman, MR and Singla, U}, title = {New and emerging therapies in treatment of Clostridium difficile infection.}, journal = {European journal of gastroenterology & hepatology}, volume = {30}, number = {6}, pages = {589-597}, doi = {10.1097/MEG.0000000000001103}, pmid = {29521664}, issn = {1473-5687}, mesh = {Anti-Bacterial Agents/adverse effects/*therapeutic use ; Clostridium Infections/diagnosis/microbiology/*therapy ; Clostridium difficile/*drug effects/pathogenicity ; Cross Infection/diagnosis/microbiology/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Humans ; Metronidazole/adverse effects/*therapeutic use ; Recurrence ; Severity of Illness Index ; Treatment Outcome ; Vancomycin/adverse effects/*therapeutic use ; Vancomycin Resistance ; }, abstract = {Clostridium difficile infection (CDI) represents one of the most serious nosocomial infections that have grown dramatically over the past decade. Vancomycin and metronidazole are currently used as a standard therapy for CDI. Metronidazole is recommended as a first-line therapy for mild-to-moderate infections and vancomycin is mainly used for severe and/or refractory cases. However, studies have demonstrated that there are quite high CDI relapse rates with both of these medications, which represents a challenge for clinicians. Over the last decade, a number of newer and novel therapeutic options have emerged as promising alternatives to these standard CDI therapies. The following review provides the updated summaries of these newer therapeutic agents and their status in the treatment of CDI.}, } @article {pmid29507020, year = {2018}, author = {Digby-Bell, J and Williams, A and Irving, P and Goldenberg, S}, title = {Successful faecal microbiota transplant for recurrent Clostridium difficile infection delivered by colonoscopy through a diverted ileostomy in a patient with severe perianal Crohn's disease.}, journal = {BMJ case reports}, volume = {2018}, number = {}, pages = {}, doi = {10.1136/bcr-2017-222958}, pmid = {29507020}, issn = {1757-790X}, mesh = {Adult ; Clostridium Infections/complications/*therapy ; Colonoscopes ; Colonoscopy/*methods ; Crohn Disease/complications ; Fecal Microbiota Transplantation/instrumentation/*methods ; Female ; Humans ; *Ileostomy ; Treatment Outcome ; }, abstract = {We present the first reported case of successful treatment of recurrent Clostridium difficile infection with faecal microbiota transplantation delivered antegrade with a colonoscope through a diverting ileostomy.}, } @article {pmid29498019, year = {2018}, author = {Rodiño-Janeiro, BK and Vicario, M and Alonso-Cotoner, C and Pascua-García, R and Santos, J}, title = {A Review of Microbiota and Irritable Bowel Syndrome: Future in Therapies.}, journal = {Advances in therapy}, volume = {35}, number = {3}, pages = {289-310}, doi = {10.1007/s12325-018-0673-5}, pmid = {29498019}, issn = {1865-8652}, abstract = {Irritable bowel syndrome (IBS), one of the most frequent digestive disorders, is characterized by chronic and recurrent abdominal pain and altered bowel habit. The origin seems to be multifactorial and is still not well defined for the different subtypes. Genetic, epigenetic and sex-related modifications of the functioning of the nervous and immune-endocrine supersystems and regulation of brain-gut physiology and bile acid production and absorption are certainly involved. Acquired predisposition may act in conjunction with infectious, toxic, dietary and life event-related factors to enhance epithelial permeability and elicit mucosal microinflammation, immune activation and dysbiosis. Notably, strong evidence supports the role of bacterial, viral and parasitic infections in triggering IBS, and targeting microbiota seems promising in view of the positive response to microbiota-related therapies in some patients. However, the lack of highly predictive diagnostic biomarkers and the complexity and heterogeneity of IBS patients make management difficult and unsatisfactory in many cases, reducing patient health-related quality of life and increasing the sanitary burden. This article reviews specific alterations and interventions targeting the gut microbiota in IBS, including prebiotics, probiotics, synbiotics, non-absorbable antibiotics, diets, fecal transplantation and other potential future approaches useful for the diagnosis, prevention and treatment of IBS.}, } @article {pmid29497269, year = {2017}, author = {Nascimento, MM}, title = {Oral microbiota transplant: a potential new therapy for oral diseases.}, journal = {Journal of the California Dental Association}, volume = {45}, number = {10}, pages = {565-568}, pmid = {29497269}, issn = {1043-2256}, support = {K23 DE023579/DE/NIDCR NIH HHS/United States ; }, mesh = {Dental Caries ; Dental Plaque ; Humans ; *Microbiota ; Mouth/*microbiology ; Mouth Diseases/*therapy ; Periodontitis ; }, abstract = {Dental caries and periodontitis are amongst the most common diseases affecting humans worldwide. There is an evolving trend for dental and medical research to share knowledge on the etiology and promising therapies for human diseases. Inspired by the success of fecal microbiota transplant to manage gastro-intestinal disordes, oral microbiome transplant has been proposed but not yet tested in humans. This article critically reviews the potential of oral microbiome transplant for managing oral diseases.}, } @article {pmid29493330, year = {2018}, author = {El-Salhy, M and Mazzawi, T}, title = {Fecal microbiota transplantation for managing irritable bowel syndrome.}, journal = {Expert review of gastroenterology & hepatology}, volume = {12}, number = {5}, pages = {439-445}, doi = {10.1080/17474124.2018.1447380}, pmid = {29493330}, issn = {1747-4132}, mesh = {Dysbiosis ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Irritable Bowel Syndrome/diagnosis/microbiology/*therapy ; Treatment Outcome ; }, abstract = {INTRODUCTION: Irritable bowel syndrome (IBS) is a widespread gastrointestinal disorder affecting 11.2% of the world adult population. The intestinal microbiome is thought to play a pivotal role in the pathophysiology of IBS. The composition of the fecal microbiome in IBS patients differs from that in healthy individuals, but the exact bacteria species involved in the development of IBS remain to be determined. There is also an imbalance between useful and harmful bacteria (dysbiosis) in the intestinal microbiome in patients with IBS. Consuming prebiotics, probiotics, or synbiotics has a limited effect on IBS symptoms. In contrast, fecal microbiome transplantation (FMT) in IBS patients reverses the dysbiosis to normobiosis and reduces the IBS symptoms in about 70% of patients, and is not associated with any serious adverse events. Area covered: The available data on the microbiome and FMT in IBS regarding the efficacy of FMT in managing IBS were found using a PubMed search of these topics. Expert commentary: FMT is a promising tool for managing irritable syndrome. It appears to be effective, easy, and inexpensive procedure. However, more controlled studies involving larger cohorts of IBS are needed before FMT can be used as a routine procedure in the clinic.}, } @article {pmid29492875, year = {2018}, author = {Cho, JA and Chinnapen, DJF}, title = {Targeting friend and foe: Emerging therapeutics in the age of gut microbiome and disease.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {56}, number = {3}, pages = {183-188}, doi = {10.1007/s12275-018-8037-z}, pmid = {29492875}, issn = {1976-3794}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Dysbiosis/microbiology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Diseases/etiology/*therapy ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*drug effects/microbiology/physiopathology ; Humans ; Hypersensitivity/etiology/therapy ; Inflammatory Bowel Diseases/etiology/therapy ; Neoplasms/therapy ; Obesity/etiology/therapy ; Probiotics/*therapeutic use ; Symbiosis ; }, abstract = {Mucosal surfaces that line our gastrointestinal tract are continuously exposed to trillions of bacteria that form a symbiotic relationship and impact host health and disease. It is only beginning to be understood that the cross-talk between the host and microbiome involve dynamic changes in commensal bacterial population, secretion, and absorption of metabolites between the host and microbiome. As emerging evidence implicates dysbiosis of gut microbiota in the pathology and progression of various diseases such as inflammatory bowel disease, obesity, and allergy, conventional treatments that either overlook the microbiome in the mechanism of action, or eliminate vast populations of microbes via wide-spectrum antibiotics need to be reconsidered. It is also becoming clear the microbiome can influence the body's response to therapeutic treatments for cancers. As such, targeting the microbiome as treatment has garnered much recent attention and excitement from numerous research labs and biotechnology companies. Treatments range from fecal microbial transplantation to precision-guided molecular approaches. Here, we survey recent progress in the development of innovative therapeutics that target the microbiome to treat disease, and highlight key findings in the interplay between host microbes and therapy.}, } @article {pmid29486930, year = {2018}, author = {The Lancet, }, title = {A new approach to treating infection.}, journal = {Lancet (London, England)}, volume = {391}, number = {10122}, pages = {714}, doi = {10.1016/S0140-6736(18)30320-9}, pmid = {29486930}, issn = {1474-547X}, mesh = {Clostridium Infections/diagnosis/*therapy ; *Clostridium difficile ; Cross Infection/diagnosis/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Infection Control ; }, } @article {pmid29471034, year = {2018}, author = {Andermann, TM and Peled, JU and Ho, C and Reddy, P and Riches, M and Storb, R and Teshima, T and van den Brink, MRM and Alousi, A and Balderman, S and Chiusolo, P and Clark, WB and Holler, E and Howard, A and Kean, LS and Koh, AY and McCarthy, PL and McCarty, JM and Mohty, M and Nakamura, R and Rezvani, K and Segal, BH and Shaw, BE and Shpall, EJ and Sung, AD and Weber, D and Whangbo, J and Wingard, JR and Wood, WA and Perales, MA and Jenq, RR and Bhatt, AS and , }, title = {The Microbiome and Hematopoietic Cell Transplantation: Past, Present, and Future.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {24}, number = {7}, pages = {1322-1340}, doi = {10.1016/j.bbmt.2018.02.009}, pmid = {29471034}, issn = {1523-6536}, support = {U10 HL069294/HL/NHLBI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; UG1 HL069301/HL/NHLBI NIH HHS/United States ; K08 CA184420/CA/NCI NIH HHS/United States ; U24 HL138660/HL/NHLBI NIH HHS/United States ; UG1 HL069315/HL/NHLBI NIH HHS/United States ; }, } @article {pmid29471030, year = {2018}, author = {Sun, MF and Zhu, YL and Zhou, ZL and Jia, XB and Xu, YD and Yang, Q and Cui, C and Shen, YQ}, title = {Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson's disease mice: Gut microbiota, glial reaction and TLR4/TNF-α signaling pathway.}, journal = {Brain, behavior, and immunity}, volume = {70}, number = {}, pages = {48-60}, doi = {10.1016/j.bbi.2018.02.005}, pmid = {29471030}, issn = {1090-2139}, abstract = {Parkinson's disease (PD) patients display alterations in gut microbiota composition. However, mechanism between gut microbial dysbiosis and pathogenesis of PD remains unexplored, and no recognized therapies are available to halt or slow progression of PD. Here we identified that gut microbiota from PD mice induced motor impairment and striatal neurotransmitter decrease on normal mice. Sequencing of 16S rRNA revealed that phylum Firmicutes and order Clostridiales decreased, while phylum Proteobacteria, order Turicibacterales and Enterobacteriales increased in fecal samples of PD mice, along with increased fecal short-chain fatty acids (SCFAs). Remarkably, fecal microbiota transplantation (FMT) reduced gut microbial dysbiosis, decreased fecal SCFAs, alleviated physical impairment, and increased striatal DA and 5-HT content of PD mice. Further, FMT reduced the activation of microglia and astrocytes in the substantia nigra, and reduced expression of TLR4/TNF-α signaling pathway components in gut and brain. Our study demonstrates that gut microbial dysbiosis is involved in PD pathogenesis, and FMT can protect PD mice by suppressing neuroinflammation and reducing TLR4/TNF-α signaling.}, } @article {pmid29470297, year = {2018}, author = {Barnes, D and Ng, K and Smits, S and Sonnenburg, J and Kassam, Z and Park, KT}, title = {Competitively Selected Donor Fecal Microbiota Transplantation: Butyrate Concentration and Diversity as Measures of Donor Quality.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {67}, number = {2}, pages = {185-187}, doi = {10.1097/MPG.0000000000001940}, pmid = {29470297}, issn = {1536-4801}, abstract = {In this prospective cohort study, we examine the feasibility of a protocol to optimize microbiota for fecal microbiota transplantation (FMT). Donor stool metrics generally accepted as markers of gut health were used to select a stool donor based on superior microbial diversity, balanced constitution of Bacteroidetes versus Firmicutes and high concentration of fecal butyrate. Selected donor microbiota was then administered via FMT. A total of 10 patients with median age of 12 years with recurrent Clostridium difficile infection received the intervention. The rate of recurrence-free resolution with 1-2 FMTs was 100% at Week 10. With a single FMT, 80% of patients cleared Clostridium difficile infection without recurrence, whereas 20% of patients required a single re-treatment. No serious adverse events occurred. Microbiota sequencing revealed that recipients' gut microbiota phylogenic diversity increased by 72-hours post-transplantation, with sustainment over 10-week follow-up. This study highlights the feasibility of purposefully selecting the most ideal microbiota for transplantation.}, } @article {pmid29467322, year = {2018}, author = {Uribe-Herranz, M and Bittinger, K and Rafail, S and Guedan, S and Pierini, S and Tanes, C and Ganetsky, A and Morgan, MA and Gill, S and Tanyi, JL and Bushman, FD and June, CH and Facciabene, A}, title = {Gut microbiota modulates adoptive cell therapy via CD8α dendritic cells and IL-12.}, journal = {JCI insight}, volume = {3}, number = {4}, pages = {}, doi = {10.1172/jci.insight.94952}, pmid = {29467322}, issn = {2379-3708}, support = {P30 DK050306/DK/NIDDK NIH HHS/United States ; }, abstract = {Adoptive T cell therapy (ACT) is a promising new modality for malignancies. Here, we report that adoptive T cell efficacy in tumor-bearing mice is significantly affected by differences in the native composition of the gut microbiome or treatment with antibiotics, or by heterologous fecal transfer. Depletion of bacteria with vancomycin decreased the rate of tumor growth in mice from The Jackson Laboratory receiving ACT, whereas treatment with neomycin and metronidazole had no effect, indicating the role of specific bacteria in host response. Vancomycin treatment induced an increase in systemic CD8α+ DCs, which sustained systemic adoptively transferred antitumor T cells in an IL-12-dependent manner. In subjects undergoing allogeneic hematopoietic cell transplantation, we found that oral vancomycin also increased IL-12 levels. Collectively, our findings demonstrate an important role played by the gut microbiota in the antitumor effectiveness of ACT and suggest potentially new avenues to improve response to ACT by altering the gut microbiota.}, } @article {pmid29463339, year = {2018}, author = {Le, P and Nghiem, VT and Mullen, PD and Deshpande, A}, title = {Cost-Effectiveness of Competing Treatment Strategies for Clostridium difficile Infection: A Systematic Review.}, journal = {Infection control and hospital epidemiology}, volume = {39}, number = {4}, pages = {412-424}, doi = {10.1017/ice.2017.303}, pmid = {29463339}, issn = {1559-6834}, support = {K08 HS025026/HS/AHRQ HHS/United States ; R25 CA057712/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND Clostridium difficile infection (CDI) presents a substantial economic burden and is associated with significant morbidity. While multiple treatment strategies have been evaluated, a cost-effective management strategy remains unclear. OBJECTIVE We conducted a systematic review to assess cost-effectiveness analyses of CDI treatment and to summarize key issues for clinicians and policy makers to consider. METHODS We searched PubMed and 5 other databases from inception to August 2016. These searches were not limited by study design or language of publication. Two reviewers independently screened the literature, abstracted data, and assessed methodological quality using the Drummond and Jefferson checklist. We extracted data on study characteristics, type of CDI, treatment characteristics, and model structure and inputs. RESULTS We included 14 studies, and 13 of these were from high-income countries. More than 90% of these studies were deemed moderate-to-high or high quality. Overall, 6 studies used a decision-tree model and 7 studies used a Markov model. Cost of therapy, time horizon, treatment cure rates, and recurrence rates were common influential factors in the study results. For initial CDI, fidaxomicin was a more cost-effective therapy than metronidazole or vancomycin in 2 of 3 studies. For severe initial CDI, 2 of 3 studies found fidaxomicin to be the most cost-effective therapy. For recurrent CDI, fidaxomicin was cost-effective in 3 of 5 studies, while fecal microbiota transplantation (FMT) by colonoscopy was consistently cost-effective in 4 of 4 studies. CONCLUSIONS The cost-effectiveness of fidaxomicin compared with other pharmacologic therapies was not definitive for either initial or recurrent CDI. Despite its high cost, FMT by colonoscopy may be a cost-effective therapy for recurrent CDI. A consensus on model design and assumptions are necessary for future comparison of CDI treatment. Infect Control Hosp Epidemiol 2018;39:412-424.}, } @article {pmid29463185, year = {2018}, author = {Bruno, G and Colangelo, L and Badiali, D and Minisola, S and Corazziari, ES and Gianni, W}, title = {Concomitant resolution through fecal microbiota transplantation of Clostridium difficile and OXA-48-producing Klebsiella pneumoniae.}, journal = {Infectious diseases (London, England)}, volume = {50}, number = {7}, pages = {565-566}, doi = {10.1080/23744235.2018.1442019}, pmid = {29463185}, issn = {2374-4243}, mesh = {Clostridium Infections ; *Clostridium difficile ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Klebsiella pneumoniae ; Recurrence ; }, } @article {pmid29460302, year = {2018}, author = {Pereira, GQ and Gomes, LA and Santos, IS and Alfieri, AF and Weese, JS and Costa, MC}, title = {Fecal microbiota transplantation in puppies with canine parvovirus infection.}, journal = {Journal of veterinary internal medicine}, volume = {32}, number = {2}, pages = {707-711}, doi = {10.1111/jvim.15072}, pmid = {29460302}, issn = {1939-1676}, mesh = {Animals ; Diarrhea/therapy/*veterinary ; Dog Diseases/*therapy/virology ; Dogs ; Fecal Microbiota Transplantation/*veterinary ; Gastrointestinal Hemorrhage/therapy/veterinary ; Parvoviridae Infections/microbiology/therapy/*veterinary ; Parvovirus, Canine/classification ; Treatment Outcome ; }, abstract = {BACKGROUND: Diarrhea associated with parvovirus infection is common in dogs. Supportive care is the mainstay of treatment, but recovery may be prolonged and mortality rate can be high. Modification of the intestinal bacterial microbiota has been promising in human and veterinary medicine as an adjunctive treatment of various enteric diseases.

OBJECTIVES: To investigate the safety and efficacy of fecal microbiota transplantation (FMT) on the clinical recovery of puppies with acute hemorrhagic diarrhea syndrome.

ANIMALS: Sixty-six puppies with parvovirus infection were evaluated at 2 veterinary hospitals.

METHODS: Randomized clinical trial. Puppies were randomly distributed into 2 groups: standard treatment (STD) and standard treatment + FMT (STD + FMT). The STD puppies (n = 33) received only treatment with IV fluids and antimicrobials and the STD + FMT puppies (n = 33) received FMT in addition to standard treatment. For FMT, 10 g of feces from a healthy dog diluted in 10 mL of saline were administered rectally 6-12 hours post-admission.

RESULTS: Among survivors, treatment with FMT was associated with faster resolution of diarrhea (P < .001) and shorter hospitalization time (P = .001; median, 3 days in STD + FMT; median, 6 days in STD) compared to standard treatment. Mortality in STD was 36.4% (12/33) as compared to 21.2% (7/33) in puppies treated with FMT, but there was no statistical difference between groups (P = .174). Polymerase chain reaction indicated that all animals carried canine parvovirus, strain CPV-2b.

CONCLUSIONS: Fecal microbiota transplantation in parvovirus-infected puppies was associated with faster resolution of diarrhea.}, } @article {pmid29454797, year = {2018}, author = {Tedesco, D and Thapa, M and Chin, CY and Ge, Y and Gong, M and Li, J and Gumber, S and Speck, P and Elrod, EJ and Burd, EM and Kitchens, WH and Magliocca, JF and Adams, AB and Weiss, DS and Mohamadzadeh, M and Grakoui, A}, title = {Alterations in Intestinal Microbiota Lead to Production of Interleukin 17 by Intrahepatic γδ T-Cell Receptor-Positive Cells and Pathogenesis of Cholestatic Liver Disease.}, journal = {Gastroenterology}, volume = {154}, number = {8}, pages = {2178-2193}, doi = {10.1053/j.gastro.2018.02.019}, pmid = {29454797}, issn = {1528-0012}, support = {P30 AI050409/AI/NIAID NIH HHS/United States ; R01 AI136533/AI/NIAID NIH HHS/United States ; P51 OD011132/OD/NIH HHS/United States ; P51 RR000165/RR/NCRR NIH HHS/United States ; R01 AI070101/AI/NIAID NIH HHS/United States ; K01 DK109025/DK/NIDDK NIH HHS/United States ; R01 AI126890/AI/NIAID NIH HHS/United States ; R01 AI124680/AI/NIAID NIH HHS/United States ; }, mesh = {ATP Binding Cassette Transporter, Sub-Family B/genetics ; Adult ; Aged ; Animals ; Bile Ducts/cytology/immunology/microbiology ; Cells, Cultured ; Cholangitis, Sclerosing/microbiology/pathology/surgery ; Cholestasis/immunology/microbiology/*pathology/surgery ; Disease Models, Animal ; End Stage Liver Disease/microbiology/pathology/surgery ; Female ; *Gastrointestinal Microbiome ; Hepatitis C, Chronic/pathology/surgery/virology ; Humans ; Interleukin-17/antagonists & inhibitors/blood/immunology/*metabolism ; Intraepithelial Lymphocytes/*metabolism ; Lactobacillus gasseri/immunology ; Liver/cytology/immunology/microbiology/pathology ; Liver Cirrhosis/immunology/microbiology/*pathology/surgery ; Liver Transplantation ; Male ; Mice ; Mice, Knockout ; Middle Aged ; Receptors, Antigen, T-Cell, gamma-delta/antagonists & inhibitors/metabolism ; Young Adult ; }, abstract = {BACKGROUND & AIMS: Variants at the ABCB4 or MDR2 locus, which encodes a biliary transport protein, are associated with a spectrum of cholestatic liver diseases. Exacerbation of liver disease has been linked to increased hepatic levels of interleukin (IL) 17, yet the mechanisms of this increase are not understood. We studied mice with disruption of Mdr2 to determine how defects in liver and alteration in the microbiota contribute to production of IL17 by intrahepatic γδ T cells.

METHODS: We performed studies with Mdr2-/- and littermate FVB/NJ (control) mice. IL17 was measured in serum samples by an enzyme-linked immunosorbent assay. Mice were injected with neutralizing antibodies against the γδ T-cell receptor (TCR; anti-γδ TCR) or mouse IL17A (anti-IL17A). Livers were collected and bacteria were identified in homogenates by culture procedures; TCRγδ+ cells were isolated by flow cytometry. Fecal samples were collected from mice and analyzed by 16S ribosomal DNA sequencing. Cells were stimulated with antibodies or bacteria, and cytokine production was measured. We obtained tissues from 10 patients undergoing liver transplantation for primary sclerosing cholangitis or chronic hepatitis C virus infection. Tissues were analyzed for cytokine production by γδ TCR+ cells.

RESULTS: Mdr2-/- mice had collagen deposition around hepatic bile ducts and periportal-bridging fibrosis with influx of inflammatory cells and increased serum levels of IL17 compared with control mice. Administration of anti-IL17A reduced hepatic fibrosis. Livers from Mdr2-/- mice had increased numbers of IL17A+ γδTCR+ cells-particularly of IL17A+ Vγ6Jγ1 γδ TCR+ cells. Fecal samples from Mdr2-/- mice were enriched in Lactobacillus, and liver tissues were enriched in Lactobacillus gasseri compared with control mice. Mdr2-/- mice also had increased intestinal permeability. The γδ TCR+ cells isolated from Mdr2-/- livers produced IL17 in response to heat-killed L gasseri. Intraperitoneal injection of control mice with L gasseri led to increased serum levels of IL17 and liver infiltration by inflammatory cells; injection of these mice with anti-γδ TCR reduced serum level of IL17. Intravenous injections of Mdr2-/- mice with anti-γδ TCR reduced fibrosis; liver levels of IL17, and inflammatory cells; and serum levels of IL17. γδTCR+ cells isolated from livers of patients with primary sclerosing cholangitis, but not hepatitis C virus infection, produced IL17.

CONCLUSIONS: In Mdr2-/- mice, we found development of liver fibrosis and inflammation to require hepatic activation of γδ TCR+ cells and production of IL17 mediated by exposure to L gasseri. This pathway appears to contribute to development of cholestatic liver disease in patients.}, } @article {pmid29451873, year = {2018}, author = {Jones, EW and Carlson, JM}, title = {In silico analysis of antibiotic-induced Clostridium difficile infection: Remediation techniques and biological adaptations.}, journal = {PLoS computational biology}, volume = {14}, number = {2}, pages = {e1006001}, doi = {10.1371/journal.pcbi.1006001}, pmid = {29451873}, issn = {1553-7358}, mesh = {Adaptation, Biological ; Animals ; Anti-Bacterial Agents/*therapeutic use ; Clostridium Infections/*physiopathology ; *Clostridium difficile ; Computer Simulation ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces ; Gastrointestinal Microbiome ; Humans ; Mice ; Models, Theoretical ; Mutation ; Spores, Bacterial ; }, abstract = {In this paper we study antibiotic-induced C. difficile infection (CDI), caused by the toxin-producing C. difficile (CD), and implement clinically-inspired simulated treatments in a computational framework that synthesizes a generalized Lotka-Volterra (gLV) model with SIR modeling techniques. The gLV model uses parameters derived from an experimental mouse model, in which the mice are administered antibiotics and subsequently dosed with CD. We numerically identify which of the experimentally measured initial conditions are vulnerable to CD colonization, then formalize the notion of CD susceptibility analytically. We simulate fecal transplantation, a clinically successful treatment for CDI, and discover that both the transplant timing and transplant donor are relevant to the the efficacy of the treatment, a result which has clinical implications. We incorporate two nongeneric yet dangerous attributes of CD into the gLV model, sporulation and antibiotic-resistant mutation, and for each identify relevant SIR techniques that describe the desired attribute. Finally, we rely on the results of our framework to analyze an experimental study of fecal transplants in mice, and are able to explain observed experimental results, validate our simulated results, and suggest model-motivated experiments.}, } @article {pmid29450831, year = {2018}, author = {Goldenberg, SD and Batra, R and Beales, I and Digby-Bell, JL and Irving, PM and Kellingray, L and Narbad, A and Franslem-Elumogo, N}, title = {Comparison of Different Strategies for Providing Fecal Microbiota Transplantation to Treat Patients with Recurrent Clostridium difficile Infection in Two English Hospitals: A Review.}, journal = {Infectious diseases and therapy}, volume = {7}, number = {1}, pages = {71-86}, doi = {10.1007/s40121-018-0189-y}, pmid = {29450831}, issn = {2193-8229}, abstract = {Fecal microbiota transplant (FMT) has emerged as a highly efficacious treatment for difficult cases of refractory and/or recurrent Clostridium difficile infection (CDI). There have been many well-conducted randomized controlled trials and thousands of patients reported in case series that describe success rates of approximately 90% following one or more FMT. Although the exact mechanisms of FMT have yet to be fully elucidated, replacement or restoration of a 'normal' microbiota (or at least a microbiota resembling those who have never had CDI) appears to have a positive effect on the gut dysbiosis that is thought to exist in these patients. Furthermore, despite being aesthetically unappealing, this 'ultimate probiotic' is a particularly attractive solution to a difficult problem that avoids repeated courses of antibiotics. The lack of clarity about the exact mechanism of action and the 'active ingredient' of FMT (e.g., individual or communities of bacteria, bacteriophage, or bioactive molecules such as bile acids) has hindered the ability to produce a standardized and well-characterized FMT product. There is no standard method to produce material for FMT, and there are a multitude of factors that can vary between institutions that offer this therapy. Only a few studies have directly compared clinical efficacy in groups of patients who have been treated with FMT prepared differently (e.g., fresh vs. frozen) or administered by different route (e.g., by nasojejunal tube, colonoscopy or by oral administration of encapsulated product). More of these studies should be undertaken to clarify the superiority or otherwise of these variables. This review describes the methods and protocols that two English NHS hospitals independently adopted over the same time period to provide FMT for patients with recurrent CDI. There are several fundamental differences in the methods used, including selection and testing of donors, procedures for preparation and storage of material, and route of administration. These methods are described in detail in this review highlighting differing practice. Despite these significant methodological variations, clinical outcomes in terms of cure rate appear to be remarkably similar for both FMT providers. Although both hospitals have treated only modest numbers of patients, these findings suggest that many of the described differences may not be critical factors in influencing the success of the procedure. As FMT is increasingly being proposed for a number of conditions other than CDI, harmonization of methods and techniques may be more critical to the success of FMT, and thus it will be important to standardize these as far as practically possible.}, } @article {pmid29450212, year = {2018}, author = {Wang, T and Kraft, CS and Woodworth, MH and Dhere, T and Eaton, ME}, title = {Fecal Microbiota Transplant for Refractory Clostridium difficile Infection Interrupts 25-Year History of Recurrent Urinary Tract Infections.}, journal = {Open forum infectious diseases}, volume = {5}, number = {2}, pages = {ofy016}, doi = {10.1093/ofid/ofy016}, pmid = {29450212}, issn = {2328-8957}, support = {UL1 TR002378/TR/NCATS NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; }, } @article {pmid29449093, year = {2018}, author = {Martínez-Ayala, P and González-Hernández, LA and Amador-Lara, F and Andrade-Villanueva, J and Ramos-Solano, M}, title = {Fecal microbiota transplantation for severe complicated C. difficile colitis in a patient with acquired immunodeficiency syndrome.}, journal = {Revista de gastroenterologia de Mexico}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.rgmx.2017.12.002}, pmid = {29449093}, issn = {0375-0906}, } @article {pmid29447696, year = {2018}, author = {Smillie, CS and Sauk, J and Gevers, D and Friedman, J and Sung, J and Youngster, I and Hohmann, EL and Staley, C and Khoruts, A and Sadowsky, MJ and Allegretti, JR and Smith, MB and Xavier, RJ and Alm, EJ}, title = {Strain Tracking Reveals the Determinants of Bacterial Engraftment in the Human Gut Following Fecal Microbiota Transplantation.}, journal = {Cell host & microbe}, volume = {23}, number = {2}, pages = {229-240.e5}, doi = {10.1016/j.chom.2018.01.003}, pmid = {29447696}, issn = {1934-6069}, mesh = {Biodiversity ; Clostridium Infections/*prevention & control/therapy ; Clostridium difficile/*growth & development ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Humans ; Models, Biological ; Recurrence ; Secondary Prevention/*methods ; }, abstract = {Fecal microbiota transplantation (FMT) from healthy donor to patient is a treatment for microbiome-associated diseases. Although the success of FMT requires donor bacteria to engraft in the patient's gut, the forces governing engraftment in humans are unknown. Here we use an ongoing clinical experiment, the treatment of recurrent Clostridium difficile infection, to uncover the rules of engraftment in humans. We built a statistical model that predicts which bacterial species will engraft in a given host, and developed Strain Finder, a method to infer strain genotypes and track them over time. We find that engraftment can be predicted largely from the abundance and phylogeny of bacteria in the donor and the pre-FMT patient. Furthermore, donor strains within a species engraft in an all-or-nothing manner and previously undetected strains frequently colonize patients receiving FMT. We validated these findings for metabolic syndrome, suggesting that the same principles of engraftment extend to other indications.}, } @article {pmid29446866, year = {2018}, author = {Woodworth, MH and Kraft, CS and Meredith, EJ and Mehta, AK and Wang, T and Mamo, YT and Dhere, T and Sitchenko, KL and Patzer, RE and Friedman-Moraco, RJ}, title = {Tacrolimus concentration to dose ratio in solid organ transplant patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {20}, number = {2}, pages = {e12857}, doi = {10.1111/tid.12857}, pmid = {29446866}, issn = {1399-3062}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; }, mesh = {Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Immunosuppressive Agents/*blood/pharmacokinetics ; Organ Transplantation/*adverse effects ; Retrospective Studies ; Tacrolimus/*blood/pharmacokinetics ; }, abstract = {Fecal microbiota transplantation (FMT) is increasingly being performed for Clostridium difficile infection in solid organ transplant (SOT) patients; however, little is known about the potential pharmacokinetic or pharmacomicrobial effects this may have on tacrolimus levels. We reviewed the medical records of 10 SOT patients from September 2012-December 2016 who were taking tacrolimus at time of FMT for recurrent C. difficile infection. We compared the differences in tacrolimus concentration/dose ratio (C/D ratio) 3 months prior to FMT vs 3 months after FMT. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/kg/d) was -17.65 (95% CI -1.25 to 0.58) (ng/mL)/(mg/kg/d), P-value .43 by Wilcoxon signed-rank test. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/d) was -0.33 (95% CI -1.25 to 0.58) (ng/mL)/(mg/d), P-value .28 by Wilcoxon signed-rank test. Of these patients, 2/10 underwent allograft biopsy for allograft dysfunction in the year after FMT, with no evidence of allograft rejection on pathology. These preliminary data suggest that FMT may not predictably alter tacrolimus levels and support its safety for SOT patients however further study in randomized trials is needed.}, } @article {pmid29441452, year = {2018}, author = {Zhang, X and Tian, H and Gu, L and Nie, Y and Ding, C and Ge, X and Yang, B and Gong, J and Li, N}, title = {Long-term follow-up of the effects of fecal microbiota transplantation in combination with soluble dietary fiber as a therapeutic regimen in slow transit constipation.}, journal = {Science China. Life sciences}, volume = {61}, number = {7}, pages = {779-786}, doi = {10.1007/s11427-017-9229-1}, pmid = {29441452}, issn = {1869-1889}, abstract = {As some studies have reported that strategies targeting the gut microbiota such as fecal microbiota transplantation (FMT) with or without other microecological therapy might have efficacy in treating slow transit constipation (STC), we conducted a single-center, open-label trial to study the long-term effect of FMT combined with soluble dietary fiber (pectin) on STC. Thirty-one adult patients with STC were enrolled into the trial. Patients received 6-day FMT procedures repeatedly for the first 3 months and soluble dietary fiber (pectin) daily during the follow-up. The rate of clinical remission and improvement, stool consistency, the Wexner constipation scale, and assessment of constipation-related symptoms were evaluated at week 4 and 1 year later. The clinical remission and improvement rates at week 4 were 69.0% (20/29) and 75.9% (22/29), respectively. At the end of the study, 48.3% (14/29) of patients continued to have at least three complete spontaneous bowel movements per week and 58.6% (17/29) of patients showed clinical improvements. Stool consistency, the Wexner constipation scale, and constipation symptoms improved both at short-term and long-term follow-up. The results indicated that FMT in combination with soluble dietary fiber (pectin) had both short-term and long-term efficacy in treating STC.}, } @article {pmid29441063, year = {2018}, author = {Lu, Y and Li, X and Liu, S and Zhang, Y and Zhang, D}, title = {Toll-like Receptors and Inflammatory Bowel Disease.}, journal = {Frontiers in immunology}, volume = {9}, number = {}, pages = {72}, doi = {10.3389/fimmu.2018.00072}, pmid = {29441063}, issn = {1664-3224}, support = {R21 CA176698/CA/NCI NIH HHS/United States ; }, abstract = {Inflammatory bowel disease (IBD) is one relapsing and lifelong disease that affects millions of patients worldwide. Increasing evidence has recently highlighted immune-system dysfunction, especially toll-like receptors (TLRs)-mediated innate immune dysfunction, as central players in the pathogenesis of IBD. TLRs and TLR-activated signaling pathways are involved not only in the pathogenesis but also in the efficacy of treatment of IBD. By understanding these molecular mechanisms, we might develop a strategy for relieving the experience of long-lasting suffering of those patients and improving their quality of life. The purpose of this review article is to summarize the potential mechanisms of TLR signaling pathways in IBD and the novel potential therapeutic strategies against IBD.}, } @article {pmid29438346, year = {2018}, author = {Wang, C and Zaheer, M and Bian, F and Quach, D and Swennes, AG and Britton, RA and Pflugfelder, SC and de Paiva, CS}, title = {Sjögren-Like Lacrimal Keratoconjunctivitis in Germ-Free Mice.}, journal = {International journal of molecular sciences}, volume = {19}, number = {2}, pages = {}, doi = {10.3390/ijms19020565}, pmid = {29438346}, issn = {1422-0067}, support = {P30 CA125123/CA/NCI NIH HHS/United States ; T32 AI053831/AI/NIAID NIH HHS/United States ; P30 AI036211/AI/NIAID NIH HHS/United States ; P30 EY002520/EY/NEI NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; R01 EY026893/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology ; Fecal Microbiota Transplantation ; Female ; Germ-Free Life/*immunology ; Homeodomain Proteins/genetics/metabolism ; Immunity, Innate ; Interferon-gamma/metabolism ; Keratoconjunctivitis/immunology/*microbiology/therapy ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota ; }, abstract = {Commensal bacteria play an important role in the formation of the immune system but their role in the maintenance of immune homeostasis at the ocular surface and lacrimal gland remains poorly understood. This study investigated the eye and lacrimal gland phenotype in germ-free and conventional C57BL/6J mice. Our results showed that germ-free mice had significantly greater corneal barrier disruption, greater goblet cell loss, and greater total inflammatory cell and CD4⁺ T cell infiltration within the lacrimal gland compared to the conventionally housed group. A greater frequency of CD4⁺IFN-γ⁺ cells was observed in germ-free lacrimal glands. Females exhibited a more severe phenotype compared to males. Adoptive transfer of CD4⁺ T cells isolated from female germ-free mice into RAG1KO mice transferred Sjögren-like lacrimal keratoconjunctivitis. Fecal microbiota transplant from conventional mice reverted dry eye phenotype in germ-free mice and decreased CD4⁺IFN-γ⁺ cells to levels similar to conventional C57BL/6J mice. These findings indicate that germ-free mice have a spontaneous lacrimal keratoconjunctivitis similar to that observed in Sjögren syndrome patients and demonstrate that commensal bacteria function in maintaining immune homeostasis on the ocular surface. Thus, manipulation of intestinal commensal bacteria has the potential to become a novel therapeutic approach to treat Sjögren Syndrome.}, } @article {pmid29432297, year = {2018}, author = {McClave, SA and Patel, J and Bhutiani, N}, title = {Should fecal microbial transplantation be used in the ICU?.}, journal = {Current opinion in critical care}, volume = {24}, number = {2}, pages = {105-111}, doi = {10.1097/MCC.0000000000000489}, pmid = {29432297}, issn = {1531-7072}, abstract = {PURPOSE OF REVIEW: Maintaining gut barrier defenses, modulating immune responses, and supporting the role of commensal microbiota are major factors influencing outcome in critical illness. Of these, maintaining a commensal 'lifestyle' and preventing the emergence of a virulent pathobiome may be most important in reducing risk of infection and multiple organ failure.

RECENT FINDINGS: The polymeric formulas utilized for enteral nutrition in the ICU are absorbed high in the gastrointestinal tract and may not reach the microbial burden in the cecum where their effect is most needed. The provision of a few select probiotic organisms may be insufficient to refaunate the gut and establish a 'recovery pattern,' propelling the patient toward health and homeostasis. Use of fecal microbial transplantation (FMT) appears to be a more successful strategy for replenishing the intestinal microbiome and maintaining its commensal phenotypic expression.

SUMMARY: FMT has become an attractive option to mitigate multiple organ dysfunction in the ICU. This article discusses the physiology, rationale, early experience, and expectations for such therapy in the critically ill patient.}, } @article {pmid29431777, year = {2018}, author = {Su, A and Yang, W and Zhao, L and Pei, F and Yuan, B and Zhong, L and Ma, G and Hu, Q}, title = {Flammulina velutipes polysaccharides improve scopolamine-induced learning and memory impairment in mice by modulating gut microbiota composition.}, journal = {Food & function}, volume = {9}, number = {3}, pages = {1424-1432}, doi = {10.1039/c7fo01991b}, pmid = {29431777}, issn = {2042-650X}, mesh = {Animals ; Bacteria/classification/drug effects/genetics/isolation & purification ; Cognitive Dysfunction/*drug therapy/*microbiology/psychology ; Feces/microbiology ; Flammulina/*chemistry ; Gastrointestinal Microbiome/*drug effects ; Humans ; Interleukin-10/genetics/metabolism ; Interleukin-1beta/genetics/metabolism ; Interleukin-6/genetics/metabolism ; Male ; Maze Learning/drug effects ; Memory/drug effects ; Mice ; Mice, Inbred C57BL ; Plant Extracts/*administration & dosage ; Polysaccharides/*administration & dosage ; Scopolamine Hydrobromide/*administration & dosage ; Tumor Necrosis Factor-alpha/genetics/metabolism ; }, abstract = {Flammulina velutipes polysaccharides (FVP) have been proved to be effective in improving learning and memory impairment in mice. However, their underlying mechanism remains unclear. The aim of this study was to investigate the relationship between memory improvement and gut microbiota regulation of FVP. The results showed a significant decrease in the relative abundances of Clostridia and Bacilli but a significant increase in Bacteroidia, Erysipelotrichia and Actinobacteria in the FVP-treated group versus the control group. Fecal microbiota transplantation of mice with 'FVP microbiota' derived from FVP-fed mice resulted in improved learning and memory function compared to colonization with 'common microbiota' derived from control individuals. FVP and 'FVP microbiota' significantly increased the numbers of platform crossings and the swimming distance of mice in the probe test and decreased the escape latency and total swimming distance of mice in the hidden platform test. Moreover, FVP and 'FVP microbiota' regulated cytokines, such as IL-1β, TNF-α, IL-6 and IL-10, suggesting a mechanism involving the suppression of neuroinflammation. This study indicated that the regulation of the gut microbiome may have a causal role in improving scopolamine-induced impairment of learning and memory.}, } @article {pmid29430228, year = {2017}, author = {Adamski, JK and Jäschke, BB and Uusitalo-Seppälä, RS and Moilanen, KVJ and Pehkonen, AV and Weigl, W}, title = {Routine Treatment-Resistant Clostridium difficile Infection during Recovery from Myxedema.}, journal = {Case reports in gastroenterology}, volume = {11}, number = {3}, pages = {748-754}, doi = {10.1159/000484661}, pmid = {29430228}, issn = {1662-0631}, abstract = {Development of the extreme form of hypothyroidism defined as myxedema is very rare. Acute symptoms and their management have been described in detail previously. However, not much attention has been devoted to therapeutic challenges that are faced in the recovery phase of the treatment, especially pertaining to the gastrointestinal system. The link between myxedema and the appearance of severe Clostridium difficile infection (CDI) has not been established so far. A 61-year-old woman with no significant medical record was admitted to hospital because of infected heel pressure and thyroid dysfunction. A week later, due to hypothermia, hypotension, and unconsciousness, she was transferred to the intensive care unit. The clinical picture and the results of laboratory tests confirmed diagnosis of myxedema. After the introduction of resuscitative measures and hormonal substitution, patient's condition stabilized within 10 days. Due to concomitant sepsis, initially piperacillin/tazobactam and later cefuroxime were administered. After 20 days of antibiotic therapy, the patient developed CDI that was resistant to the routine mode of treatment. The clinical recovery was achieved only after a fecal microbiota transplantation procedure. The function of the digestive tract in myxedema is disturbed by gastric achlorydia and reduced peristalsis, which in turn can predispose the small intestine to overgrowth of bacteria. The use of antibiotics can additionally decrease the intestinal bacterial diversity, favoring the overgrowth of Clostridium difficile. The authors conclude that myxedema may increase the likelihood of a treatment-resistant form of CDI that requires the implementation of fecal microbiota transplantation.}, } @article {pmid29426057, year = {2018}, author = {Stallmach, A and Anttila, VJ and Hell, M and Gwynn, S and Merino-Amador, P and Petrosillo, N and Ráčil, Z and Warren, T and Wenisch, C and Wilcox, M}, title = {Inflammatory bowel disease and Clostridium difficile infection: contrasting views of international clinical professionals.}, journal = {Zeitschrift fur Gastroenterologie}, volume = {}, number = {}, pages = {}, doi = {10.1055/s-0044-100045}, pmid = {29426057}, issn = {1439-7803}, abstract = {INTRODUCTION: In patients with inflammatory bowel disease (IBD), Clostridium difficile infection (CDI) is a risk factor for both morbidity and mortality. Currently, appropriate management is unclear. Guidance on best practice in the diagnosis and treatment of CDI in IBD patients is therefore needed.

METHODS: A multidisciplinary group of clinicians involved in the treatment of patients with IBD and CDI developed 27 consensus statements. Respondents were asked to rate their agreement with each statement using a 4-point Likert scale. A modified Delphi methodology was used to review responses of 442 physicians from different specialties (including infectious disease specialists [n = 104], microbiologists [n = 95], and gastroenterologists [n = 73]). A threshold of 75 % agreement was predefined as consensus.

RESULTS: Consensus was achieved for 17 of the 27 statements. Unprompted recognition of risk factors for CDI was low. Intensification of immunosuppressive therapy in the absence of clinical improvement was controversial. Clear definitions of treatment failure of antibiotic therapy in CDI and recurrence of CDI in IBD are needed. Respondents require further clarity regarding the place of fecal microbiota transplantation in CDI patients with IBD. Differences were observed between the perceptions of microbiologists and gastroenterologists, as well as between countries.

CONCLUSIONS: Different perceptions both between specialties and geographical locations complicate the development of an internationally accepted algorithm for the diagnosis and treatment of CDI in patients with IBD. This study highlights the need for future studies in this area.}, } @article {pmid29422809, year = {2018}, author = {Nanki, K and Mizuno, S and Matsuoka, K and Ono, K and Sugimoto, S and Kiyohara, H and Arai, M and Nakashima, M and Takeshita, K and Saigusa, K and Senoh, M and Fukuda, T and Naganuma, M and Kato, H and Suda, W and Hattori, M and Kanai, T}, title = {Fecal microbiota transplantation for recurrent Clostridium difficile infection in a patient with ulcerative colitis.}, journal = {Intestinal research}, volume = {16}, number = {1}, pages = {142-146}, doi = {10.5217/ir.2018.16.1.142}, pmid = {29422809}, issn = {1598-9100}, abstract = {Fecal microbiota transplantation (FMT) has been reported as a safe and effective therapy in patients with refractory and recurrent Clostridium difficile infection (CDI). FMT has also been reported as a promising therapy in patients with ulcerative colitis (UC). Both, CDI and UC, are believed to be caused by dysbiosis, such as altered compositions or decreased diversity of the intestinal microbiota. This report describes a patient with UC in remission with a second recurrent episode of CDI, who was treated with FMT. A single FMT performed via colonoscopy completely resolved the patient's diarrhea and eradicated C. difficile bacteriologically without any severe complications. Molecular biological analysis of the patient's fecal microbiota showed that FMT could dramatically change the altered composition of intestinal microbiota and restore its diversity. Despite the restoration of the intestinal microbiota, FMT could not prevent a relapse of UC in this patient. However, it improved the intestinal symptoms of CDI and could prevent further recurrences of CDI.}, } @article {pmid29422802, year = {2018}, author = {Midha, V and Mahajan, R and Mehta, V and Narang, V and Singh, A and Kaur, K and Sood, A}, title = {Efficacy and safety of the adalimumab biosimilar Exemptia as induction therapy in moderate-to-severe ulcerative colitis.}, journal = {Intestinal research}, volume = {16}, number = {1}, pages = {83-89}, doi = {10.5217/ir.2018.16.1.83}, pmid = {29422802}, issn = {1598-9100}, abstract = {Background/Aims: Data on the efficacy and safety of the adalimumab biosimilar Exemptia are limited.

Methods: Patients with moderate-to-severe active steroid-refractory ulcerative colitis (UC) treated at Dayanand Medical College and Hospital, India were offered cyclosporine A, biologicals or biosimilars, or surgery. A retrospective analysis was conducted on patients who were treated with the adalimumab biosimilar, Exemptia. These patients were administered an induction dosing schedule of 160 mg Exemptia at week 0, 80 mg at week 2, and then 40 mg every other week from week 4 to 8. The clinical response and remission were assessed at week 8 using Mayo score.

Results: A total of 29 patients (62.1% male; mean age, 34.9 ± 9.7 years) with moderate-to-severe steroid-refractory active UC (mean disease duration, 6.3±5.1 years; pancolitis in 9 patients [31.1%]; left-sided colitis in 20 patients [68.9%]) were treated with the Exemptia induction dosing schedule. The mean Mayo score at presentation was 8.2±1.4. At week 8, clinical response was observed in 7 patients (24.1%), whereas clinical remission was observed only in 1 patient (3.5%). Among the non-responders (n=21), 4 patients required colectomy, 1 died, 1 was lost to follow-up, 10 were offered fecal microbiota transplant, 3 were administered infliximab, and 2 patients were administered cyclosporine and tacrolimus, respectively. Four patients (13.8%) developed extrapulmonary tuberculosis.

Conclusions: The adalimumab biosimilar Exemptia has limited efficacy for the attainment of clinical response and remission in moderate-to-severe steroid-refractory UC, with a significant risk of acquisition or reactivation of tuberculosis in developing countries such as India.}, } @article {pmid29413214, year = {2018}, author = {Moore, SC}, title = {Clostridium difficile: More Challenging than Ever.}, journal = {Critical care nursing clinics of North America}, volume = {30}, number = {1}, pages = {41-53}, doi = {10.1016/j.cnc.2017.10.004}, pmid = {29413214}, issn = {1558-3481}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Clostridium Infections/*diagnosis/*drug therapy/epidemiology ; Clostridium difficile/isolation & purification ; Cross Infection ; Drug Resistance, Microbial ; *Fecal Microbiota Transplantation ; Humans ; Risk Factors ; United States/epidemiology ; }, abstract = {Clostridium difficile infection is not new, but it is posing more problems than ever before, described by the Centers for Disease Control and Prevention as an urgent threat. Its pathophysiology allows C difficile to be very difficult to manage, both within the hospital environment and in a patient's body. This article reviews clinical manifestations of the infection, outlines both medical and surgical treatment options, and discusses risk factors and predictors. Implications for nurses are thoroughly described. The epidemic proportion of C difficile infection gives cause for serious concern, especially for vulnerable populations, such as adults over age 65.}, } @article {pmid29411989, year = {2018}, author = {Ponte, A and Pinho, R and Mota, M and Silva, J and Vieira, N and Oliveira, R and Rodrigues, J and Sousa, M and Sousa, I and Carvalho, J}, title = {Fecal microbiota transplantation in refractory or recurrent Clostridium difficile infection: a real-life experience in a non-academic center.}, journal = {Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva}, volume = {110}, number = {5}, pages = {311-315}, doi = {10.17235/reed.2018.5099/2017}, pmid = {29411989}, issn = {1130-0108}, abstract = {AIM: this study aimed to describe the efficacy and safety of fecal microbiota transplantation (FMT) for the treatment of refractory and recurrent Clostridium difficile infection (CDI).

METHODS: this was an observational study of patients with refractory or recurrent CDI treated with FMT between June 2014 and January 2017. Primary and secondary outcomes were the resolution of diarrhea without CDI recurrence within two months after one or more FMT. A descriptive analysis was performed.

RESULTS: thirty-four FMT were performed in 28 patients, 88.2% (n = 30) using an upper route with a gastroscopy and 11.8% (n = 4) with colonoscopy; 50% (n = 17) of FMT were due to recurrent CDI and 50% (n = 17) were due to refractory CDI. The overall cure rate of upper FMT was 87.5% (21/24) and 100% (4/4) when colonoscopy was performed. A cure was achieved after one FMT in 88% (22/25) of cases and after two or more FMT in 8% (2/25) of cases, resulting in an overall cure rate of 96% (24/25). No severe adverse events were reported.

CONCLUSION: FMT constitutes an effective and safe approach for the management of refractory and recurrent CDI, with an overall cure rate of 96% and no reported severe adverse events.}, } @article {pmid29408638, year = {2018}, author = {Allamneni, C and Nelson, G and Weber, F}, title = {A Rare Cause of Recurrent Abdominal Pain and Diarrhea.}, journal = {Gastroenterology}, volume = {155}, number = {2}, pages = {e11-e12}, doi = {10.1053/j.gastro.2017.12.035}, pmid = {29408638}, issn = {1528-0012}, mesh = {Abdominal Pain/blood/diagnostic imaging/*etiology/therapy ; Aged ; Angioedema/blood/diagnostic imaging/*etiology ; Anti-Infective Agents/therapeutic use ; *B-Lymphocytes ; Clostridium difficile/isolation & purification ; Colonoscopy ; Diarrhea/blood/diagnostic imaging/*etiology/therapy ; Enterocolitis, Pseudomembranous/diagnostic imaging/microbiology/therapy ; Fecal Microbiota Transplantation ; Female ; Humans ; Intestine, Small/blood supply/diagnostic imaging/microbiology/pathology ; Irritable Bowel Syndrome/diagnostic imaging/microbiology/therapy ; Lymphocytosis/*complications/diagnosis ; Recurrence ; Tomography, X-Ray Computed ; }, } @article {pmid29408609, year = {2018}, author = {Sun, X and Winglee, K and Gharaibeh, RZ and Gauthier, J and He, Z and Tripathi, P and Avram, D and Bruner, S and Fodor, A and Jobin, C}, title = {Microbiota-Derived Metabolic Factors Reduce Campylobacteriosis in Mice.}, journal = {Gastroenterology}, volume = {154}, number = {6}, pages = {1751-1763.e2}, doi = {10.1053/j.gastro.2018.01.042}, pmid = {29408609}, issn = {1528-0012}, support = {R01 DK047700/DK/NIDDK NIH HHS/United States ; R21 AI082319/AI/NIAID NIH HHS/United States ; }, mesh = {Anaerobiosis ; Animals ; Bile Acids and Salts/*administration & dosage ; Campylobacter Infections/*microbiology ; Campylobacter jejuni/*metabolism ; Cholagogues and Choleretics/administration & dosage ; Colon/microbiology ; Culture Techniques/methods ; Deoxycholic Acid/administration & dosage ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastroenteritis/*microbiology ; Gastrointestinal Microbiome/*physiology ; Intestines/cytology ; Lithocholic Acid/administration & dosage ; Mice ; Mice, Inbred C57BL ; Ursodeoxycholic Acid/administration & dosage ; }, abstract = {BACKGROUND & AIMS: Campylobacter jejuni, a prevalent foodborne bacterial pathogen, exploits the host innate response to induce colitis. Little is known about the roles of microbiota in C jejuni-induced intestinal inflammation. We investigated interactions between microbiota and intestinal cells during C jejuni infection of mice.

METHODS: Germ-free C57BL/6 Il10-/- mice were colonized with conventional microbiota and infected with a single dose of C jejuni (109 colony-forming units/mouse) via gavage. Conventional microbiota were cultured under aerobic, microaerobic, or anaerobic conditions and orally transplanted into germ-free Il10-/- mice. Colon tissues were collected from mice and analyzed by histology, real-time polymerase chain reaction, and immunoblotting. Fecal microbiota and bile acids were analyzed with 16S sequencing and high-performance liquid chromatography with mass spectrometry, respectively.

RESULTS: Introduction of conventional microbiota reduced C jejuni-induced colitis in previously germ-free Il10-/- mice, independent of fecal load of C jejuni, accompanied by reduced activation of mammalian target of rapamycin. Microbiota transplantation and 16S ribosomal DNA sequencing experiments showed that Clostridium XI, Bifidobacterium, and Lactobacillus were enriched in fecal samples from mice colonized with microbiota cultured in anaerobic conditions (which reduce colitis) compared with mice fed microbiota cultured under aerobic conditions (susceptible to colitis). Oral administration to mice of microbiota-derived secondary bile acid sodium deoxycholate, but not ursodeoxycholic acid or lithocholic acid, reduced C jejuni-induced colitis. Depletion of secondary bile acid-producing bacteria with antibiotics that kill anaerobic bacteria (clindamycin) promoted C jejuni-induced colitis in specific pathogen-free Il10-/- mice compared with the nonspecific antibiotic nalidixic acid; colitis induction by antibiotics was associated with reduced level of luminal deoxycholate.

CONCLUSIONS: We identified a mechanism by which the microbiota controls susceptibility to C jejuni infection in mice, via bacteria-derived secondary bile acids.}, } @article {pmid29402478, year = {2018}, author = {Schoster, A}, title = {Probiotic Use in Equine Gastrointestinal Disease.}, journal = {The Veterinary clinics of North America. Equine practice}, volume = {34}, number = {1}, pages = {13-24}, doi = {10.1016/j.cveq.2017.11.004}, pmid = {29402478}, issn = {1558-4224}, mesh = {Animals ; Gastrointestinal Diseases/therapy/*veterinary ; Horse Diseases/*therapy ; Horses ; Probiotics/*therapeutic use ; }, abstract = {Probiotics are commonly used in human and veterinary medicine due to their postulated positive effects on overall and specifically gastrointestinal health. Although some beneficial effects have been shown in several human diseases, a general beneficial effect of probiotics is currently not supported. In horses, well-designed studies to date are few, results are conflicting, and the effects of probiotics are questionable. Adverse effects are rare; however, intestinal adverse effects (diarrhea) have been reported in foals. Quality control of over-the-counter probiotics is not tightly regulated, and labels often do not reflect the content.}, } @article {pmid29391359, year = {2018}, author = {Evans, TJ and Hilton, R and Douthwaite, S}, title = {Treating chronic hepatitis E: when is enough enough?.}, journal = {BMJ case reports}, volume = {2018}, number = {}, pages = {}, doi = {10.1136/bcr-2017-223592}, pmid = {29391359}, issn = {1757-790X}, mesh = {Adult ; Alanine Transaminase/metabolism ; Antiviral Agents/*therapeutic use ; Feces/*virology ; Hepatitis E/*drug therapy/immunology/physiopathology ; Hepatitis, Chronic/*drug therapy/immunology/physiopathology ; Humans ; Immunocompromised Host ; Kidney Transplantation ; Male ; Opportunistic Infections/*drug therapy/immunology/virology ; Ribavirin/*therapeutic use ; Treatment Outcome ; *Viral Load ; Virus Shedding ; }, abstract = {We present a 38-year-old white British man who was taking long-term immunosuppressive medication following kidney transplantation. On routine review, he was noted to have an isolated and asymptomatic rise in alanine aminotransferase. After thorough investigation, he was found to have positive IgM and IgG serology to hepatitis E virus-and given the duration of his transaminitis, he was determined to have chronic hepatitis E infection. Treatment options were complicated by the presence of his kidney transplant, by chronic anaemia and by his wish for concomitant fertility treatment. Ribavirin therapy was instituted with a dramatic and immediate drop in serum viral load, although stool viraemia persisted. No clear protocols guide duration of treatment in chronic hepatitis E infection, but protracted faecal virus shedding predicts viral recrudescence, and treatment should continue at least until the stool is clear of virus.}, } @article {pmid29391279, year = {2018}, author = {Xiao, HW and Ge, C and Feng, GX and Li, Y and Luo, D and Dong, JL and Li, H and Wang, H and Cui, M and Fan, SJ}, title = {Gut microbiota modulates alcohol withdrawal-induced anxiety in mice.}, journal = {Toxicology letters}, volume = {287}, number = {}, pages = {23-30}, doi = {10.1016/j.toxlet.2018.01.021}, pmid = {29391279}, issn = {1879-3169}, support = {R01 AT005076/AT/NCCIH NIH HHS/United States ; R01 GM063075/GM/NIGMS NIH HHS/United States ; }, mesh = {Alcoholism/genetics/metabolism/*microbiology/psychology ; Animals ; Anxiety/genetics/metabolism/*microbiology/psychology ; Bacteria/classification/genetics/*growth & development ; *Behavior, Animal ; Brain-Derived Neurotrophic Factor/genetics/metabolism ; Disease Models, Animal ; *Ethanol ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Hippocampus/metabolism ; Host-Pathogen Interactions ; Intestines/*microbiology ; Male ; Mice, Inbred C57BL ; Motor Activity ; Receptors, Corticotropin-Releasing Hormone/genetics/metabolism ; Receptors, Opioid, mu/genetics/metabolism ; Ribotyping ; Substance Withdrawal Syndrome/genetics/metabolism/*microbiology/psychology ; }, abstract = {Excessive alcohol consumption remains a major public health problem that affects millions of people worldwide. Accumulative experimental evidence has suggested an important involvement of gut microbiota in the modulation of host's immunological and neurological functions. However, it is previously unknown whether enteric microbiota is implicated in the formation of alcohol withdrawal-induced anxiety. Using a murine model of chronic alcoholism and withdrawal, we examined the impact of alcohol consumption on the possible alterations of gut microbiota as well as alcohol withdrawal-induced anxiety and behavior changes. The 16S rRNA sequencing revealed that alcohol consumption did not alter the abundance of bacteria, but markedly changed the composition of gut microbiota. Moreover, the transplantation of enteric microbes from alcohol-fed mice to normal healthy controls remarkably shaped the composition of gut bacteria, and elicited behavioral signs of alcohol withdrawal-induced anxiety. Using quantitative real-time polymerase chain reaction, we further confirmed that the expression of genes implicated in alcohol addiction, BDNF, CRHR1 and OPRM1, was also altered by transplantation of gut microbes from alcohol-exposed donors. Collectively, our findings suggested a possibility that the alterations of gut microbiota composition might contribute to the development of alcohol withdrawal-induced anxiety, and reveal potentially new etiologies for treating alcohol addiction.}, } @article {pmid29388040, year = {2018}, author = {Huang, L and Zhu, Q and Qu, X and Qin, H}, title = {Microbial treatment in chronic constipation.}, journal = {Science China. Life sciences}, volume = {61}, number = {7}, pages = {744-752}, doi = {10.1007/s11427-017-9220-7}, pmid = {29388040}, issn = {1869-1889}, abstract = {Chronic functional constipation is a kind of common intestinal disease that occurs in children, adults and elderly people. This disease not only causes great influence to physiological function, but also results in varying degrees of psychological barriers. At present, constipation treatments continue to rely on traditional methods such as purgative therapy and surgery. However, these approaches can disrupt intestinal function. Recent research between intestinal diseases and gut microbiota has gradually revealed a connection between constipation and intestinal flora disturbance, providing a theoretical basis for microbial treatment in chronic constipation. Microbial treatment mainly includes probiotic preparations such as probiotics, prebiotics, synbiotics and fecal microbiota transplantation (FMT). Due to its safety, convenience and curative effect, probiotic preparations have been widely accepted, especially gradually developed FMT with higher curative effects. Microbial treatment improves clinical symptoms, promotes the recovery of intestinal flora, and has no complications during the treatment process. Compared with traditional treatments, microbial treatment in chronic constipation has advantages, and is worthy of further promotion from clinical research to clinical application.}, } @article {pmid29385143, year = {2018}, author = {Mintz, M and Khair, S and Grewal, S and LaComb, JF and Park, J and Channer, B and Rajapakse, R and Bucobo, JC and Buscaglia, JM and Monzur, F and Chawla, A and Yang, J and Robertson, CE and Frank, DN and Li, E}, title = {Longitudinal microbiome analysis of single donor fecal microbiota transplantation in patients with recurrent Clostridium difficile infection and/or ulcerative colitis.}, journal = {PloS one}, volume = {13}, number = {1}, pages = {e0190997}, doi = {10.1371/journal.pone.0190997}, pmid = {29385143}, issn = {1932-6203}, support = {P30 DK048520/DK/NIDDK NIH HHS/United States ; }, mesh = {Clostridium Infections/microbiology/*therapy ; Clostridium difficile/*isolation & purification ; Colitis, Ulcerative/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; Longitudinal Studies ; *Microbiota ; Polymerase Chain Reaction ; Prospective Studies ; Recurrence ; Treatment Outcome ; }, abstract = {BACKGROUND: Studies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only).

METHOD: V3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group.

RESULTS: Significant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the CDI-only and CDI + UC recipients, were restored after FMT.

CONCLUSION: The results from this pilot study suggest that the microbial imbalances in the CDI + UC recipients more closely resemble those of the CDI-only recipients than the UC-only recipients.}, } @article {pmid29383670, year = {2018}, author = {Maida, M and Mcilroy, J and Ianiro, G and Cammarota, G}, title = {Faecal Microbiota Transplantation as Emerging Treatment in European Countries.}, journal = {Advances in experimental medicine and biology}, volume = {1050}, number = {}, pages = {177-195}, doi = {10.1007/978-3-319-72799-8_11}, pmid = {29383670}, issn = {0065-2598}, mesh = {Clinical Studies as Topic ; Clostridium Infections/microbiology/*therapy ; Clostridium difficile ; Europe ; *Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/therapy ; }, abstract = {Clostridium difficile infection (CDI) is one of the most common healthcare-associated infections in the world and is a leading cause of morbidity and mortality in hospitalized patients.Although several antibiotics effectively treat CDI, some individuals do not respond to these drugs and may be cured by transplanting stool from healthy donors. This procedure, termed Faecal Microbiota Transplantation (FMT), has demonstrated remarkable efficacy as a treatment for recurrent CDI.FMT has also been investigated in other diseases and disorders where perturbations to the gut microbiota have been theorized to play a causative role in pathogenesis and severity, such as inflammatory bowel disease (IBD). Although FMT is currently not recommended to cure IBD patients in clinical practice, several studies have recently been carried out with promising results. The aim of future research is therefore to standardize protocols and develop FMT as a therapeutic option for these patients.This review summarizes data on the use of FMT as a treatment for CDI and IBD, with special attention given to studies conducted in European countries.}, } @article {pmid29382834, year = {2018}, author = {Li, B and Guo, K and Zeng, L and Zeng, B and Huo, R and Luo, Y and Wang, H and Dong, M and Zheng, P and Zhou, C and Chen, J and Liu, Y and Liu, Z and Fang, L and Wei, H and Xie, P}, title = {Metabolite identification in fecal microbiota transplantation mouse livers and combined proteomics with chronic unpredictive mild stress mouse livers.}, journal = {Translational psychiatry}, volume = {8}, number = {1}, pages = {34}, doi = {10.1038/s41398-017-0078-2}, pmid = {29382834}, issn = {2158-3188}, abstract = {Major depressive disorder (MDD) is a common mood disorder. Gut microbiota may be involved in the pathogenesis of depression via the microbe-gut-brain axis. Liver is vulnerable to exposure of bacterial products translocated from the gut via the portal vein and may be involved in the axis. In this study, germ-free mice underwent fecal microbiota transplantation from MDD patients and healthy controls. Behavioral tests verified the depression model. Metabolomics using gas chromatography-mass spectrometry, nuclear magnetic resonance, and liquid chromatography-mass spectrometry determined the influence of microbes on liver metabolism. With multivariate statistical analysis, 191 metabolites were distinguishable in MDD mice from control (CON) mice. Compared with CON mice, MDD mice showed lower levels for 106 metabolites and higher levels for 85 metabolites. These metabolites are associated with lipid and energy metabolism and oxidative stress. Combined analyses of significantly changed proteins in livers from another depression model induced by chronic unpredictive mild stress returned a high score for the Lipid Metabolism, Free Radical Scavenging, and Molecule Transports network, and canonical pathways were involved in energy metabolism and tryptophan degradation. The two mouse models of depression suggest that changes in liver metabolism might be involved in the pathogenesis of MDD. Conjoint analyses of fecal, serum, liver, and hippocampal metabolites from fecal microbiota transplantation mice suggested that aminoacyl-tRNA biosynthesis significantly changed and fecal metabolites showed a close relationship with the liver. These findings may help determine the biological mechanisms of depression and provide evidence about "depression microbes" impacting on liver metabolism.}, } @article {pmid29382125, year = {2018}, author = {Nishimura, N and Tanabe, H and Komori, E and Sasaki, Y and Inoue, R and Yamamoto, T}, title = {Transplantation of High Hydrogen-Producing Microbiota Leads to Generation of Large Amounts of Colonic Hydrogen in Recipient Rats Fed High Amylose Maize Starch.}, journal = {Nutrients}, volume = {10}, number = {2}, pages = {}, doi = {10.3390/nu10020144}, pmid = {29382125}, issn = {2072-6643}, mesh = {Amylose/*administration & dosage ; Animals ; Bacteroidetes ; Bifidobacterium ; Colon/metabolism/*microbiology ; Diet, High-Fat ; *Fecal Microbiota Transplantation ; Firmicutes ; *Gastrointestinal Microbiome ; Hydrogen/*metabolism ; RNA, Ribosomal, 16S/isolation & purification ; Rats ; Ruminococcus ; Sequence Analysis, DNA ; Starch/*administration & dosage ; Zea mays/chemistry ; }, abstract = {The hydrogen molecule (H₂), which has low redox potential, is produced by colonic fermentation. We examined whether increased hydrogen (H₂) concentration in the portal vein in rats fed high amylose maize starch (HAS) helped alleviate oxidative stress, and whether the transplantation of rat colonic microbiota with high H₂ production can shift low H₂-generating rats (LG) to high H₂-generating rats (HG). Rats were fed a 20% HAS diet for 10 days and 13 days in experiments 1 and 2, respectively. After 10 days (experiment 1), rats underwent a hepatic ischemia-reperfusion (IR) operation. Rats were then categorized into quintiles of portal H₂ concentration. Plasma alanine aminotransferase activity and hepatic oxidized glutathione concentration were significantly lower as portal H₂ concentration increased. In experiment 2, microbiota derived from HG (the transplantation group) or saline (the control group) were orally inoculated into LG on days 3 and 4. On day 13, portal H₂ concentration in the transplantation group was significantly higher compared with the control group, and positively correlated with genera Bifidobacterium, Allobaculum, and Parabacteroides, and negatively correlated with genera Bacteroides, Ruminococcus, and Escherichia. In conclusion, the transplantation of microbiota derived from HG leads to stable, high H₂ production in LG, with the resultant high production of H₂ contributing to the alleviation of oxidative stress.}, } @article {pmid29375527, year = {2017}, author = {Hu, L and Geng, S and Li, Y and Cheng, S and Fu, X and Yue, X and Han, X}, title = {Exogenous Fecal Microbiota Transplantation from Local Adult Pigs to Crossbred Newborn Piglets.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {2663}, doi = {10.3389/fmicb.2017.02663}, pmid = {29375527}, issn = {1664-302X}, abstract = {This study was conducted to investigate the effect of exogenous fecal microbiota transplantation on gut bacterial community structure, gut barrier and growth performance in recipient piglets. Twelve litters of Duroc × Landrace × Yorkshire piglets of the same birth and parity were weighed and divided into two groups. One group (recipient piglets) was inoculated orally with fecal microbiota suspension of healthy adult Jinhua pigs daily from day 1 to day 11. The other (control) was given orally the same volume of sterile physiological saline at the same time. The experiment lasted 27 days. The results showed that the relative abundance of Firmicutes, Prevotellaceae, Lachnospiraceae, Ruminococcus, Prevotella, and Oscillospira in the colon of recipient piglets was increased. Proteobacteria, Fusobacteriaceae, Clostridiaceae, Pasteuriaceae, Alcaligenaceae, Bacteroidaceae, Veillonellaceae, Sutterella, Escherichia, and Bacteroides in the colon of recipient piglets were decreased. An average daily weight gain of recipient piglets was increased, and diarrhea incidence of the recipient was decreased during the trial. Intestinal morphology and tight junction barrier of recipient piglets were improved. The optical density of sIgA+ cells, the number of goblet cells and relative expressions of MUC2 in the intestinal mucosa of recipient piglets were enhanced. Protein expressions of β-defensin 2 and mRNA expressions of TLR2 and TLR4 in the intestinal mucosa of recipient piglets were also increased. These findings supported that the exogenous fecal microbiota had significant effects on animal's growth performance, intestinal barrier function, and innate immune via modulating the composition of the gut microbiota.}, } @article {pmid29367525, year = {2017}, author = {Tanemoto, S and Sujino, T and Kanai, T}, title = {[Intestinal immune response is regulated by gut microbe].}, journal = {Nihon Rinsho Men'eki Gakkai kaishi = Japanese journal of clinical immunology}, volume = {40}, number = {6}, pages = {408-415}, doi = {10.2177/jsci.40.408}, pmid = {29367525}, issn = {1349-7413}, mesh = {Dysbiosis/immunology/microbiology/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology/*physiology ; Homeostasis/immunology ; Humans ; Inflammatory Bowel Diseases/immunology/microbiology/therapy ; Intestines/*immunology/*microbiology ; Symbiosis ; }, abstract = {Human Intestine has a diverse population of bacteria which induces pathogens to disrupt not only the intestinal homeostasis but whole body immune systems. Dysbiosis, the abnormal proliferation and reduction of the microbiota, breaks down the homeostasis of the immunity and metabolisms in the host. The evolution of the microbiota analysis technology contributed to reveal the molecular biological complex interaction between the microbiota and its host systemically as well as locally. Because several diseases are caused by the dysbiosis, fecal transplantation would be the new therapeutic target for them. It has been investigated in some intestinal diseases such as CD infection, or inflammatory bowel disease. Here, we review these symbiotic interactions and the current state for the clinical application.}, } @article {pmid29363436, year = {2018}, author = {Jamot, S and Raghunathan, V and Patel, K and Kelly, CR and Lim, SH}, title = {Factors Associated with the Use of Fecal Microbiota Transplant in Patients with Recurrent Clostridium difficile Infections.}, journal = {Infection control and hospital epidemiology}, volume = {39}, number = {3}, pages = {302-306}, doi = {10.1017/ice.2017.314}, pmid = {29363436}, issn = {1559-6834}, abstract = {OBJECTIVE To identify the factors associated with first Clostridium difficile infection (CDI) that predict fecal microbiota transplantation (FMT) for recurrent CDI DESIGN We carried out a retrospective single-center cohort study to compare the clinical characteristics of 200 patients who underwent FMT for recurrent CDI to 75 patients who did not. SETTING A single academic hospital in the United States PATIENTS Adult patients RESULTS The time from first to second CDI correlated to subsequent FMT use. Concomitant inflammatory bowel disease (IBD; P=.002), use of immunosuppressive therapy (P=.04), and use of metronidazole within 2 months before the first CDI (P=.02) correlated positively to subsequent FMT in univariate analysis. The use of oral vancomycin for first CDI was more common in those who required FMT than those who did not in univariate (P=.02) and multivariate (P=.03) analyses. In contrast, intravenous vancomycin use within 2 months before the first CDI reduced the risk for FMT in univariate P=.000003) and multivariate (P=.0001) analyses. Black patients with recurrent CDI were less likely to receive FMT than white patients (P=.00005). Patients who received FMT were also less likely to have comorbidities. CONCLUSIONS This study provides important insights into the factors predictive for FMT in patients with recurrent CDI and highlights the potential racial and medical characteristics that affect the access of the patients to FMT. Infect Control Hosp Epidemiol 2018;39:302-306.}, } @article {pmid29361092, year = {2018}, author = {Goyal, A and Yeh, A and Bush, BR and Firek, BA and Siebold, LM and Rogers, MB and Kufen, AD and Morowitz, MJ}, title = {Safety, Clinical Response, and Microbiome Findings Following Fecal Microbiota Transplant in Children With Inflammatory Bowel Disease.}, journal = {Inflammatory bowel diseases}, volume = {24}, number = {2}, pages = {410-421}, doi = {10.1093/ibd/izx035}, pmid = {29361092}, issn = {1536-4844}, abstract = {Background: The role of fecal microbiota transplant (FMT) in the treatment of pediatric inflammatory bowel disease (IBD) is unknown. The aims of this study were to assess safety, clinical response, and gut microbiome alterations in children with Crohn's disease (CD), ulcerative colitis (UC), or indeterminate colitis (IC).

Methods: In this open-label, single-center prospective trial, patients with IBD refractory to medical therapy underwent a single FMT by upper and lower endoscopy. Adverse events, clinical response, gut microbiome, and biomarkers were assessed at baseline, 1 week, 1 month, and 6 months following FMT.

Results: Twenty-one subjects were analyzed, with a median age of 12 years, of whom 57% and 28% demonstrated clinical response at 1 and 6 months post-FMT, respectively. Two CD patients were in remission at 6 months. Adverse events attributable to FMT were mild to moderate and self-limited. Patients prior to FMT showed decreased species diversity and significant microbiome compositional differences characterized by increased Enterobacteriaceae, Enterococcus, Haemophilus, and Fusobacterium compared with donors and demonstrated increased species diversity at 30 days post-FMT. At 6 months, these changes shifted toward baseline. Clinical responders had a higher relative abundance of Fusobacterium and a lower diversity at baseline, as well as a greater shift toward donor-like microbiome after FMT compared with nonresponders.

Conclusions: A single FMT is relatively safe and can result in a short-term response in young patients with active IBD. Responders possessed increased Fusobacterium prior to FMT and demonstrated more significant microbiome changes compared with nonresponders after FMT. Microbiome characteristics may help in predicting response.}, } @article {pmid29358877, year = {2018}, author = {Shen, ZH and Zhu, CX and Quan, YS and Yang, ZY and Wu, S and Luo, WW and Tan, B and Wang, XY}, title = {Relationship between intestinal microbiota and ulcerative colitis: Mechanisms and clinical application of probiotics and fecal microbiota transplantation.}, journal = {World journal of gastroenterology}, volume = {24}, number = {1}, pages = {5-14}, doi = {10.3748/wjg.v24.i1.5}, pmid = {29358877}, issn = {2219-2840}, mesh = {Animals ; Bacteria/*growth & development/immunology ; Colitis, Ulcerative/diagnosis/immunology/microbiology/*therapy ; Colon/immunology/*microbiology ; *Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Host-Pathogen Interactions ; Humans ; Probiotics/adverse effects/*therapeutic use ; Treatment Outcome ; }, abstract = {Ulcerative colitis (UC) is an inflammatory disease that mainly affects the colon and rectum. It is believed that genetic factors, host immune system disorders, intestinal microbiota dysbiosis, and environmental factors contribute to the pathogenesis of UC. However, studies on the role of intestinal microbiota in the pathogenesis of UC have been inconclusive. Studies have shown that probiotics improve intestinal mucosa barrier function and immune system function and promote secretion of anti-inflammatory factors, thereby inhibiting the growth of harmful bacteria in the intestine. Fecal microbiota transplantation (FMT) can reduce bowel permeability and thus the severity of disease by increasing the production of short-chain fatty acids, especially butyrate, which help maintain the integrity of the epithelial barrier. FMT can also restore immune dysbiosis by inhibiting Th1 differentiation, activity of T cells, leukocyte adhesion, and production of inflammatory factors. Probiotics and FMT are being increasingly used to treat UC, but their use is controversial because of uncertain efficacy. Here, we briefly review the role of intestinal microbiota in the pathogenesis and treatment of UC.}, } @article {pmid29358865, year = {2017}, author = {Liu, SX and Li, YH and Dai, WK and Li, XS and Qiu, CZ and Ruan, ML and Zou, B and Dong, C and Liu, YH and He, JY and Huang, ZH and Shu, SN}, title = {Fecal microbiota transplantation induces remission of infantile allergic colitis through gut microbiota re-establishment.}, journal = {World journal of gastroenterology}, volume = {23}, number = {48}, pages = {8570-8581}, doi = {10.3748/wjg.v23.i48.8570}, pmid = {29358865}, issn = {2219-2840}, mesh = {Colitis/immunology/microbiology/*therapy ; Diarrhea/immunology/microbiology/therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Hemorrhage/immunology/microbiology/therapy ; Gastrointestinal Microbiome/*immunology ; Humans ; Infant ; Male ; Recurrence ; Treatment Outcome ; }, abstract = {AIM: To investigate the impact of fecal microbiota transplantation (FMT) treatment on allergic colitis (AC) and gut microbiota (GM).

METHODS: We selected a total of 19 AC infants, who suffered from severe diarrhea/hematochezia, did not relieve completely after routine therapy or cannot adhere to the therapy, and were free from organ congenital malformations and other contraindications for FMT. Qualified donor-derived stools were collected and injected to the AC infants via a rectal tube. Clinical outcomes and follow-up observations were noted. Stools were collected from ten AC infants before and after FMT, and GM composition was assessed for infants and donors using 16S rDNA sequencing analysis.

RESULTS: After FMT treatment, AC symptoms in 17 infants were relieved within 2 d, and no relapse was observed in the next 15 mo. Clinical improvement was also detected in the other two AC infants who were lost to follow-up. During follow-up, one AC infant suffered from mild eczema and recovered shortly after hormone therapy. Based on the 16S rDNA analysis in ten AC infants, most of them (n = 6) had greater GM diversity after FMT. As a result, Proteobacteria decreased (n = 6) and Firmicutes increased (n = 10) in post-FMT AC infants. Moreover, Firmicutes accounted for the greatest proportion of GM in the patients. At the genus level, Bacteroides (n = 6), Escherichia (n = 8), and Lactobacillus (n = 4) were enriched in some AC infants after FMT treatment, but the relative abundances of Clostridium (n = 5), Veillonella (n = 7), Streptococcus (n = 6), and Klebsiella (n = 8) decreased dramatically.

CONCLUSION: FMT is a safe and effective method for treating pediatric patients with AC and restoring GM balance.}, } @article {pmid29358788, year = {2018}, author = {Radovanovic-Dinic, B and Tesic-Rajkovic, S and Grgov, S and Petrovic, G and Zivkovic, V}, title = {Irritable bowel syndrome - from etiopathogenesis to therapy.}, journal = {Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia}, volume = {162}, number = {1}, pages = {1-9}, doi = {10.5507/bp.2017.057}, pmid = {29358788}, issn = {1213-8118}, mesh = {Diet ; Exercise ; Fecal Microbiota Transplantation ; *Genetic Predisposition to Disease ; Humans ; Irritable Bowel Syndrome/*diagnosis/etiology/physiopathology/therapy ; Laxatives ; Parasympatholytics ; Patient Education as Topic ; Practice Guidelines as Topic ; Prevalence ; Probiotics ; Quality of Life ; Risk Factors ; *Risk Reduction Behavior ; Stress, Psychological/*complications ; }, abstract = {Irritable bowel syndrome (IBS) is a chronic and relapsing functional gastrointestinal disorder that affects 9-23% of the population across the world. Patients with IBS are often referred to gastroenterology, undergo various investigations, take various medicines, take time off work and have a poor quality of life. The pathophysiology of IBS is not yet completely understood and seems to be multifactorial. Many pathogenetic factors, in various combinations, and not all necessarily present in each patient, can play an important role. Discomfort or abdominal pain relieived by defacation, asociated with a change in stool form, is a typical clinical manifestation of IBS. Many factors, such as emotional stress and eating, may exacerbate the symptoms. A timely diagnosis of IBS is important so that treatment which will provide adequate symptomatic relief (diarrhoea, constipation, pain and boaring) can be introduced. The diagnosis of IBS is not confirmed by a specific test or structural abnormality. It is made using criteria based on clinical symptoms such as Rome criteria, unless the symptoms are thought to be atypical. Today the Rome Criteria IV is the current gold-standard for the diagnoses of IBS. Treatment of patients with IBS requires a multidisciplinary approach. Some patients respond well to non-pharmacological treatment, while others also require pharmacological treatment. This review will provide a summary of pathophysiology, diagnostic criteria and therapies for IBS.}, } @article {pmid29343312, year = {2018}, author = {Gopalsamy, SN and Sherman, A and Woodworth, MH and Lutgring, JD and Kraft, CS}, title = {Fecal Microbiota Transplant for Multidrug-Resistant Organism Decolonization Administered During Septic Shock.}, journal = {Infection control and hospital epidemiology}, volume = {39}, number = {4}, pages = {490-492}, doi = {10.1017/ice.2017.300}, pmid = {29343312}, issn = {1559-6834}, support = {UL1 TR002378/TR/NCATS NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; }, } @article {pmid29336930, year = {2018}, author = {Galpérine, T and Guery, B and , }, title = {Exploring ways to improve CDI outcomes.}, journal = {Medecine et maladies infectieuses}, volume = {48}, number = {1}, pages = {10-17}, doi = {10.1016/j.medmal.2017.10.009}, pmid = {29336930}, issn = {1769-6690}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Bacterial Vaccines ; Clostridium Infections/drug therapy/microbiology/prevention & control/*therapy ; Clostridium difficile/drug effects ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Immunization, Passive ; Recurrence ; Therapies, Investigational ; Treatment Outcome ; Vaccines, Synthetic ; }, abstract = {Clostridium difficile is an anaerobic spore-forming Gram-positive bacillus recognized as an evolving international health problem. Metronidazole and vancomycin were - until recently - the only drugs available to treat C. difficile infection (CDI). Better knowledge of the pathophysiology and the development of new drugs completely modified the management of initial episodes and recurrences of CDI. Fidaxomicin significantly reduced recurrences compared with vancomycin. New drugs are also currently evaluated (cadazolid, surotomycin, ridinilazole, rifaximin). Gut microbiota homeostasis was clearly shown to be a key determinant in recurrences as demonstrated by the development of gut microbiota transplantation and alternative microbiota substitution. Passive immunotherapy and vaccinal approaches are also currently being evaluated. In conclusion, CDI treatment has evolved with the development of new therapeutic pathways which now need to be implemented in international guidelines.}, } @article {pmid29336929, year = {2018}, author = {Heimann, SM and Cruz Aguilar, MR and Mellinghof, S and Vehreschild, MJGT}, title = {Economic burden and cost-effective management of Clostridium difficile infections.}, journal = {Medecine et maladies infectieuses}, volume = {48}, number = {1}, pages = {23-29}, doi = {10.1016/j.medmal.2017.10.010}, pmid = {29336929}, issn = {1769-6690}, mesh = {Anti-Bacterial Agents/economics/therapeutic use ; Australia ; Case-Control Studies ; Clostridium Infections/diagnosis/*economics/therapy ; Cohort Studies ; Colonoscopy/economics ; Cost of Illness ; Cost-Benefit Analysis ; Decision Support Techniques ; Disease Management ; Drug Costs ; Europe ; Hospitalization/economics ; Humans ; Length of Stay/economics ; Meta-Analysis as Topic ; Multicenter Studies as Topic ; North America ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridium difficile infection (CDI) is the most important cause of healthcare-associated infectious diarrhea in industrialized countries. We performed a literature review of the overall economic burden of initial and recurrent CDI as well as of the cost-effectiveness of the various treatment strategies applied in these settings. Even though analysis of health economic data is complicated by the limited comparability of results, our review identified several internationally consistent results. Authors from different countries have shown that recurrent CDI disproportionally contributes to the overall economic burden of CDI and therefore offers considerable saving potential. Subsequent cost-effectiveness analyses almost exclusively identified fidaxomicin as the preferred treatment option for initial CDI and fecal microbiota transplant (FMT) for recurrent CDI. Among the various FMT protocols, optimum results were obtained using early colonoscopy-based FMT.}, } @article {pmid29321764, year = {2017}, author = {Ekmekciu, I and von Klitzing, E and Neumann, C and Bacher, P and Scheffold, A and Bereswill, S and Heimesaat, MM}, title = {Fecal Microbiota Transplantation, Commensal Escherichia coli and Lactobacillus johnsonii Strains Differentially Restore Intestinal and Systemic Adaptive Immune Cell Populations Following Broad-spectrum Antibiotic Treatment.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {2430}, doi = {10.3389/fmicb.2017.02430}, pmid = {29321764}, issn = {1664-302X}, abstract = {The essential role of the intestinal microbiota in the well-functioning of host immunity necessitates the investigation of species-specific impacts on this interplay. Aim of this study was to examine the ability of defined Gram-positive and Gram-negative intestinal commensal bacterial species, namely Escherichia coli and Lactobacillus johnsonii, respectively, to restore immune functions in mice that were immunosuppressed by antibiotics-induced microbiota depletion. Conventional mice were subjected to broad-spectrum antibiotic treatment for 8 weeks and perorally reassociated with E. coli, L. johnsonii or with a complex murine microbiota by fecal microbiota transplantation (FMT). Analyses at days (d) 7 and 28 revealed that immune cell populations in the small and large intestines, mesenteric lymph nodes and spleens of mice were decreased after antibiotic treatment but were completely or at least partially restored upon FMT or by recolonization with the respective bacterial species. Remarkably, L. johnsonii recolonization resulted in the highest CD4+ and CD8+ cell numbers in the small intestine and spleen, whereas neither of the commensal species could stably restore those cell populations in the colon until d28. Meanwhile less efficient than FMT, both species increased the frequencies of regulatory T cells and activated dendritic cells and completely restored intestinal memory/effector T cell populations at d28. Furthermore, recolonization with either single species maintained pro- and anti-inflammatory immune functions in parallel. However, FMT could most effectively recover the decreased frequencies of cytokine producing CD4+ lymphocytes in mucosal and systemic compartments. E. coli recolonization increased the production of cytokines such as TNF, IFN-γ, IL-17, and IL-22, particularly in the small intestine. Conversely, only L. johnsonii recolonization maintained colonic IL-10 production. In summary, FMT appears to be most efficient in the restoration of antibiotics-induced collateral damages to the immune system. However, defined intestinal commensals such as E. coli and L. johnsonii have the potential to restore individual functions of intestinal and systemic immunity. In conclusion, our data provide novel insights into the distinct role of individual commensal bacteria in maintaining immune functions during/following dysbiosis induced by antibiotic therapy thereby shaping host immunity and might thus open novel therapeutical avenues in conditions of perturbed microbiota composition.}, } @article {pmid29316256, year = {2018}, author = {Zhang, Z and Liu, L and Tang, H and Jiao, W and Zeng, S and Xu, Y and Zhang, Q and Sun, Z and Mukherjee, A and Zhang, X and Hu, X}, title = {Immunosuppressive effect of the gut microbiome altered by high-dose tacrolimus in mice.}, journal = {American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons}, volume = {18}, number = {7}, pages = {1646-1656}, doi = {10.1111/ajt.14661}, pmid = {29316256}, issn = {1600-6143}, abstract = {The alterations induced in gut microbiota by tacrolimus may affect immune function and organ transplantation. Mice were treated with high-dose tacrolimus for 14 days. The fecal microbiota were analyzed by pyrosequencing the 16S rRNA genes, and the effect on metabolism was predicted using the sequence data. The subgroups of T cells in the serum, gut-associated lymphoid tissue, and draining lymph nodes were determined by flow cytometry. Tacrolimus treatment significantly altered the relative abundance of Allobaculum, Bacteroides, and Lactobacillus and CD4+ CD25hi FoxP3+ regulatory T cells in the colonic mucosa and the circulation. These were significantly increased after either tacrolimus treatment or treatment by fecal microbiota transfer from tacrolimus-treated donors. Further, treatment with low-dose tacrolimus plus fecal microbiota transfer from high-dose tacrolimus-altered mice increased skin allograft survival rate in a skin transplantation model. Thus, high-dose tacrolimus alters the compositions and taxa of the gut microbiota. Administration of these conditioned gut microbiota plus low-dose tacrolimus resulted in regulation of colonic and systemic immune responses and an increased allograft survival rate. This study demonstrated a new strategy for controlling allograft rejection by combining an immunosuppressive agent with gut microbiome transplantation.}, } @article {pmid29312905, year = {2017}, author = {Ge, T and Wang, Y and Che, Y and Xiao, Y and Zhang, T}, title = {Atypical Late-Onset Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome with Intractable Diarrhea: A Case Report.}, journal = {Frontiers in pediatrics}, volume = {5}, number = {}, pages = {267}, doi = {10.3389/fped.2017.00267}, pmid = {29312905}, issn = {2296-2360}, abstract = {Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare life threatening congenital autoimmune disorder caused by mutations in the forkhead box protein 3 (FOXP3) gene. The main typical clinical manifestations of IPEX are enteropathy, type 1 diabetes mellitus, and skin diseases, which usually appear in the first months of life and cause death without treatment. Here, we report a 6-year-old boy with late-onset IPEX syndrome due to a c.1190G>A (p. R397Q) mutation in exon 11 of the FOXP3 gene. The boy had intractable diarrhea, abdominal pain, recurrent infections, and failure to thrive. However, diabetes and skin diseases were not observed in the patient. The patient was received metronidazole, teicoplanin, fluconazole, mycamine, ceftriaxone, azithromycin, and fecal microbiota transplantation for treating infections, methylprednisolone and infliximab for suspicion of Crohn's disease after admission. Finally, the boy was diagnosed as IPEX syndrome by genetic test and received hematopoietic stem cell transplantation (HSCT). Our findings suggests that IPEX should be considered in cases of late-onset, mild forms, and less typical clinical manifestations to avoid diagnostic delay.}, } @article {pmid29312263, year = {2017}, author = {von Klitzing, E and Ekmekciu, I and Bereswill, S and Heimesaat, MM}, title = {Intestinal and Systemic Immune Responses upon Multi-drug Resistant Pseudomonas aeruginosa Colonization of Mice Harboring a Human Gut Microbiota.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {2590}, doi = {10.3389/fmicb.2017.02590}, pmid = {29312263}, issn = {1664-302X}, abstract = {The World Health Organization has rated multi-drug resistant (MDR) Pseudomonas aeruginosa as serious threat for human health. It is, however, unclear, whether intestinal MDR P. aeruginosa carriage is associated with inflammatory responses in intestinal or even systemic compartments. In the present study, we generated with respect to their microbiota "humanized" mice by human fecal microbiota transplantation of secondary abiotic mice. Following peroral challenge with a clinical P. aeruginosa isolate on two consecutive days, mice harboring a human or murine microbiota were only partially protected from stable intestinal P. aeruginosa colonization given that up to 78% of mice were P. aeruginosa-positive at day 28 post-infection (p.i.). Irrespective of the host-specificity of the microbiota, P. aeruginosa colonized mice were clinically uncompromised. However, P. aeruginosa colonization resulted in increased intestinal epithelial apoptosis that was accompanied by pronounced proliferative/regenerative cell responses. Furthermore, at day 7 p.i. increased innate immune cell populations such as macrophages and monocytes could be observed in the colon of mice harboring either a human or murine microbiota, whereas this held true at day 28 p.i. for adaptive immune cells such as B lymphocytes in both the small and large intestines of mice with murine microbiota. At day 7 p.i., pro-inflammatory cytokine secretion was enhanced in the colon and mesenteric lymph nodes, whereas the anti-inflammatory cytokine IL-10 was down-regulated in the former at day 28 p.i. Strikingly, cytokine responses upon intestinal P. aeruginosa colonization were not restricted to the intestinal tract, but could also be observed systemically, given that TNF and IFN-γ concentrations were elevated in spleens as early as 7 days p.i., whereas splenic IL-10 levels were dampened at day 28 p.i. of mice with human microbiota. In conclusion, mere intestinal carriage of MDR P. aeruginosa by clinically unaffected mice results in pro-inflammatory sequelae not only in intestinal, but also systemic compartments.}, } @article {pmid29311138, year = {2018}, author = {Gao, XJ and Li, T and Wei, B and Yan, ZX and Hu, N and Huang, YJ and Han, BL and Wai, TS and Yang, W and Yan, R}, title = {Bacterial Outer Membrane Vesicles from Dextran Sulfate Sodium-Induced Colitis Differentially Regulate Intestinal UDP-Glucuronosyltransferase 1A1 Partially Through Toll-Like Receptor 4/Mitogen-Activated Protein Kinase/Phosphatidylinositol 3-Kinase Pathway.}, journal = {Drug metabolism and disposition: the biological fate of chemicals}, volume = {46}, number = {3}, pages = {292-302}, doi = {10.1124/dmd.117.079046}, pmid = {29311138}, issn = {1521-009X}, mesh = {Animals ; Bacterial Outer Membrane Proteins/*metabolism ; Caco-2 Cells ; Colitis/*metabolism ; Colon/metabolism ; Dextran Sulfate/*metabolism ; Gastrointestinal Microbiome/physiology ; Glucuronosyltransferase/*metabolism ; Humans ; Male ; Mitogen-Activated Protein Kinases/*metabolism ; Phosphatidylinositol 3-Kinases/*metabolism ; Rats ; Rats, Sprague-Dawley ; Toll-Like Receptor 4/*metabolism ; }, abstract = {UDP-glucuronosyltransferase 1A1 (UGT1A1) constitutes an important part of intestinal epithelial barrier and catalyzes glucuronidation of many endogenous compounds and drugs. Downregulation of UGT1A1 in inflammation has been reported, whereas the association with gut dysbiosis is poorly defined. This study verified the involvement of gut microbiota in intestinal UGT1A1 regulation using dextran sulfate sodium (DSS)-induced rat colitis model plus fecal microbiota transplantation (FMT). Generally, both DSS induction and colitis-to-normal FMT suppressed mRNA and protein expressions of UGT1A1 and nuclear xenobiotic receptors (NRs) in colon, but enhanced mRNA and decreased protein of rat UGT1A1/rat NRs in small intestine. Normal-to-colitis FMT alleviated DSS-induced changes. Bacterial outer membrane vesicles (OMVs) from colitis rats and rats receiving colitis feces reduced both mRNA and protein of human UGT1A1 (hUGT1A1)/human NRs (hNRs) in Caco-2 cells. Interestingly, using deoxycholate to reduce lipopolysaccharide, normal OMVs upregulated hUGT1A1/hNRs, whereas colitis OMVs decreased, indicating the involvement of other OMVs components in UGT1A1 regulation. The 10- to 50-kDa fractions from both normal and colitis OMVs downregulated hUGT1A1, human PXR, and human PPAR-γ, whereas >50-kDa fractions from normal rats upregulated hUGT1A1 and human CAR. Additionally, the conditioned medium from OMVs-stimulated rat primary macrophages also reduced hUGT1A1/hNRs expression. Both Toll-like receptor (TLR)2 and TLR4 were activated by DSS, colitis-to-normal FMT, and the opposite, whereas only TLR4 was increased in OMVs-treated cells. TLR4 small interfering RNA blocked hUGT1A1/hNRs downregulation and phosphatidylinositol 3-kinase/Akt, extracellular signal-regulated kinase, and nuclear factor κB phosphorylation evoked by bacterial OMVs. Taken together, this study demonstrated that gut microbiota regulate intestinal UGT1A1 partially through secreting OMVs, which interact with intestinal epithelial cells directly or via activating macrophage.}, } @article {pmid29311119, year = {2018}, author = {Clemente, JC and Manasson, J and Scher, JU}, title = {The role of the gut microbiome in systemic inflammatory disease.}, journal = {BMJ (Clinical research ed.)}, volume = {360}, number = {}, pages = {j5145}, pmid = {29311119}, issn = {1756-1833}, support = {S10 OD018522/OD/NIH HHS/United States ; T32 AR069515/AR/NIAMS NIH HHS/United States ; K23 AR064318/AR/NIAMS NIH HHS/United States ; R03 AR072182/AR/NIAMS NIH HHS/United States ; }, mesh = {Autoimmune Diseases/immunology/*microbiology ; Fecal Microbiota Transplantation/methods ; Feeding Behavior/*physiology ; Gastrointestinal Microbiome/*immunology/physiology ; Humans ; Inflammation/immunology/*microbiology ; Inflammatory Bowel Diseases/immunology/*microbiology/pathology ; Microbiota ; Mucous Membrane/immunology/*microbiology ; Prebiotics ; Probiotics ; }, abstract = {The role of the gut microbiome in models of inflammatory and autoimmune disease is now well characterized. Renewed interest in the human microbiome and its metabolites, as well as notable advances in host mucosal immunology, has opened multiple avenues of research to potentially modulate inflammatory responses. The complexity and interdependence of these diet-microbe-metabolite-host interactions are rapidly being unraveled. Importantly, most of the progress in the field comes from new knowledge about the functional properties of these microorganisms in physiology and their effect in mucosal immunity and distal inflammation. This review summarizes the preclinical and clinical evidence on how dietary, probiotic, prebiotic, and microbiome based therapeutics affect our understanding of wellness and disease, particularly in autoimmunity.}, } @article {pmid29309934, year = {2018}, author = {Ooijevaar, RE and van Beurden, YH and Terveer, EM and Goorhuis, A and Bauer, MP and Keller, JJ and Mulder, CJJ and Kuijper, EJ}, title = {Update of treatment algorithms for Clostridium difficile infection.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {24}, number = {5}, pages = {452-462}, doi = {10.1016/j.cmi.2017.12.022}, pmid = {29309934}, issn = {1469-0691}, mesh = {Algorithms ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Clinical Trials as Topic ; Clostridium Infections/*microbiology/*therapy ; Clostridium difficile/*drug effects/physiology ; Disease Management ; Drug Discovery ; Fecal Microbiota Transplantation ; Humans ; Practice Guidelines as Topic ; }, abstract = {BACKGROUND: Clostridium difficile is the leading cause of antibiotic-associated diarrhoea, both in healthcare facilities and in the community. The recurrence rate of C. difficile infection (CDI) remains high, up to 20%. Since the publication of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidance document on CDI treatment in 2014, new therapeutic approaches have been developed and tested to achieve higher sustained clinical cure in CDI.

AIM: To review novel treatments and approaches for CDI, except probiotics and vaccines. We focused on new antibiotics, antibiotic inactivators, monoclonal antibodies and gut microbiota modulating therapies.

SOURCES: A literature review was performed for clinical trials published in PubMed, Embase or Cochrane Library between January 2013 and November 2017.

CONTENT: We analysed 28 clinical trials and identified 14 novel agents. Completed phase 2 studies were found for cadazolid, LFF571, ridinilazole and nontoxigenic C. difficile strains. Four phase 3 active comparator studies comparing vancomycin with bezlotoxumab, surotomycin (n = 2) and rifaximin have been published. Seven clinical trials for treatment of multiple recurrent CDI with faecal microbiota transplantation were analysed, describing faecal microbiota transplantation by upper or lower gastrointestinal route (n = 5) or by capsules (n = 2).

IMPLICATIONS: Metronidazole is mentioned in the ESCMID guideline as first-line therapy, but we propose that oral vancomycin will become the first choice when antibiotic treatment for CDI is necessary. Fidaxomicin is a good alternative, especially in patients at risk of relapse. Vancomycin combined with faecal microbiota transplantation remains the primary therapy for multiple recurrent CDI. We anticipate that new medication that protects the gut microbiota will be further developed and tested to prevent CDI during antibiotic therapy.}, } @article {pmid29299467, year = {2017}, author = {Juncadella, AC and Moss, A}, title = {Fecal microbiota transplantation as a possible treatment of irritable bowel syndrome.}, journal = {Annals of translational medicine}, volume = {5}, number = {24}, pages = {506}, doi = {10.21037/atm.2017.09.13}, pmid = {29299467}, issn = {2305-5839}, } @article {pmid29299452, year = {2017}, author = {Craven, LJ and Silverman, M and Burton, JP}, title = {Transfer of altered behaviour and irritable bowel syndrome with diarrhea (IBS-D) through fecal microbiota transplant in mouse model indicates need for stricter donor screening criteria.}, journal = {Annals of translational medicine}, volume = {5}, number = {24}, pages = {490}, doi = {10.21037/atm.2017.10.03}, pmid = {29299452}, issn = {2305-5839}, } @article {pmid29290658, year = {2017}, author = {Zhang, J and Ren, FG and Liu, P and Zhang, HK and Zhu, HY and Feng, Z and Zhang, XF and Wang, B and Liu, XM and Zhang, XG and Wu, RQ and Lv, Y}, title = {Characteristics of fecal microbial communities in patients with non-anastomotic biliary strictures after liver transplantation.}, journal = {World journal of gastroenterology}, volume = {23}, number = {46}, pages = {8217-8226}, doi = {10.3748/wjg.v23.i46.8217}, pmid = {29290658}, issn = {2219-2840}, mesh = {Adult ; Bacteria/genetics/*isolation & purification/pathogenicity ; Biliary Tract Diseases/etiology/*microbiology ; Constriction, Pathologic/etiology/microbiology ; DNA, Bacterial/isolation & purification ; Dysbiosis/etiology/microbiology ; End Stage Liver Disease/surgery ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Liver Transplantation/*adverse effects ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {AIM: To explore the possible relationship between fecal microbial communities and non-anastomotic stricture (NAS) after liver transplantation (LT).

METHODS: A total of 30 subjects including 10 patients with NAS, 10 patients with no complications after LT, and 10 non-LT healthy individuals were enrolled. Fecal microbial communities were assessed by the 16S rRNA gene sequencing technology.

RESULTS: Different from the uncomplicated and healthy groups, unbalanced fecal bacterium ratio existed in patients with NAS after LT. The results showed that NAS patients were associated with a decrease of Firmicutes and Bacteroidetes and an increase of Proteobacteria at the phylum level, with the proportion-ratio imbalance between potential pathogenic families including Enterococcaceae, Streptococcaceae, Enterobacteriaceae, Pseudomonadaceae and dominant families including Bacteroidaceae.

CONCLUSION: The compositional shifts of the increase of potential pathogenic bacteria as well as the decrease of dominant bacteria might contribute to the incidence of NAS.}, } @article {pmid29285689, year = {2018}, author = {Nishida, A and Inoue, R and Inatomi, O and Bamba, S and Naito, Y and Andoh, A}, title = {Gut microbiota in the pathogenesis of inflammatory bowel disease.}, journal = {Clinical journal of gastroenterology}, volume = {11}, number = {1}, pages = {1-10}, doi = {10.1007/s12328-017-0813-5}, pmid = {29285689}, issn = {1865-7265}, mesh = {Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/drug effects/*physiology ; Humans ; Immunity, Innate ; Inflammatory Bowel Diseases/*microbiology/therapy ; Nutritional Physiological Phenomena ; Probiotics/therapeutic use ; }, abstract = {Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a chronic and relapsing inflammatory disorder of the intestine. Although its incidence is increasing globally, the precise etiology remains unclear and a cure for IBD has yet to be discovered. The most accepted hypothesis of IBD pathogenesis is that complex interactions between genetics, environmental factors, and the host immune system lead to aberrant immune responses and chronic intestinal inflammation. The human gut harbors a complex and abundant aggregation of microbes, collectively referred to as the gut microbiota. The gut microbiota has physiological functions associated with nutrition, the immune system, and defense of the host. Recent advances in next-generation sequencing technology have identified alteration of the composition and function of the gut microbiota, which is referred to as dysbiosis, in IBD. Clinical and experimental data suggest dysbiosis may play a pivotal role in the pathogenesis of IBD. This review is focused on the physiological function of the gut microbiota and the association between the gut microbiota and pathogenesis in IBD. In addition, we review the therapeutic options for manipulating the altered gut microbiota, such as probiotics and fecal microbiota transplantation.}, } @article {pmid29280116, year = {2017}, author = {Zhang, X and Tian, H and Ma, C and Yang, B and Hua, Y and Zhu, Y and Gu, L and Li, N}, title = {[Efficacy observation of periodic fecal microbiota transplantation in the treatment of refractory constipation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {20}, number = {12}, pages = {1355-1359}, pmid = {29280116}, issn = {1671-0274}, abstract = {OBJECTIVE: To evaluate the efficacy of periodic fecal microbiota transplantation (FMT) for refractory constipation.

METHODS: Clinical data of 49 patients with refractory constipation undergoing FMT through standard transplantation path of nasojejunal tube between April 2015 and April 2016 in Intestinal Microenvironment Treatment Centre of Nanjing General Hospital were analyzed retrospectively. Of 49 patients, 25 received single FMT for only 6 days (single group), and 24 received periodic FMT with another 6 days FMT 1 month after the first 6 days FMT (periodic group). The follow up was at 12 weeks after treatment. Autonomous defecation frequency, Wexner constipation score, gastrointestinal quality of life index and related adverse reaction were evaluated and compared at 4-, 8- and 12-week after treatment. Statistical analysis was performed on the difference after treatment at each time point, and the greater difference indicated the better improvement.

RESULTS: There were no statistically significant differences in general characteristics between the two groups (all P<0.05). Before treatment, Wexner constipation score was 17.32±2.66 and 16.25±2.47, gastrointestinal quality of life index was 81.84±8.73 and 83.25±7.87, autonomous defecation frequency was (1.64±0.57) time/week and (1.42±0.65) time/week in single group and periodic group respectively, whose differences were not significant (all P>0.05). Compared with before FMT treatment, the autonomous defecation frequency, Wexner constipation score, gastrointestinal quality of life index were obviously improved at the 4-, 8-, 12-week (all P=0.000). At the 4-week after FMT treatment, the improvement degree of autonomous defecation frequency, Wexner constipation score, gastrointestinal quality of life index was compared between two groups, and no statistically significant differences were found (all P>0.05). While at 8-week and 12-week after FMT treatment, as compared to single group, periodic group had greater Wexner constipation score (at 8-week: 7.29±2.05 vs. 5.96±2.30, t=2.135, P=0.038; at 12-week: 7.21±1.98 vs. 5.80±2.43, t=2.218, P=0.031), greater gastrointestinal quality of life index (at 8-week: 25.71±8.91 vs. 20.20±8.53, t=2.211, P=0.032; at 12-week: 24.16±8.99 vs. 18.92±8.28, t=2.127, P=0.039) and better autonomous defecation frequency [at 8-week: (2.42±0.93) time/week vs. (1.72±0.61) time/week, t=3.110, P=0.003; at 12-week: (1.37±0.88) time/week vs. (0.84±0.62) time/week, t=2.454, P=0.018].

CONCLUSION: Periodic FMT has better efficacy than single FMT in the treatment of refractory constipation.}, } @article {pmid29278509, year = {2017}, author = {Kang, Y and Cai, Y}, title = {Gut microbiota and obesity: implications for fecal microbiota transplantation therapy.}, journal = {Hormones (Athens, Greece)}, volume = {16}, number = {3}, pages = {223-234}, doi = {10.14310/horm.2002.1742}, pmid = {29278509}, issn = {2520-8721}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Metabolic Syndrome/*microbiology/*therapy ; Obesity/*microbiology/*therapy ; }, abstract = {Obesity is a major public health issue as it is causally associated with several chronic disorders, including type-2 diabetes, cerebrovascular disease (CVD), and cancer. In the United States and other countries worldwide, the obesity epidemic has drastically impacted the status of health of millions as well as healthcare costs. Aside from poor diet, hygiene, and genetics, there are many other factors thought to play an important role in the emergence of obesity. Nowadays, accumulating evidence is elucidating the relation of dysbiosis of intestinal bacteria with obesity and metabolic disorders. Certain gut microbial strains have been shown to inhibit or attenuate immune responses related to chronic inflammation in experimental models, suggesting that specific species among gut microbiota may play either a protective or a pathogenic role in the progression of obesity. Fecal microbiota transplantation (FMT) can therefore represent a therapeutic approach for obesity treatment. FMT is a relatively straightforward therapy that manipulates the human gastrointestinal (GI) microbiota by transferring healthy donor microbiota into an existing but disturbed microbial ecosystem. However, the relevant scientific work is still in its early stages. In this review, we summarize the cutting-edge research being done into FMT treatment of obesity, current issues in FMT treatment, and the future of FMT and microbial therapeutics.}, } @article {pmid29277311, year = {2018}, author = {Yang, Y and Tian, J and Yang, B}, title = {Targeting gut microbiome: A novel and potential therapy for autism.}, journal = {Life sciences}, volume = {194}, number = {}, pages = {111-119}, doi = {10.1016/j.lfs.2017.12.027}, pmid = {29277311}, issn = {1879-0631}, mesh = {Animals ; Autism Spectrum Disorder/*microbiology/pathology/*therapy ; Brain/pathology ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Humans ; Probiotics/*therapeutic use ; }, abstract = {Autism spectrum disorder (ASD) is a severely neurodevelopmental disorder that impairs a child's ability to communicate and interact with others. Children with neurodevelopmental disorder, including ASD, are regularly affected by gastrointestinal problems and dysbiosis of gut microbiota. On the other hand, humans live in a co-evolutionary association with plenty of microorganisms that resident on the exposed and internal surfaces of our bodies. The microbiome, refers to the collection of microbes and their genetic material, confers a variety of physiologic benefits to the host in many key aspects of life as well as being responsible for some diseases. A large body of preclinical literature indicates that gut microbiome plays an important role in the bidirectional gut-brain axis that communicates between the gut and central nervous system. Moreover, accumulating evidences suggest that the gut microbiome is involved in the pathogenesis of ASD. The present review introduces the increasing evidence suggesting the reciprocal interaction network among microbiome, gut and brain. It also discusses the possible mechanisms by which gut microbiome influences the etiology of ASD via altering gut-brain axis. Most importantly, it highlights the new findings of targeting gut microbiome, including probiotic treatment and fecal microbiota transplant, as novel and potential therapeutics for ASD diseases.}, } @article {pmid29276171, year = {2018}, author = {Schroeder, BO and Birchenough, GMH and Ståhlman, M and Arike, L and Johansson, MEV and Hansson, GC and Bäckhed, F}, title = {Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration.}, journal = {Cell host & microbe}, volume = {23}, number = {1}, pages = {27-40.e7}, doi = {10.1016/j.chom.2017.11.004}, pmid = {29276171}, issn = {1934-6069}, support = {U01 AI095473/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bifidobacterium longum/*metabolism ; Colon/*microbiology/pathology ; Diet, Western/*adverse effects ; Dietary Fiber/*therapeutic use ; Dietary Supplements ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Intestinal Mucosa/*microbiology/pathology ; Inulin/therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/pathology ; }, abstract = {Diet strongly affects gut microbiota composition, and gut bacteria can influence the colonic mucus layer, a physical barrier that separates trillions of gut bacteria from the host. However, the interplay between a Western style diet (WSD), gut microbiota composition, and the intestinal mucus layer is less clear. Here we show that mice fed a WSD have an altered colonic microbiota composition that causes increased penetrability and a reduced growth rate of the inner mucus layer. Both barrier defects can be prevented by transplanting microbiota from chow-fed mice. In addition, we found that administration of Bifidobacterium longum was sufficient to restore mucus growth, whereas administration of the fiber inulin prevented increased mucus penetrability in WSD-fed mice. We hypothesize that the presence of distinct bacteria is crucial for proper mucus function. If confirmed in humans, these findings may help to better understand diseases with an affected mucus layer, such as ulcerative colitis.}, } @article {pmid29274895, year = {2018}, author = {Lifschitz, C and Sieczkowska, A}, title = {New insights into the fecal microbiota of children living in a slum: association with small bowel bacterial overgrowth.}, journal = {Jornal de pediatria}, volume = {94}, number = {5}, pages = {455-457}, doi = {10.1016/j.jped.2017.12.002}, pmid = {29274895}, issn = {1678-4782}, } @article {pmid29272401, year = {2018}, author = {Mamo, Y and Woodworth, MH and Wang, T and Dhere, T and Kraft, CS}, title = {Durability and Long-term Clinical Outcomes of Fecal Microbiota Transplant Treatment in Patients With Recurrent Clostridium difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {11}, pages = {1705-1711}, doi = {10.1093/cid/cix1097}, pmid = {29272401}, issn = {1537-6591}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; }, abstract = {Background: Fecal microbiota transplant (FMT) appears safe and effective for treatment of recurrent Clostridium difficile infection (RCDI). However, durability, long-term clinical outcomes, and patient satisfaction after FMT are not well described.

Methods: Eligible patients who received FMT for RCDI at Emory Hospital between 1 July 2012 and 31 December 2016 were contacted via telephone for a follow-up survey. Of 190 eligible patients, 137 (72%) completed the survey.

Results: Median time from last FMT to follow-up was 22 months. Overall, 82% (113/137) of patients at follow-up had no recurrence of C. difficile infection (CDI) post-FMT (non-RCDI group) and 18% (24/137) of patients had CDI post-FMT (RCDI group). Antibiotic exposure for non-CDI infections after FMT was more common in the RCDI group compared to the non-RCDI group (75% vs 38%, P = .0009). Overall, 11% of patients reported improvement or resolution of diagnoses not related to CDI post-FMT, and 33% reported development of a new medical condition or symptom post-FMT. Ninety-five percent of patients (122/128) indicated that they would undergo FMT again, and 70% of these 122 reported that they would prefer FMT to antibiotics as initial treatment if they were to have a CDI recurrence.

Conclusions: In this follow-up survey of outcomes after FMT at a median of 22 months follow-up, 82% of patients had durable cure of CDI. Patients with recurrence had more post-FMT antibiotic exposure, underscoring the need for thoughtful antibiotic use and a potential role for prophylactic microbiome enrichment to reduce recurrence.}, } @article {pmid29272347, year = {2018}, author = {Davido, B and Salomon, J and Lawrence, C and Duran, C and Batista, R and de Truchis, P and Dinh, A}, title = {Impact of Fecal Microbiota Transplantation for Decolonization of Multidrug-Resistant Organisms May Vary According to Donor Microbiota.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {8}, pages = {1316-1317}, doi = {10.1093/cid/cix963}, pmid = {29272347}, issn = {1537-6591}, } @article {pmid29271225, year = {2018}, author = {Sebastián Domingo, JJ and Sánchez Sánchez, C}, title = {From the intestinal flora to the microbiome.}, journal = {Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva}, volume = {110}, number = {1}, pages = {51-56}, doi = {10.17235/reed.2017.4947/2017}, pmid = {29271225}, issn = {1130-0108}, mesh = {Gastroenterology/*history ; Gastrointestinal Diseases/microbiology ; *Gastrointestinal Microbiome ; History, 17th Century ; History, 19th Century ; Humans ; Intestines/*microbiology ; }, abstract = {In this article, the history of the microbiota is reviewed and the related concepts of the microbiota, microbiome, metagenome, pathobiont, dysbiosis, holobiont, phylotype and enterotype are defined. The most precise and current knowledge about the microbiota is presented and the metabolic, nutritional and immunomodulatory functions are reviewed. Some gastrointestinal diseases whose pathogenesis is associated with the intestinal microbiota, including inflammatory bowel disease, irritable bowel syndrome and celiac disease, among others, are briefly discussed. Finally, some prominent and promising data with regard to the fecal microbiota transplantation in certain digestive illness are discussed.}, } @article {pmid29270794, year = {2017}, author = {Qin, C and Zhang, H and Zhao, L and Zeng, M and Huang, W and Fu, G and Zhou, W and Wang, H and Yan, H}, title = {Microbiota transplantation reveals beneficial impact of berberine on hepatotoxicity by improving gut homeostasis.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11427-017-9202-0}, pmid = {29270794}, issn = {1869-1889}, abstract = {Berberine has been shown to reduce acute liver injury although the underlying mechanism is not fully understood. Because of the anatomic connection, the liver is constantly exposed to gut-derived bacterial products and metabolites. In this study, we showed that berberine has beneficial effects on both hepatotoxicity and intestinal damage in a rat model of chronic or acute liver injury. Microbiota transplantation from the rats with chronic hepatotoxicity could aggravate acute hepatotoxicity in mice treated with diethylnitrosamine (DEN). In rat models with gut homeostasis disruption induced by penicillin or dextran sulfate sodium (DSS), their fecal microbiota could also cause an enhanced hepatotoxicity of recipient mice. When treated with berberine, the DSS-induced enteric dysbacteriosis could be mitigated and their fecal bacteria were able to reduce acute hepatotoxicity in recipient mice. This study indicates that berberine could improve intestinal dysbacteriosis, which reduces the hepatotoxicity caused by pathological or pharmacological intervention. Fecal microbiota transplantation might be a useful method to directly explore homeostatic alteration in gut microbiota.}, } @article {pmid29261736, year = {2017}, author = {Camacho-Ortiz, A and Gutiérrez-Delgado, EM and Garcia-Mazcorro, JF and Mendoza-Olazarán, S and Martínez-Meléndez, A and Palau-Davila, L and Baines, SD and Maldonado-Garza, H and Garza-González, E}, title = {Randomized clinical trial to evaluate the effect of fecal microbiota transplant for initial Clostridium difficile infection in intestinal microbiome.}, journal = {PloS one}, volume = {12}, number = {12}, pages = {e0189768}, doi = {10.1371/journal.pone.0189768}, pmid = {29261736}, issn = {1932-6203}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacteria/genetics ; Biodiversity ; Clostridium Infections/drug therapy/*therapy ; Demography ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/genetics ; Genotype ; Humans ; Male ; Metagenomics ; Microbial Sensitivity Tests ; Middle Aged ; Phylogeny ; Principal Component Analysis ; RNA, Ribosomal, 16S/genetics ; Species Specificity ; Tissue Donors ; Vancomycin/therapeutic use ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate the impact of fecal donor-unrelated donor mix (FMT-FURM) transplantation as first-line therapy for C. difficile infection (CDI) in intestinal microbiome.

METHODS: We designed an open, two-arm pilot study with oral vancomycin (250mg every 6 h for 10-14 days) or FMT-FURM as treatments for the first CDI episode in hospitalized adult patients in Hospital Universitario "Dr. Jose Eleuterio Gonzalez". Patients were randomized by a closed envelope method in a 1: 1 ratio to either oral vancomycin or FMT-FURM. CDI resolution was considered when there was a reduction on the Bristol scale of at least 2 points, a reduction of at least 50% in the number of bowel movements, absence of fever, and resolution of abdominal pain (at least two criteria). From each patient, a fecal sample was obtained at days 0, 3, and 7 after treatment. Specimens were cultured to isolate C. difficile, and isolates were characterized by PCR. Susceptibility testing of isolates was performed using the agar dilution method. Fecal samples and FMT-FURM were analyzed by 16S rRNA sequencing.

RESULTS: We included 19 patients; 10 in the vancomycin arm and 9 in the FMT-FURM arm. However, one of the patients in the vancomycin arm and two patients in the FMT-FURM arm were eliminated. Symptoms resolved in 8/9 patients (88.9%) in the vancomycin group, while symptoms resolved in 4/7 patients (57.1%) after the first FMT-FURM dose (P = 0.26) and in 5/7 patients (71.4%) after the second dose (P = 0.55). During the study, no adverse effects attributable to FMT-FURM were observed in patients. Twelve isolates were recovered, most isolates carried tcdB, tcdA, cdtA, and cdtB, with an 18-bp deletion in tcdC. All isolates were resistant to ciprofloxacin and moxifloxacin but susceptible to metronidazole, linezolid, fidaxomicin, and tetracycline. In the FMT-FURM group, the bacterial composition was dominated by Firmicutes, Bacteroidetes, and Proteobacteria at all-time points and the microbiota were remarkably stable over time. The vancomycin group showed a very different pattern of the microbial composition when comparing to the FMT-FURM group over time.

CONCLUSION: The results of this preliminary study showed that FMT-FURM for initial CDI is associated with specific bacterial communities that do not resemble the donors' sample.}, } @article {pmid29257783, year = {2018}, author = {Akrami, K and Sweeney, DA}, title = {The microbiome of the critically ill patient.}, journal = {Current opinion in critical care}, volume = {24}, number = {1}, pages = {49-54}, doi = {10.1097/MCC.0000000000000469}, pmid = {29257783}, issn = {1531-7072}, mesh = {Clostridium Infections/microbiology/therapy ; Colitis, Ulcerative/microbiology/therapy ; *Critical Illness/therapy ; Dysbiosis/etiology/*microbiology/therapy ; Fecal Microbiota Transplantation ; Humans ; Intensive Care Units ; Microbiota/*physiology ; Pneumonia, Ventilator-Associated/microbiology/therapy ; Probiotics/therapeutic use ; Treatment Outcome ; }, abstract = {PURPOSE OF REVIEW: Advances in the understanding of the human microbiome outside of the ICU have led investigators to consider the role of the microbiome in critical illness. The picture that is being elucidated is one of dysbiosis occurring at multiple sites in the critically ill patient. This review describes the changes that occur in the various microbiomes of a critically ill patient, the implications of these changes and shows how advances in the understanding of dysbiosis may lead to microbiome-targeted therapies.

RECENT FINDINGS: Critically ill patients undergo dysbiosis at several organ sites including the skin, gastrointestinal system and the lungs with loss of microbial diversity and a propensity for potentially pathogenic organisms to dominate a particular microbiome. These microbiome changes appear to be predictive of clinical outcome. While the use of fecal microbial transplantation has been demonstrated to be an effective treatment for recurrent Clostridium difficile infection, the use of fecal microbial transplantation and other microbiome modifying therapies may have a role in managing critical illness in the ICU.

SUMMARY: A growing understanding of the microbiome in the critically ill may modify current dogma regarding the pathogenesis of sepsis and other life-threatening conditions seen in the ICU, thereby fundamentally changing antibiotic stewardship and the management of the critically ill patient.}, } @article {pmid29255739, year = {2017}, author = {Craven, LJ and Nair Parvathy, S and Tat-Ko, J and Burton, JP and Silverman, MS}, title = {Extended Screening Costs Associated With Selecting Donors for Fecal Microbiota Transplantation for Treatment of Metabolic Syndrome-Associated Diseases.}, journal = {Open forum infectious diseases}, volume = {4}, number = {4}, pages = {ofx243}, doi = {10.1093/ofid/ofx243}, pmid = {29255739}, issn = {2328-8957}, abstract = {Background: Knowledge of the impact of the gut microbiome on conditions other than Clostridium difficile infection has been rapidly increasing, and the potential usefulness of fecal microbiota transplantation (FMT) in these indications is being explored. The need to exclude donors with an increased risk of these diseases has left uncertainties regarding the cost and feasibility of donor screening. The aim of this study was to compare our experience to other donor-screening programs and report the costs associated with establishing a donor-screening program, for the treatment of metabolic syndrome-related conditions.

Methods: Forty-six potential donors (PDs) had their medical histories and physical examinations undertaken by a physician. Blood, stool, and urine were screened for 31 viral, bacterial, fungal, and protozoan agents in addition to biochemical characteristics. The price of advertising, doctor's visits and diagnostic tests were calculated to determine the cost of finding a donor.

Results: Of the PDs screened, 5 of 46 passed the history, examination, blood, stool, and urine tests. The most common reasons for exclusion included a body mass index >25 or the detection of Blastocystis hominis, Dientamoeba fragilis, or Helicobacter pylori. Four of five eligible donors had subsequent travel or illness that contraindicated donation, so only 1 of 46 PDs was suitable. The total cost for finding a single suitable donor was $15190 US dollars. This screening was performed in Canada, and costs in the United States would be substantially higher.

Conclusions: New potential therapeutic uses for FMT have created a demand for stricter exclusion criteria for donors. This study illustrates that screening many individuals to find a donor and the subsequent associated costs may make central processing and shipment a more reasonable alternative.}, } @article {pmid29246701, year = {2018}, author = {Fischer, M and Kao, D and Kassam, Z and Smith, J and Louie, T and Sipe, B and Torbeck, M and Xu, H and Ouyang, F and Mozaffarian, D and Allegretti, JR}, title = {Stool Donor Body Mass Index Does Not Affect Recipient Weight After a Single Fecal Microbiota Transplantation for Clostridium difficile Infection.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {16}, number = {8}, pages = {1351-1353}, doi = {10.1016/j.cgh.2017.12.007}, pmid = {29246701}, issn = {1542-7714}, } @article {pmid29242336, year = {2017}, author = {Hoffmann, D and Palumbo, F and Ravel, J and Roghmann, MC and Rowthorn, V and von Rosenvinge, E}, title = {Improving regulation of microbiota transplants.}, journal = {Science (New York, N.Y.)}, volume = {358}, number = {6369}, pages = {1390-1391}, doi = {10.1126/science.aaq0034}, pmid = {29242336}, issn = {1095-9203}, support = {R21 AI119633/AI/NIAID NIH HHS/United States ; }, mesh = {Biological Specimen Banks ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*standards ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Policy ; Safety ; }, } @article {pmid29217301, year = {2018}, author = {Bruneau, A and Baylatry, MT and Joly, AC and Sokol, H}, title = {[Gut microbiota: What impact on colorectal carcinogenesis and treatment?].}, journal = {Bulletin du cancer}, volume = {105}, number = {1}, pages = {70-80}, doi = {10.1016/j.bulcan.2017.10.025}, pmid = {29217301}, issn = {1769-6917}, mesh = {Bacterial Toxins/metabolism ; Bacteroides fragilis ; Cell Proliferation ; Colorectal Neoplasms/*microbiology/*therapy ; Drug Resistance, Neoplasm ; Dysbiosis/chemically induced/complications ; Enterococcus faecalis ; Escherichia coli ; Faecalibacterium prausnitzii ; Fecal Microbiota Transplantation ; Fusobacterium nucleatum ; *Gastrointestinal Microbiome/physiology ; Humans ; Neovascularization, Pathologic/microbiology ; Probiotics/therapeutic use ; Streptococcus gallolyticus ; }, abstract = {The gut microbiota, composed of 1014 microorganisms, is now considered as a "hidden organ", regarding to its digestive, metabolic and immune functions, which are helpful to its host. For the last 15 years, advances in molecular biology have highlighted the association of gut microbiota dysbiosis with several diseases, including colorectal cancer. An increased abundance of some bacteria (including Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli) is associated with cancer, whereas others seem to be protective (Faecalibacterium prausnitzii). Several mechanisms, which are species-specific, are involved in colorectal carcinogenesis. Most of the time, bacterial toxins are involved in pro-inflammatory processes and in activation of angiogenesis and cellular proliferation pathways. The identification of these bacteria leads to envisage the gut microbiota as potential screening tool for colorectal cancer. Recent studies showed a relation between the gut microbiota and the efficacy and toxicity of chemotherapies (oxaliplatin, irinotecan) and immunotherapies (including ipilimumab). Therapeutic approaches targeting the gut microbiota are now available (probiotics, fecal microbiota transplantation…). New therapeutic strategy combining both chemotherapy and/or immunotherapy with an adjuvant treatment targeting the gut microbiota can now be developed in order to improve treatment response and tolerance.}, } @article {pmid29214770, year = {2018}, author = {Yoon, MY and Yoon, SS}, title = {Disruption of the Gut Ecosystem by Antibiotics.}, journal = {Yonsei medical journal}, volume = {59}, number = {1}, pages = {4-12}, doi = {10.3349/ymj.2018.59.1.4}, pmid = {29214770}, issn = {1976-2437}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteria/drug effects/growth & development ; Dysbiosis/microbiology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Intestines/drug effects/microbiology ; Symbiosis/drug effects ; }, abstract = {The intestinal microbiota is a complex ecosystem consisting of various microorganisms that expands human genetic repertoire and therefore affects human health and disease. The metabolic processes and signal transduction pathways of the host and intestinal microorganisms are intimately linked, and abnormal progression of each process leads to changes in the intestinal environment. Alterations in microbial communities lead to changes in functional structures based on the metabolites produced in the gut, and these environmental changes result in various bacterial infections and chronic enteric inflammatory diseases. Here, we illustrate how antibiotics are associated with an increased risk of antibiotic-associated diseases by driving intestinal environment changes that favor the proliferation and virulence of pathogens. Understanding the pathogenesis caused by antibiotics would be a crucial key to the treatment of antibiotic-associated diseases by mitigating changes in the intestinal environment and restoring it to its original state.}, } @article {pmid29211757, year = {2017}, author = {de Groot, PF and Belzer, C and Aydin, Ö and Levin, E and Levels, JH and Aalvink, S and Boot, F and Holleman, F and van Raalte, DH and Scheithauer, TP and Simsek, S and Schaap, FG and Olde Damink, SWM and Roep, BO and Hoekstra, JB and de Vos, WM and Nieuwdorp, M}, title = {Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study.}, journal = {PloS one}, volume = {12}, number = {12}, pages = {e0188475}, doi = {10.1371/journal.pone.0188475}, pmid = {29211757}, issn = {1932-6203}, mesh = {Diabetes Mellitus, Type 1/*microbiology ; Feces/*microbiology ; Humans ; *Microbiota ; Mouth/*microbiology ; }, abstract = {OBJECTIVE: Environmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production of short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy controls (HC) is lacking.

RESEARCH DESIGN AND METHODS: We included 53 T1D patients without complications or medication and 50 HC matched for age, sex and BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade systemic inflammation were measured.

RESULTS: Oral microbiota were markedly different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis showed decreased butyrate producing species in T1D and less butyryl-CoA transferase genes. Also, plasma levels of acetate and propionate were lower in T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and Subdoligranulum correlated with glycemic control, inflammatory parameters and SCFA.

CONCLUSIONS: We conclude that T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels. Future research should disentangle cause and effect and whether supplementation of SCFA-producing bacteria or SCFA alone can have disease-modifying effects in T1D.}, } @article {pmid29209564, year = {2017}, author = {Jala, VR and Maturu, P and Bodduluri, SR and Krishnan, E and Mathis, S and Subbarao, K and Wang, M and Jenson, AB and Proctor, ML and Rouchka, EC and Knight, R and Haribabu, B}, title = {Leukotriene B4-receptor-1 mediated host response shapes gut microbiota and controls colon tumor progression.}, journal = {Oncoimmunology}, volume = {6}, number = {12}, pages = {e1361593}, doi = {10.1080/2162402X.2017.1361593}, pmid = {29209564}, issn = {2162-4011}, support = {P20 GM103436/GM/NIGMS NIH HHS/United States ; }, abstract = {Inflammation and infection are key promoters of colon cancer but the molecular interplay between these events is largely unknown. Mice deficient in leukotriene B4 receptor1 (BLT1) are protected in inflammatory disease models of arthritis, asthma and atherosclerosis. In this study, we show that BLT1-/- mice when bred onto a spontaneous tumor (ApcMin/+) model displayed an increase in the rate of intestinal tumor development and mortality. A paradoxical increase in inflammation in the tumors from the BLT1-/-ApcMin/+ mice is coincidental with defective host response to infection. Germ-free BLT1-/-ApcMin/+ mice are free from colon tumors that reappeared upon fecal transplantation. Analysis of microbiota showed defective host response in BLT1-/- ApcMin/+ mice reshapes the gut microbiota to promote colon tumor development. The BLT1-/-MyD88-/- double deficient mice are susceptible to lethal neonatal infections. Broad-spectrum antibiotic treatment eliminated neonatal lethality in BLT1-/-MyD88-/- mice and the BLT1-/-MyD88-/-ApcMin+ mice are protected from colon tumor development. These results identify a novel interplay between the Toll-like receptor mediated microbial sensing mechanisms and BLT1-mediated host response in the control of colon tumor development.}, } @article {pmid29208562, year = {2018}, author = {Chilton, CH and Pickering, DS and Freeman, J}, title = {Microbiologic factors affecting Clostridium difficile recurrence.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {24}, number = {5}, pages = {476-482}, doi = {10.1016/j.cmi.2017.11.017}, pmid = {29208562}, issn = {1469-0691}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Clostridium Infections/diagnosis/*microbiology/therapy ; *Clostridium difficile/classification/genetics ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; Humans ; Microbial Viability/drug effects ; Recurrence ; Risk Factors ; Spores, Bacterial/drug effects ; Superinfection ; }, abstract = {BACKGROUND: Recurrent Clostridium difficile infection (rCDI) places a huge economic and practical burden on healthcare facilities. Furthermore, rCDI may affect quality of life, leaving patients in an rCDI cycle and dependant on antibiotic therapy.

AIMS: To discuss the importance of microbiologic factors in the development of rCDI.

SOURCES: Literature was drawn from a search of PubMed from 2000 onwards with the search term 'recurrent Clostridium difficile infection' and further references cited within these articles.

CONTENT: Meta-analyses and systematic reviews have shown that CDI and rCDI risk factors are similar. Development of rCDI is attendant on many factors, including immune status or function, comorbidities and concomitant treatments. Studies suggest that poor bacterial diversity is correlated with clinical rCDI. Narrow-spectrum gut microflora-sparing antimicrobials (e.g. surotomycin, cadazolid, ridinilazole) are in development for CDI treatment, while microbiota therapeutics (faecal microbiota transplantation, nontoxigenic C. difficile, stool substitutes) are increasingly being explored. rCDI can only occur when viable C. difficile spores are present, either within the gut lumen after infection or when reacquired from the environment. C. difficile spore germination can be influenced by gut environmental factors resulting from dysbiosis, and spore outgrowth may be affected stage by some antimicrobials (e.g. fidaxomicin, ramoplanin, oritavancin).

IMPLICATIONS: rCDI is a significant challenge for healthcare professionals, requiring a multifaceted approach; optimized infection control to minimize reinfection; C. difficile-targeted antibiotics to minimize dysbiosis; and gut microflora restoration to promote colonization resistance. These elements should be informed by our understanding of the microbiologic factors involved in both C. difficile itself and the gut microbiome.}, } @article {pmid29204952, year = {2017}, author = {Konturek, PC and Zopf, Y}, title = {[Therapeutic modulation of intestinal microbiota in irritable bowel syndrome. From probiotics to fecal microbiota therapy].}, journal = {MMW Fortschritte der Medizin}, volume = {159}, number = {Suppl 7}, pages = {1-5}, doi = {10.1007/s15006-017-0338-3}, pmid = {29204952}, issn = {1613-3560}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Humans ; Irritable Bowel Syndrome/therapy ; Probiotics/*therapeutic use ; }, abstract = {BACKGROUND: An abnormal intestinal microbiota (dysbiosis) plays a central role in the pathogenesis of the irritable bowel syndrome.

METHOD: An overview of four current options for the treatment of irritable bowel syndrome, which are characterized by modulation of intestinal microbiota, is given.

RESULTS AND CONCLUSIONS: Probiotics have very different effects on the individual symptoms of the irritable bowel. The choice of the appropriate preparation should therefore be based on the clinical symptomatology. The antibiotic rifaximin is effective in selected patients. Some patients also benefit from the repetition of this therapy. A FODMAP-reduced diet has shown significant alleviation of irritable bowel symptoms in studies. The fecal microbiota therapy (FMT) is a promising treatment option. At present, however, there are no such placebo-controlled studies to assess the effectiveness of this method.}, } @article {pmid29198923, year = {2017}, author = {Ren, X and Liu, L and Gamallat, Y and Zhang, B and Xin, Y}, title = {Enteromorpha and polysaccharides from enteromorpha ameliorate loperamide-induced constipation in mice.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {96}, number = {}, pages = {1075-1081}, doi = {10.1016/j.biopha.2017.11.119}, pmid = {29198923}, issn = {1950-6007}, mesh = {Animals ; Antidiarrheals/toxicity ; Constipation/*chemically induced/*drug therapy/metabolism ; Female ; Gastrointestinal Transit/drug effects/physiology ; Laxatives/isolation & purification/pharmacology/therapeutic use ; Loperamide/*toxicity ; Mice ; Plant Extracts/isolation & purification/pharmacology/*therapeutic use ; Polysaccharides/isolation & purification/pharmacology/*therapeutic use ; *Ulva ; }, abstract = {Slow-transit constipation(STC)is a disease characterized by functional gastrointestinal disorder. Common laxatives used in clinical practice against constipation such as Senna have side effects. Enteromorpha(EP)is a common marine alga, and the polysaccharide extracted from EP has been reported possessing anti-cancer and anti-inflammation effects. The aim of this study is to investigate the effects of EP and Polysaccharides from Enteromorpha (PEP) on loperamide induced constipated mice model and illustrating mechanism of action. We investigated the effect of EP and PEP on fecal water content, defecation frequency and gastrointestinal transit (GI) time of loperamide-induced STC mice. In addition, serum Nitric Oxide (NO) content and vasoactive intestinal peptide receptor1 (VIPR1) as well as serotonin receptor (5-HT4) expression in the distal colon were analyzed. Furthermore, we determined the role of EP and PEP on microbiota distribution using stool genomic 16S rRNA sequencing. EP and PEP significantly enhanced intestinal motility function, and alleviated constipation associated intestinal inflammation. Moreover, EP and PEP significantly decreased serum NO concentration, down-regulated VIPR1 expression and up-regulated 5-HT4 expression in distal colon. Genomic stool DNA MiSeq Sequencing Analysis of microbiota community structures and distribution revealed that intestinal microecological changes caused by constipation recovered after both EP and PEP treatment. Our results indicate that EP and PEP are potent natural products which could be suggested in constipation therapy strategies.}, } @article {pmid29198534, year = {2018}, author = {Brumbaugh, DE and De Zoeten, EF and Pyo-Twist, A and Fidanza, S and Hughes, S and Dolan, SA and Child, J and Dominguez, SR}, title = {An Intragastric Fecal Microbiota Transplantation Program for Treatment of Recurrent Clostridium difficile in Children is Efficacious, Safe, and Inexpensive.}, journal = {The Journal of pediatrics}, volume = {194}, number = {}, pages = {123-127.e1}, doi = {10.1016/j.jpeds.2017.10.016}, pmid = {29198534}, issn = {1097-6833}, abstract = {OBJECTIVE: To assess the safety, efficacy, and relative expense of a nurse-led fecal microbiota transplantation (FMT) program for the treatment of recurrent Clostridium difficile infection (CDI).

STUDY DESIGN: Retrospective cohort study design in children aged 1-18 years with recurrent CDI. The intervention was an intragastric FMT with stool derived from a donor stool bank. Primary outcome was resolution of diarrhea at 3 months post-transplantation. A secondary analysis compared charge data associated with FMT by intragastric delivery vs administration by colonoscopy or nasoduodenal tube.

RESULTS: A total of 47 intragastric FMT procedures were performed in 42 children (median age 9 years) with recurrent CDI. Response to treatment varied by disease status, with 94% success in previously healthy children, 75% in medically complex children, and 54% in children with inflammatory bowel disease (P = .04). FMT via intragastric delivery showed lower facility and professional charges by 85% and 78% compared with delivery via colonoscopy and radiology-placed nasoduodenal tube, respectively. The use of stool derived from a donor stool bank decreased charges by 49% compared with charges associated with the use of a donor who was a relative.

CONCLUSION: A nurse-led intragastric FMT procedure using stool derived from a donor stool bank is a relatively inexpensive and efficacious treatment for recurrent CDI in children. Intragastric FMT success in children was attenuated by the presence of underlying disease, particularly inflammatory bowel disease.}, } @article {pmid29193949, year = {2017}, author = {Pérez-Topete, SE and Miranda-Aquino, T and Ayala-Gaytan, JJ}, title = {[Case series of Clostridium difficile NAP1/027/BI with novels treatments].}, journal = {Revista medica del Instituto Mexicano del Seguro Social}, volume = {55}, number = {5}, pages = {654-659}, pmid = {29193949}, issn = {2448-5667}, mesh = {Aged ; Anti-Bacterial Agents/*therapeutic use ; Clostridium Infections/diagnosis/microbiology/*therapy ; Clostridium difficile/*classification/isolation & purification ; Drug Therapy, Combination ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Minocycline/*analogs & derivatives/therapeutic use ; Naphthalenes ; Oligopeptides ; Ribotyping ; Vancomycin/*therapeutic use ; }, abstract = {BACKGROUND: Clostridium difficile is a spore-forming bacterium, producing exotoxins, causing potentially fatal nosocomial diarrhea. They have recently reported outbreaks of C. difficile ribotype 027, which is characterized by a hypervirulent strain and high resistance to standard therapy.

CLINICAL CASE: We present three cases of Clostridium difficile NAP1/027/BI associated infection, they were presented with different clinical manifestations. Two of the patients were successfully treated with the combination of vancomycin plus tigecycline. The other case was treated with fecal microbiota transplant, with resolution of the disease.

CONCLUSION: in patients with Clostridium difficile NAP1/027/BI associated infection is a good therapeutic option to consider the use of tigecycline in conjunction with vancomycin, as well as fecal microbiota transplantation.}, } @article {pmid29189354, year = {2018}, author = {Mills, JP and Rao, K and Young, VB}, title = {Probiotics for prevention of Clostridium difficile infection.}, journal = {Current opinion in gastroenterology}, volume = {34}, number = {1}, pages = {3-10}, doi = {10.1097/MOG.0000000000000410}, pmid = {29189354}, issn = {1531-7056}, support = {U01 AI124255/AI/NIAID NIH HHS/United States ; }, mesh = {Clinical Trials as Topic ; Clostridium Infections/diet therapy/microbiology/*prevention & control/*therapy ; *Clostridium difficile ; Enterocolitis, Pseudomembranous/diet therapy/microbiology/*prevention & control/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Microbiota/physiology ; Primary Prevention/*methods ; Probiotics/*therapeutic use ; }, abstract = {PURPOSE OF REVIEW: Probiotics may prevent Clostridium difficile infection (CDI), a leading healthcare-associated infection in the United States. However, prior studies were limited by heterogeneity in products and patient populations. Recent clinical evidence and new approaches to probiotic development are reviewed.

RECENT FINDINGS: Probiotic use may reduce incident CDI in high-risk populations by as much as 50%, though prior clinical trials have yielded conflicting results. Combining probiotics with prebiotics improves growth and engraftment in the host. Bacillus clausii and Lactobacillus reuteri secrete compounds that directly inhibit C. difficile. Organisms that produce secondary bile acids, such as Clostridium scindens, enhance C. difficile colonization resistance. Nontoxigenic C. difficile, which provides nutritional niche competition, may prevent CDI. Refinements to fecal microbiota transplantation (FMT) blur the line between probiotics and FMT. These include a quality-controlled stool product (RBX2660), purified Firmicutes spores (SER-109) and sterile fecal filtrate. Bacteriophages may treat CDI but have unknown safety and efficacy in humans.

SUMMARY: There have been a number of advances in probiotics and our understanding of their role in prevention of CDI, but a number of important safety and efficacy questions remain. An improved understanding of the native microbiota structure and function will allow for continued development of rationally designed probiotic therapy to provide enhanced protection against CDI.}, } @article {pmid29188472, year = {2018}, author = {Allegretti, JR and Kassam, Z and Chan, WW}, title = {Small Intestinal Bacterial Overgrowth: Should Screening Be Included in the Pre-fecal Microbiota Transplantation Evaluation?.}, journal = {Digestive diseases and sciences}, volume = {63}, number = {1}, pages = {193-197}, doi = {10.1007/s10620-017-4864-8}, pmid = {29188472}, issn = {1573-2568}, support = {P30 DK034854/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridium Infections/microbiology/therapy ; Clostridium difficile ; Fecal Microbiota Transplantation/*adverse effects ; Female ; Humans ; Intestine, Small/*microbiology ; Male ; Middle Aged ; Risk Factors ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is safe and effective for recurrent Clostridium difficile infection (rCDI) and often involves terminal ileal (TI) stool infusion. Patients report gastrointestinal (GI) symptoms post-FMT despite rCDI resolution. Small intestinal bacterial overgrowth (SIBO) screening is not routinely performed pre-FMT. The effect of donor/recipient SIBO status on FMT outcomes and post-FMT GI symptoms is unclear. We aim to evaluate the value of pre-FMT SIBO screening on post-FMT outcomes and symptoms.

METHODS: This was a prospective pilot study of consecutive adults with rCDI undergoing FMT by colonoscopy at a tertiary center. Routine pre-FMT screening and baseline lactulose breath tests (LBTs) were performed for donors and recipients. Positive LBT required a rise > 20 ppm in breath hydrogen or any methane level > 10 ppm within 90 min. The presence of GI symptoms and CDI resolution were assessed 8 weeks post-FMT. Fisher's exact/Student's t tests were performed for statistical analyses.

RESULTS: Twenty recipients (58.3 years, 85% women) enrolled in the study. Fourteen (70%) FMTs involved TI stool infusion. Four (20%) recipients and six (30%) donors had positive LBT pre-FMT. At 8 weeks post-FMT, 17 (85%) recipients had CDI resolution and five (25%) reported GI symptoms. Pre-FMT LBT result was not associated with post-FMT CDI resolution or GI symptoms. There was a trend toward increased GI symptoms among recipients receiving stool from LBT-positive donors (50 vs 14.2%, p = 0.09).

CONCLUSIONS: FMT is effective and well tolerated for rCDI. Positive LBT in asymptomatic donors may have an effect on post-FMT GI symptoms. Larger studies are needed.}, } @article {pmid29183720, year = {2017}, author = {Staley, C and Khoruts, A and Sadowsky, MJ}, title = {Contemporary Applications of Fecal Microbiota Transplantation to Treat Intestinal Diseases in Humans.}, journal = {Archives of medical research}, volume = {48}, number = {8}, pages = {766-773}, doi = {10.1016/j.arcmed.2017.11.006}, pmid = {29183720}, issn = {1873-5487}, abstract = {The intestinal microbiota comprise an important organ that plays a vital role in host digestion, development, energy maintenance, hemostasis, and immunity. Disruption of the gut microbial community due to diet, lifestyle, or antibiotic exposure increases susceptibility to chronic infection and disease. Fecal microbiota transplantation (FMT) involves the transfer of gut microbiota from a healthy donor to a patient in order to restore normal diversity and function of the microbial community. This method has become a well established alternative therapy for the treatment of recurrent Clostridium difficile infection. Recent clinical trials and studies in animal models suggest promise for this method to treat inflammatory bowel diseases, as well as metabolic syndrome. In addition, due to signaling interactions between the gut microbiota and brain, FMT has been suggested as a potential treatment for some psychological disorders, including autism spectrum disorder. Importantly, advances in next-generation sequencing and multi-omics approaches are increasingly improving our understanding of the mechanisms by which FMT results in cure of these various conditions. In this review, we summarize the current applications of FMT and highlight potential future uses and current challenges in understanding and optimizing FMT procedures.}, } @article {pmid29183074, year = {2017}, author = {Kao, D and Roach, B and Silva, M and Beck, P and Rioux, K and Kaplan, GG and Chang, HJ and Coward, S and Goodman, KJ and Xu, H and Madsen, K and Mason, A and Wong, GK and Jovel, J and Patterson, J and Louie, T}, title = {Effect of Oral Capsule- vs Colonoscopy-Delivered Fecal Microbiota Transplantation on Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.}, journal = {JAMA}, volume = {318}, number = {20}, pages = {1985-1993}, doi = {10.1001/jama.2017.17077}, pmid = {29183074}, issn = {1538-3598}, mesh = {*Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Capsules ; Clostridium Infections/prevention & control/*therapy ; *Colonoscopy ; Fecal Microbiota Transplantation/adverse effects/*methods ; Feces/microbiology ; Female ; Humans ; Male ; Middle Aged ; Patient Satisfaction ; Quality of Life ; Secondary Prevention ; Young Adult ; }, abstract = {Importance: Fecal microbiota transplantation (FMT) is effective in preventing recurrent Clostridium difficile infection (RCDI). However, it is not known whether clinical efficacy differs by route of delivery.

Objective: To determine whether FMT by oral capsule is noninferior to colonoscopy delivery in efficacy.

Noninferiority, unblinded, randomized trial conducted in 3 academic centers in Alberta, Canada. A total of 116 adult patients with RCDI were enrolled between October 2014 and September 2016, with follow-up to December 2016. The noninferiority margin was 15%.

Interventions: Participants were randomly assigned to FMT by capsule or by colonoscopy at a 1:1 ratio.

Main Outcomes and Measures: The primary outcome was the proportion of patients without RCDI 12 weeks after FMT. Secondary outcomes included (1) serious and minor adverse events, (2) changes in quality of life by the 36-Item Short Form Survey on a scale of 0 (worst possible quality of life) to 100 (best quality of life), and (3) patient perception on a scale of 1 (not at all unpleasant) to 10 (extremely unpleasant) and satisfaction on a scale of 1 (best) to 10 (worst).

Results: Among 116 patients randomized (mean [SD] age, 58 [19] years; 79 women [68%]), 105 (91%) completed the trial, with 57 patients randomized to the capsule group and 59 to the colonoscopy group. In per-protocol analysis, prevention of RCDI after a single treatment was achieved in 96.2% in both the capsule group (51/53) and the colonoscopy group (50/52) (difference, 0%; 1-sided 95% CI, -6.1% to infinity; P < .001), meeting the criterion for noninferiority. One patient in each group died of underlying cardiopulmonary illness unrelated to FMT. Rates of minor adverse events were 5.4% for the capsule group vs 12.5% for the colonoscopy group. There was no significant between-group difference in improvement in quality of life. A significantly greater proportion of participants receiving capsules rated their experience as "not at all unpleasant" (66% vs 44%; difference, 22% [95% CI, 3%-40%]; P = .01).

Conclusions and Relevance: Among adults with RCDI, FMT via oral capsules was not inferior to delivery by colonoscopy for preventing recurrent infection over 12 weeks. Treatment with oral capsules may be an effective approach to treating RCDI.

Trial Registration: clinicaltrials.gov Identifier: NCT02254811.}, } @article {pmid29183052, year = {2017}, author = {Rao, K and Young, VB and Malani, PN}, title = {Capsules for Fecal Microbiota Transplantation in Recurrent Clostridium difficile Infection: The New Way Forward or a Tough Pill to Swallow?.}, journal = {JAMA}, volume = {318}, number = {20}, pages = {1979-1980}, doi = {10.1001/jama.2017.17969}, pmid = {29183052}, issn = {1538-3598}, support = {U01 AI124255/AI/NIAID NIH HHS/United States ; }, mesh = {*Capsules ; Clostridium Infections ; Clostridium difficile ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Microbiota ; }, } @article {pmid29179687, year = {2017}, author = {Verbeke, F and Janssens, Y and Wynendaele, E and De Spiegeleer, B}, title = {Faecal microbiota transplantation: a regulatory hurdle?.}, journal = {BMC gastroenterology}, volume = {17}, number = {1}, pages = {128}, doi = {10.1186/s12876-017-0687-5}, pmid = {29179687}, issn = {1471-230X}, support = {131356//Agentschap voor Innovatie door Wetenschap en Technologie/ ; }, mesh = {Clostridium Infections/*therapy ; *Clostridium difficile ; Europe ; *Fecal Microbiota Transplantation ; Humans ; *Legislation, Medical ; Recurrence ; United States ; }, abstract = {During faecal microbiota transplantation, stool from a healthy donor is transplanted to treat a variety of dysbiosis-associated gut diseases. Competent authorities are faced with the challenge to provide adequate regulation. Currently, regulatory harmonization is completely lacking and authorities apply non-existing to most stringent requirements. A regulatory approach for faecal microbiota transplantation could be inserting faecal microbiota transplantation in the gene-, cell- and tissue regulations, including the hospital exemption system in the European Advanced Therapy Medicinal Products regulation, providing a pragmatic and efficacy-risk balanced approach and granting all patients as a matter of principle access to this therapy.}, } @article {pmid29179485, year = {2017}, author = {Zhang, T and Xiang, J and Cui, B and He, Z and Li, P and Chen, H and Xu, L and Ji, G and Nie, Y and Wu, K and Fan, D and Huang, G and Bai, J and Zhang, F}, title = {Cost-effectiveness analysis of fecal microbiota transplantation for inflammatory bowel disease.}, journal = {Oncotarget}, volume = {8}, number = {51}, pages = {88894-88903}, doi = {10.18632/oncotarget.21491}, pmid = {29179485}, issn = {1949-2553}, abstract = {There is a lack of health economics evidence on the use of fecal microbiota transplantation (FMT) for inflammatory bowel disease (IBD). This study aims to evaluate the cost-effectiveness before (with conventional therapy) and after introducing FMT for treating IBD. 104 patients with IBD received FMT were recruited. Health status was evaluated by European dimension health table (ED-5Q). Incremental cost-effectiveness ratio (ICER) and net monetary benefit (NB) were calculated by different age groups, genders, smoking status, and disease subtypes. The willingness-to-pay threshold was set to the value equal to three times China's per capita GDP (141240 CNY/QALY, 2014). From the health-care perspective, FMT strategy was 73% likely to be cost-effective compared with the conventional therapy before FMT with an ICER of -185712 CNY/QALY and a positive NB of CNY 45150. From the societal perspective, FMT strategy was 75% likely to be cost-effective with an ICER of -207417 CNY/QALY and a positive NB of CNY 48395. Moreover, younger patients (≤ 24), females, non-smokers and Crohn's disease (CD) achieved more benefits. This study for the first time demonstrated that FMT showed its cost-effectiveness, especially on improving the life quality and decreasing the medical and societal cost, for the moderate to severe IBD in a Chinese cohort.}, } @article {pmid29173524, year = {2017}, author = {Browne, AS and Kelly, CR}, title = {Fecal Transplant in Inflammatory Bowel Disease.}, journal = {Gastroenterology clinics of North America}, volume = {46}, number = {4}, pages = {825-837}, doi = {10.1016/j.gtc.2017.08.005}, pmid = {29173524}, issn = {1558-1942}, mesh = {*Fecal Microbiota Transplantation/adverse effects ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Observational Studies as Topic ; Randomized Controlled Trials as Topic ; }, abstract = {Patients with inflammatory bowel disease (IBD) have differences in their gastrointestinal microbiome compared with healthy individuals, although it is unclear whether this is a cause or consequence of chronic inflammation. There is hope that manipulation of the gut microbiome through fecal microbiota transplant (FMT), commonly used to treat patients with Clostridium difficile infection, may also be an effective therapy in IBD. This article reviews the evidence supporting FMT in IBD, including case reports, case series, and randomized controlled trials. The article also focuses on questions of safety and speculates on the future of this therapy.}, } @article {pmid29173517, year = {2017}, author = {Basson, AR and Lam, M and Cominelli, F}, title = {Complementary and Alternative Medicine Strategies for Therapeutic Gut Microbiota Modulation in Inflammatory Bowel Disease and their Next-Generation Approaches.}, journal = {Gastroenterology clinics of North America}, volume = {46}, number = {4}, pages = {689-729}, doi = {10.1016/j.gtc.2017.08.002}, pmid = {29173517}, issn = {1558-1942}, support = {P01 DK091222/DK/NIDDK NIH HHS/United States ; R01 DK042191/DK/NIDDK NIH HHS/United States ; T32 DK083251/DK/NIDDK NIH HHS/United States ; P30 DK097948/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Caseins/therapeutic use ; *Complementary Therapies ; *Diet ; *Dietary Supplements ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*therapy ; Medical Marijuana/therapeutic use ; Peptide Fragments/therapeutic use ; Phytochemicals/therapeutic use ; Polysaccharides/therapeutic use ; Prebiotics ; Probiotics/*therapeutic use ; Psychophysiology ; }, abstract = {The human gut microbiome exerts a major impact on human health and disease, and therapeutic gut microbiota modulation is now a well-advocated strategy in the management of many diseases, including inflammatory bowel disease (IBD). Scientific and clinical evidence in support of complementary and alternative medicine, in targeting intestinal dysbiosis among patients with IBD, or other disorders, has increased dramatically over the past years. Delivery of "artificial" stool replacements for fecal microbiota transplantation (FMT) could provide an effective, safer alternative to that of human donor stool. Nevertheless, optimum timing of FMT administration in IBD remains unexplored, and future investigations are essential.}, } @article {pmid29158082, year = {2017}, author = {Bamba, S and Nishida, A and Imaeda, H and Inatomi, O and Sasaki, M and Sugimoto, M and Andoh, A}, title = {Successful treatment by fecal microbiota transplantation for Japanese patients with refractory Clostridium difficile infection: A prospective case series.}, journal = {Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jmii.2017.08.027}, pmid = {29158082}, issn = {1995-9133}, abstract = {We prospectively enrolled four Japanese patients with refractory Clostridium difficile infection (CDI) and were treated with a single fecal microbiota transplantation (FMT). The average age of the patients was 83.7 years. All patients had a successful clinical course for up to 3 months without any adverse events.}, } @article {pmid29157127, year = {2018}, author = {Lee, H and Lee, Y and Kim, J and An, J and Lee, S and Kong, H and Song, Y and Lee, CK and Kim, K}, title = {Modulation of the gut microbiota by metformin improves metabolic profiles in aged obese mice.}, journal = {Gut microbes}, volume = {9}, number = {2}, pages = {155-165}, doi = {10.1080/19490976.2017.1405209}, pmid = {29157127}, issn = {1949-0984}, mesh = {Age Factors ; Animals ; Bacteria/classification/drug effects ; Blood Glucose/drug effects ; Body Weight/drug effects ; Diet, High-Fat/*adverse effects ; Disease Models, Animal ; Epididymis/drug effects/*immunology ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects/physiology ; Gene Expression Regulation/immunology ; Interleukin-1beta/genetics ; Interleukin-6/genetics ; Lipid Metabolism/drug effects ; Male ; Metformin/*pharmacology/therapeutic use ; Mice ; Mice, Inbred C57BL ; Obesity/drug therapy/immunology/*metabolism/*microbiology ; }, abstract = {The gut microbiota is a contributing factor in obesity-related metabolic disorders. The effect of metformin on the gut microbiota has been reported; however, the relationship between the gut microbiota and the mechanism of action of metformin in elderly individuals is unclear. In this study, the effect of metformin on the gut microbiota was investigated in aged obese mice. The abundance of the genera Akkermansia, Bacteroides, Butyricimonas, and Parabacteroides was significantly increased by metformin in mice fed a high-fat diet. Metformin treatment decreased the expression of IL-1β and IL-6 in epididymal fat, which was correlated with the abundance of various bacterial genera. In addition, both fecal microbiota transplantation from metformin-treated mice and extracellular vesicles of Akkermansia muciniphila improved the body weight and lipid profiles of the mice. Our findings suggest that modulation of the gut microbiota by metformin results in metabolic improvements in aged mice, and that these effects are associated with inflammatory immune responses.}, } @article {pmid29152407, year = {2017}, author = {Abadi, ATB}, title = {Fecal microbiota transplantation against irritable bowel syndrome? Rigorous randomized clinical trials are required.}, journal = {World journal of gastrointestinal pharmacology and therapeutics}, volume = {8}, number = {4}, pages = {208-209}, doi = {10.4292/wjgpt.v8.i4.208}, pmid = {29152407}, issn = {2150-5349}, abstract = {Halkjær et al searched systematically nine articles including 48 patients, and concluded that fecal microbiota transplantation (FMT) can be an ideal treatment option for irritable bowel syndrome (IBS) subjects. Regardless of the few successes in current traditional therapies (change in diet, herbal medicine and antibiotics) in IBS, a sharp increase in interests in the FMT option has been reported in the current century. However, there is a long list of unclear issues concerning the application of FMT for the treatment of IBS. Route of delivery and optimum dosage are the major concerns to consider before using in clinical practice.}, } @article {pmid29151253, year = {2018}, author = {Karolewska-Bochenek, K and Grzesiowski, P and Banaszkiewicz, A and Gawronska, A and Kotowska, M and Dziekiewicz, M and Albrecht, P and Radzikowski, A and Lazowska-Przeorek, I}, title = {A Two-Week Fecal Microbiota Transplantation Course in Pediatric Patients with Inflammatory Bowel Disease.}, journal = {Advances in experimental medicine and biology}, volume = {1047}, number = {}, pages = {81-87}, doi = {10.1007/5584_2017_123}, pmid = {29151253}, issn = {0065-2598}, abstract = {Dysbiosis plays a major role in the etiology of inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) is a new promising option for IBD treatment. We aimed to assess the effectiveness of a two-week FMT course in children with IBD. Ten patients, 10-17 years of age with moderate to severe IBD received a course of eight doses of freshly prepared FMT via a naso-duodenal tube or gastroscopy. All of the patients had pancolitis. There were eight cases of ulcerative colitis (UC) and two of Crohn's disease (CD). Disease activity was evaluated using the Pediatric UC Activity Index (PUCAI) and Pediatric CD Activity Index (PCDAI) for UC and CD, respectively, CRP, and fecal calprotectin on the day before the first infusion and then on the day before the next course of FMT. Clinical response, defined as a decrease of 15 points in either index, was observed in 9/10 patients (seven UC and two CD). Clinical remission, defined as a PCDAI score ≤ 10 and PUCAI score < 10 measured at the same time point, was observed in 3/8 UC patients and 2/2 CD patients. Side effects observed were self-limiting and benign. We conclude that a short, intensive course of FMT has a beneficial effect on UC and CD colitis. FMT was well-tolerated and safe. Nonetheless, an optimal protocol of FMT administration is crucial for treatment efficacy.}, } @article {pmid29140453, year = {2017}, author = {Quraishi, MN and Critchlow, T and Bhala, N and Sharma, N and Iqbal, T}, title = {Faecal transplantation for IBD management-pitfalls and promises.}, journal = {British medical bulletin}, volume = {124}, number = {1}, pages = {181-190}, doi = {10.1093/bmb/ldx040}, pmid = {29140453}, issn = {1471-8391}, support = {EME/13/179/01//Department of Health/United Kingdom ; }, mesh = {Evidence-Based Medicine ; *Fecal Microbiota Transplantation/methods/trends ; Gastrointestinal Microbiome/immunology/physiology ; Humans ; Inflammatory Bowel Diseases/immunology/microbiology/*therapy ; Randomized Controlled Trials as Topic ; Remission Induction ; Treatment Outcome ; }, abstract = {Background: Faecal microbiota transplantation (FMT) as a potential treatment for inflammatory bowel disease (IBD) is an area of active current research, having been stimulated by the remarkable efficacy of FMT in treatment of Clostridium difficile-associated colitis.

Sources of data: This review is based on data from numerous case series on FMT in IBD since 1989 and results of four RCTs in ulcerative colitis (UC); three fully published.

Areas of agreement: Early signals of short to medium-term efficacy of FMT for UC are promising.

Areas of controversy: Methodology, underlying mechanisms and questions regarding safety of FMT remain controversial.

Growing points: Many trials of FMT in adults and children are currently recruiting.

Future trials of FMT will likely revisit Crohn's disease and patients undergoing pouch surgery. Advances in microbial culture complementing genetic sequencing and investigations into the virome and mycobiome in IBD will be of great future interest.}, } @article {pmid29134299, year = {2018}, author = {Friedman-Korn, T and Livovsky, DM and Maharshak, N and Aviv Cohen, N and Paz, K and Bar-Gil Shitrit, A and Goldin, E and Koslowsky, B}, title = {Fecal Transplantation for Treatment of Clostridium Difficile Infection in Elderly and Debilitated Patients.}, journal = {Digestive diseases and sciences}, volume = {63}, number = {1}, pages = {198-203}, doi = {10.1007/s10620-017-4833-2}, pmid = {29134299}, issn = {1573-2568}, mesh = {Aged ; Aged, 80 and over ; Clostridium Infections/*therapy ; *Clostridium difficile ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Male ; Middle Aged ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a new technique recently introduced to treat recurrent Clostridium difficile infection (CDI). Little is known about the efficacy and risks of FMT in elderly and ill patients.

AIM: To investigate FMT efficacy in ill and elderly patients compared to conventional treatment.

METHODS: The study comprised two groups of patients between 2012 and 2016 with recurrent CDI at two medical centers in Israel. The study group received FMT and the controls conventional therapy. The primary end points were CDI recurrence, length of hospitalization, and short-term survival.

RESULTS: Thirty-four patients altogether, (21 females, mean age 82 years) participated, 11 received FMT and 23 controls. Demographics and clinical characteristics were similar between the two groups. Comorbidity indexes, i.e., Charlson index was high in both groups. In the FMT group, 10/11 (90%) patients showed clinical improvement 3 days after initiating treatment compared to 9/23 (39%) in the control group, p = 0.02. Survival at 2 months did not differ between the groups (FMT 54%, Control 50%, p = 0.816), but mean survival in the FMT group was higher than in the control (12 vs. 4 months, respectively, p = 0.015). Two significant adverse events from the FMT group included suspected aspirations, both occurring during gastroscopy route of administration.

CONCLUSIONS: FMT is effective for elderly and very ill patients. Safety is a concern, but is rare even in patients with much comorbidity. Colonoscopy may be the preferred route of FMT infusion.}, } @article {pmid29133078, year = {2018}, author = {Darnaud, M and Dos Santos, A and Gonzalez, P and Augui, S and Lacoste, C and Desterke, C and De Hertogh, G and Valentino, E and Braun, E and Zheng, J and Boisgard, R and Neut, C and Dubuquoy, L and Chiappini, F and Samuel, D and Lepage, P and Guerrieri, F and Doré, J and Bréchot, C and Moniaux, N and Faivre, J}, title = {Enteric Delivery of Regenerating Family Member 3 alpha Alters the Intestinal Microbiota and Controls Inflammation in Mice With Colitis.}, journal = {Gastroenterology}, volume = {154}, number = {4}, pages = {1009-1023.e14}, doi = {10.1053/j.gastro.2017.11.003}, pmid = {29133078}, issn = {1528-0012}, mesh = {Animals ; Bacteria/classification/growth & development/*metabolism ; Colitis/chemically induced/metabolism/microbiology/*prevention & control ; Colon/*metabolism/microbiology ; Dextran Sulfate ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Hepatocytes/*metabolism ; Humans ; Mice, Inbred C57BL ; Mice, Transgenic ; Microbial Viability ; Oxidative Stress/drug effects ; Pancreatitis-Associated Proteins/genetics/*metabolism ; Reactive Oxygen Species/metabolism ; Time Factors ; Trinitrobenzenesulfonic Acid ; }, abstract = {BACKGROUND & AIMS: Paneth cell dysfunction causes deficiencies in intestinal C-type lectins and antimicrobial peptides, which leads to dysbiosis of the intestinal microbiota, alters the mucosal barrier, and promotes development of inflammatory bowel diseases. We investigated whether transgenic (TG) expression of the human regenerating family member 3 alpha gene (REG3A) alters the fecal microbiota and affects development of colitis in mice.

METHODS: We performed studies with C57BL/6 mice that express human regenerating family member 3 alpha (hREG3A) in hepatocytes, via the albumin gene promoter. In these mice, hREG3A travels via the bile to the intestinal lumen. Some mice were given dextran sodium sulfate (DSS) to induce colitis. Feces were collected from mice and the composition of the microbiota was analyzed by 16S ribosomal RNA sequencing. The fecal microbiome was also analyzed from mice that express only 1 copy of human REG3A transgene but were fed feces from control mice (not expressing hREG3A) as newborns. Mice expressing hREG3A were monitored for DSS-induced colitis after cohousing or feeding feces from control mice. Colitis was induced in another set of control and hREG3A-TG mice by administration of trinitrobenzene sulfonic acid; some mice were given intrarectal injections of the hREG3A protein. Colon tissues were collected from mice and analyzed by histology and immunohistochemistry to detect mucin 2, as well as by 16S ribosomal RNA fluorescence in situ hybridization, transcriptional analyses, and quantitative polymerase chain reaction. We measured levels of reactive oxygen species (ROS) in bacterial cultures and fecal microbiota using 2',7'-dichlorofluorescein diacetate and flow cytometry.

RESULTS: The fecal microbiota of mice that express hREG3A had a significant shift in composition, compared with control mice, with enrichment of Clostridiales (Ruminococcaceae, Lachnospiraceae) and depletion of Bacteroidetes (Prevotellaceae); the TG mice developed less-severe colitis following administration of DSS than control mice, associated with preserved gut barrier integrity and reduced bacterial translocation, epithelial inflammation, and oxidative damage. A similar shift in the composition of the fecal microbiota occurred after a few months in TG mice heterozygous for REG3A that harbored a wild-type maternal microbiota at birth; these mice developed less-severe forms of colitis following DSS administration. Cohoused and germ-free mice fed feces from REG3A-TG mice and given DSS developed less-severe forms of colitis and had reduced lipopolysaccharide activation of the toll-like receptor 4 and increased survival times compared with mice not fed feces from REG3A-TG mice. REG3A TG mice developed only mild colonic inflammation after exposure to 2,4,6-trinitrobenzene sulfonic acid, compared with control mice. Control mice given intrarectal hREG3A and exposed to 2,4,6-trinitrobenzene sulfonic acid showed less colon damage and inflammation than mice not given intrarectal hREG3A. Fecal samples from REG3A-TG mice had lower levels of ROS than feces from control mice during DSS administration. Addition of hREG3A to bacterial cultures reduced levels of ROS and increased survival of oxygen-sensitive commensal bacteria (Faecalibacterium prausnitzii and Roseburia intestinalis).

CONCLUSIONS: Mice with hepatocytes that express hREG3A, which travels to the intestinal lumen, are less sensitive to colitis than control mice. We found hREG3A to alter the colonic microbiota by decreasing levels of ROS. Fecal microbiota from REG3A-TG mice protect non-TG mice from induction of colitis. These findings indicate a role for reduction of oxidative stress in preserving the gut microbiota and its ability to prevent inflammation.}, } @article {pmid29132532, year = {2017}, author = {Irwin, G and Mayans, L and Kellerman, R}, title = {Emerging Topics in Gastroenterology.}, journal = {Primary care}, volume = {44}, number = {4}, pages = {733-742}, doi = {10.1016/j.pop.2017.07.008}, pmid = {29132532}, issn = {1558-299X}, mesh = {Colitis, Microscopic/physiopathology/therapy ; Eosinophilic Esophagitis/physiopathology/therapy ; Fecal Microbiota Transplantation/methods ; *Gastroenterology ; Gastrointestinal Microbiome/physiology ; Humans ; Primary Health Care ; Probiotics/pharmacology ; Vomiting/physiopathology/therapy ; }, abstract = {The bacteria and fungi in the human gut make up a community of microorganisms that lives in symbiosis with humans, engaging in numerous diverse interactions that influence health. This article outlines the current knowledge on emerging topics in gastroenterology, including microbiome and probiotics, fecal microbiota transplantation, cyclic vomiting syndrome, eosinophilic esophagitis, and microscopic colitis.}, } @article {pmid29130220, year = {2017}, author = {Li, N and Tian, H}, title = {[Current research progress and thinking of fecal microbiota transplantation for the treatment of gastrointestinal disorders].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {20}, number = {10}, pages = {1104-1108}, pmid = {29130220}, issn = {1671-0274}, abstract = {Fecal microbiota transplantation (FMT), also known as fecal bacteriotherapy or fecal infusion, consists of injection of a liquid filtrate of feces from a healthy donor into the gastrointestinal tract of a recipient individual. FMT has been proposed as a therapeutic approach for functional diseases of the gastrointestinal tract by reestablishment of a wide diversity of intestinal flora. Clostridium difficile infection (CDI) treatment guideline from American Gastroenterology Association (AGA) recommends that FMT can be used as the treatment protocols of relapse CDI. Numerous case reports, retrospective case series, and randomized controlled trials have shown the benefit of FMT in patients with functional bowel disorders, including inflammatory bowel disease, irritable bowel syndrome and constipation, etc. Evidence regarding the safety of FMT is relatively limited because the very rapid adoption of FMT as a therapeutic modality for CDI occurred before the performance of large, long prospective trials that are typically conducted to assess the safety of new interventions. Potential adverse events can be categorized as short-term and long-term, and short-term events can further be divided into those related to the method of FMT delivery (colonoscopy, sedation) and those related to the FMT itself. Due to the recent emergence of FMT, little data exist regarding long-term events and many safety concerns are speculative. Capsulized FMT therapy solves the clinical problems associated with the use of fresh FMT suspensions for long-term maintenance i.e. repeat transplantation and invasive procedures, which is of great significance to optimize the traditional FMT clinical strategy. Future work will focus on establishing best practices and more robust safety data than exist currently, as well as refining FMT beyond current "whole-stool" transplants to increase safety and tolerability. Encapsulated formulations, full-spectrum stool-based products, and defined microbial consortia are all in the immediate future. Although challenges exist, regulatory agencies have been willing to work with stakeholders and will continue to evolve and adapt policy as therapeutics based on human gut microbiota research emerge.}, } @article {pmid29124320, year = {2018}, author = {Witkowski, M and Witkowski, M and Gagliani, N and Huber, S}, title = {Recipe for IBD: can we use food to control inflammatory bowel disease?.}, journal = {Seminars in immunopathology}, volume = {40}, number = {2}, pages = {145-156}, doi = {10.1007/s00281-017-0658-5}, pmid = {29124320}, issn = {1863-2300}, support = {337251//FP7 Ideas: European Research Council/ ; 715271//FP7 Ideas: European Research Council/ ; }, abstract = {The mucosal immune system and the microbiota in the intestinal tract have recently been shown to play a key role in the pathogenesis of inflammatory bowel disease (IBD). Both of these can be influenced by food. Thus, we propose dietary intervention as a therapeutic option for IBD. In this review, we discuss the interaction of the intestinal mucosal immune system and the intestinal microbiota in the context of IBD. In addition, we discuss the impact of food components on immune responses in IBD. Finally, we address the current evidence of how this interaction (i.e., immune system-microbiota) can be modulated by food components, pre/probiotics, and fecal microbiota transplantation (FMT) and how these approaches can support intestinal homeostasis. By gathering the vast amount of literature available on the impact of food on IBD, we aim to distinguish between scientifically sound data and theories, which have not been included in this review.}, } @article {pmid29124041, year = {2017}, author = {Li, HL and Lu, L and Wang, XS and Qin, LY and Wang, P and Qiu, SP and Wu, H and Huang, F and Zhang, BB and Shi, HL and Wu, XJ}, title = {Alteration of Gut Microbiota and Inflammatory Cytokine/Chemokine Profiles in 5-Fluorouracil Induced Intestinal Mucositis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {7}, number = {}, pages = {455}, doi = {10.3389/fcimb.2017.00455}, pmid = {29124041}, issn = {2235-2988}, mesh = {Animals ; Antigens, CD/metabolism ; Bacteria/classification/drug effects/genetics/metabolism ; Body Weight/drug effects ; Cadherins/metabolism ; Cell Adhesion Molecules/metabolism ; Chemokines/*metabolism ; Colon/metabolism/pathology ; Cytokines/*metabolism ; Fecal Microbiota Transplantation ; Feces/microbiology ; Fluorouracil/*adverse effects ; Gastrointestinal Microbiome/*drug effects ; Immunohistochemistry ; Inflammation/complications/pathology ; Intercellular Adhesion Molecule-1/metabolism ; Intestinal Mucosa/*metabolism/pathology ; Intestines/*metabolism/pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mitogen-Activated Protein Kinases/metabolism ; Mucositis/chemically induced/*metabolism/*microbiology/pathology ; NF-kappa B/metabolism ; RNA, Ribosomal, 16S/genetics ; Receptors, Cell Surface/metabolism ; Vascular Cell Adhesion Molecule-1/metabolism ; Zonula Occludens-1 Protein/metabolism ; }, abstract = {Disturbed homeostasis of gut microbiota has been suggested to be closely associated with 5-fluorouracil (5-Fu) induced mucositis. However, current knowledge of the overall profiles of 5-Fu-disturbed gut microbiota is limited, and so far there is no direct convincing evidence proving the causality between 5-Fu-disturbed microbiota and colonic mucositis. In mice, in agreement with previous reports, 5-Fu resulted in severe colonic mucositis indicated by weight loss, diarrhea, bloody stool, shortened colon, and infiltration of inflammatory cells. It significantly changed the profiles of inflammatory cytokines/chemokines in serum and colon. Adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and VE-Cadherin were increased. While tight junction protein occludin was reduced, however, zonula occludens-1 (ZO-1) and junctional adhesion molecule-A (JAM-A) were increased in colonic tissues of 5-Fu treated mice. Meanwhile, inflammation related signaling pathways including NF-κB and mitogen activated protein kinase (MAPKs) in the colon were activated. Further study disclosed that 5-Fu diminished bacterial community richness and diversity, leading to the relative lower abundance of Firmicutes and decreased Firmicutes/Bacteroidetes (F/B) ratio in feces and cecum contents. 5-Fu also reduced the proportion of Proteobacteria, Tenericutes, Cyanobacteria, and Candidate division TM7, but increased that of Verrucomicrobia and Actinobacteria in feces and/or cecum contents. The fecal transplant from healthy mice prevented body weight loss and colon shortening of 5-Fu treated mice. In addition, the fecal transplant from 5-Fu treated mice reduced body weight and colon length of vancomycin-pretreated mice. Taken together, our study demonstrated that gut microbiota was actively involved in the pathological process of 5-Fu induced intestinal mucositis, suggesting potential attenuation of 5-Fu induced intestinal mucositis by manipulating gut microbiota homeostasis.}, } @article {pmid29123385, year = {2017}, author = {Asempa, TE and Nicolau, DP}, title = {Clostridium difficile infection in the elderly: an update on management.}, journal = {Clinical interventions in aging}, volume = {12}, number = {}, pages = {1799-1809}, doi = {10.2147/CIA.S149089}, pmid = {29123385}, issn = {1178-1998}, mesh = {Aged ; Anti-Bacterial Agents/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing/therapeutic use ; Clostridium Infections/economics/epidemiology/*physiopathology/*therapy ; Clostridium difficile ; Fecal Microbiota Transplantation/methods ; Health Expenditures ; Humans ; Prospective Studies ; Recurrence ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; }, abstract = {The burden of Clostridium difficile infection (CDI) is profound and growing. CDI now represents a common cause of health care-associated diarrhea, and is associated with significant morbidity, mortality, and health care costs. CDI disproportionally affects the elderly, possibly explained by the following risk factors: age-related impairment of the immune system, increasing antibiotic utilization, and frequent health care exposure. In the USA, recent epidemiological studies estimate that two out of every three health care-associated CDIs occur in patients 65 years or older. Additionally, the elderly are at higher risk for recurrent CDI. Existing therapeutic options include metronidazole, oral vancomycin, and fidaxomicin. Choice of agent depends on disease severity, history of recurrence, and, increasingly, the drug cost. Bezlotoxumab, a recently approved monoclonal antibody targeting C. difficile toxin B, offers an exciting advancement into immunologic therapies. Similarly, fecal microbiota transplantation is gaining popularity as an effective option mainly for recurrent CDI. The challenge of decreasing CDI burden in the elderly involves adopting preventative strategies, optimizing initial treatment, and decreasing the risk of recurrence. Expanded strategies are certainly needed to improve outcomes in this high-risk population. This review considers available data from prospective and retrospective studies as well as case reports to illustrate the merits and gaps in care related to the management of CDI in the elderly.}, } @article {pmid29122905, year = {2017}, author = {Philips, CA and Phadke, N and Ganesan, K and Augustine, P}, title = {Healthy donor faecal transplant for corticosteroid non-responsive severe alcoholic hepatitis.}, journal = {BMJ case reports}, volume = {2017}, number = {}, pages = {}, doi = {10.1136/bcr-2017-222310}, pmid = {29122905}, issn = {1757-790X}, mesh = {Adrenal Cortex Hormones/pharmacology ; Adult ; Drug Resistance ; Fecal Microbiota Transplantation/*methods ; Hepatitis, Alcoholic/diagnosis/*therapy ; Humans ; Liver Diseases, Alcoholic/*therapy ; Liver Transplantation ; Male ; Tissue Donors ; Treatment Outcome ; Waiting Lists ; }, abstract = {Patients with severe alcoholic hepatitis (SAH) have high mortality in the presence of steroid unresponsiveness in the absence of clear treatment recommendations. Liver transplantation is the curative option in such cases but is controversial in the wake of severe infections, post-transplant recidivism and long waiting on deceased donor listing. Animal and human studies have shed light on the beneficial effects of gut microbiota modulation in alcoholic liver disease. We present the first report of faecal microbiota transplantation (FMT) in a steroid non-responder in whom, clinical, biochemical and liver disease severity scores improved post-FMT and demonstrate distinct bacterial population changes pre-FMT and post-FMT. Healthy donor FMT could be safe and efficacious in SAH not responding to corticosteroid treatment, as a bridge to liver transplantation (LT) or in candidates who are unwilling or not ideal for LT for improvement in short-term transplant free survival. Larger controlled studies are required for confirmation.}, } @article {pmid29113028, year = {2018}, author = {García-Lezana, T and Raurell, I and Bravo, M and Torres-Arauz, M and Salcedo, MT and Santiago, A and Schoenenberger, A and Manichanh, C and Genescà, J and Martell, M and Augustin, S}, title = {Restoration of a healthy intestinal microbiota normalizes portal hypertension in a rat model of nonalcoholic steatohepatitis.}, journal = {Hepatology (Baltimore, Md.)}, volume = {67}, number = {4}, pages = {1485-1498}, doi = {10.1002/hep.29646}, pmid = {29113028}, issn = {1527-3350}, mesh = {Animals ; Disease Models, Animal ; Dysbiosis/*complications ; Fecal Microbiota Transplantation/methods ; *Gastrointestinal Microbiome ; Hypertension, Portal/*etiology/microbiology ; Insulin Resistance ; Liver/pathology ; Male ; Non-alcoholic Fatty Liver Disease/*complications ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Portal hypertension (PH) drives most of the clinical complications in chronic liver diseases. However, its progression in nonalcoholic steatohepatitis (NASH) and its association with the intestinal microbiota (IM) have been scarcely studied. Our aim was to investigate the role of the IM in the mechanisms leading to PH in early NASH. The experimental design was divided in two stages. In stage 1, Sprague-Dawley rats were fed for 8 weeks a high-fat, high-glucose/fructose diet (HFGFD) or a control diet/water (CD). Representative rats were selected as IM donors for stage 2. In stage 2, additional HFGFD and CD rats underwent intestinal decontamination, followed by IM transplantation with feces from opposite-diet donors (heterologous transplant) or autologous fecal transplant (as controls), generating four groups: CD-autotransplanted, CD-transplanted, HFGFD-autotransplanted, HFGFD-transplanted. After IM transplantation, the original diet was maintained for 12-14 days until death. HFGFD rats developed obesity, insulin resistance, NASH without fibrosis but with PH, intrahepatic endothelial dysfunction, and IM dysbiosis. In HFGFD rats, transplantation with feces from CD donors caused a significant reduction of PH to levels comparable to CD without significant changes in NASH histology. The reduction in PH was due to a 31% decrease of intrahepatic vascular resistance compared to the HFGFD-autotransplanted group (P < 0.05). This effect occurs through restoration of the sensitivity to insulin of the hepatic protein kinase B-dependent endothelial nitric oxide synthase signaling pathway.

CONCLUSION: The IM exerts a direct influence in the development of PH in rats with diet-induced NASH and dysbiosis; PH, insulin resistance, and endothelial dysfunction revert when a healthy IM is restored. (Hepatology 2018;67:1485-1498).}, } @article {pmid29110105, year = {2017}, author = {Clayton, JA and Toltzis, P}, title = {Recent Issues in Pediatric Clostridium difficile Infection.}, journal = {Current infectious disease reports}, volume = {19}, number = {12}, pages = {49}, doi = {10.1007/s11908-017-0603-8}, pmid = {29110105}, issn = {1523-3847}, abstract = {PURPOSE OF REVIEW: We focus on two recent aspects of Clostridium difficile infection (CDI) in children, namely the emergence of community-associated CDI (CA-CDI) and the incidence and prevention of recurrent CDI.

RECENT FINDINGS: Current surveys suggest that a large proportion of all pediatric CDI is acquired in the community. Risk factors and frequency estimates of pediatric CA-CDI, however, are confounded in babies and toddlers by a high rate of asymptomatic excretion, whose detection likely is exaggerated by the wide use of highly sensitive nucleic acid amplification tests. Recurrent diarrhea occurs in up to 25% of children with CDI. Preventative strategies for recurrent CDI in adults, namely pulse and taper antibiotic dosing, use of anti-CDI drugs with mild effect on the colonic microbiome, fecal microbiota transplantation, and passive immune therapy, currently are being tested in children. Future studies are required to better characterize community acquisition of CDI in children and to define the safety and effectiveness of preventative strategies for recurrent CDI.}, } @article {pmid29107964, year = {2017}, author = {Lee, JC and Lee, HY and Kim, TK and Kim, MS and Park, YM and Kim, J and Park, K and Kweon, MN and Kim, SH and Bae, JW and Hur, KY and Lee, MS}, title = {Obesogenic diet-induced gut barrier dysfunction and pathobiont expansion aggravate experimental colitis.}, journal = {PloS one}, volume = {12}, number = {11}, pages = {e0187515}, doi = {10.1371/journal.pone.0187515}, pmid = {29107964}, issn = {1932-6203}, mesh = {Animals ; Colitis/*pathology ; Diet, High-Fat/*adverse effects ; Intestinal Mucosa/microbiology/*physiopathology ; Mice ; Mice, Inbred C57BL ; Microbiota/genetics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Consumption of a typical Western diet is a risk factor for several disorders. Metabolic syndrome is the most common disease associated with intake of excess fat. However, the incidence of inflammatory bowel disease is also greater in subjects consuming a Western diet, although the mechanism of this phenomenon is not clearly understood. We examined the morphological and functional changes of the intestine, the first site contacting dietary fat, in mice fed a high-fat diet (HFD) inducing obesity. Paneth cell area and production of antimicrobial peptides by Paneth cells were decreased in HFD-fed mice. Goblet cell number and secretion of mucin by goblet cells were also decreased, while intestinal permeability was increased in HFD-fed mice. HFD-fed mice were more susceptible to experimental colitis, and exhibited severe colonic inflammation, accompanied by the expansion of selected pathobionts such as Atopobium sp. and Proteobacteria. Fecal microbiota transplantation transferred the susceptibility to DSS-colitis, and antibiotic treatment abrogated colitis progression. These data suggest that an experimental HFD-induced Paneth cell dysfunction and subsequent intestinal dysbiosis characterized by pathobiont expansion can be predisposing factors to the development of inflammatory bowel disease.}, } @article {pmid29104169, year = {2018}, author = {Allegretti, JR and Allegretti, AS and Phelps, E and Xu, H and Kassam, Z and Fischer, M}, title = {Asymptomatic Clostridium difficile carriage rate post-fecal microbiota transplant is low: a prospective clinical and stool assessment.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {24}, number = {7}, pages = {780.e1-780.e3}, doi = {10.1016/j.cmi.2017.10.022}, pmid = {29104169}, issn = {1469-0691}, support = {P30 DK034854/DK/NIDDK NIH HHS/United States ; }, abstract = {OBJECTIVES: We aimed to assess the asymptomatic Clostridium difficile carriage rates following fecal microbiota transplantation (FMT).

METHODS: All patients who underwent FMT for recurrent Clostridium difficile infection (CDI) via colonoscopy or sigmoidoscopy between June 2013 and April 2015 and had a minimum of 8-week follow-up post FMT at two tertiary care referral centres were included in the study. Patients were prospectively followed both clinically and with stool assessments for 8 weeks post FMT. Assessments occurred at 1 week and 4 weeks post FMT to assess for failure. Failure was defined as presence of diarrhoeal symptoms and a positive CDI stool test by polymerase chain reaction for toxin gene (PCR) at any time point during the 8-week follow-up period. CDI stool testing using PCR was performed at weeks 1 and 4 post FMT in asymptomatic patients as well.

RESULTS: 167 patients were included. Twenty-eight patients (16.7% (28/167)) were FMT failures throughout the 8-week period. At week 1, seven patients had already failed the FMT. Of the remaining 160 patients, 144 were asymptomatic, and among these, 141 were negative for C. difficile toxin gene by PCR. This resulted in an asymptomatic carriage rate of 2.1% (3/144). At week 4, 143 patients had not yet failed FMT. Of these patients 129 patients were asymptomatic and among those, 125 were negative by PCR, resulting in an asymptomatic carriage rate of 3% (3/129).

CONCLUSIONS: Asymptomatic carriage after FMT is rare. This suggests that testing for cure after FMT in asymptomatic patients is not necessary.}, } @article {pmid29104129, year = {2017}, author = {Allegretti, JR and Allegretti, AS and Phelps, E and Xu, H and Fischer, M and Kassam, Z}, title = {Classifying Fecal Microbiota Transplantation Failure: An Observational Study Examining Timing and Characteristics of Fecal Microbiota Transplantation Failures.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2017.10.031}, pmid = {29104129}, issn = {1542-7714}, } @article {pmid29101931, year = {2017}, author = {Hefazi, M and Patnaik, MM and Hogan, WJ and Litzow, MR and Pardi, DS and Khanna, S}, title = {Safety and Efficacy of Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection in Patients With Cancer Treated With Cytotoxic Chemotherapy: A Single-Institution Retrospective Case Series.}, journal = {Mayo Clinic proceedings}, volume = {92}, number = {11}, pages = {1617-1624}, doi = {10.1016/j.mayocp.2017.08.016}, pmid = {29101931}, issn = {1942-5546}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridium difficile/*isolation & purification ; Cytotoxins/*therapeutic use ; Enterocolitis, Pseudomembranous/complications/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasms/complications/*drug therapy ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: To study the safety and efficacy of fecal microbiota transplant (FMT) for Clostridium difficile infection (CDI) in patients with cancer treated with cytotoxic chemotherapy in a single-institution retrospective case series.

PATIENTS AND METHODS: Twenty-three consecutive patients with underlying hematologic (n=13) or solid (n=10) malignancies who underwent FMT for recurrent CDI from August 1, 2012, through June 30, 2016, were studied.

RESULTS: All the patients had received cytotoxic chemotherapy a median of 12 months (range, 1-340 months) before FMT. Patients had experienced a median of 4 (range, 2-9) CDI episodes and had been treated with a median of 106 days (range, 42-495 days) of vancomycin, metronidazole, or fidaxomicin before FMT. Twelve patients (52%) had severe/severe-complicated CDI at some stage. Eight patients (35%) had active cancer and 5 (22%) had received chemotherapy within 12 weeks of FMT. Diarrhea resolved without recurrence within 60 days of FMT in all but 3 patients (13%) (all had negative C difficile results). Of the 22 patients who were alive 60 days or more after FMT, 11 (48%) underwent further chemotherapy and 10 (43%) received more antibiotics. Two patients (9%) developed recurrent CDI 14 and 22 months after FMT. One death occurred 5 days after FMT as a result of cardiac arrest unrelated to FMT. There were no other severe adverse events and no infectious complications directly attributable to FMT.

CONCLUSION: This series demonstrates that FMT is a highly effective and safe therapeutic option for multiply recurrent CDI in patients with cancer treated with cytotoxic chemotherapy.}, } @article {pmid29101192, year = {2018}, author = {Siegerstetter, SC and Petri, RM and Magowan, E and Lawlor, PG and Zebeli, Q and O'Connell, NE and Metzler-Zebeli, BU}, title = {Fecal Microbiota Transplant from Highly Feed-Efficient Donors Shows Little Effect on Age-Related Changes in Feed-Efficiency-Associated Fecal Microbiota from Chickens.}, journal = {Applied and environmental microbiology}, volume = {84}, number = {2}, pages = {}, doi = {10.1128/AEM.02330-17}, pmid = {29101192}, issn = {1098-5336}, abstract = {Chickens with good or poor feed efficiency (FE) have been shown to differ in their intestinal microbiota composition. This study investigated differences in the fecal bacterial community of highly and poorly feed-efficient chickens at 16 and 29 days posthatch (dph) and evaluated whether a fecal microbiota transplant (FMT) from feed-efficient donors early in life can affect the fecal microbiota in chickens at 16 and 29 dph and chicken FE and nutrient retention at 4 weeks of age. A total of 110 chickens were inoculated with a FMT or a control transplant (CT) on dph 1, 6, and 9 and ranked according to residual feed intake (RFI; the metric for FE) on 30 dph. Fifty-six chickens across both inoculation groups were selected as the extremes in RFI (29 low, 27 high). RFI-related fecal bacterial profiles were discernible at 16 and 29 dph. In particular, Lactobacillus salivarius, Lactobacillus crispatus, and Anaerobacterium operational taxonomic units were associated with low RFI (good FE). Multiple administrations of the FMT only slightly changed the fecal bacterial composition, which was supported by weighted UniFrac analysis, showing similar bacterial communities in the feces of both inoculation groups at 16 and 29 dph. Moreover, the FMT did not change the RFI and nutrient retention of highly and poorly feed-efficient recipients, whereas it tended to increase feed intake and body weight gain in female chickens. This finding suggests that host- and environment-related factors may more strongly affect chicken fecal microbiota and FE than the FMT.IMPORTANCE Modulating the chicken's early microbial colonization using a FMT from highly feed-efficient donor chickens may be a promising tool to establish a more desirable bacterial profile in recipient chickens, thereby improving host FE. Although FE-associated fecal bacterial profiles at 16 and 29 dph could be established, the microbiota composition of a FMT, when administered early in life, may not be a strong factor modulating the fecal microbiota at 2 to 4 weeks of life and reducing the variation in chicken's FE. Nevertheless, the present FMT may have potential benefits for growth performance in female chickens.}, } @article {pmid29100842, year = {2018}, author = {Johnsen, PH and Hilpüsch, F and Cavanagh, JP and Leikanger, IS and Kolstad, C and Valle, PC and Goll, R}, title = {Faecal microbiota transplantation versus placebo for moderate-to-severe irritable bowel syndrome: a double-blind, randomised, placebo-controlled, parallel-group, single-centre trial.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {3}, number = {1}, pages = {17-24}, doi = {10.1016/S2468-1253(17)30338-2}, pmid = {29100842}, issn = {2468-1253}, mesh = {Abdominal Pain/etiology ; Adult ; Double-Blind Method ; *Fecal Microbiota Transplantation/adverse effects ; Female ; Humans ; Irritable Bowel Syndrome/physiopathology/*therapy ; Male ; Middle Aged ; Nausea/etiology ; Proof of Concept Study ; Vertigo/etiology ; }, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is a common condition characterised by abdominal pain, bloating, and poor quality of life. IBS might be caused by a gut dysbiosis. We aimed to compare faecal microbiota transplantation (FMT) with placebo in patients with IBS.

METHODS: In this double-blind, randomised, placebo-controlled, parallel-group, single-centre study, we enrolled patients with IBS with diarrhoea or with diarrhoea and constipation (excluding dominating constipation) defined by the ROME III criteria, scored as moderate to severe according to the IBS severity scoring system (IBS-SSS; a score of ≥175). Eligible participants were aged 18-75 years and were recruited locally by general practitioners in northern Norway. We randomly assigned participants (2:1) in blocks of six to active or placebo FMT. Personnel not involved in the clinical performance of the trial generated the randomisation sequence using a randomisation website. Non-study personnel performed the final allocation and standardised the active and placebo transplants to make them identical in appearance and temperature. The faeces were freshly processed, and were used the same day (fresh transplant) or were stored in a freezer for later use (frozen transplant); participants' own faeces served as placebo. A dose of 8 mg loperamide was administered orally 2 h before endoscopy to retain the transplant. The transplant (50-80 g of faeces mixed with 200 mL of isotonic saline and 50 mL of 85% glycerol) was administered by a colonoscope to the caecum. The primary endpoint was symptom relief of more than 75 points assessed by IBS-SSS, 3 months after FMT. The primary analysis was done in the modified intention-to-treat population, excluding participants who did not undergo treatment or who were diagnosed with any other disease by pinch biopsies obtained during the treatment procedure. For the safety analysis, only participants who did not undergo treatment were excluded. The study is registered with ClinicalTrials.gov, number NCT02154867. The trial has been extended with an open-labelled study treating the placebo group with frozen FMT for further exploratory studies.

FINDINGS: Between Jan 1, and Oct 30, 2015, we recruited 90 participants and randomly assigned them to active treatment (n=60) or placebo (n=30). Three participants did not undergo FMT and four were excluded after diagnosis of microscopic colitis, leaving 83 for final modified intention-to-treat analysis (55 in the active treatment group and 28 in the placebo group). 36 (65%) of 55 participants receiving active treatment versus 12 (43%) of 28 receiving the placebo showed response at 3 months (p=0·049). One participant had transient nausea and vertigo (active group) and was observed at the hospital for a few hours after the procedure. Two participants had soiling of transplant on their way home from treatment (one in each group) and three experienced self-limiting intermittent abdominal pain (one in the active group and two in the placebo group). No serious adverse events could be attributed to FMT.

INTERPRETATION: FMT induced significant symptom relief in patients with IBS. However, larger multicentre studies are needed to confirm the results.

FUNDING: HelseNord and the Norwegian Centre of Rural Medicine, University of Tromsø.}, } @article {pmid29097871, year = {2017}, author = {Wang, WW and Zhang, Y and Huang, XB and You, N and Zheng, L and Li, J}, title = {Fecal microbiota transplantation prevents hepatic encephalopathy in rats with carbon tetrachloride-induced acute hepatic dysfunction.}, journal = {World journal of gastroenterology}, volume = {23}, number = {38}, pages = {6983-6994}, doi = {10.3748/wjg.v23.i38.6983}, pmid = {29097871}, issn = {2219-2840}, mesh = {Ammonia/blood ; Animals ; Carbon Tetrachloride Poisoning/complications ; *Fecal Microbiota Transplantation ; Hepatic Encephalopathy/blood/etiology/*prevention & control ; Intestinal Mucosa/metabolism ; Male ; Memory ; Rats, Sprague-Dawley ; }, abstract = {AIM: To investigate whether fecal microbiota transplantation (FMT) prevents hepatic encephalopathy (HE) in rats with carbon tetrachloride (CCl4)-induced acute hepatic dysfunction.

METHODS: A rat model of HE was established with CCl4. Rat behaviors and spatial learning capability were observed, and hepatic necrosis, intestinal mucosal barrier, serum ammonia levels and intestinal permeability were determined in HE rats receiving FMT treatment. Furthermore, the expression of tight junction proteins (Claudin-1, Claudin-6 and Occludin), Toll-like receptor (TLR) 4/TLR9, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was examined.

RESULTS: FMT improved rat behaviors, HE grade and spatial learning capability. Moreover, FMT prevented hepatic necrosis and intestinal mucosal barrier damage, leading to hepatic clearance of serum ammonia levels and reduced intestinal permeability. The expression of TLR4 and TLR9, two potent mediators of inflammatory response, was significantly downregulated in the liver of rats treated with FMT. Consistently, circulating pro-inflammatory factors such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α were remarkably decreased, indicating that FMT is able to limit systemic inflammation by decreasing the expression of TLR4 and TLR9. Importantly, HE-induced loss of tight junction proteins (Claudin-1, Claudin-6 and Occludin) was restored in intestinal tissues of rats receiving FMT treatment.

CONCLUSION: FMT enables protective effects in HE rats, and it improves the cognitive function and reduces the liver function indexes. FMT may cure HE by altering the intestinal permeability and improving the TLR response of the liver.}, } @article {pmid29097494, year = {2018}, author = {Routy, B and Le Chatelier, E and Derosa, L and Duong, CPM and Alou, MT and Daillère, R and Fluckiger, A and Messaoudene, M and Rauber, C and Roberti, MP and Fidelle, M and Flament, C and Poirier-Colame, V and Opolon, P and Klein, C and Iribarren, K and Mondragón, L and Jacquelot, N and Qu, B and Ferrere, G and Clémenson, C and Mezquita, L and Masip, JR and Naltet, C and Brosseau, S and Kaderbhai, C and Richard, C and Rizvi, H and Levenez, F and Galleron, N and Quinquis, B and Pons, N and Ryffel, B and Minard-Colin, V and Gonin, P and Soria, JC and Deutsch, E and Loriot, Y and Ghiringhelli, F and Zalcman, G and Goldwasser, F and Escudier, B and Hellmann, MD and Eggermont, A and Raoult, D and Albiges, L and Kroemer, G and Zitvogel, L}, title = {Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {91-97}, doi = {10.1126/science.aan3706}, pmid = {29097494}, issn = {1095-9203}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; CD4 Antigens/immunology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/genetics/*immunology ; Humans ; Immunotherapy/*methods ; Interleukin-12/immunology ; Metagenome/genetics ; Mice ; Neoplasms/*therapy ; Programmed Cell Death 1 Receptor/*antagonists & inhibitors ; Receptors, CCR/immunology ; Receptors, CXCR3/immunology ; T-Lymphocytes/immunology ; Verrucomicrobia/genetics/immunology ; }, abstract = {Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition. Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade, whereas FMT from nonresponding patients failed to do so. Metagenomics of patient stool samples at diagnosis revealed correlations between clinical responses to ICIs and the relative abundance of Akkermansia muciniphila Oral supplementation with A. muciniphila after FMT with nonresponder feces restored the efficacy of PD-1 blockade in an interleukin-12-dependent manner by increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes into mouse tumor beds.}, } @article {pmid29097493, year = {2018}, author = {Gopalakrishnan, V and Spencer, CN and Nezi, L and Reuben, A and Andrews, MC and Karpinets, TV and Prieto, PA and Vicente, D and Hoffman, K and Wei, SC and Cogdill, AP and Zhao, L and Hudgens, CW and Hutchinson, DS and Manzo, T and Petaccia de Macedo, M and Cotechini, T and Kumar, T and Chen, WS and Reddy, SM and Szczepaniak Sloane, R and Galloway-Pena, J and Jiang, H and Chen, PL and Shpall, EJ and Rezvani, K and Alousi, AM and Chemaly, RF and Shelburne, S and Vence, LM and Okhuysen, PC and Jensen, VB and Swennes, AG and McAllister, F and Marcelo Riquelme Sanchez, E and Zhang, Y and Le Chatelier, E and Zitvogel, L and Pons, N and Austin-Breneman, JL and Haydu, LE and Burton, EM and Gardner, JM and Sirmans, E and Hu, J and Lazar, AJ and Tsujikawa, T and Diab, A and Tawbi, H and Glitza, IC and Hwu, WJ and Patel, SP and Woodman, SE and Amaria, RN and Davies, MA and Gershenwald, JE and Hwu, P and Lee, JE and Zhang, J and Coussens, LM and Cooper, ZA and Futreal, PA and Daniel, CR and Ajami, NJ and Petrosino, JF and Tetzlaff, MT and Sharma, P and Allison, JP and Jenq, RR and Wargo, JA}, title = {Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {97-103}, doi = {10.1126/science.aan4236}, pmid = {29097493}, issn = {1095-9203}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R25 CA057730/CA/NCI NIH HHS/United States ; R25 CA056452/CA/NCI NIH HHS/United States ; UL1 TR000128/TR/NCATS NIH HHS/United States ; K12 CA088084/CA/NCI NIH HHS/United States ; K08 CA160692/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/genetics/*immunology ; Humans ; *Immunotherapy ; Melanoma/immunology/*therapy ; Metagenome ; Mice ; Programmed Cell Death 1 Receptor/*antagonists & inhibitors ; Skin Neoplasms/immunology/*therapy ; }, abstract = {Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.}, } @article {pmid29093626, year = {2017}, author = {Lahtinen, P and Mattila, E and Anttila, VJ and Tillonen, J and Teittinen, M and Nevalainen, P and Salminen, S and Satokari, R and Arkkila, P}, title = {Faecal microbiota transplantation in patients with Clostridium difficile and significant comorbidities as well as in patients with new indications: A case series.}, journal = {World journal of gastroenterology}, volume = {23}, number = {39}, pages = {7174-7184}, doi = {10.3748/wjg.v23.i39.7174}, pmid = {29093626}, issn = {2219-2840}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Clostridium difficile/*pathogenicity ; Coinfection ; Comorbidity ; Drug Resistance, Bacterial ; Enterocolitis, Pseudomembranous/diagnosis/immunology/microbiology/*therapy ; *Fecal Microbiota Transplantation/adverse effects ; Feces/*microbiology ; Female ; Humans ; Immunocompromised Host ; Male ; Middle Aged ; Recurrence ; Risk Factors ; Treatment Outcome ; Young Adult ; }, abstract = {Fecal microbiota transplantation (FMT) is effective in recurrent Clostridium difficile infection (rCDI). Knowledge of the safety and efficacy of FMT treatment in immune deficient patients is scarce. FMT has been suggested as a potential method for an increasing number of new indications besides rCDI. Among our FMT-treated rCDI patients, we reviewed those with major comorbidities: two human immunodeficiency virus patients, six haemodialysis patients, two kidney transplant patients, two liver transplant patients and a patient with chronic lymphatic leukaemia. We also reviewed those treated with FMT for indications other than rCDI: Salmonella carriage (two patients), trimethylaminuria (two patients), small intestinal bacterial overgrowth (SIBO; one patient), and lymphocytic colitis (one patient), as well as a common variable immunodeficiency patient with chronic norovirus infection and ESBL-producing Escherichia coli (E. coli) carriage. Of the thirteen rCDI patients treated with FMT, eleven cleared the CDI. The observed adverse events were not directly attributable to FMT. Concerning the special indications, both Salmonellas and ESBL-producing E. coli were eradicated. One trimethylaminuria patient and one SIBO-patient reported a reduction of symptoms. Three patients did not experience a benefit from FMT: chronic norovirus, lymphocytic colitis and the other fish malodour syndrome. There were no reported side effects in this group. FMT appeared to be safe and effective for immunocompromised patients with rCDI. FMT showed promise for the eradication of antibiotic-resistant bacteria, but further research is warranted.}, } @article {pmid29084074, year = {2018}, author = {Kvasnovsky, CL and Leong, LEX and Choo, JM and Abell, GCJ and Papagrigoriadis, S and Bruce, KD and Rogers, GB}, title = {Clinical and symptom scores are significantly correlated with fecal microbiota features in patients with symptomatic uncomplicated diverticular disease: a pilot study.}, journal = {European journal of gastroenterology & hepatology}, volume = {30}, number = {1}, pages = {107-112}, doi = {10.1097/MEG.0000000000000995}, pmid = {29084074}, issn = {1473-5687}, mesh = {Abdominal Pain/microbiology ; Aged ; Aged, 80 and over ; Bacteria/classification/genetics/*isolation & purification ; Colon/*microbiology ; Diverticulitis, Colonic/complications/diagnosis/*microbiology ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Middle Aged ; Pain Measurement ; Pilot Projects ; Prognosis ; Ribotyping ; Risk Factors ; Severity of Illness Index ; }, abstract = {BACKGROUND: There is growing consensus that symptomatic uncomplicated diverticular disease is a chronic inflammatory condition, and that alterations in the fecal microbiota may contribute to its pathogenesis.

OBJECTIVE: The aim of this study was to relate the fecal microbiota composition in symptomatic uncomplicated diverticular disease to measures of inflammation, symptoms, and history of previous acute diverticulitis.

PARTICIPANTS AND METHODS: Fecal microbiota composition in 28 individuals with symptomatic uncomplicated diverticular disease was characterized by 16S RNA gene amplicon sequencing. Microbiota composition was related to clinical history, symptom and inflammation measures, and demographic variables.

RESULTS: Previous acute diverticulitis was associated with higher relative abundance of Pseudobutyrivibrio, Bifidobacterium, Christensenellaceae family, and Mollicutes RF9 order (P=0.004, 0.006, 0.010, and 0.019, respectively), but not microbiota alpha or beta diversity. A higher bloating severity score was significantly correlated with a higher relative abundance of Ruminococcus (P=0.032), and significantly inversely correlated with the relative abundance of the Roseburia (P=0.002). Fecal calprotectin levels were positively correlated with alpha diversity (Shannon index, P=0.005) and the relative abundance of Lactobacillus (P=0.004). Pain score was positively correlated with the relative abundance of Cyanobacterium (adjusted P=0.032).

CONCLUSION: Patient symptoms in symptomatic diverticular disease are significantly correlated with features of the fecal microbiota. Our findings suggest the potential utility of therapies that target intestinal microbiology, such as dietary prebiotic supplements.}, } @article {pmid29083037, year = {2018}, author = {Woodhouse, CA and Patel, VC and Singanayagam, A and Shawcross, DL}, title = {Review article: the gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease.}, journal = {Alimentary pharmacology & therapeutics}, volume = {47}, number = {2}, pages = {192-202}, doi = {10.1111/apt.14397}, pmid = {29083037}, issn = {1365-2036}, mesh = {Animals ; Dysbiosis/*complications/microbiology/therapy ; End Stage Liver Disease/*etiology/microbiology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestines/metabolism/microbiology ; Liver Cirrhosis/etiology/microbiology/therapy ; Non-alcoholic Fatty Liver Disease/etiology/microbiology/therapy ; Probiotics/therapeutic use ; }, abstract = {BACKGROUND: Mortality from chronic liver disease is rising exponentially. The liver is intimately linked to the gut via the portal vein, and exposure to gut microbiota and their metabolites translocating across the gut lumen may impact upon both the healthy and diseased liver. Modulation of gut microbiota could prove to be a potential therapeutic target.

AIM: To characterise the changes in the gut microbiome that occur in chronic liver disease and to assess the impact of manipulation of the microbiome on the liver.

METHODS: We conducted a PubMed search using search terms including 'microbiome', 'liver' and 'cirrhosis' as well as 'non-alcoholic fatty liver disease', 'steatohepatitis', 'alcohol' and 'primary sclerosing cholangitis'. Relevant articles were also selected from references of articles and review of the ClinicalTrials.gov website.

RESULTS: Reduced bacterial diversity, alcohol sensitivity and the development of gut dysbiosis are seen in several chronic liver diseases, including non-alcoholic fatty liver disease, alcohol-related liver disease and primary sclerosing cholangitis. Perturbations in gut commensals could lead to deficient priming of the immune system predisposing the development of immune-mediated diseases. Furthermore, transfer of stool from an animal with the metabolic syndrome may induce steatosis in a healthy counterpart. Patients with cirrhosis develop dysbiosis, small bowel bacterial overgrowth and increased gut wall permeability, allowing bacterial translocation and uptake of endotoxin inducing hepatic and systemic inflammation.

CONCLUSIONS: Manipulation of the gut microbiota with diet, probiotics or faecal microbiota transplantation to promote the growth of "healthy" bacteria may ameliorate the dysbiosis and alter prognosis.}, } @article {pmid29079158, year = {2017}, author = {Donskey, CJ}, title = {Clostridium difficile in Older Adults.}, journal = {Infectious disease clinics of North America}, volume = {31}, number = {4}, pages = {743-756}, doi = {10.1016/j.idc.2017.07.003}, pmid = {29079158}, issn = {1557-9824}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/therapeutic use ; Clostridium Infections/epidemiology/*microbiology/*pathology/therapy ; Clostridium difficile/*isolation & purification ; Feces/microbiology ; Humans ; Infection Control/methods ; *Nursing Homes ; }, abstract = {Recent increases in the incidence of Clostridium difficile infection (CDI) have been observed in all age groups, but the elderly have been disproportionately affected and long-term care facilities (LTCFs) have borne a significant proportion of the increasing burden. Recurrences are common in older adults and may have significant adverse effects on quality of life. Ensuring appropriate diagnostic testing and management is challenging for older adults in the community and in LTCFs. This review focuses on current concepts related to the epidemiology, diagnosis, and management of CDI in older adults.}, } @article {pmid29076444, year = {2017}, author = {van Beurden, YH and Terveer, EM and Keller, JJ and Kuijper, EJ and Mulder, CJJ and Vandenbroucke-Grauls, CMJE}, title = {[Faecal microbiota transplantation: indications in perspective].}, journal = {Nederlands tijdschrift voor geneeskunde}, volume = {161}, number = {}, pages = {D1623}, pmid = {29076444}, issn = {1876-8784}, mesh = {Clostridium Infections/complications ; Colitis, Ulcerative/*microbiology/*therapy ; Crohn Disease/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; }, abstract = {- As yet, with cure rates around 85%, recurrent Clostridium difficile infection is the only definite indication for faecal microbiota transplantation.- Faecal microbiota transplantation induces clinical remission and endoscopic improvements in 24-30% of patients with ulcerative colitis, compared to 5% (water) to 20% (autologous faeces) in placebo-treated patients. Current research focuses on the identification of 'super donors', and subgroups of patients in which faecal microbiota transplantation is effective.- In patients with metabolic syndrome, faecal microbiota transplantation may increase insulin sensitivity. Weight, body mass index, and energy metabolism are not affected by faecal microbiota transplantation in humans.- In addition to the aforementioned indications, faecal microbiota transplantation is an emerging treatment modality for patients with Crohn's disease, irritable bowel syndrome, graft-versus-host-disease, and carriage of multidrug-resistant micro-organisms. Randomized controlled trials, comparing faecal microbiota transplantation with placebo treatment, are required to determine the effectiveness of faecal microbiota transplantation in these patient groups.}, } @article {pmid29076071, year = {2017}, author = {Yoon, S and Yu, J and McDowell, A and Kim, SH and You, HJ and Ko, G}, title = {Bile salt hydrolase-mediated inhibitory effect of Bacteroides ovatus on growth of Clostridium difficile.}, journal = {Journal of microbiology (Seoul, Korea)}, volume = {55}, number = {11}, pages = {892-899}, doi = {10.1007/s12275-017-7340-4}, pmid = {29076071}, issn = {1976-3794}, mesh = {Antibiosis ; Bacteroides/*enzymology/metabolism ; Bile Acids and Salts/chemistry/*metabolism/pharmacology ; Clostridium Infections/microbiology/therapy ; Clostridium difficile/*drug effects/*growth & development ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Hydrolases/*metabolism ; }, abstract = {Clostridium difficile infection (CDI) is one of the most common nosocomial infections. Dysbiosis of the gut microbiota due to consumption of antibiotics is a major contributor to CDI. Recently, fecal microbiota transplantation (FMT) has been applied to treat CDI. However, FMT has important limitations including uncontrolled exposure to pathogens and standardization issues. Therefore, it is necessary to evaluate alternative treatment methods, such as bacteriotherapy, as well as the mechanism through which beneficial bacteria inhibit the growth of C. difficile. Here, we report bile acid-mediated inhibition of C. difficile by Bacteroides strains which can produce bile salt hydrolase (BSH). Bacteroides strains are not commonly used to treat CDI; however, as they comprise a large proportion of the intestinal microbiota, they can contribute to bile acid-mediated inhibition of C. difficile. The inhibitory effect on C. difficile growth increased with increasing bile acid concentration in the presence of Bacteroides ovatus SNUG 40239. Furthermore, this inhibitory effect on C. difficile growth was significantly attenuated when bile acid availability was reduced by cholestyramine, a bile acid sequestrant. The findings of this study are important due to the discovery of a new bacterial strain that in the presence of available bile acids inhibits growth of C. difficile. These results will facilitate development of novel bacteriotherapy strategies to control CDI.}, } @article {pmid29071710, year = {2018}, author = {Khanna, S}, title = {Microbiota Replacement Therapies: Innovation in Gastrointestinal Care.}, journal = {Clinical pharmacology and therapeutics}, volume = {103}, number = {1}, pages = {102-111}, doi = {10.1002/cpt.923}, pmid = {29071710}, issn = {1532-6535}, mesh = {Biological Therapy/methods ; Clostridium Infections/physiopathology/*therapy ; Drug Resistance, Multiple/immunology ; Dysbiosis/therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Immune System Diseases/physiopathology/*therapy ; Inflammation/immunology/*therapy ; Treatment Outcome ; }, abstract = {There has been an increasing interest in the association between human disease and altered gut microbiota, and therapeutics to modulate microbiota to treat disease. Healthy human gastrointestinal microbiota is highly diverse and rich, and harbors between 500 and 2,000 species. Diseases associated with dysbiotic microbiota include antibiotic-associated diarrhea, Clostridium difficile infection, multidrug-resistant organisms, inflammatory bowel disease, obesity, metabolic syndrome, diabetes mellitus, neuropsychiatric diseases, and systemic autoimmune diseases. Microbiota replacement therapies have shown immense promise in treatment of recurrent C. difficile infection and are being studied for other indications. Microbiota replacement therapies for indications other than C. difficile infection should be performed only in research settings. There is an immense need for standardized microbiota replacement therapies for C. difficile infection. Studies are needed to elucidate long-term safety and adverse events from these therapies.}, } @article {pmid29071167, year = {2017}, author = {Liu, T and Yang, Z and Zhang, X and Han, N and Yuan, J and Cheng, Y}, title = {16S rDNA analysis of the effect of fecal microbiota transplantation on pulmonary and intestinal flora.}, journal = {3 Biotech}, volume = {7}, number = {6}, pages = {370}, doi = {10.1007/s13205-017-0997-x}, pmid = {29071167}, issn = {2190-572X}, abstract = {This study aims to explore the effect of FMT on regulations of dysbacteriosis of pulmonary and intestinal flora in rats with 16S rDNA sequencing technology. A total of 27 SPF rats (3-4 weeks old) were randomly divided into three groups: normal control group (K), model control group (MX), and fecal microbiota transplantation group (FMT); each group contained nine rats. The OTU values of the pulmonary and intestinal flora of the MX group decreased significantly compared with the normal control group. After FMT, the OTU value of pulmonary flora increased, while the value of OTU in intestinal flora declined. At the phylum level, FMT down-regulated Proteobacteria, Firmicutes, and Bacteroidetes in the pulmonary flora. At the genus level, FMT down-regulated Pseudomonas, Sphingobium, Lactobacillus, Rhizobium, and Acinetobacter, thus maintaining the balance of the pulmonary flora. Moreover, FMT could change the structure and diversity of the pulmonary and intestinal flora by positively regulating the pulmonary flora and negatively regulating intestinal flora. This study may provide a scientific basis for FMT treatment of respiratory diseases.}, } @article {pmid29067223, year = {2017}, author = {Arbel, LT and Hsu, E and McNally, K}, title = {Cost-Effectiveness of Fecal Microbiota Transplantation in the Treatment of Recurrent Clostridium Difficile Infection: A Literature Review.}, journal = {Cureus}, volume = {9}, number = {8}, pages = {e1599}, doi = {10.7759/cureus.1599}, pmid = {29067223}, issn = {2168-8184}, abstract = {Clostridium difficile (C. difficile) is a common cause of antibiotic--associated diarrhea (AAD), being responsible for 15--25% of all AAD cases. The purpose of this literature review is to determine the cost-effectiveness of fecal microbiota transplantation (FMT) and how it compares in this regard to the standard treatments of choice for recurrent C. difficile infection (CDI). The review of the literature along with the evaluation of three comparative cost effective analyses yielded findings consistent with the view that FMT is the most cost-effective option in treating recurrent CDI. There are some (but considerably less) data indicating that FMT may be a cost effective strategy in treating initial CDI, as well. The superior cost-effectiveness of FMT as compared to the preferred standards of treatment for recurrent CDI suggest FMT use should become more integrated in routine clinical practice. Increased utilization of FMTs would allow for better control of this increasingly problematic disease as well as lower costs associated with its management.}, } @article {pmid29066578, year = {2017}, author = {Hayase, E and Hashimoto, D and Nakamura, K and Noizat, C and Ogasawara, R and Takahashi, S and Ohigashi, H and Yokoi, Y and Sugimoto, R and Matsuoka, S and Ara, T and Yokoyama, E and Yamakawa, T and Ebata, K and Kondo, T and Hiramine, R and Aizawa, T and Ogura, Y and Hayashi, T and Mori, H and Kurokawa, K and Tomizuka, K and Ayabe, T and Teshima, T}, title = {R-Spondin1 expands Paneth cells and prevents dysbiosis induced by graft-versus-host disease.}, journal = {The Journal of experimental medicine}, volume = {214}, number = {12}, pages = {3507-3518}, doi = {10.1084/jem.20170418}, pmid = {29066578}, issn = {1540-9538}, mesh = {Administration, Oral ; Animals ; Bacteria/metabolism ; Cell Differentiation/drug effects ; Cytoprotection/drug effects ; Dysbiosis/*etiology/pathology/*prevention & control ; Female ; Graft vs Host Disease/*complications/pathology ; Humans ; Intestines/pathology ; Mice, Inbred C57BL ; Paneth Cells/drug effects/metabolism/*pathology ; Recombinant Proteins/administration & dosage/pharmacology/therapeutic use ; Stem Cell Transplantation ; Stem Cells/drug effects/metabolism ; Thrombospondins/*pharmacology/*therapeutic use ; alpha-Defensins/metabolism ; }, abstract = {The intestinal microbial ecosystem is actively regulated by Paneth cell-derived antimicrobial peptides such as α-defensins. Various disorders, including graft-versus-host disease (GVHD), disrupt Paneth cell functions, resulting in unfavorably altered intestinal microbiota (dysbiosis), which further accelerates the underlying diseases. Current strategies to restore the gut ecosystem are bacteriotherapy such as fecal microbiota transplantation and probiotics, and no physiological approach has been developed so far. In this study, we demonstrate a novel approach to restore gut microbial ecology by Wnt agonist R-Spondin1 (R-Spo1) or recombinant α-defensin in mice. R-Spo1 stimulates intestinal stem cells to differentiate to Paneth cells and enhances luminal secretion of α-defensins. Administration of R-Spo1 or recombinant α-defensin prevents GVHD-mediated dysbiosis, thus representing a novel and physiological approach at modifying the gut ecosystem to restore intestinal homeostasis and host-microbiota cross talk toward therapeutic benefits.}, } @article {pmid29066574, year = {2018}, author = {Conceição-Neto, N and Deboutte, W and Dierckx, T and Machiels, K and Wang, J and Yinda, KC and Maes, P and Van Ranst, M and Joossens, M and Raes, J and Vermeire, S and Matthijnssens, J}, title = {Low eukaryotic viral richness is associated with faecal microbiota transplantation success in patients with UC.}, journal = {Gut}, volume = {67}, number = {8}, pages = {1558-1559}, doi = {10.1136/gutjnl-2017-315281}, pmid = {29066574}, issn = {1468-3288}, mesh = {Colitis, Ulcerative ; *Eukaryota ; *Fecal Microbiota Transplantation ; Feces ; Humans ; }, } @article {pmid29052237, year = {2018}, author = {Kump, P and Wurm, P and Gröchenig, HP and Wenzl, H and Petritsch, W and Halwachs, B and Wagner, M and Stadlbauer, V and Eherer, A and Hoffmann, KM and Deutschmann, A and Reicht, G and Reiter, L and Slawitsch, P and Gorkiewicz, G and Högenauer, C}, title = {The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis.}, journal = {Alimentary pharmacology & therapeutics}, volume = {47}, number = {1}, pages = {67-77}, doi = {10.1111/apt.14387}, pmid = {29052237}, issn = {1365-2036}, mesh = {Adult ; Anti-Bacterial Agents/administration & dosage ; Colitis, Ulcerative/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Male ; Microbiota ; Middle Aged ; Prospective Studies ; Remission Induction ; Ruminococcus ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Faecal microbiota transplantation is an experimental approach for the treatment of patients with ulcerative colitis. Although there is growing evidence that faecal microbiota transplantation is effective in this disease, factors affecting its response are unknown.

AIMS: To establish a faecal microbiota transplantation treatment protocol in ulcerative colitis patients, and to investigate which patient or donor factors are responsible for the treatment success.

METHODS: This is an open controlled trial of repeated faecal microbiota transplantation after antibiotic pre-treatment (FMT-group, n = 17) vs antibiotic pre-treatment only (AB-group, n = 10) in 27 therapy refractory ulcerative colitis patients over 90 days. Faecal samples of donors and patients were analysed by 16SrRNA gene-based microbiota analysis.

RESULTS: In the FMT-group, 10/17 (59%) of patients showed a response and 4/17 (24%) a remission to faecal microbiota transplantation. Response to faecal microbiota transplantation was mainly influenced by the taxonomic composition of the donor's microbiota. Stool of donors with a high bacterial richness (observed species remission 946 ± 93 vs no response 797 ± 181 at 15367 rps) and a high relative abundance of Akkermansia muciniphila (3.3 ± 3.1% vs 0.1 ± 0.2%), unclassified Ruminococcaceae (13.8 ± 5.0% vs 7.5 ± 3.7%), and Ruminococcus spp. (4.9 ± 3.5% vs 1.0 ± 0.7%) were more likely to induce remission. In contrast antibiotic treatment alone (AB-group) was poorly tolerated, probably because of a sustained decrease of intestinal microbial richness.

CONCLUSIONS: The taxonomic composition of the donor's intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in ulcerative colitis patients. The design of specific microbial preparation might lead to new treatments for ulcerative colitis.}, } @article {pmid29045252, year = {2018}, author = {Bandera, A and De Benedetto, I and Bozzi, G and Gori, A}, title = {Altered gut microbiome composition in HIV infection: causes, effects and potential intervention.}, journal = {Current opinion in HIV and AIDS}, volume = {13}, number = {1}, pages = {73-80}, doi = {10.1097/COH.0000000000000429}, pmid = {29045252}, issn = {1746-6318}, mesh = {Anti-HIV Agents/therapeutic use ; Bacterial Translocation ; *Dysbiosis ; *Gastrointestinal Microbiome ; HIV Infections/*complications/drug therapy/*pathology ; *Host-Pathogen Interactions ; Humans ; Inflammation/pathology ; Lymphocyte Activation ; *Microbiota ; }, abstract = {PURPOSE OF REVIEW: Aim of this review is to summarize the alterations occurring in gut microbiome composition after HIV infection, and to underline how intestinal dysbiosis can affect immune homeostasis, immune recovery, and persisting immune activation under antiretroviral therapy (ART). Many interventions have been suggested, mostly with inconclusive results.

RECENT FINDINGS: Recent evidence showed that gut microbiota from HIV-infected patients harbor reproducible differences compared to uninfected individuals. In this line, there is growing evidence that alterations in gut ecology during HIV infection correlate with persistence of immune defects and chronic inflammation. A reduced microbial diversity in feces of HIV-infected patients is highly associated with microbial translocation and monocyte activation markers; moreover, changes in mucosa-associated bacteria correlate with inflammation and T-cell activation.

SUMMARY: Studying the human host-microbiota interaction suggests that the consequences of HIV infection on microbial composition can influence immune status in HIV patients. ART induces microbiome changes that are independent of HIV infection, and some imply that ART may enhance dysbiosis. Studies and trials evaluated the effects of administering probiotics and prebiotics, finding a potential benefit on inflammation markers and immune cell activation. Emerging data on fecal microbial transplantation need to be assessed with further studies.}, } @article {pmid29040661, year = {2018}, author = {Bluestone, H and Kronman, MP and Suskind, DL}, title = {Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infections in Pediatric Hematopoietic Stem Cell Transplant Recipients.}, journal = {Journal of the Pediatric Infectious Diseases Society}, volume = {7}, number = {1}, pages = {e6-e8}, doi = {10.1093/jpids/pix076}, pmid = {29040661}, issn = {2048-7207}, } @article {pmid29039256, year = {2017}, author = {Woodworth, MH and Sitchenko, KL and Carpentieri, C and Friedman-Moraco, RJ and Wang, T and Kraft, CS}, title = {Ethical Considerations in Microbial Therapeutic Clinical Trials.}, journal = {The New bioethics : a multidisciplinary journal of biotechnology and the body}, volume = {23}, number = {3}, pages = {210-218}, doi = {10.1080/20502877.2017.1387386}, pmid = {29039256}, issn = {2050-2885}, support = {UL1 TR000454/TR/NCATS NIH HHS/United States ; }, mesh = {Clinical Trials as Topic/*ethics ; Clostridium Infections/*therapy ; Clostridium difficile/isolation & purification ; Fecal Microbiota Transplantation/*ethics ; Gastrointestinal Microbiome ; Humans ; }, abstract = {As understanding of the human microbiome improves, novel therapeutic targets to improve human health with microbial therapeutics will continue to expand. We outline key considerations of balancing risks and benefits, optimising access, returning key results to research participants, and potential conflicts of interest.}, } @article {pmid29039142, year = {2017}, author = {Quigley, EMM}, title = {Microbiota-Brain-Gut Axis and Neurodegenerative Diseases.}, journal = {Current neurology and neuroscience reports}, volume = {17}, number = {12}, pages = {94}, doi = {10.1007/s11910-017-0802-6}, pmid = {29039142}, issn = {1534-6293}, mesh = {Animals ; Brain/*drug effects/*physiopathology ; Gastrointestinal Microbiome/*drug effects/*physiology ; Humans ; *Molecular Targeted Therapy ; Neurodegenerative Diseases/*drug therapy/*physiopathology ; }, abstract = {PURPOSE OF REVIEW: The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson's disease, and, finally, to assess the potential for microbiota-targeted therapies.

RECENT FINDINGS: Work on animal models has established the microbiota-gut-brain axis as a real phenomenon; to date, the evidence for its operation in man has been limited and has been confronted by considerable logistical challenges. Animal and translational models have incriminated a disturbed gut microbiota in a number of CNS disorders, including Parkinson's disease; data from human studies is scanty. While a theoretical basis can be developed for the use of microbiota-directed therapies in neurodegenerative disorders, support is yet to come from high-quality clinical trials. In theory, a role for the microbiota-gut-brain axis is highly plausible; clinical confirmation is awaited.}, } @article {pmid29035948, year = {2018}, author = {Desai, SN and Landay, AL}, title = {HIV and aging: role of the microbiome.}, journal = {Current opinion in HIV and AIDS}, volume = {13}, number = {1}, pages = {22-27}, doi = {10.1097/COH.0000000000000433}, pmid = {29035948}, issn = {1746-6318}, mesh = {Aging/*pathology ; Biological Therapy/methods ; Dysbiosis/pathology ; Gastrointestinal Microbiome/*immunology ; HIV Infections/complications/*pathology ; Humans ; Microbiota/*immunology ; }, abstract = {PURPOSE OF REVIEW: The purpose of this article is to review age-associated alterations in microbiota composition, diversity and functional features in context of immune senescence, chronic inflammation and comorbidities associated with HIV infection. The overall goal is to assess whether modulating the microbiome will likely improve resilience of the immune system and augment return to health.

RECENT FINDINGS: Alteration in the gut microbiota composition diversity and function occur in HIV and aging. Importantly, butyrate producing bacteria are reduced in both HIV and aging individuals. There is increasing relevance of studying metabolomics in the context of HIV-associated non-AIDS comorbidities and aging. Interventional prospects of probiotics, prebiotics and fecal microbiota transplantation in HIV and aging will provide novel therapeutic approaches.

SUMMARY: Increasing evidence suggests a significant link in changes in the composition, diversity and functional aspects of intestinal microbiome with normal aging and HIV infection. Data on association of metabolites produced by the microbiome with HIV-associated non-AIDS comorbidities is mounting. The impact of the microbiome alterations on inflammation, immune and organ senescence and mechanisms by which bio-behavioral pathways will exacerbate these outcomes needs to be further evaluated.}, } @article {pmid29034981, year = {2018}, author = {McIlroy, J and Ianiro, G and Mukhopadhya, I and Hansen, R and Hold, GL}, title = {Review article: the gut microbiome in inflammatory bowel disease-avenues for microbial management.}, journal = {Alimentary pharmacology & therapeutics}, volume = {47}, number = {1}, pages = {26-42}, doi = {10.1111/apt.14384}, pmid = {29034981}, issn = {1365-2036}, mesh = {Colitis, Ulcerative/diagnosis/*therapy ; Crohn Disease/diagnosis/*therapy ; Diet ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Microbiota ; Recurrence ; }, abstract = {BACKGROUND: The concept of an altered collective gut microbiota rather than identification of a single culprit is possibly the most significant development in inflammatory bowel disease research. We have entered the "omics" era, which now allows us to undertake large-scale/high-throughput microbiota analysis which may well define how we approach diagnosis and treatment of inflammatory bowel disease (IBD) in the future, with a strong steer towards personalised therapeutics.

AIM: To assess current epidemiological, experimental and clinical evidence of the current status of knowledge relating to the gut microbiome, and its role in IBD, with emphasis on reviewing the evidence relating to microbial therapeutics and future microbiome modulating therapeutics.

METHODS: A Medline search including items 'intestinal microbiota/microbiome', 'inflammatory bowel disease', 'ulcerative colitis', 'Crohn's disease', 'faecal microbial transplantation', 'dietary manipulation' was performed.

RESULTS: Disease remission and relapse are associated with microbial changes in both mucosal and luminal samples. In particular, a loss of species richness in Crohn's disease has been widely observed. Existing therapeutic approaches broadly fall into 3 categories, namely: accession, reduction or indirect modulation of the microbiome. In terms of microbial therapeutics, faecal microbial transplantation appears to hold the most promise; however, differences in study design/methodology mean it is currently challenging to elegantly translate results into clinical practice.

CONCLUSIONS: Existing approaches to modulate the gut microbiome are relatively unrefined. Looking forward, the future of microbiome-modulating therapeutics looks bright with several novel strategies/technologies on the horizon. Taken collectively, it is clear that ignoring the microbiome in IBD is not an option.}, } @article {pmid29033923, year = {2017}, author = {El Hage, R and Hernandez-Sanabria, E and Van de Wiele, T}, title = {Emerging Trends in "Smart Probiotics": Functional Consideration for the Development of Novel Health and Industrial Applications.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1889}, doi = {10.3389/fmicb.2017.01889}, pmid = {29033923}, issn = {1664-302X}, abstract = {The link between gut microbiota and human health is well-recognized and described. This ultimate impact on the host has contributed to explain the mutual dependence between humans and their gut bacteria. Gut microbiota can be manipulated through passive or active strategies. The former includes diet, lifestyle, and environment, while the latter comprise antibiotics, pre- and probiotics. Historically, conventional probiotic strategies included a phylogenetically limited diversity of bacteria and some yeast strains. However, biotherapeutic strategies evolved in the last years with the advent of fecal microbiota transplant (FMT), successfully applied for treating CDI, IBD, and other diseases. Despite the positive outcomes, long-term effects resulting from the uncharacterized nature of FMT are not sufficiently studied. Thus, developing strategies to simulate the FMT, using characterized gut colonizers with identified phylogenetic diversity, may be a promising alternative. As the definition of probiotics states that the microorganism should have beneficial effects on the host, several bacterial species with proven efficacy have been considered next generation probiotics. Non-conventional candidate strains include Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides fragilis, and members of the Clostridia clusters IV, XIVa, and XVIII. However, viable intestinal delivery is one of the current challenges, due to their stringent survival conditions. In this review, we will cover current perspectives on the development and assessment of next generation probiotics and the approaches that industry and stakeholders must consider for a successful outcome.}, } @article {pmid29030396, year = {2018}, author = {Speck, PG and Mitchell, JG}, title = {Faecal microbiota transplantation donor stools need screening for poliovirus.}, journal = {Gut}, volume = {67}, number = {8}, pages = {1559-1560}, doi = {10.1136/gutjnl-2017-314356}, pmid = {29030396}, issn = {1468-3288}, mesh = {Clostridium Infections ; Clostridium difficile ; *Fecal Microbiota Transplantation ; Feces ; *Poliovirus ; }, } @article {pmid29026601, year = {2017}, author = {van Beurden, YH and de Groot, PF and van Nood, E and Nieuwdorp, M and Keller, JJ and Goorhuis, A}, title = {Complications, effectiveness, and long term follow-up of fecal microbiota transfer by nasoduodenal tube for treatment of recurrent Clostridium difficile infection.}, journal = {United European gastroenterology journal}, volume = {5}, number = {6}, pages = {868-879}, doi = {10.1177/2050640616678099}, pmid = {29026601}, issn = {2050-6406}, abstract = {BACKGROUND: Fecal microbiota transfer (FMT) is an effective treatment for recurrent Clostridium difficile infection (CDI), but data on procedure-related complications and long-term outcome are scarce.

METHODS: All patients treated with FMT for recurrent CDI at the Academic Medical Center between July 2010 and January 2016 were included. FMT was performed according to the FECAL trial protocol: administration of fresh donor feces (related or unrelated donor) through a duodenal tube after pre-treatment with vancomycin and bowel lavage. We collected information on FMT-related complications, recurrent CDI, and short- and long-term adverse events by telephone interviews using a structured questionnaire at three months after FMT, and at the time of data collection of this study.

RESULTS: In total, 39 patients were treated with FMT. The primary cure rate (no recurrence ≤8 weeks after one infusion with donor feces) was 82% (32 of 39 patients). Of the seven patients with recurrent CDI after FMT, four were cured by antibiotic therapy alone (fidaxomicin in three patients, metronidazole in one patient) and three by repeat FMT. Peri-procedural complications occurred in five patients, comprising fecal regurgitation or vomiting. One patient died one week post-FMT due to pneumonia; a causal relation with FMT could not be excluded. The follow-up period ranged between 3 and 68 months. No long-term side effects were reported.

CONCLUSIONS: Our data underline the efficacy of FMT as treatment for recurrent CDI. Importantly, it is possible to cure post-FMT recurrences with antibiotic therapy alone. Peri-procedural complications do occur and should be closely monitored to help identify high-risk patients. To minimize the risk of complications, all FMT candidates should be evaluated to assess the most ideal delivery method.}, } @article {pmid29026445, year = {2017}, author = {Aggarwala, V and Liang, G and Bushman, FD}, title = {Viral communities of the human gut: metagenomic analysis of composition and dynamics.}, journal = {Mobile DNA}, volume = {8}, number = {}, pages = {12}, doi = {10.1186/s13100-017-0095-y}, pmid = {29026445}, issn = {1759-8753}, abstract = {BACKGROUND: The numerically most abundant biological entities on Earth are viruses. Vast populations prey on the cellular microbiota in all habitats, including the human gut.

MAIN BODY: Here we review approaches for studying the human virome, and some recent results on movement of viral sequences between bacterial cells and eukaryotic hosts. We first overview biochemical and bioinformatic methods, emphasizing that specific choices in the methods used can have strong effects on the results obtained. We then review studies characterizing the virome of the healthy human gut, which reveal that most of the viruses detected are typically uncharacterized phage - the viral dark matter - and that viruses that infect human cells are encountered only rarely. We then review movement of phage between bacterial cells during antibiotic treatment. Here a radical proposal for extensive movement of antibiotic genes on phage has been challenged by a careful reanalysis of the metagenomic annotation methods used. We then review two recent studies of movement of whole phage communities between human individuals during fecal microbial transplantation, which emphasize the possible role of lysogeny in dispersal.

SHORT CONCLUSION: Methods for studying the human gut virome are improving, yielding interesting data on movement of phage genes between cells and mammalian host organisms. However, viral populations are vast, and studies of their composition and function are just beginning.}, } @article {pmid29020328, year = {2018}, author = {Hocquart, M and Lagier, JC and Cassir, N and Saidani, N and Eldin, C and Kerbaj, J and Delord, M and Valles, C and Brouqui, P and Raoult, D and Million, M}, title = {Early Fecal Microbiota Transplantation Improves Survival in Severe Clostridium difficile Infections.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {5}, pages = {645-650}, doi = {10.1093/cid/cix762}, pmid = {29020328}, issn = {1537-6591}, abstract = {Background: Severe Clostridium difficile infections (CDIs) are associated with a high mortality rate despite medical and/or surgical treatment. Fecal microbiota transplantation (FMT) prevents recurrences, but its effect on survival has been shown only in patients with O27 ribotype CDI. Here, we investigated whether early FMT could improve survival in hospitalized CDI patients, particularly those with severe infection.

Methods: We performed a retrospective cohort study between May 2013 and April 2016 at the infectious diseases department of the North University Hospital of Marseille, France. Patients received either medical treatment alone or treatment with early FMT. The primary outcome was the 3-month mortality rate.

Results: A total of 111 patients were included: 66 in the FMT group and 45 in the non-FMT group. No patient underwent surgery. The O27 ribotype (odds ratio [OR], 3.64 [95% confidence interval {CI}, 1.05- 12.6], P = .04), severe CDI (OR, 9.62 [95% CI, 2.16-42.8], P = .003), and FMT (OR, 0.13 [95% CI, .04-.44], P = .001) were independent predictors of 3-month mortality. FMT improved survival in severe cases (OR, 0.08 [95% CI, .016-.34], P = .001) but not in nonsevere cases (OR, 1.07 [95% CI, .02-56.3], P = .97), independent of age, sex, comorbidities (Charlson score), and ribotype. The number of severe patients who needed to be treated to save 1 life at 3 months was 2.

Conclusions: Early FMT dramatically reduces mortality and should be proposed as a first-line treatment for severe CDI. Further studies are needed to clarify complications and contraindications. Surgery should be reassessed in this context.}, } @article {pmid29020255, year = {2018}, author = {Orenstein, R and King, K and Patron, RL and DiBaise, JK and Etzioni, D}, title = {Mini-Fecal Microbiota Transplantation for Treatment of Clostridium difficile Proctitis Following Total Colectomy.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {2}, pages = {299-300}, doi = {10.1093/cid/cix736}, pmid = {29020255}, issn = {1537-6591}, abstract = {Rarely, in fulminant Clostridium difficile infection (CDI), the rectal stump is persistently infected following total abdominal colectomy. We report cure of a septic patient with proctitis by fecal microbiota transplant via rectal swabs (mini-FMT). This novel procedure offers a management option for recurrent CDI following total abdominal colectomy.}, } @article {pmid29020240, year = {2018}, author = {Andremont, A}, title = {Too Early to Recommend Early Fecal Microbiota Transplantation in Patients With Severe Clostridium difficile Infection, or Not Too Early?.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {5}, pages = {651-652}, doi = {10.1093/cid/cix763}, pmid = {29020240}, issn = {1537-6591}, } @article {pmid29020225, year = {2018}, author = {Davido, B and Dinh, A and Deconinck, L and de Truchis, P}, title = {Fecal Microbiota Transplantation and Urinary Tract Infection: An Interesting Approach.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {3}, pages = {483}, doi = {10.1093/cid/cix788}, pmid = {29020225}, issn = {1537-6591}, } @article {pmid29020222, year = {2018}, author = {Leung, V and Vincent, C and Edens, TJ and Miller, M and Manges, AR}, title = {Antimicrobial Resistance Gene Acquisition and Depletion Following Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {3}, pages = {456-457}, doi = {10.1093/cid/cix821}, pmid = {29020222}, issn = {1537-6591}, abstract = {Fecal microbiota transplantation (FMT) may be a novel approach to eliminate multidrug-resistant bacteria from the gut and to prevent future infections. Using whole metagenome sequencing data from 8 FMT donor-recipient pairs, we identified 37 and 95 antimicrobial resistance genes that were acquired by or removed from FMT recipients, respectively.}, } @article {pmid29020210, year = {2017}, author = {Tariq, R and Pardi, DS and Tosh, PK and Walker, RC and Razonable, RR and Khanna, S}, title = {Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection Reduces Recurrent Urinary Tract Infection Frequency.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {65}, number = {10}, pages = {1745-1747}, doi = {10.1093/cid/cix618}, pmid = {29020210}, issn = {1537-6591}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Clostridium Infections/complications/drug therapy/*epidemiology/*therapy ; Clostridium difficile/drug effects ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Recurrence ; Retrospective Studies ; Urinary Tract Infections/*complications/*epidemiology ; }, abstract = {Broad-spectrum antibiotics for recurrent multidrug-resistant urinary tract infections (UTIs) disrupt the gut microbiome and promote antibiotic resistance. Fecal microbiota transplantation led to resolution of recurrent Clostridium difficile, significantly decreased recurrent UTI frequency, and improved antibiotic susceptibility profile of UTI-causing organisms.}, } @article {pmid29020157, year = {2018}, author = {Allegretti, JR and Kao, D and Sitko, J and Fischer, M and Kassam, Z}, title = {Early Antibiotic Use After Fecal Microbiota Transplantation Increases Risk of Treatment Failure.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {66}, number = {1}, pages = {134-135}, doi = {10.1093/cid/cix684}, pmid = {29020157}, issn = {1537-6591}, abstract = {Antibiotic use within the first 8 weeks after fecal microbiota transplantation (FMT) may disrupt microbial engraftment and limit FMT effectiveness. We aimed to assess the burden of antibiotic use within 8 weeks of FMT and its impact on FMT efficacy.}, } @article {pmid28993208, year = {2018}, author = {Li, S and Lv, J and Li, J and Zhao, Z and Guo, H and Zhang, Y and Cheng, S and Sun, J and Pan, H and Fan, S and Li, Z}, title = {Intestinal microbiota impact sepsis associated encephalopathy via the vagus nerve.}, journal = {Neuroscience letters}, volume = {662}, number = {}, pages = {98-104}, doi = {10.1016/j.neulet.2017.10.008}, pmid = {28993208}, issn = {1872-7972}, mesh = {Animals ; Cerebral Cortex/metabolism/pathology ; Cytokines/metabolism ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Hippocampus/metabolism ; Lipopolysaccharides/pharmacology ; Male ; Memory ; Microglia/metabolism ; Rats, Sprague-Dawley ; Sepsis-Associated Encephalopathy/*microbiology/*physiopathology/psychology ; Spatial Learning ; Vagus Nerve/microbiology/*physiopathology ; }, abstract = {OBJECTIVE: The pathogenesis of sepsis associated encephalopathy (SAE) remains poorly understood. Vagus nerve plays an important role in gut-microbiota-brain axis. This study aimed to investigate whether vague nerve is a key mediator of the impact of intestinal microbiota on SAE.

METHODS: Male rats were randomly divided into four groups (n=20): SHAM (SH) group, lipopolysaccharide (LPS) group, fecal microbiota transplantation (FMT) +LPS group, and vagotomy (VGX)+LPS+FMT group. The left cervical vagotomy was performed 30min before LPS administration in LPS+FMT+VGX group. LPS+ FMT and LPS+FMT+VGX groups received nasogastric infusion of feces from healthy donor three times a day. Fecal samples were collected every two days to monitor changes in microbiota composition by 16S rDNA analysis. Brain function was evaluated by behavioral tests and EEG. The levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, IL-10 in brain cortex were detected by ELISA. The expression of Iba-1 in brain cortex was assessed by immunohistochemistry and Western blot analysis.

RESULTS: Significant modification of microbiota composition, characterized by a profound increase of commensals in the Firmicutes phylum and depletion of opportunistic organisms in the Proteobacteria phylum, was observed in FMT groups compared to LPS group. Furthermore, we identified a reconstituted bacterial community enriched in Firmicutes and depleted of Proteobacteria. In both FMT groups the diversity of the fecal microbiota and the microbiota composition were similar to SH group. LPS mice treated with FMT demonstrated a better spatial memory and less EEG abnormalities, significantly attenuated levels of IL-1β, IL-6, TNF-α, and decreased number of Iba-1 positive microglia in the cortex, but these beneficial effects of FMT were reversed by VGX.

CONCLUSIONS: FMT can change intestinal microbiota in sepsis patients, and vagus nerve is a key mediator between intestinal microbiota and SAE. These findings suggest that FMT and vagus nerve are potential therapy targets for treating SAE.}, } @article {pmid28990516, year = {2018}, author = {Okubo, H and Nakatsu, Y and Kushiyama, A and Yamamotoya, T and Matsunaga, Y and Inoue, MK and Fujishiro, M and Sakoda, H and Ohno, H and Yoneda, M and Ono, H and Asano, T}, title = {Gut Microbiota as a Therapeutic Target for Metabolic Disorders.}, journal = {Current medicinal chemistry}, volume = {25}, number = {9}, pages = {984-1001}, doi = {10.2174/0929867324666171009121702}, pmid = {28990516}, issn = {1875-533X}, abstract = {BACKGROUND: Gut microbiota play a vital role not only in the digestion and absorption of nutrients, but also in homeostatic maintenance of host immunity, metabolism and the gut barrier. Recent evidence suggests that gut microbiota alterations contribute to the pathogenesis of metabolic disorders.

OBJECTIVE AND METHOD: In this review, we discuss the association between the gut microbiota and metabolic disorders, such as obesity, type 2 diabetes mellitus and non-alcoholic fatty liver disease, and the contribution of relevant modulating interventions, focusing on recent human studies.

RESULTS: Several studies have identified potential causal associations between gut microbiota and metabolic disorders, as well as the underlying mechanisms. The effects of modulating interventions, such as prebiotics, probiotics, fecal microbiota transplantation, and other new treatment possibilities on these metabolic disorders have also been reported.

CONCLUSION: A growing body of evidence highlights the role of gut microbiota in the development of dysbiosis, which in turn influences host metabolism and disease phenotypes. Further studies are required to elucidate the precise mechanisms by which gut microbiota-derived mediators induce metabolic disorders and modulating interventions exert their beneficial effects in humans. The gut microbiota represents a novel potential therapeutic target for a range of metabolic disorders.}, } @article {pmid28987073, year = {2017}, author = {Ejtahed, HS and Hasani-Ranjbar, S and Larijani, B}, title = {Human Microbiome as an Approach to Personalized Medicine.}, journal = {Alternative therapies in health and medicine}, volume = {23}, number = {6}, pages = {8-9}, pmid = {28987073}, issn = {1078-6791}, mesh = {Biodiversity ; Humans ; Microbiology/trends ; *Microbiota ; Pharmacogenetics/*trends ; Precision Medicine/*trends ; }, abstract = {Personalized medicine is an approach for medical decisions, practices, and interventions that considers individual variations in genes, environment, and lifestyle for each person. Regarding complex metabolic patterns associated with different diseases, characterizing unique metabolic patterns of each patient seems like a practical approach. We can imagine a future in which routinely analyzing the microbiome allows us to predict individualized responses to different foods and drugs. Microbiome analysis of individuals may be added to future routine personalized medicine protocols after comparing the costs and benefits of microbiome-sequencing technology. Moreover, improved understanding of the human microbiome could lead to the development of novel therapeutic strategies for different diseases. Potential therapeutic agents, such as personalized probiotic and prebiotic supplements, dietary interventions, and fecal microbiota transplantation that can be used to reshape the gut microbiome, represent a reasonable strategy in an era of personalized medicine.}, } @article {pmid28985671, year = {2017}, author = {Tse, BN and Adalja, AA and Houchens, C and Larsen, J and Inglesby, TV and Hatchett, R}, title = {Challenges and Opportunities of Nontraditional Approaches to Treating Bacterial Infections.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {65}, number = {3}, pages = {495-500}, doi = {10.1093/cid/cix320}, pmid = {28985671}, issn = {1537-6591}, support = {U38 CE002353/CE/NCIPC CDC HHS/United States ; }, mesh = {Antibodies, Monoclonal/therapeutic use ; Bacterial Infections/*therapy ; Drug Resistance, Bacterial ; Fecal Microbiota Transplantation ; Humans ; Immunologic Factors/therapeutic use ; Microbiota ; Phage Therapy ; Therapeutics/methods/trends ; }, abstract = {Due to increasing rates of antimicrobial-resistant infections and the current inadequacy of the antibiotic pipeline, there is increasing interest in nontraditional approaches to antibacterial therapies. We define "traditional" agents as small-molecule agents that directly target bacterial components to exert a bacteriostatic or bactericidal effect, and "nontraditional approaches" as antimicrobial therapeutics that work through other means (ie, not a small molecule and/or utilizes a nontraditional target). Due to their atypical features, such therapies may be less susceptible to the emergence of resistance than traditional antibiotics. They include approaches such as monoclonal antibodies, virulence disruptors, immunomodulators, phage therapies, microbiome-based therapies, antibiotic potentiators, and antisense approaches. This article discusses both the developmental and regulatory advantages and challenges associated with each of these technologies. By identifying existing regulatory and developmental gaps, we hope to provide a sense of where focusing resources may provide the greatest impact on successful product development.}, } @article {pmid28980505, year = {2017}, author = {Cataldo, MA and Granata, G and Petrosillo, N}, title = {Clostridium difficile infection: new approaches to prevention, non-antimicrobial treatment, and stewardship.}, journal = {Expert review of anti-infective therapy}, volume = {15}, number = {11}, pages = {1027-1040}, doi = {10.1080/14787210.2017.1387535}, pmid = {28980505}, issn = {1744-8336}, mesh = {Aminoglycosides/metabolism/*therapeutic use ; Anti-Bacterial Agents/*therapeutic use ; Antimicrobial Stewardship/*organization & administration ; Clostridium Infections/microbiology/pathology/*therapy ; Clostridium difficile/drug effects/growth & development/pathogenicity ; Cross Infection/prevention & control ; *Fecal Microbiota Transplantation ; Hand Hygiene/organization & administration ; Humans ; Incidence ; Infection Control/*methods ; Probiotics/therapeutic use ; Spores, Bacterial/drug effects/growth & development/pathogenicity ; }, abstract = {INTRODUCTION: Despite the large amount of scientific publications exploring the epidemiology and the clinical management of Clostridium difficile (CD) infection, some issues remain unsolved or need further studies. The aim of this review is to give an update on the hot topics on CD prevention, including stewardship programs, and on the non-microbiological treatment of CD infection. Areas covered: This article will review the importance of minimizing the CD spore shedding in the healthcare environment for potentially reducing CD transmission. Moreover, antimicrobial stewardship programs aimed to reduce CD incidence will be reviewed. Finally, new strategies for reducing CD infection recurrence will be described. Expert commentary: Besides the basic infection control and prevention practices, including hand hygiene, contact isolation and environmental cleaning, in the prevention of CD infection other issues should be addressed including minimizing the spread of CD in the healthcare setting, and implementing the best strategy for reducing CD infection occurrence, including tailored antimicrobial stewardship programs. Regarding new advancements in treatment and management of CDI episodes, non-antimicrobial approaches seem to be promising in reducing and managing recurrent CD infection.}, } @article {pmid28978426, year = {2017}, author = {Kootte, RS and Levin, E and Salojärvi, J and Smits, LP and Hartstra, AV and Udayappan, SD and Hermes, G and Bouter, KE and Koopen, AM and Holst, JJ and Knop, FK and Blaak, EE and Zhao, J and Smidt, H and Harms, AC and Hankemeijer, T and Bergman, JJGHM and Romijn, HA and Schaap, FG and Olde Damink, SWM and Ackermans, MT and Dallinga-Thie, GM and Zoetendal, E and de Vos, WM and Serlie, MJ and Stroes, ESG and Groen, AK and Nieuwdorp, M}, title = {Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition.}, journal = {Cell metabolism}, volume = {26}, number = {4}, pages = {611-619.e6}, doi = {10.1016/j.cmet.2017.09.008}, pmid = {28978426}, issn = {1932-7420}, mesh = {Blood Glucose/analysis/metabolism ; *Fecal Microbiota Transplantation/methods ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Insulin Resistance ; Male ; Metabolic Syndrome/blood/metabolism/microbiology/*therapy ; Middle Aged ; Transplantation, Autologous/methods ; Transplantation, Homologous/methods ; gamma-Aminobutyric Acid/blood/metabolism ; }, abstract = {The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own (autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition. We also observed changes in plasma metabolites such as γ-aminobutyric acid and show that metabolic response upon allogenic FMT (defined as improved insulin sensitivity 6 weeks after FMT) is dependent on decreased fecal microbial diversity at baseline. In conclusion, the beneficial effects of lean donor FMT on glucose metabolism are associated with changes in intestinal microbiota and plasma metabolites and can be predicted based on baseline fecal microbiota composition.}, } @article {pmid28976455, year = {2017}, author = {Brandt, LJ}, title = {Fecal Microbiota Therapy With a Focus on Clostridium difficile Infection.}, journal = {Psychosomatic medicine}, volume = {79}, number = {8}, pages = {868-873}, doi = {10.1097/PSY.0000000000000511}, pmid = {28976455}, issn = {1534-7796}, mesh = {Clostridium Infections/*therapy ; Dysbiosis/*therapy ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {There has been a paradigm shift in our view of bacteria away from their role as just pathogens. We now have a deepening appreciation of their critical influences in our health maintenance, including energy harvest, metabolism, intestinal development, cell proliferation, nervous system and immune function, as well as their role to protect against intestinal and other infections. A perturbed intestinal microbiome has been associated with an increasing number of gastrointestinal and nongastrointestinal diseases but particularly with Clostridium difficile infection (CDI). Although such association does not imply causation, it has been shown that fecal microbiota transplantation (FMT) can correct the dysbiosis that characterizes chronic and recurring CDI and that FMT can effect a seemingly safe and rapidly effective cure for most patients with CDI so treated. FMT has been used to treat a wide range of other diseases, although conclusions about efficacy in any disease other than CDI must await appropriate well-designed trials. More work needs to be conducted with FMT, especially to evaluate and ensure its long-term safety. Future studies are likely to narrow the spectrum of organisms that needs to be given to patients to cure CDI, and perhaps other diseases, and to elucidate the mechanisms whereby such therapeutic benefit occurs. FMT is but the first step in this journey.}, } @article {pmid28968189, year = {2018}, author = {Vázquez-Baeza, Y and Callewaert, C and Debelius, J and Hyde, E and Marotz, C and Morton, JT and Swafford, A and Vrbanac, A and Dorrestein, PC and Knight, R}, title = {Impacts of the Human Gut Microbiome on Therapeutics.}, journal = {Annual review of pharmacology and toxicology}, volume = {58}, number = {}, pages = {253-270}, doi = {10.1146/annurev-pharmtox-042017-031849}, pmid = {28968189}, issn = {1545-4304}, abstract = {The human microbiome contains a vast source of genetic and biochemical variation, and its impacts on therapeutic responses are just beginning to be understood. This expanded understanding is especially important because the human microbiome differs far more among different people than does the human genome, and it is also dramatically easier to change. Here, we describe some of the major factors driving differences in the human microbiome among individuals and populations. We then describe some of the many ways in which gut microbes modify the action of specific chemotherapeutic agents, including nonsteroidal anti-inflammatory drugs and cardiac glycosides, and outline the potential of fecal microbiota transplant as a therapeutic. Intriguingly, microbes also alter how hosts respond to therapeutic agents through various pathways acting at distal sites. Finally, we discuss some of the computational and practical issues surrounding use of the microbiome to stratify individuals for drug response, and we envision a future where the microbiome will be modified to increase everyone's potential to benefit from therapy.}, } @article {pmid28967895, year = {2017}, author = {Liu, C and Frank, DN and Horch, M and Chau, S and Ir, D and Horch, EA and Tretina, K and van Besien, K and Lozupone, CA and Nguyen, VH}, title = {Associations between acute gastrointestinal GvHD and the baseline gut microbiota of allogeneic hematopoietic stem cell transplant recipients and donors.}, journal = {Bone marrow transplantation}, volume = {52}, number = {12}, pages = {1643-1650}, doi = {10.1038/bmt.2017.200}, pmid = {28967895}, issn = {1476-5365}, mesh = {Adult ; Aged ; Female ; Gastrointestinal Diseases/*etiology ; *Gastrointestinal Microbiome ; Graft vs Host Disease/*pathology ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Male ; Middle Aged ; RNA, Ribosomal, 16S/analysis ; Tissue Donors ; Transplant Recipients ; }, abstract = {Growing evidence suggests that host-microbiota interactions influence GvHD risk following allogeneic hematopoietic stem cell transplant. However, little is known about the influence of the transplant recipient's pre-conditioning microbiota nor the influence of the transplant donor's microbiota. Our study examines associations between acute gastrointestinal GvHD (agGvHD) and 16S rRNA fecal bacterial profiles in a prospective cohort of N=57 recipients before preparative conditioning, as well as N=22 of their paired HLA-matched sibling donors. On average, recipients had lower fecal bacterial diversity (P=0.0002) and different phylogenetic membership (UniFrac P=0.001) than the healthy transplant donors. Recipients with lower phylogenetic diversity had higher overall mortality rates (hazard ratio=0.37, P=0.008), but no statistically significant difference in agGvHD risk. In contrast, high bacterial donor diversity was associated with decreased agGvHD risk (odds ratio=0.12, P=0.038). Further investigation is warranted as to whether selection of hematopoietic stem cell transplant donors with high gut microbiota diversity and/or other specific compositional attributes may reduce agGvHD incidence, and by what mechanisms.}, } @article {pmid28957971, year = {2017}, author = {Walton, J and Burns, D and Gaehle, KE}, title = {Process and Outcome of Fecal Microbiota Transplants in Patients With Recurrent Clostridium difficile Infection: A Prospective Study.}, journal = {Gastroenterology nursing : the official journal of the Society of Gastroenterology Nurses and Associates}, volume = {40}, number = {5}, pages = {411-419}, doi = {10.1097/SGA.0000000000000233}, pmid = {28957971}, issn = {1538-9766}, mesh = {Clostridium Infections/diagnosis/therapy ; Clostridium difficile/*isolation & purification ; Cohort Studies ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Follow-Up Studies ; Humans ; Male ; Prospective Studies ; *Quality of Life ; Recurrence ; Risk Assessment ; Severity of Illness Index ; Treatment Outcome ; }, abstract = {The incidence of Clostridium difficile infection is on the rise worldwide, causing high mortality rates and costing patients, hospitals, and insurance companies millions of dollars annually. Fecal microbiota transplants successfully treat recurrent C. difficile infections unresponsive to standard pharmacologic treatment such as flagyl, vancomycin, or rifaximin. Evidence in the literature provided the foundation for the development and refinement of this fecal microbiota transplant protocol. During the initial phase of the project, the protocol included patient selection criteria, donor screening/selection, infection control, fecal processing and delivery, and patient pre and postprocedure education. This article highlights the second phase of prospective testing of a nurse-driven protocol to implement fecal microbiota transplantation in patients with recurrent C. difficile infection. All stages of the protocol are explained as well as rationale for component parts to achieve successful patient outcomes when the protocol is carefully followed.}, } @article {pmid28951890, year = {2017}, author = {Miller, AW and Dale, C and Dearing, MD}, title = {The Induction of Oxalate Metabolism In Vivo Is More Effective with Functional Microbial Communities than with Functional Microbial Species.}, journal = {mSystems}, volume = {2}, number = {5}, pages = {}, doi = {10.1128/mSystems.00088-17}, pmid = {28951890}, issn = {2379-5077}, abstract = {For mammals, oxalate enters the body through the diet or is endogenously produced by the liver; it is removed by microbial oxalate metabolism in the gut and/or excretion in feces or urine. Deficiencies in any one of the these pathways can lead to complications, such as calcium oxalate urinary stones. While considerable research has been conducted on individual oxalate-degrading bacterial isolates, interactions between oxalate and the gut microbiota as a whole are unknown. We examined the reduction in oxalate excretion in a rat model following oral administration of fecal microbes from a mammalian herbivore adapted to a high oxalate diet or to fecal transplants consisting of two different formulations of mixed oxalate-degrading isolates. While all transplants elicited a significant reduction in oxalate excretion initially, the greatest effect was seen with fecal microbial transplants, which persisted even in the absence of dietary oxalate. The reduction in oxalate excretion in animals given fecal transplants corresponded with the establishment of diverse bacteria, including known oxalate-degrading bacteria and a cohesive network of bacteria centered on oxalate-degrading specialists from the Oxalobacteraceae family. Results suggested that the administration of a complete community of bacteria facilitates a cohesive balance in terms of microbial interactions. Our work offers important insights into the development of targeted bacteriotherapies intended to reduce urinary oxalate excretion in patients at risk for recurrent calcium oxalate stones as well as bacteriotherapies targeting other toxins for elimination. IMPORTANCE Oxalate is a central component in 80% of kidney stones. While mammals do not possess the enzymes to degrade oxalate, many gastrointestinal bacteria are efficient oxalate degraders. We examined the role of cohesive microbial networks for oxalate metabolism, using Sprague-Dawley rats as a model host. While the transplantation of oxalate-degrading bacteria alone to the Sprague-Dawley hosts did increase oxalate metabolism, fecal transplants from a wild mammalian herbivore, Neotoma albigula, had a significantly greater effect. Furthermore, the boost for oxalate metabolism persisted only in animals that received fecal transplants. Animals receiving fecal transplants had a more diverse and cohesive network of bacteria associated with the Oxalobacteraceae, a family known to consist of specialist oxalate-degrading bacteria, than did animals that received oxalate-degrading bacteria alone. Our results indicate that fecal transplants are more effective at transferring specific functions than are microbial specialists alone, which has broad implications for the development of bacteriotherapies.}, } @article {pmid28939450, year = {2018}, author = {Cobo, J and Merino, E and Martínez, C and Cózar-Llistó, A and Shaw, E and Marrodán, T and Calbo, E and Bereciartúa, E and Sánchez-Muñoz, LA and Salavert, M and Pérez-Rodríguez, MT and García-Rosado, D and Bravo-Ferrer, JM and Gálvez-Acebal, J and Henríquez-Camacho, C and Cuquet, J and Pino-Calm, B and Torres, L and Sánchez-Porto, A and Fernández-Félix, BM and , }, title = {Prediction of recurrent clostridium difficile infection at the bedside: the GEIH-CDI score.}, journal = {International journal of antimicrobial agents}, volume = {51}, number = {3}, pages = {393-398}, doi = {10.1016/j.ijantimicag.2017.09.010}, pmid = {28939450}, issn = {1872-7913}, mesh = {Aged ; Aged, 80 and over ; Clostridium Infections/*diagnosis ; *Decision Support Techniques ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; *Recurrence ; }, abstract = {Recurrence of Clostridium difficile infection (CDI) has major consequences for both patients and the health system. The ability to predict which patients are at increased risk of recurrent CDI makes it possible to select candidates for treatment with new drugs and therapies (including fecal microbiota transplantation) that have proven to reduce the incidence of recurrence of CDI. Our objective was to develop a clinical prediction tool, the GEIH-CDI score, to determine the risk of recurrence of CDI. Predictors of recurrence of CDI were investigated using logistic regression in a prospective cohort of 274 patients diagnosed with CDI. The model was calibrated using the Hosmer-Lemeshow test. The tool comprises four factors: age (70-79 years and ≥80 years), history of CDI during the previous year, direct detection of toxin in stool, and persistence of diarrhea on the fifth day of treatment. The functioning of the GEIH-CDI score was validated in a prospective cohort of 183 patients. The area under the ROC curve was 0.72 (0.65-0.79). Application of the tool makes it possible to select patients at high risk (>50%) of recurrence and patients at low risk (<10%) of recurrence. GEIH-CDI score may be useful for clinicians treating patients with CDI.}, } @article {pmid28936973, year = {2017}, author = {Karakan, T}, title = {Fecal microbiota transplantation for treating recurrent hepatic encephalopathy: Ready for clinical application?.}, journal = {The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology}, volume = {28}, number = {5}, pages = {425-426}, doi = {10.5152/tjg.2017.18817}, pmid = {28936973}, issn = {2148-5607}, mesh = {Clostridium difficile ; Enterocolitis, Pseudomembranous ; *Fecal Microbiota Transplantation ; Feces ; *Hepatic Encephalopathy ; Humans ; Microbiota ; }, } @article {pmid28936948, year = {2017}, author = {Collins, J and Auchtung, JM}, title = {Control of Clostridium difficile Infection by Defined Microbial Communities.}, journal = {Microbiology spectrum}, volume = {5}, number = {5}, pages = {}, doi = {10.1128/microbiolspec.BAD-0009-2016}, pmid = {28936948}, issn = {2165-0497}, support = {R21 AI121522/AI/NIAID NIH HHS/United States ; R33 AI121522/AI/NIAID NIH HHS/United States ; U01 AI124290/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Clostridium Infections/*microbiology/*therapy ; Clostridium difficile/genetics/isolation & purification/*physiology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; }, abstract = {Each year in the United States, billions of dollars are spent combating almost half a million Clostridium difficile infections (CDIs) and trying to reduce the ∼29,000 patient deaths in which C. difficile has an attributed role. In Europe, disease prevalence varies by country and level of surveillance, though yearly costs are estimated at €3 billion. One factor contributing to the significant health care burden of C. difficile is the relatively high frequency of recurrent CDIs. Recurrent CDI, i.e., a second episode of symptomatic CDI occurring within 8 weeks of successful initial CDI treatment, occurs in ∼25% of patients, with 35 to 65% of these patients experiencing multiple episodes of recurrent disease. Using microbial communities to treat recurrent CDI, either as whole fecal transplants or as defined consortia of bacterial isolates, has shown great success (in the case of fecal transplants) or potential promise (in the case of defined consortia of isolates). This review will briefly summarize the epidemiology and physiology of C. difficile infection, describe our current understanding of how fecal microbiota transplants treat recurrent CDI, and outline potential ways that knowledge can be used to rationally design and test alternative microbe-based therapeutics.}, } @article {pmid28932754, year = {2017}, author = {Rebello, D and Wang, E and Yen, E and Lio, PA and Kelly, CR}, title = {Hair Growth in Two Alopecia Patients after Fecal Microbiota Transplant.}, journal = {ACG case reports journal}, volume = {4}, number = {}, pages = {e107}, doi = {10.14309/crj.2017.107}, pmid = {28932754}, issn = {2326-3253}, abstract = {Clostridium difficile infections can be life-threatening but are increasingly being treated successfully with fecal microbiota transplantation (FMT). We report two patients with alopecia universalis who developed subsequent hair regrowth after FMT for treatment of recurrent C. difficile infections. Gut microbiota may have immunomodulatory effects in autoimmune conditions such as alopecia areata, and further study may elucidate disease mechanisms and lead to alternative treatment options for these patients for whom treatment options are currently limited.}, } @article {pmid28927251, year = {2017}, author = {Bibbò, S and Ianiro, G and Gasbarrini, A and Cammarota, G}, title = {Fecal microbiota transplantation: past, present and future perspectives.}, journal = {Minerva gastroenterologica e dietologica}, volume = {63}, number = {4}, pages = {420-430}, doi = {10.23736/S1121-421X.17.02374-1}, pmid = {28927251}, issn = {1827-1642}, mesh = {Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/methods/*trends ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*therapy ; Irritable Bowel Syndrome/therapy ; Metabolic Diseases/*therapy ; Treatment Outcome ; }, abstract = {Gut microbiota is known to play a main role in regulating both health and disease in humans. Strategies for the therapeutic modulation of gut microbiota are therefore expected to give a relevant contribution in the management of disorders associated with its impairment. Among these options, one of the most renowned is fecal microbiota transplantation (FMT). A growing body of evidence showed clearly that FMT is an effective treatment against recurrent Clostridium difficile infection. Moreover, it was shown to be a promising therapy for the management of several noncommunicable disorders, including inflammatory bowel diseases and metabolic disorders. Standardization of procedural protocols for different disorders will surely increase the therapeutic power of FMT. The aim of this narrative review was to make an overview of methodology, indications, and future perspectives of FMT for the management of disorders associated with gut microbiota impairment.}, } @article {pmid28923757, year = {2018}, author = {Kelly, BJ and Tebas, P}, title = {Clinical Practice and Infrastructure Review of Fecal Microbiota Transplantation for Clostridium difficile Infection.}, journal = {Chest}, volume = {153}, number = {1}, pages = {266-277}, doi = {10.1016/j.chest.2017.09.002}, pmid = {28923757}, issn = {1931-3543}, support = {K23 AI121485/AI/NIAID NIH HHS/United States ; L30 AI120149/AI/NIAID NIH HHS/United States ; U54 CK000485/CK/NCEZID CDC HHS/United States ; }, abstract = {A substantial proportion of Clostridium difficile infection (CDI) cases recur after completion of antibiotic therapy, and antibiotic cure rates diminish with each recurrence of CDI. Fecal microbiota transplantation (FMT) is an effective therapy for recurrent FMT, which otherwise requires prolonged or indefinite antibiotic treatment. FMT is performed by introducing the fecal microbial community obtained from a healthy donor or pool of donors into the stomach, small intestine, or colon of a patient with CDI. Multiple clinical trials support the usefulness of FMT in treating recurrent CDI, and CDI treatment guidelines now include consideration of FMT at the third CDI recurrence. However, there remain challenges to incorporating FMT into clinical practice. First, methods of fecal bacterial community processing vary, as do methods of FMT administration. Second, the optimal dosing strategy and expected benefit of FMT for refractory CDI, particularly for severe and severe complicated cases, are uncertain. Third, the US Food and Drug Administration (FDA) considers FMT an investigational treatment. Fourth, insurance reimbursement for FMT usually falls short of FMT administration costs. In the setting of rising C difficile incidence and growing evidence for FMT efficacy, the demand for FMT has increased. However, uncertainty surrounding optimal FMT preparation and administration methods, FDA oversight, and insurance reimbursement presently limits the clinical practice of FMT.}, } @article {pmid28916525, year = {2017}, author = {Redfern, A and Suchodolski, J and Jergens, A}, title = {Role of the gastrointestinal microbiota in small animal health and disease.}, journal = {The Veterinary record}, volume = {181}, number = {14}, pages = {370}, doi = {10.1136/vr.103826}, pmid = {28916525}, issn = {2042-7670}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Dog Diseases/*microbiology/*therapy ; Dogs ; Dysbiosis/veterinary ; Fecal Microbiota Transplantation/veterinary ; Feces/microbiology ; Gastrointestinal Diseases/microbiology/therapy/*veterinary ; *Gastrointestinal Microbiome ; Prebiotics ; Probiotics/therapeutic use ; }, abstract = {There is a large and emerging interest in the role of the gastrointestinal microbiota in health and disease. This paper serves to review the current knowledge and recommendations of the gastrointestinal microbiota in health and gastrointestinal disease. Further, this review evaluates the current literature and suggests guidelines for faecal microbial transplantation, a novel therapy for dysbiosis in veterinary medicine.}, } @article {pmid28914862, year = {2017}, author = {Aitbaev, KA and Murkamilov, IT and Fomin, VV}, title = {[Liver diseases: The pathogenetic role of the gut microbiome and the potential of treatment for its modulation].}, journal = {Terapevticheskii arkhiv}, volume = {89}, number = {8}, pages = {120-128}, doi = {10.17116/terarkh2017898120-128}, pmid = {28914862}, issn = {0040-3660}, mesh = {Disease Progression ; *Dysbiosis/diagnosis/therapy ; Fecal Microbiota Transplantation/*methods ; *Gastrointestinal Microbiome/drug effects/physiology ; Humans ; *Liver Diseases/diagnosis/microbiology/physiopathology/prevention & control ; Probiotics/*therapeutic use ; Treatment Outcome ; }, abstract = {The paper gives an update on the role of the gut microbiome (GM) in the development of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, alcoholic liver disease, liver cirrhosis (LC), and its complications, such as hepatic encephalopathy (HE) and hepatocellular carcinoma (HCC), and discusses the possibilities of its correction with prebiotics, probiotics, synbiotics, antibiotics, and fecal microbiota transplantation (FMT). The pathophysiology of the liver diseases in question demonstrates some common features that are characterized by pathogenic changes in the composition of the gastrointestinal tract microflora, by intestinal barrier impairments, by development of endotoxemia, by increased liver expression of proinflammatory factors, and by development of liver inflammation. In progressive liver disease, the above changes are more pronounced, which contributes to the development of LC, HE, and HCC. GM modulation using prebiotics, probiotics, synbiotics, antibiotics, and FMT diminishes dysbacteriosis, strengthens the intestinal mucosal barrier, reduces endotoxemia and liver damage, and positively affects the clinical manifestations of HE. Further investigations are needed, especially in humans, firstly, to assess a relationship of GM to the development of liver diseases in more detail and, secondly, to obtain evidence indicating the therapeutic efficacy of GM-modulating agents in large-scale, well-designed, randomized, controlled, multicenter studies.}, } @article {pmid28906291, year = {2017}, author = {Narula, N and Kassam, Z and Yuan, Y and Colombel, JF and Ponsioen, C and Reinisch, W and Moayyedi, P}, title = {Systematic Review and Meta-analysis: Fecal Microbiota Transplantation for Treatment of Active Ulcerative Colitis.}, journal = {Inflammatory bowel diseases}, volume = {23}, number = {10}, pages = {1702-1709}, doi = {10.1097/MIB.0000000000001228}, pmid = {28906291}, issn = {1536-4844}, mesh = {Colitis, Ulcerative/*microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Randomized Controlled Trials as Topic ; Remission Induction ; Treatment Outcome ; }, abstract = {BACKGROUND: Changes in the colonic microbiota may play a role in the pathogenesis of ulcerative colitis (UC) and restoration of healthy gut microbiota may ameliorate disease. A systematic review and meta-analysis was conducted to assess fecal microbiota transplantation (FMT) as a treatment for active UC.

METHODS: A literature search was conducted to identify high-quality studies of FMT as a treatment for patients with UC. The primary outcome was combined clinical remission and endoscopic remission or response. Secondary outcomes included clinical remission, endoscopic remission, and serious adverse events. Odds ratios with 95% confidence intervals (CIs) are reported.

RESULTS: Overall, 4 studies with 277 participants were eligible for inclusion. Among 4 randomized controlled trials, FMT was associated with higher combined clinical and endoscopic remission compared with placebo (risk ratio UC not in remission was 0.80; 95% CI: 0.71-0.89) with a number needed to treat of 5 (95% CI: 4-10). There was no statistically significant increase in serious adverse events with FMT compared with controls (risk ratio adverse event was 1.4; 95% CI: 0.55-3.58).

CONCLUSIONS: Among randomized controlled trials, short-term use of FMT shows promise as a treatment to induce remission in active UC based on the efficacy and safety observed. However, there remain many unanswered questions that require further research before FMT can be considered for use in clinical practice.}, } @article {pmid28902124, year = {2017}, author = {Tronstad, RR and Kummen, M and Holm, K and von Volkmann, HL and Anmarkrud, JA and Høivik, ML and Moum, B and Gilja, OH and Hausken, T and Baines, J and Karlsen, TH and Fiskerstrand, T and Hov, JR}, title = {Guanylate Cyclase C Activation Shapes the Intestinal Microbiota in Patients with Familial Diarrhea and Increased Susceptibility for Crohn's Disease.}, journal = {Inflammatory bowel diseases}, volume = {23}, number = {10}, pages = {1752-1761}, doi = {10.1097/MIB.0000000000001264}, pmid = {28902124}, issn = {1536-4844}, mesh = {Adult ; Case-Control Studies ; Crohn Disease/complications/*microbiology ; DNA, Bacterial/genetics ; Diarrhea/*genetics/microbiology ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Genetic Linkage ; Genetic Predisposition to Disease ; Humans ; Intestines/metabolism ; Male ; Middle Aged ; Mutation, Missense ; Norway ; RNA, Ribosomal, 16S/genetics ; Receptors, Enterotoxin/*genetics ; }, abstract = {BACKGROUND: With 25% prevalence of Crohn's disease, Familial GUCY2C diarrhea syndrome (FGDS) is a monogenic disorder potentially suited to study initiating factors in inflammatory bowel disease (IBD). We aimed to characterize the impact of an activating GUCY2C mutation on the gut microbiota in patients with FGDS controlling for Crohn's disease status and to determine whether changes share features with those observed in unrelated patients with IBD.

METHODS: Bacterial DNA from fecal samples collected from patients with FGDS (N = 20), healthy relatives (N = 11), unrelated healthy individuals (N = 263), and IBD controls (N = 46) was subjected to sequencing of the V3-V4 region of the 16S rRNA gene to determine gut microbiota composition. Food frequency questionnaires were obtained from patients with FGDS and their relatives.

RESULTS: Compared with healthy controls, FGDS displayed prominent changes in many microbial lineages including increase in Enterobacteriaceae, loss of Bifidobacterium and Faecalibacterium prausnitzii but an unchanged intraindividual (alpha) diversity. The depletion of F. prausnitzii is in line with what is typically observed in Crohn's disease. There was no significant difference in the dietary profile between the patients and related controls. The gut microbiota in related and unrelated healthy controls was also similar, suggesting that diet and familial factors do not explain the gut microbiota alterations in FGDS.

CONCLUSIONS: The findings support that the activating mutation in GUCY2C creates an intestinal environment with a major influence on the microbiota, which could contribute to the increased susceptibility to IBD in patients with FGDS.}, } @article {pmid28892150, year = {2017}, author = {Sheng, L and Jena, PK and Hu, Y and Liu, HX and Nagar, N and Kalanetra, KM and French, SW and French, SW and Mills, DA and Wan, YY}, title = {Hepatic inflammation caused by dysregulated bile acid synthesis is reversible by butyrate supplementation.}, journal = {The Journal of pathology}, volume = {243}, number = {4}, pages = {431-441}, doi = {10.1002/path.4983}, pmid = {28892150}, issn = {1096-9896}, support = {U01 CA179582/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bacteria/metabolism ; Bile Acids and Salts/*metabolism ; Butyrates/metabolism/*pharmacology ; Colon/microbiology ; Diet, Western ; Disease Models, Animal ; Dysbiosis ; Fatty Acids/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Genetic Predisposition to Disease ; Hepatitis/*drug therapy/metabolism/microbiology/pathology ; Humans ; Liver/*drug effects/metabolism/pathology ; Liver Neoplasms/*drug therapy/metabolism/microbiology/pathology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Neoplasm Transplantation ; Phenotype ; Receptors, Cytoplasmic and Nuclear/deficiency/genetics/*metabolism ; Signal Transduction ; }, abstract = {Dysregulated bile acid (BA) synthesis or reduced farnesoid X receptor (FXR) levels are found in patients having metabolic diseases, autoimmune hepatitis, and liver cirrhosis or cancer. The objective of this study was to establish the relationship between butyrate and dysregulated BA synthesis-induced hepatitis as well as the effect of butyrate in reversing the liver pathology. Wild-type (WT) and FXR knockout (KO) male mice were placed on a control (CD) or western diet (WD) for 15 months. In the presence or absence of butyrate supplementation, feces obtained from 15-month-old WD-fed FXR KO mice, which had severe hepatitis and liver tumors, were transplanted to 7-month-old WD-fed FXR KO for 3 months. Hepatic phenotypes, microbiota profile, and BA composition were analyzed. Butyrate-generating bacteria and colonic butyrate concentration were reduced due to FXR inactivation and further reduced by WD intake. In addition, WD-fed FXR KO male mice had the highest concentration of hepatic β-muricholic acid (β-MCA) and bacteria-generated deoxycholic acid (DCA) accompanied by serious hepatitis. Moreover, dysregulated BA and reduced SCFA signaling co-existed in both human liver cancers and WD-fed FXR KO mice. Microbiota transplantation using butyrate-deficient feces derived from 15-month-old WD-fed FXR KO mice increased hepatic lymphocyte numbers as well as hepatic β-MCA and DCA concentrations. Furthermore, butyrate supplementation reduced hepatic β-MCA as well as DCA and eliminated hepatic lymphocyte infiltration. In conclusion, reduced butyrate contributes to the development of hepatitis in the FXR KO mouse model. In addition, butyrate reverses dysregulated BA synthesis and its associated hepatitis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.}, } @article {pmid28871143, year = {2017}, author = {Cao, H and Liu, X and An, Y and Zhou, G and Liu, Y and Xu, M and Dong, W and Wang, S and Yan, F and Jiang, K and Wang, B}, title = {Dysbiosis contributes to chronic constipation development via regulation of serotonin transporter in the intestine.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {10322}, doi = {10.1038/s41598-017-10835-8}, pmid = {28871143}, issn = {2045-2322}, abstract = {Chronic constipation is a prevalent functional gastrointestinal disorder accompanied with intestinal dysbiosis. However, causal relationship between dysbiosis and constipation remains poorly understood. Serotonin transporter (SERT) is a transmembrane transport protein which re-uptakes excessive 5-hydroxytryptamine (5-HT) from effective location to terminate its physiological effects and involves in regulating gastrointestinal motility. In this study, fecal microbiota from patients with constipation and healthy controls were transplanted into the antibiotic depletion mice model. The mice which received fecal microbiota from patients with constipation presented a reducing in intestinal peristalsis and abnormal defecation parameters including the frequency of pellet expulsion, fecal weight and fecal water content. After fecal microbiota transplantation, the SERT expression in the colonic tissue was significantly upregulated, and the content of 5-HT was decreased which negatively correlated with the gastrointestinal transit time. Moverover, fecal microbiota from the mice which received fecal microbiota from patients with constipation also upregulated SERT in Caco-2 cells. Besides, this process accompanied with the decreased abundance of Clostridium, Lactobacillus, Desulfovibrio, and Methylobacterium and an increased tend of Bacteroides and Akkermansia, which also involved in the impairment of intestinal barrier after FMT. Taken together, intestinal dysbiosis may upregulate the SERT expression and contribute to the development of chronic constipation.}, } @article {pmid28863010, year = {2017}, author = {Jørgensen, SMD and Hansen, MM and Erikstrup, C and Dahlerup, JF and Hvas, CL}, title = {Faecal microbiota transplantation: establishment of a clinical application framework.}, journal = {European journal of gastroenterology & hepatology}, volume = {29}, number = {11}, pages = {e36-e45}, doi = {10.1097/MEG.0000000000000958}, pmid = {28863010}, issn = {1473-5687}, mesh = {Clinical Protocols ; *Clostridium difficile ; Cryopreservation ; Documentation/standards ; Donor Selection/*standards ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Europe ; *Fecal Microbiota Transplantation ; *Feces/chemistry/microbiology/parasitology ; Forms and Records Control ; Hematologic Tests ; Humans ; Specimen Handling/*standards ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is currently being established as a second-line treatment for recurrent Clostridium difficile infection. FMT is further being considered for other infectious and inflammatory conditions. Safe and reproducible methods for donor screening, laboratory processing and clinical application of FMT are warranted.

METHODS: Here, we describe the development of a complete clinical application framework for FMT. The framework has been developed to comply with the European Tissue Act, thus considering donor faeces for FMT comparable to a human tissue and not a drug.

RESULTS: Recruitment and screening of potential faeces donors took place in the public blood donor setting and consisted of questionnaires, blood sampling and faecal sample analysis. Once approved, and following their written informed consent, eligible donors were invited for voluntary faecal donation. Laboratory processing protocols describe the initial handling, cryopreservation and thawing for clinical application. The clinical FMT procedures took place in a gastroenterological setting using a nasojejunal tube or colonoscopy, and follow-ups were performed at 1, 8 and 26 weeks after FMT. Complete traceability of essential equipment, faecal samples and donor-recipient matching data will be maintained and secured for 30 years.

CONCLUSION: A clinical FMT service should be consolidated by a complete documentation system that complies with the European Tissue Act. In this paper, we provide a description of such a framework.}, } @article {pmid28862530, year = {2018}, author = {Allen, JM and Mailing, LJ and Cohrs, J and Salmonson, C and Fryer, JD and Nehra, V and Hale, VL and Kashyap, P and White, BA and Woods, JA}, title = {Exercise training-induced modification of the gut microbiota persists after microbiota colonization and attenuates the response to chemically-induced colitis in gnotobiotic mice.}, journal = {Gut microbes}, volume = {9}, number = {2}, pages = {115-130}, doi = {10.1080/19490976.2017.1372077}, pmid = {28862530}, issn = {1949-0984}, support = {R01 DK114007/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Body Weight ; Cecum/metabolism/*microbiology ; Colitis/chemically induced/*prevention & control ; Colon/anatomy & histology/*immunology/pathology ; Cytokines/genetics ; Dextran Sulfate/administration & dosage ; Disease Models, Animal ; Fatty Acids, Volatile/analysis ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Gene Expression Regulation/immunology ; Germ-Free Life ; Homeostasis/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Physical Conditioning, Animal/*physiology ; Sex Factors ; }, abstract = {Exercise reduces the risk of inflammatory disease by modulating a variety of tissue and cell types, including those within the gastrointestinal tract. Recent data indicates that exercise can also alter the gut microbiota, but little is known as to whether these changes affect host function. Here, we use a germ-free (GF) animal model to test whether exercise-induced modifications in the gut microbiota can directly affect host responses to microbiota colonization and chemically-induced colitis. Donor mice (n = 19) received access to a running wheel (n = 10) or remained without access (n = 9) for a period of six weeks. After euthanasia, cecal contents were pooled by activity treatment and transplanted into two separate cohorts of GF mice. Two experiments were then conducted. First, mice were euthanized five weeks after the microbiota transplant and tissues were collected for analysis. A second cohort of GF mice were colonized by donor microbiotas for four weeks before dextran-sodium-sulfate was administered to induce acute colitis, after which mice were euthanized for tissue analysis. We observed that microbial transplants from donor (exercised or control) mice led to differences in microbiota β-diversity, metabolite profiles, colon inflammation, and body mass in recipient mice five weeks after colonization. We also demonstrate that colonization of mice with a gut microbiota from exercise-trained mice led to an attenuated response to chemical colitis, evidenced by reduced colon shortening, attenuated mucus depletion and augmented expression of cytokines involved in tissue regeneration. Exercise-induced modifications in the gut microbiota can mediate host-microbial interactions with potentially beneficial outcomes for the host.}, } @article {pmid28859349, year = {2017}, author = {Lagier, JC and Aubry, C and Delord, M and Michelet, P and Tissot-Dupont, H and Million, M and Brouqui, P and Raoult, D and Parola, P}, title = {From Expert Protocols to Standardized Management of Infectious Diseases.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {65}, number = {suppl_1}, pages = {S12-S19}, doi = {10.1093/cid/cix403}, pmid = {28859349}, issn = {1537-6591}, mesh = {Administration, Oral ; Anti-Bacterial Agents/administration & dosage/therapeutic use ; *Antimicrobial Stewardship ; Clinical Protocols ; Clostridium Infections/therapy ; Clostridium difficile/drug effects/isolation & purification ; *Communicable Disease Control/methods ; Coxiella burnetii/drug effects/isolation & purification ; *Disease Management ; Endocarditis, Bacterial/drug therapy/epidemiology ; Fecal Microbiota Transplantation ; France/epidemiology ; Humans ; *Infection Control ; Q Fever/epidemiology/therapy ; }, abstract = {We report here 4 examples of management of infectious diseases (IDs) at the University Hospital Institute Méditerranée Infection in Marseille, France, to illustrate the value of expert protocols feeding standardized management of IDs. First, we describe our experience on Q fever and Tropheryma whipplei infection management based on in vitro data and clinical outcome. Second, we describe our management-based approach for the treatment of infective endocarditis, leading to a strong reduction of mortality rate. Third, we report our use of fecal microbiota transplantation to face severe Clostridium difficile infections and to perform decolonization of patients colonized by emerging highly resistant bacteria. Finally, we present the standardized management of the main acute infections in patients admitted in the emergency department, promoting antibiotics by oral route, checking compliance with the protocol, and avoiding the unnecessary use of intravenous and urinary tract catheters. Overall, the standardization of the management is the keystone to reduce both mortality and morbidity related to IDs.}, } @article {pmid28858073, year = {2017}, author = {Allegretti, J and Eysenbach, LM and El-Nachef, N and Fischer, M and Kelly, C and Kassam, Z}, title = {The Current Landscape and Lessons from Fecal Microbiota Transplantation for Inflammatory Bowel Disease: Past, Present, and Future.}, journal = {Inflammatory bowel diseases}, volume = {23}, number = {10}, pages = {1710-1717}, doi = {10.1097/MIB.0000000000001247}, pmid = {28858073}, issn = {1536-4844}, mesh = {Clostridium Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Forecasting ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*complications/microbiology/*therapy ; Randomized Controlled Trials as Topic ; }, abstract = {Fecal microbiota transplantation (FMT) has changed the standard of care for Clostridium difficile infection. However, there is limited data focusing on efficacy and safety profile of FMT in patients with C. difficile infection with underlying inflammatory bowel disease (IBD), including the risk of IBD flare. Recently, there is also emerging evidence supporting the role of FMT to treat IBD including promising randomized trials in ulcerative colitis. However, with heterogeneity across these studies, the clinical application of this emerging therapy has yet to be fully elucidated. Here, we aim to review the current landscape of this rapidly developing field, mapping the efficacy and safety of FMT (1) to treat C. difficile infection in patients with IBD, (2) to treat underlying IBD, and (3) outline ongoing clinical trials and the future of the microbiome space.}, } @article {pmid28852524, year = {2017}, author = {Lan, N and Ashburn, J and Shen, B}, title = {Fecal microbiota transplantation for Clostridium difficile infection in patients with ileal pouches.}, journal = {Gastroenterology report}, volume = {5}, number = {3}, pages = {200-207}, doi = {10.1093/gastro/gox018}, pmid = {28852524}, issn = {2052-0034}, abstract = {Background:Clostridium difficile infection (CDI) in patients with ileal pouch-anal anastomosis (IPAA) has been increasingly recognized. The aim of this study was to evaluate the outcome of fecal microbiota transplantation (FMT) in patients with pouch and CDI. Methods: All consecutive patients that underwent FMT for CDI from 2012 to 2016 were extracted from our IRB-approved, prospectively maintained Registry of Pouch Disorders. The primary outcome was negative stool tests for Clostridium difficile after FMT and the secondary outcomes were symptomatic and endoscopic responses. Results: A total of 13 patients were included in this study, with 10 being Caucasian males (76.9%). All patients had underlying ulcerative colitis for J pouch surgery. After a mean of 2.8±0.8 courses of antibiotic treatments was given and failed, 22 sessions of FMT were administered with an average of 1.7±1.1 sessions each. Within the 22 sessions, 16 were given via pouchoscopy, 4 via esophagogastroduodenoscopy and 2 via enemas. All patients tested negative on C. difficile polymerase chain reaction (PCR) after the initial FMT with a total of 7/12 (58.3%) documented patients showed symptomatic improvements and 3/11 (27.3%) patients showed endoscopic improvement according to the modified Pouchitis Disease Activity Index. During the follow-up of 1.2±1.1 years, there were a total of five patients (38.5%) that had recurrence after the successful initial treatment and four of them were successfully treated again with FMT. Conclusions: FMT appeared to be effective in eradication of CDI in patients with ileal pouches. However, FMT had a modest impact on endoscopic inflammation and recurrence after FMT and recurrence was common.}, } @article {pmid28852308, year = {2017}, author = {Cenit, MC and Sanz, Y and Codoñer-Franch, P}, title = {Influence of gut microbiota on neuropsychiatric disorders.}, journal = {World journal of gastroenterology}, volume = {23}, number = {30}, pages = {5486-5498}, doi = {10.3748/wjg.v23.i30.5486}, pmid = {28852308}, issn = {2219-2840}, mesh = {Animals ; Brain/growth & development/*physiopathology ; DNA Methylation ; Disease Models, Animal ; Epigenesis, Genetic ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Hypothalamo-Hypophyseal System/physiopathology ; Neurodegenerative Diseases/*etiology/prevention & control ; Neurodevelopmental Disorders/*etiology/prevention & control ; Pituitary-Adrenal System/physiopathology ; Stress, Psychological/*complications/physiopathology ; }, abstract = {The last decade has witnessed a growing appreciation of the fundamental role played by an early assembly of a diverse and balanced gut microbiota and its subsequent maintenance for future health of the host. Gut microbiota is currently viewed as a key regulator of a fluent bidirectional dialogue between the gut and the brain (gut-brain axis). A number of preclinical studies have suggested that the microbiota and its genome (microbiome) may play a key role in neurodevelopmental and neurodegenerative disorders. Furthermore, alterations in the gut microbiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson's disease. However, it is not yet clear whether these changes in the microbiome are causally related to such diseases or are secondary effects thereof. In this respect, recent studies in animals have indicated that gut microbiota transplantation can transfer a behavioral phenotype, suggesting that the gut microbiota may be a modifiable factor modulating the development or pathogenesis of neuropsychiatric conditions. Further studies are warranted to establish whether or not the findings of preclinical animal experiments can be generalized to humans. Moreover, although different communication routes between the microbiota and brain have been identified, further studies must elucidate all the underlying mechanisms involved. Such research is expected to contribute to the design of strategies to modulate the gut microbiota and its functions with a view to improving mental health, and thus provide opportunities to improve the management of psychiatric diseases. Here, we review the evidence supporting a role of the gut microbiota in neuropsychiatric disorders and the state of the art regarding the mechanisms underlying its contribution to mental illness and health. We also consider the stages of life where the gut microbiota is more susceptible to the effects of environmental stressors, and the possible microbiota-targeted intervention strategies that could improve health status and prevent psychiatric disorders in the near future.}, } @article {pmid28852307, year = {2017}, author = {Guariso, G and Gasparetto, M}, title = {Treating children with inflammatory bowel disease: Current and new perspectives.}, journal = {World journal of gastroenterology}, volume = {23}, number = {30}, pages = {5469-5485}, doi = {10.3748/wjg.v23.i30.5469}, pmid = {28852307}, issn = {2219-2840}, mesh = {Age Factors ; Biological Products/pharmacology/*therapeutic use ; Biosimilar Pharmaceuticals/pharmacology/therapeutic use ; Child ; Clinical Trials as Topic ; Colitis, Ulcerative/immunology/*therapy ; Crohn Disease/immunology/*therapy ; Diet Therapy/methods ; Fecal Microbiota Transplantation/*methods/trends ; Gastrointestinal Microbiome/immunology ; Humans ; Immunosuppression/methods/trends ; Immunosuppressive Agents/pharmacology/*therapeutic use ; Treatment Outcome ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gut characterised by alternating periods of remission and relapse. Whilst the mechanism underlying this disease is yet to be fully understood, old and newer generation treatments can only target selected pathways of this complex inflammatory process. This narrative review aims to provide an update on the most recent advances in treatment of paediatric IBD. A MEDLINE search was conducted using "paediatric inflammatory bowel disease", "paediatric Crohn's disease", "paediatric ulcerative colitis", "treatment", "therapy", "immunosuppressant", "biologic", "monitoring" and "biomarkers" as key words. Clinical trials, systematic reviews, and meta-analyses published between 2014 and 2016 were selected. Studies referring to earlier periods were also considered in case the data was relevant to our scope. Major advances have been achieved in monitoring the individual metabolism, toxicity and response to relevant medications in IBD including thiopurines and biologics. New biologics acting on novel mechanisms such as selective interference with lymphocyte trafficking are emerging treatment options. Current research is investing in the development of reliable prognostic biomarkers, aiming to move towards personalised treatments targeted to individual patients.}, } @article {pmid28844808, year = {2017}, author = {Torres-Fuentes, C and Schellekens, H and Dinan, TG and Cryan, JF}, title = {The microbiota-gut-brain axis in obesity.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {2}, number = {10}, pages = {747-756}, doi = {10.1016/S2468-1253(17)30147-4}, pmid = {28844808}, issn = {2468-1253}, mesh = {Affect ; Appetite Regulation ; Brain/*metabolism ; Diet, Reducing ; Energy Metabolism ; Fecal Microbiota Transplantation ; Feeding Behavior/psychology ; *Gastrointestinal Microbiome ; Humans ; Metagenomics ; Obesity/*metabolism/psychology/therapy ; Prebiotics ; Probiotics/therapeutic use ; Reward ; }, abstract = {Changes in microbial diversity and composition are increasingly associated with several disease states including obesity and behavioural disorders. Obesity-associated microbiota alter host energy harvesting, insulin resistance, inflammation, and fat deposition. Additionally, intestinal microbiota can regulate metabolism, adiposity, homoeostasis, and energy balance as well as central appetite and food reward signalling, which together have crucial roles in obesity. Moreover, some strains of bacteria and their metabolites might target the brain directly via vagal stimulation or indirectly through immune-neuroendocrine mechanisms. Therefore, the gut microbiota is becoming a target for new anti-obesity therapies. Further investigations are needed to elucidate the intricate gut-microbiota-host relationship and the potential of gut-microbiota-targeted strategies, such as dietary interventions and faecal microbiota transplantation, as promising metabolic therapies that help patients to maintain a healthy weight throughout life.}, } @article {pmid28840819, year = {2017}, author = {Collins, FL and Rios-Arce, ND and Schepper, JD and Parameswaran, N and McCabe, LR}, title = {The Potential of Probiotics as a Therapy for Osteoporosis.}, journal = {Microbiology spectrum}, volume = {5}, number = {4}, pages = {}, doi = {10.1128/microbiolspec.BAD-0015-2016}, pmid = {28840819}, issn = {2165-0497}, support = {P30 DK020572/DK/NIDDK NIH HHS/United States ; R01 AT007695/AT/NCCIH NIH HHS/United States ; R01 DK101050/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bone Density ; Bone Remodeling/*physiology ; Bone and Bones ; Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Female ; Fractures, Bone/*prevention & control ; Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Osteoporosis/pathology/prevention & control/*therapy ; Probiotics/*therapeutic use ; }, abstract = {Osteoporosis, characterized by low bone mass and micro-architectural deterioration of bone tissue with increased risk of fracture, can be categorized into two forms: primary and secondary, depending on whether it occurs as part of the natural aging process (estrogen deficiency) or as part of disease pathology. In both forms bone loss is due to an imbalance in the bone remodeling process, with resorption/formation skewed more toward bone loss. Recent studies and emerging evidence consistently demonstrate the potential of the intestinal microbiota to modulate bone health. This review discusses the process of bone remodeling and the pathology of osteoporosis and introduces the intestinal microbiota and its potential to influence bone health. In particular, we highlight recent murine studies that examine how probiotic supplementation can both increase bone density in healthy individuals and protect against primary (estrogen deficiency) as well as secondary osteoporosis. Potential mechanisms are described to account for how probiotic treatments could be exerting their beneficial effect on bone health.}, } @article {pmid28840809, year = {2017}, author = {Bakker, GJ and Nieuwdorp, M}, title = {Fecal Microbiota Transplantation: Therapeutic Potential for a Multitude of Diseases beyond Clostridium difficile.}, journal = {Microbiology spectrum}, volume = {5}, number = {4}, pages = {}, doi = {10.1128/microbiolspec.BAD-0008-2017}, pmid = {28840809}, issn = {2165-0497}, mesh = {Diabetes Mellitus, Type 2/microbiology/*therapy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/microbiology ; Humans ; Inflammatory Bowel Diseases/microbiology/*therapy ; Non-alcoholic Fatty Liver Disease/microbiology/*therapy ; }, abstract = {The human intestinal tract contains trillions of bacteria, collectively called the gut microbiota. Recent insights have linked the gut microbiota to a plethora of diseases, including Clostridium difficile infection (CDI), inflammatory bowel disease (IBD), and metabolic diseases such as obesity, type 2 diabetes (T2D), and nonalcoholic steatohepatitis (NASH). Fecal microbiota transplantation (FMT) is currently tested as a therapeutic option in various diseases and can also help to dissect association from causality with respect to gut microbiota and disease. In CDI, FMT has been shown to be superior to antibiotic treatment. For IBD, T2D, and NASH, several placebo-controlled randomized controlled trials are under way. Moreover, techniques and standardization are developing. With the extension of FMT as a treatment modality in diseases other than CDI, a whole new treatment option may be emerging. Moreover, correlating alterations in specific strains to disease outcome may prove pivotal in finding new bacterial targets. Thus, although causality of the gut microbiota in various diseases still needs to be proven, FMT may prove to be a powerful tool providing us with diagnostic and therapeutic leads.}, } @article {pmid28840580, year = {2017}, author = {Kelly, CR and Allegretti, JR}, title = {FMT in IBD: What Have We Learned?.}, journal = {Digestive diseases and sciences}, volume = {62}, number = {10}, pages = {2618-2620}, doi = {10.1007/s10620-017-4713-9}, pmid = {28840580}, issn = {1573-2568}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Inflammatory Bowel Diseases ; }, } @article {pmid28838410, year = {2017}, author = {Khanna, S and Raffals, LE}, title = {The Microbiome in Crohn's Disease: Role in Pathogenesis and Role of Microbiome Replacement Therapies.}, journal = {Gastroenterology clinics of North America}, volume = {46}, number = {3}, pages = {481-492}, doi = {10.1016/j.gtc.2017.05.004}, pmid = {28838410}, issn = {1558-1942}, mesh = {Crohn Disease/complications/immunology/*microbiology/therapy ; Diet Therapy ; Dysbiosis/complications/*microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/immunology ; Humans ; Immunity, Mucosal/immunology ; Probiotics/therapeutic use ; }, abstract = {Individuals with a genetic predisposition to Crohn's disease develop aberrant immune responses to environmental triggers. The gastrointestinal microbiota is increasingly recognized to play an important role in the development of Crohn's disease. Decrease in global gut microbial diversity and specific bacterial alterations have been implicated in Crohn's disease. Advances in sequencing techniques and bioinformatics and correlation with host genetics continue to improve insight into the structure and function of the microbial community and interactions with the host immune system. This article summarizes the existing literature on the role of the gut microbiome and its manipulation in the development and management of Crohn's disease.}, } @article {pmid28827811, year = {2017}, author = {Moss, EL and Falconer, SB and Tkachenko, E and Wang, M and Systrom, H and Mahabamunuge, J and Relman, DA and Hohmann, EL and Bhatt, AS}, title = {Long-term taxonomic and functional divergence from donor bacterial strains following fecal microbiota transplantation in immunocompromised patients.}, journal = {PloS one}, volume = {12}, number = {8}, pages = {e0182585}, doi = {10.1371/journal.pone.0182585}, pmid = {28827811}, issn = {1932-6203}, support = {T32 HG000044/HG/NHGRI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Bacteria/classification ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; *Immunocompromised Host ; Male ; Middle Aged ; Treatment Outcome ; }, abstract = {Immunocompromised individuals are at high risk of developing Clostridium difficile-associated disease (CDAD). Fecal microbiota transplantation (FMT) is a highly effective therapy for refractory or recurrent CDAD and, despite safety concerns, has recently been offered to immunocompromised patients. We investigated the genomics of bacterial composition following FMT in immunocompromised patients over a 1-year period. Metagenomic, strain and gene-level bacterial dynamics were characterized in two CDAD-affected hematopoietic stem cell (HCT) recipients following FMT. We found alterations in gene content, including loss of virulence and antibiotic resistance genes. These alterations were accompanied by long-term bacterial divergence at the species and strain levels. Our findings suggest limited durability of the specific bacterial consortium introduced with FMT and indicate that alterations of the functional potential of the microbiome are more complex than can be inferred by taxonomic information alone. Our observation that FMT alone cannot induce long-term donor-like alterations of the microbiota of HCT recipients suggests that FMT cannot indefinitely supersede environmental and/or host factors in shaping bacterial composition.}, } @article {pmid28827258, year = {2017}, author = {Pai, N and Popov, J}, title = {Protocol for a randomised, placebo-controlled pilot study for assessing feasibility and efficacy of faecal microbiota transplantation in a paediatric ulcerative colitis population: PediFETCh trial.}, journal = {BMJ open}, volume = {7}, number = {8}, pages = {e016698}, doi = {10.1136/bmjopen-2017-016698}, pmid = {28827258}, issn = {2044-6055}, mesh = {Adolescent ; Biomarkers/*analysis ; Canada ; Child ; Child, Preschool ; Colitis, Ulcerative/*therapy ; Feasibility Studies ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Microbiome ; Humans ; Pilot Projects ; Recurrence ; Research Design ; Single-Blind Method ; Treatment Outcome ; }, abstract = {INTRODUCTION: Ulcerative colitis (UC) is a chronic, relapsing condition characterised by colonic inflammation. Increasing prevalence in early-age diagnosis provides opportunities for additional complications in later life as a result of prolonged exposure to inflammatory and therapeutic insults, necessitating novel avenues for therapeutics which may result in fewer side effects. Faecal microbiota transplantation (FMT) has previously demonstrated potential therapeutic benefit in an adult randomised-controlled trial and several recurrent Clostridium difficile infection studies. This phase Ib pilot will be the first randomised, single-blinded, placebo-controlled trial to assess feasibility and patient outcomes in a paediatric inflammatory bowel disease (IBD) population.

METHODS AND ANALYSIS: Fifty patients will be randomised 1:1 to receive normal saline control or active sample. Enema administrations will be performed two times per week for 6 weeks, followed at a 6-month follow-up period. Feasibility outcomes will include measures of patient eligibility, recruitment, willingness to participate, samples collections, hospitalizations and drop-out rate. Improvements in disease symptoms will determine the efficacy of treatment. Clinical disease scores will be taken throughout the study period using the Paediatric Ulcerative Colitis Activity Index (PUCAI). Monitoring of inflammatory markers in blood and stool will be performed at regular intervals. Microbiome analysis will be conducted on stool samples collected throughout the trials period. Imaging and endoscopic surveillance will be conducted if clinically necessary.

ETHICS AND DISSEMINATION: Ethics was obtained from local hospital research ethics boards across all three sites. Health Canada and FDA approval was obtained for the use of an Investigatory New Drug product. Results from this trial will be presented in international conferences and published in peer-review journals.

TRIAL REGISTRATION NUMBER: Trial registration number: NCT02487238; preresults.}, } @article {pmid28823860, year = {2017}, author = {Wong, SH and Zhao, L and Zhang, X and Nakatsu, G and Han, J and Xu, W and Xiao, X and Kwong, TNY and Tsoi, H and Wu, WKK and Zeng, B and Chan, FKL and Sung, JJY and Wei, H and Yu, J}, title = {Gavage of Fecal Samples From Patients With Colorectal Cancer Promotes Intestinal Carcinogenesis in Germ-Free and Conventional Mice.}, journal = {Gastroenterology}, volume = {153}, number = {6}, pages = {1621-1633.e6}, doi = {10.1053/j.gastro.2017.08.022}, pmid = {28823860}, issn = {1528-0012}, mesh = {Animals ; Azoxymethane ; Case-Control Studies ; Cell Proliferation ; *Cell Transformation, Neoplastic/metabolism/pathology ; Colon/metabolism/*microbiology/pathology ; Colonic Polyps/chemically induced/metabolism/*microbiology/pathology ; Colorectal Neoplasms/chemically induced/metabolism/*microbiology/pathology ; Disease Models, Animal ; Feces/*microbiology ; *Gastrointestinal Microbiome ; Gene Expression Regulation, Neoplastic ; Germ-Free Life ; Host-Pathogen Interactions ; Humans ; Inflammation Mediators/metabolism ; Ki-67 Antigen/metabolism ; Lymphocytes, Tumor-Infiltrating/metabolism/microbiology ; Male ; Mice, Inbred C57BL ; Th1 Cells/metabolism/microbiology ; Th17 Cells/metabolism/microbiology ; }, abstract = {BACKGROUND & AIMS: Altered gut microbiota is implicated in development of colorectal cancer (CRC). Some intestinal bacteria have been reported to potentiate intestinal carcinogenesis by producing genotoxins, altering the immune response and intestinal microenvironment, and activating oncogenic signaling pathways. We investigated whether stool from patients with CRC could directly induce colorectal carcinogenesis in mice.

METHODS: We obtained stored stool samples from participants in a metagenome study performed in Hong Kong. Conventional (male C57BL/6) mice were given azoxymethane to induce colon neoplasia after receiving a course of antibiotics in drinking water. Mice were gavaged twice weekly with stool from 5 patients with CRC or 5 healthy individuals (controls) for 5 weeks. Germ-free C57BL/6 mice were gavaged once with stool from 5 patients with CRC or 5 controls. We collected intestinal tissues from mice and performed histology, immunohistochemistry, expression microarray, quantitative polymerase chain reaction, immunoblot, and flow cytometry analyses. We performed 16S ribosomal RNA gene sequencing analysis of feces from mice.

RESULTS: Significantly higher proportions of conventional mice fed with stool from individuals with CRC than control stool developed high-grade dysplasia (P < .05) and macroscopic polyps (P < .01). We observed a higher proportion of proliferating (Ki-67-positive) cells in colons of germ-free mice fed with stool from patients with CRC vs those fed with stool from controls (P < .05). Feces from germ-free and conventional mice fed with stool from patients with CRC vs controls contained different microbial compositions, with lower richness in mice fed with stool from patients with CRC. Intestines collected from conventional and germ-free mice fed with stool from patients with CRC had increased expression of cytokines that modulate inflammation, including C-X-C motif chemokine receptor 1, C-X-C motif chemokine receptor 2, interleukin 17A (IL17A), IL22, and IL23A. Intestines from conventional and germ-free mice fed with stool from patients with CRC contained higher proportions of T-helper 1 (Th1) cells (2.25% vs 0.44%) and Th17 cells (2.08% vs 0.31%) (P < .05 for each) than mice fed with stool from controls. Real-time polymerase chain reaction arrays revealed up-regulation of genes involved in cell proliferation, stemness, apoptosis, angiogenesis, invasiveness, and metastasis in mice fed with stool from patients with CRC.

CONCLUSIONS: We fed stool samples from patients with CRC and heathy individuals to germ-free mice and conventional mice with azoxymethane. We found stool from patients with CRC to increase the numbers of polyps, levels of intestinal dysplasia and proliferation, markers of inflammation, and proportions of Th1 and Th17 cells in colon, compared with stool from individuals without CRC. This study provides evidence that the fecal microbiota from patients with CRC can promote tumorigenesis in germ-free mice and mice given a carcinogen.}, } @article {pmid28814217, year = {2017}, author = {Razik, R and Osman, M and Lieberman, A and Allegretti, JR and Kassam, Z}, title = {Faecal microbiota transplantation for Clostridium difficile infection: a multicentre study of non-responders.}, journal = {The Medical journal of Australia}, volume = {207}, number = {4}, pages = {159-160}, pmid = {28814217}, issn = {1326-5377}, mesh = {Aged ; Aged, 80 and over ; Clostridium Infections/*therapy ; *Clostridium difficile ; Fecal Microbiota Transplantation/adverse effects/*methods ; Female ; *Guideline Adherence ; Humans ; Male ; Middle Aged ; Netherlands ; Prospective Studies ; Proton Pump Inhibitors/administration & dosage ; Recurrence ; Risk Factors ; Treatment Failure ; Treatment Outcome ; United States ; }, } @article {pmid28814214, year = {2017}, author = {Brandt, LJ}, title = {Faecal microbiota transplantation: past, present and future.}, journal = {The Medical journal of Australia}, volume = {207}, number = {4}, pages = {151-152}, pmid = {28814214}, issn = {1326-5377}, mesh = {Clostridium difficile ; *Fecal Microbiota Transplantation ; *Feces ; Gastrointestinal Microbiome ; }, } @article {pmid28814204, year = {2017}, author = {Moayyedi, P and Yuan, Y and Baharith, H and Ford, AC}, title = {Faecal microbiota transplantation for Clostridium difficile-associated diarrhoea: a systematic review of randomised controlled trials.}, journal = {The Medical journal of Australia}, volume = {207}, number = {4}, pages = {166-172}, pmid = {28814204}, issn = {1326-5377}, mesh = {Adult ; Anti-Bacterial Agents/therapeutic use ; Clostridium difficile ; Diarrhea/microbiology/*therapy ; Enterocolitis, Pseudomembranous/microbiology/*therapy ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Humans ; Randomized Controlled Trials as Topic ; Vancomycin/therapeutic use ; }, abstract = {OBJECTIVES: Faecal microbiota transplantation (FMT) has emerged as a useful approach for treating Clostridium difficile-associated diarrhoea (CDAD). Randomised controlled trials (RCTs) have recently evaluated its effectiveness, but systematic reviews have focused on evidence from case series. We therefore conducted a systematic review and meta-analysis of RCTs evaluating the effectiveness of FMT for treating CDAD.

STUDY DESIGN: We included RCTs that primarily recruited adults with CDAD and compared the effectiveness of FMT with that of placebo, antibiotic therapy, or autologous stool transplantation, or compared different preparations or modes of delivery of FMT. Dichotomous symptom data were pooled to calculate a relative risk (RR) of CDAD persisting after therapy, and the number needed to treat (NNT).

DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register and Database of Systematic Reviews were searched to 6 February 2017.

DATA SYNTHESIS: We identified ten RCTs that evaluated the treatment of a total of 657 patients with CDAD. Five RCTs compared FMT with placebo (including autologous FMT) or vancomycin treatment (total of 284 patients); FMT was statistically significantly more effective (RR, 0.41; 95% CI, 0.22-0.74; NNT, 3; 95% CI, 2-7). Heterogeneity across studies was significant (I2 = 61%); this heterogeneity was attributable to the mode of delivery of FMT, and to the therapy being more successful in European than in North American trials. The other five RCTs evaluated different approaches to FMT therapy. Frozen FMT preparations were as efficacious as fresh material in one RCT, but the numbers of patients in the remaining RCTs were too small to allow definitive conclusions.

CONCLUSIONS: Moderate quality evidence from RCT trials indicates that FMT is more effective in patients with CDAD than vancomycin or placebo. Further investigations are needed to determine the best route of administration and FMT preparation.}, } @article {pmid28811841, year = {2017}, author = {Łusiak-Szelachowska, M and Weber-Dąbrowska, B and Jończyk-Matysiak, E and Wojciechowska, R and Górski, A}, title = {Bacteriophages in the gastrointestinal tract and their implications.}, journal = {Gut pathogens}, volume = {9}, number = {}, pages = {44}, doi = {10.1186/s13099-017-0196-7}, pmid = {28811841}, issn = {1757-4749}, abstract = {The gut microbiota plays an essential role in health and disease of humans. Bacteriophages are the most abundant members of the gut virobiota and display great diversity. Phages can translocate through the mucosa to lymph and internal organs and play a role as regulators of the bacterial population in the gut. Increasing abundance of phages in the gut mucosa may reduce colonization by bacteria. Moreover, phages may have an immunomodulatory role in the immune response in the human gut. The role of phages in inflammatory bowel disease (IBD) remains unknown. Phages may take part in the development of IBD, but there are also data suggesting the protective role of phages in the gut of patients with IBD. Furthermore, recent data suggest that phages may mediate the beneficial effects of fecal microbiota transplantation (FMT). Therefore, evidence is accumulating to highlight the protective immunomodulating activity of the gut phages.}, } @article {pmid28807067, year = {2017}, author = {Mahieu, R and Cassisa, V and Sanderink, D and Chenouard, R and Pailhoriès, H and Kempf, M and Dubée, V and Eveillard, M}, title = {Iterative Fecal Microbiota Transplantations for Eradicating Digestive Colonization With Carbapenemase-Producing Enterobacteriaceae: Is It Worth It?.}, journal = {Infection control and hospital epidemiology}, volume = {38}, number = {10}, pages = {1265-1266}, doi = {10.1017/ice.2017.173}, pmid = {28807067}, issn = {1559-6834}, mesh = {Animals ; Carbapenem-Resistant Enterobacteriaceae/isolation & purification/*pathogenicity ; Colony Count, Microbial ; Disease Models, Animal ; Enterobacteriaceae Infections/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Mice ; Random Allocation ; }, } @article {pmid28805322, year = {2017}, author = {Lim, MH and Radford-Smith, GL}, title = {Editorial: faecal microbiota transplantation for ulcerative colitis-not quite there yet?.}, journal = {Alimentary pharmacology & therapeutics}, volume = {46}, number = {6}, pages = {630-631}, doi = {10.1111/apt.14228}, pmid = {28805322}, issn = {1365-2036}, mesh = {*Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Microbiota ; }, } @article {pmid28805321, year = {2017}, author = {Costello, SP and Soo, W and Bryant, RV and Jairath, V and Hart, AL and Andrews, JM}, title = {Editorial: faecal microbiota transplantation for ulcerative colitis-not quite there yet? Authors' reply.}, journal = {Alimentary pharmacology & therapeutics}, volume = {46}, number = {6}, pages = {631-632}, doi = {10.1111/apt.14246}, pmid = {28805321}, issn = {1365-2036}, mesh = {*Colitis, Ulcerative ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Microbiota ; }, } @article {pmid28803667, year = {2018}, author = {Kang, Y and Cai, Y}, title = {Future prospect of faecal microbiota transplantation as a potential therapy in asthma.}, journal = {Allergologia et immunopathologia}, volume = {46}, number = {3}, pages = {307-309}, doi = {10.1016/j.aller.2017.04.008}, pmid = {28803667}, issn = {1578-1267}, mesh = {Asthma/*therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Humans ; Probiotics/therapeutic use ; }, abstract = {There is convincing evidence from both human and animal studies suggesting that the gut microbiota plays an important role in regulating immune responses associated with the development of asthma. Certain intestinal microbial strains have been demonstrated to suppress or impair immune responsiveness in asthma experimental models, suggesting that specific species among gut commensal microbiota may play either a morbific or phylactic role in the progression of asthma. Evidence to date suggests that the intestinal microbiota represent fertile targets for prevention or management of asthma. The faecal microbiota transplantation (FMT) is a rather straightforward therapy that manipulates the human gastrointestinal (GI) microbiota, by which a healthy donor microbiota is transferred into an existing but disturbed microbial ecosystem. The FMT may therefore represent a therapeutic approach for asthma treatment in the foreseeable future. At present, FMT therapy for asthma is very limited and should be actively studied. Considerable efforts are needed to increase our knowledge in the field of FMT therapy for asthma. In this review, we aimed to provide several insights into the development of FMT therapy for asthma.}, } @article {pmid28801119, year = {2017}, author = {Jiang, ZD and Alexander, A and Ke, S and Valilis, EM and Hu, S and Li, B and DuPont, HL}, title = {Stability and efficacy of frozen and lyophilized fecal microbiota transplant (FMT) product in a mouse model of Clostridium difficile infection (CDI).}, journal = {Anaerobe}, volume = {48}, number = {}, pages = {110-114}, doi = {10.1016/j.anaerobe.2017.08.003}, pmid = {28801119}, issn = {1095-8274}, mesh = {Animals ; Clostridium Infections/microbiology/*therapy ; Clostridium difficile/growth & development/pathogenicity ; Cryopreservation/*methods ; Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Freezing ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Treatment Outcome ; }, abstract = {Freezing donor fecal microbiota has simplified fecal microbiota transplantation (FMT) in the treatment of recurrent C. difficile infection (CDI). However, the optimal storage time for the frozen FMT products remains unknown. Using an established murine model of CDI, stability and efficacy of frozen and lyophilized FMT product was studied at time points from 2 months to 15 months. DNA was extracted from fecal samples from the mice with identification of specific bacterial species by real-time quantitative PCR (qPCR). FMT product stability and efficacy were measured by occurrence of diarrhea in the challenged mice together with stability of the microbiota composition. The results were analyzed and compared by SAS statistical software. All mice treated with only C. difficile developed diarrhea within 72 h. Mice treated with frozen (n = 5/group), lyophilized (n = 5/group) products stored for ≤ 7-month or fresh FMT product (n = 22) were protected from post C. difficile challenge diarrhea. There was no difference between frozen and lyophilized products (n = 5/group) stored for ≤ 7 months 95% CI 1.00 (0.38-2.64) and 1.00 (0.38-2.64), respectively. Prevention if CDI by frozen and lyophilized product was not different for storage of 9-, 11- and 15-months. qPCR results demonstrated there were no significant quantitative change in Bacteroides and Clostridium species during any of the storage times (P > 0.05). In the present study, frozen and lyophilized FMT products were stored up to 7 months without losing microbiota composition and therapeutic efficacy. The animal model described may be useful to study stability of human microbiota designed for FMT.}, } @article {pmid28799154, year = {2017}, author = {Reinshagen, M and Stallmach, A}, title = {[Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial].}, journal = {Zeitschrift fur Gastroenterologie}, volume = {55}, number = {8}, pages = {779-780}, doi = {10.1055/s-0043-109349}, pmid = {28799154}, issn = {1439-7803}, mesh = {*Colitis, Ulcerative ; Double-Blind Method ; *Fecal Microbiota Transplantation ; Feces ; Humans ; }, } @article {pmid28796069, year = {2017}, author = {Zhu, J and Zhang, F and Zhou, J and Li, H}, title = {Assessment of therapeutic response in Crohn's disease using quantitative dynamic contrast enhanced MRI (DCE-MRI) parameters: A preliminary study.}, journal = {Medicine}, volume = {96}, number = {32}, pages = {e7759}, doi = {10.1097/MD.0000000000007759}, pmid = {28796069}, issn = {1536-5964}, mesh = {Adult ; C-Reactive Protein ; Contrast Media/*administration & dosage ; Crohn Disease/*diagnostic imaging/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Humans ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; ROC Curve ; Reproducibility of Results ; Sensitivity and Specificity ; Severity of Illness Index ; Young Adult ; }, abstract = {The aim of the study was to investigate dynamic contrast enhanced MRI (DCE-MRI) as a potential marker to assess the therapeutic responses of fecal microbiota transplantation (FMT) in patients with Crohn's disease (CD) and to determine the parameter or combination of parameters most strongly associated with changes in clinical indicators after treatment.In 22 CD patients, DCE-MRI was performed with a 3.0T scanner. Parameters of DCE-MRI (vascular transfer constant [K] and blood volume [BV]) in the terminal ileum were compared between before and day 90 after FMT treatment. The differences of clinical indicators (C-reactive protein [CRP], Harvey-Bradshaw index [HBI]) and DCE-MRI parameters (K, BV) between pre- and post-treatment was calculated by Student's 2-tailed, paired t-test. The correlations between percent change of clinical indicators (ΔCRP, ΔHBI) with DCE-MRI parameters (ΔK, ΔBV) were analyzed by Pearson's correlation coefficients. A logistic regression model was used to identify the changes of DCE-MRI parameters related to the treatment outcomes. Receiver operating characteristic curves (ROCs) were generated to assess which DCE-MRI parameter showed the best accuracy for evaluation of therapeutic response.After treatment, mean values of clinical indicators decreased significantly (CRP: 62.68 ± 31.86 vs 43.55 ± 29.63 mg/L, P = .008; HBI: 7.18 ± 2.10 vs 5.73 ± 2.33, P = 0.012). Both DCE-MRI parameters showed prominent differences before and after treatment: K (1.86 ± 0.87 vs 1.39 ± 0.83 min, P = .017), BV (61.02 ± 28.49 vs 41.96 ± 22.75 mL/100 g, P = .005). There were significant correlations between ΔCRP or ΔHBI and percent change of CDE-MRI parameters (ΔK to ΔCRP: 0.659; ΔK to ΔHBI: 0.496; ΔBV to ΔCRP: 0.442; ΔBV to ΔHBI: 0.476). Compared to ΔK and ΔBV individually, the combination of both parameters performed best in assessment of therapeutic response with an area under the ROCs (AUC) of 0.948.K and BV parameters derived from DCE-MRI have the potential to assess for therapeutic response after FMT treatment for CD. The combination of K and BV measurements improved the predictive capability compared to the individual parameters.}, } @article {pmid28789710, year = {2017}, author = {Brooks, PT and Brakel, KA and Bell, JA and Bejcek, CE and Gilpin, T and Brudvig, JM and Mansfield, LS}, title = {Transplanted human fecal microbiota enhanced Guillain Barré syndrome autoantibody responses after Campylobacter jejuni infection in C57BL/6 mice.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {92}, doi = {10.1186/s40168-017-0284-4}, pmid = {28789710}, issn = {2049-2618}, support = {N01AI30058/AI/NIAID NIH HHS/United States ; T35 RR017491/RR/NCRR NIH HHS/United States ; U19 AI090872/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Autoantibodies/*biosynthesis/blood/immunology ; Autoimmunity ; Campylobacter Infections/*immunology/microbiology ; Campylobacter jejuni/immunology ; Colitis/etiology/immunology/microbiology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Guillain-Barre Syndrome/*immunology/*microbiology ; Host-Pathogen Interactions ; Humans ; Inflammation ; Interleukin-10/immunology ; Interleukin-4/immunology ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S ; }, abstract = {BACKGROUND: Campylobacter jejuni is the leading antecedent infection to the autoimmune neuropathy Guillain-Barré syndrome (GBS), which is accompanied by an autoimmune anti-ganglioside antibody attack on peripheral nerves. Previously, we showed that contrasting immune responses mediate C. jejuni induced colitis and autoimmunity in interleukin-10 (IL-10)-deficient mice, dependent upon the infecting strain. Strains from colitis patients elicited T helper 1 (TH1)-dependent inflammatory responses while strains from GBS patients elicited TH2-dependent autoantibody production. Both syndromes were exacerbated by antibiotic depletion of the microbiota, but other factors controlling susceptibility to GBS are unknown.

METHODS: Using 16S rRNA gene high-throughput sequencing, we examined whether structure of the gut microbial community alters host (1) gastrointestinal inflammation or (2) anti-ganglioside antibody responses after infection with C. jejuni strains from colitis or GBS patients. We compared these responses in C57BL/6 mice with either (1) stable human gut microbiota (Humicrobiota) transplants or (2) conventional mouse microbiota (Convmicrobiota).

RESULTS: Inoculating germ-free C57BL/6 wild-type (WT) mice with a mixed human fecal slurry provided a murine model that stably passed its microbiota over >20 generations. Mice were housed in specific pathogen-free (SPF) facilities, while extra precautions of having caretakers wear sterile garb along with limited access ensured that no mouse pathogens were acquired. Humicrobiota conferred many changes upon the WT model in contrast to previous results, which showed only colonization with no disease after C. jejuni challenge. When compared to Convmicrobiota mice for susceptibility to C. jejuni enteric or GBS patient strains, infected Humicrobiota mice had (1) 10-100 fold increases in C. jejuni colonization of both strains, (2) pathologic change in draining lymph nodes but only mild changes in colon or cecal lamina propria, (3) significantly lower Th1/Th17-dependent anti-C. jejuni responses, (4) significantly higher IL-4 responses at 5 but not 7 weeks post infection (PI), (5) significantly higher Th2-dependent anti-C. jejuni responses, and (6) significantly elevated anti-ganglioside autoantibodies after C. jejuni infection. These responses in Humicrobiota mice were correlated with a dominant Bacteroidetes and Firmicutes microbiota.

CONCLUSIONS: These data demonstrate that Humicrobiota altered host-pathogen interactions in infected mice, increasing colonization and Th-2 and autoimmune responses in a C. jejuni strain-dependent manner. Thus, microbiota composition is another factor controlling susceptibility to GBS.}, } @article {pmid28779831, year = {2017}, author = {Bartlett, JG}, title = {Clostridium difficile Infection.}, journal = {Infectious disease clinics of North America}, volume = {31}, number = {3}, pages = {489-495}, doi = {10.1016/j.idc.2017.05.012}, pmid = {28779831}, issn = {1557-9824}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Centers for Disease Control and Prevention (U.S.) ; Clostridium Infections/diagnosis/microbiology/*prevention & control/*therapy ; Clostridium difficile/*isolation & purification ; Cross Infection/diagnosis/microbiology/therapy ; Diarrhea/microbiology/therapy ; Fecal Microbiota Transplantation ; Humans ; Iatrogenic Disease ; Intensive Care Units ; Risk Factors ; United States/epidemiology ; }, abstract = {Clostridium difficile infection is a major health care challenge in terms of patient and economic consequences. For the patient, it is a morbid and sometimes a life-threatening iatrogenic complication of antibiotic treatment. In the United States, the provider's institution may face financial penalties, because the Centers for Disease Control and Prevention views this as an iatrogenic health care-associated complication that may not be reimbursable by the Centers for Medicare and Medicaid Services; this has resulted in substantial incentives for new approaches to prevention and treatment.}, } @article {pmid28770495, year = {2017}, author = {Millan, B and Laffin, M and Madsen, K}, title = {Fecal Microbiota Transplantation: Beyond Clostridium difficile.}, journal = {Current infectious disease reports}, volume = {19}, number = {9}, pages = {31}, doi = {10.1007/s11908-017-0586-5}, pmid = {28770495}, issn = {1523-3847}, abstract = {PURPOSE OF REVIEW: Fecal microbiota transplantation (FMT) has been established as standard of care in the treatment of antibiotic refractory Clostridium difficile infection (RCDI). This review examines the current evidence that exists to support the use of FMT in the treatment of human disease beyond C. difficile infection.

RECENT FINDINGS: Beneficial effects of FMT have been described in case series or small prospective trials on a wide spectrum of conditions, including inflammatory bowel disease, functional gastrointestinal disorders, non-alcoholic steatohepatitis, alcoholic hepatitis, hepatic encephalopathy, and neuropsychiatric conditions, and in limiting antibiotic-resistant bacterial infections. Each of these proposed indications for FMT is associated with an underlying dysbiosis of the gastrointestinal microbiota and generally a clinical response is linked with a restoration of the gut microbiota. The potential of fecal microbial transplantation to alter disease course shows promise but further large-scale studies are necessary to understand limitations as well as how best to utilize this therapy.}, } @article {pmid28766951, year = {2017}, author = {Manthey, CF and Eckmann, L and Fuhrmann, V}, title = {Therapy for Clostridium difficile infection - any news beyond Metronidazole and Vancomycin?.}, journal = {Expert review of clinical pharmacology}, volume = {10}, number = {11}, pages = {1239-1250}, doi = {10.1080/17512433.2017.1362978}, pmid = {28766951}, issn = {1751-2441}, mesh = {Animals ; Anti-Bacterial Agents/*therapeutic use ; Clostridium Infections/*drug therapy/microbiology ; Clostridium difficile/*isolation & purification ; Drug Design ; Humans ; Metronidazole/therapeutic use ; Practice Guidelines as Topic ; Recurrence ; Severity of Illness Index ; Vancomycin/therapeutic use ; }, abstract = {INTRODUCTION: Infections with Clostridium difficile (CDI) represent a major burden for the health care system. Treatment is generally by antibiotic therapy with metronidazole and vancomycin, but efficacy remains suboptimal. Areas covered: This review discusses established and emerging treatment options for CDI, and current therapeutic guidelines, taking into account disease severity and risk of relapse. Expert commentary: New therapeutic approaches, including antibodies and new classes of antibiotics, and new measures for preventing infection with vaccines are under development in phase II/III clinical trials. We performed a systematic literature review using the search terms 'Clostridium difficile' and 'treatment'.}, } @article {pmid28764868, year = {2017}, author = {Leber, A and Hontecillas, R and Abedi, V and Tubau-Juni, N and Zoccoli-Rodriguez, V and Stewart, C and Bassaganya-Riera, J}, title = {Modeling new immunoregulatory therapeutics as antimicrobial alternatives for treating Clostridium difficile infection.}, journal = {Artificial intelligence in medicine}, volume = {78}, number = {}, pages = {1-13}, doi = {10.1016/j.artmed.2017.05.003}, pmid = {28764868}, issn = {1873-2860}, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Anti-Infective Agents ; Clostridium Infections/*therapy ; *Clostridium difficile ; Computer Simulation ; *Fecal Microbiota Transplantation ; Microbiota ; }, abstract = {The current treatment paradigm in Clostridium difficile infection is the administration of antibiotics contributing to the high rates of recurrent infections. Recent alternative strategies, such as fecal microbiome transplantation and anti-toxin antibodies, have shown similar efficacy in the treatment of C. difficile associated disease (CDAD). However, barriers exist for either treatment or other novel treatments to displace antibiotics as the standard of care. To aid in the comparison of these and future treatments in CDAD, we developed an in silico pipeline to predict clinical efficacy with nonclinical results. The pipeline combines an ordinary differential equation (ODE)-based model, describing the immunological and microbial interactions in the gastrointestinal (GI) mucosa, with machine learning algorithms to translate simulated output quantities (i.e. time of clearance, quantity of commensal bacteria, T cell ratios) into clinical predictions based on prior preclinical, translational and clinical trial data. As a use case, we compare the efficacy of lanthionine synthetase C-like 2 (LANCL2), a novel immunoregulatory target with promising efficacy in inflammatory bowel disease (IBD), activation with antibiotics, fecal microbiome transplantation and anti-toxin antibodies in the treatment of CDAD. We further validate the potential of LANCL2 pathway activation, in a mouse model of C. difficile infection in which it displays an ability to decrease weight loss and inflammatory cell types while protecting against mortality. The computational pipeline can serve as an important resource in the development of new treatment modalities.}, } @article {pmid28761890, year = {2017}, author = {Fasullo, MJ and Al-Azzawi, Y and Abergel, J}, title = {Microscopic Colitis After Fecal Microbiota Transplant.}, journal = {ACG case reports journal}, volume = {4}, number = {}, pages = {e87}, doi = {10.14309/crj.2017.87}, pmid = {28761890}, issn = {2326-3253}, abstract = {Microscopic colitis (MC) is an inflammatory condition of the large bowel that is associated with chronic, nonbloody diarrhea. Colonoscopy usually demonstrates normal mucosa, while tissue biopsy reveals intraepithelial lymphocytes or a subepithelial collagen band. Although no specific antibody has been discovered, MC is associated with several autoimmune disorders such as celiac disease, Hashimoto's thyroiditis, and rheumatoid arthritis. There are only a small number of case reports documenting possible hereditary MC cases, but up to 12% of patients with MC have a family history of inflammatory bowel disease. Other associations include proton pump inhibitor use, cigarette smoking, HLA-DQ2/86, and possibly some gastrointestinal infections.}, } @article {pmid28760488, year = {2017}, author = {Ma, B and Pan, Q and Peppelenbosch, MP}, title = {Genetically Engineered Bacteria for Treating Human Disease.}, journal = {Trends in pharmacological sciences}, volume = {38}, number = {9}, pages = {763-764}, doi = {10.1016/j.tips.2017.07.001}, pmid = {28760488}, issn = {1873-3735}, mesh = {Bacteria/*genetics ; Bacterial Infections/*microbiology/*therapy ; Bacterial Physiological Phenomena ; Fecal Microbiota Transplantation ; Genetic Engineering ; Humans ; }, abstract = {Bacteria have now been harnessed to combat human diseases, especially to meet the challenge of antimicrobial resistance. Modulating the microbiome, particularly by genetically engineering the bacteria, has provided proof-of-concept as potential pharmacotherapy, but those involved in this field should engage in discussion as how to move forward.}, } @article {pmid28760163, year = {2017}, author = {Staley, C and Kaiser, T and Beura, LK and Hamilton, MJ and Weingarden, AR and Bobr, A and Kang, J and Masopust, D and Sadowsky, MJ and Khoruts, A}, title = {Stable engraftment of human microbiota into mice with a single oral gavage following antibiotic conditioning.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {87}, doi = {10.1186/s40168-017-0306-2}, pmid = {28760163}, issn = {2049-2618}, support = {R21 AI114722/AI/NIAID NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Anti-Bacterial Agents/*administration & dosage ; Bacteria/isolation & purification ; Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Germ-Free Life ; Humans ; Mice ; *Microbiota ; *Models, Animal ; }, abstract = {BACKGROUND: Human microbiota-associated (HMA) animal models relying on germ-free recipient mice are being used to study the relationship between intestinal microbiota and human disease. However, transfer of microbiota into germ-free animals also triggers global developmental changes in the recipient intestine, which can mask disease-specific attributes of the donor material. Therefore, a simple model of replacing microbiota into a developmentally mature intestinal environment remains highly desirable.

RESULTS: Here we report on the development of a sequential, three-course antibiotic conditioning regimen that allows sustained engraftment of intestinal microorganisms following a single oral gavage with human donor microbiota. SourceTracker, a Bayesian, OTU-based algorithm, indicated that 59.3 ± 3.0% of the fecal bacterial communities in treated mice were attributable to the donor source. This overall degree of microbiota engraftment was similar in mice conditioned with antibiotics and germ-free mice. Limited surveys of systemic and mucosal immune sites did not show evidence of immune activation following introduction of human microbiota.

CONCLUSIONS: The antibiotic treatment protocol described here followed by a single gavage of human microbiota may provide a useful, complimentary HMA model to that established in germ-free facilities. The model has the potential for further in-depth translational investigations of microbiota in a variety of human disease states.}, } @article {pmid28756077, year = {2017}, author = {Chong-Nguyen, C and Duboc, H and Sokol, H}, title = {[The gut microbiota, a new cardiovascular risk factor?].}, journal = {Presse medicale (Paris, France : 1983)}, volume = {46}, number = {7-8 Pt 1}, pages = {708-713}, doi = {10.1016/j.lpm.2017.06.005}, pmid = {28756077}, issn = {2213-0276}, mesh = {Anti-Bacterial Agents/therapeutic use ; Cardiovascular Diseases/*physiopathology ; Dysbiosis/*physiopathology/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Prebiotics ; Probiotics/therapeutic use ; Risk Factors ; }, abstract = {The gut microbiota is considered as our other "brain" and is implicated in several regulation of physiological metabolisms. The circulating level of TMAO, a metabolite of the gut microbiota, is directly correlated to the occurrence of cardiovascular events. Bile acids are protective metabolites against cardiovascular diseases through their anti-inflammatory and anti-atherogenic effects. The disturbance in the metabolism and the composition of the gut microbiota is called "dysbiosis". Understanding the implication of the gut microbiota and developing new therapeutic strategies are promising research fields to manage metabolic and cardiovascular diseases.}, } @article {pmid28748314, year = {2017}, author = {Cheng, YW and Fischer, M}, title = {The Present Status of Fecal Microbiota Transplantation and Its Value in the Elderly.}, journal = {Current treatment options in gastroenterology}, volume = {15}, number = {3}, pages = {349-362}, doi = {10.1007/s11938-017-0143-1}, pmid = {28748314}, issn = {1092-8472}, abstract = {OPINION STATEMENT: PURPOSE OF REVIEW: This article will review current literature describing fecal microbiota transplantation (FMT) in the treatment of various diseases, and its potential role in elderly patients (age ≥ 65 years).

RECENT FINDINGS: Research on FMT has blossomed in the last decade and its pivotal role in the treatment of recurrent Clostridium difficile infection (CDI) has been recognized by the American College of Gastroenterology in the latest guidelines. There is also emerging evidence that FMT may be beneficial in the treatment of severe and/or complicated CDI refractory to medical therapy, resulting in decreased rates of colectomy and mortality. In the elderly, CDI is associated with markedly higher rates of mortality and colectomy; outcomes are even worse when patients have underlying inflammatory bowel disease (IBD). While the majority of patients who receive FMT for CDI are older, only a handful of studies focused specifically on FMT treatment outcomes and safety in this age group. Current data corroborate the efficacy and safety profile of FMT, while also supporting its use for recurrent, severe, and/or complicated CDI in the elderly population. FMT is recommended for the treatment of recurrent, severe, and/or complicated CDI in patients older than 65 years of age. It may be prudent to offer FMT earlier in the disease course, possibly after just the second recurrence and for the first episode of severe CDI to avert complications including colectomy and end-organ failure that elderly patients are more prone to developing.}, } @article {pmid28747917, year = {2017}, author = {Li, M and Wang, B and Sun, X and Tang, Y and Wei, X and Ge, B and Tang, Y and Deng, Y and He, C and Yuan, J and Li, X}, title = {Upregulation of Intestinal Barrier Function in Mice with DSS-Induced Colitis by a Defined Bacterial Consortium Is Associated with Expansion of IL-17A Producing Gamma Delta T Cells.}, journal = {Frontiers in immunology}, volume = {8}, number = {}, pages = {824}, doi = {10.3389/fimmu.2017.00824}, pmid = {28747917}, issn = {1664-3224}, abstract = {Bacterial consortium transplantation (BCT) is a promising alternative to fecal microbiota transplantation in treating inflammatory bowel disease (IBD). Here, we showed that a defined bacterial consortium derived from healthy mice was able to enhance the intestinal barrier function of mice with dextran sulfate sodium (DSS)-induced colitis. Interestingly, we found that the bacterial consortium significantly promoted the expansion of IL-17A-producing γδT (γδT17) cells in colonic lamina propria, which was closely associated with changing of intestinal microbial composition. The increased IL-17A secretion upon treatment with microbial products derived from the bacterial consortium was accompanied with upregulation of TLR2 expression by γδT cells, and it might be responsible for the upregulation of mucosal barrier function through IL-17R-ACT1-mediated recovery of the disrupted occludin subcellular location. Changing of some specific microbial groups such as Bifidobacterium and Bacillus spp. was closely correlated with the promotion of TLR2+ γδT cells. Our results support that BCT can restore the alliance between commensal microbiota and intestinal γδT cells, which contributes to the improvement of intestinal barrier function. This study provides new insight into the development of bacteria transplantation therapy for the treatment of IBD.}, } @article {pmid28747056, year = {2017}, author = {Izquierdo Romero, M and Varela Trastoy, P and Mancebo Mata, A}, title = {Fecal transplantation as a treatment for Clostridium difficile infection in patients with ulcerative colitis.}, journal = {Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva}, volume = {109}, number = {9}, pages = {670}, doi = {10.17235/reed.2017.4941/2017}, pmid = {28747056}, issn = {1130-0108}, mesh = {Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; *Clostridium difficile ; Colitis, Ulcerative/complications/diagnostic imaging/*drug therapy ; Enterocolitis, Pseudomembranous/complications/drug therapy/*therapy ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Agents/therapeutic use ; Humans ; Infliximab/therapeutic use ; Mesalamine/therapeutic use ; Middle Aged ; }, abstract = {Clostridium difficile (CD) infection is currently the most frequent etiology of nosocomial diarrhea. Besides, its incidence is progressively increasing in ambulatory patients. Inflammatory bowel disease (IBD) is a risk factor of CD infection itself, but also due to the regular immunosuppressive treatment used in these patients. At the present time, fecal transplantation (FT) is a safe and cost-effective alternative if the previous antibiotic treatments have failed. Similar outcomes between patients with IBD and general population have been reported. We present a case of a patient with ulcerative colitis and recurrent CD infection successfully treated with FT.}, } @article {pmid28734127, year = {2017}, author = {Tandon, P and Madsen, K and Kao, D}, title = {Fecal microbiota transplantation for hepatic encephalopathy: Ready for prime time?.}, journal = {Hepatology (Baltimore, Md.)}, volume = {66}, number = {6}, pages = {1713-1715}, doi = {10.1002/hep.29396}, pmid = {28734127}, issn = {1527-3350}, mesh = {Clostridium difficile ; Enterocolitis, Pseudomembranous ; *Fecal Microbiota Transplantation ; Feces ; *Hepatic Encephalopathy ; Humans ; Microbiota ; }, } @article {pmid28733895, year = {2017}, author = {Doki, N and Suyama, M and Sasajima, S and Ota, J and Igarashi, A and Mimura, I and Morita, H and Fujioka, Y and Sugiyama, D and Nishikawa, H and Shimazu, Y and Suda, W and Takeshita, K and Atarashi, K and Hattori, M and Sato, E and Watakabe-Inamoto, K and Yoshioka, K and Najima, Y and Kobayashi, T and Kakihana, K and Takahashi, N and Sakamaki, H and Honda, K and Ohashi, K}, title = {Clinical impact of pre-transplant gut microbial diversity on outcomes of allogeneic hematopoietic stem cell transplantation.}, journal = {Annals of hematology}, volume = {96}, number = {9}, pages = {1517-1523}, doi = {10.1007/s00277-017-3069-8}, pmid = {28733895}, issn = {1432-0584}, mesh = {Acute Disease ; Adult ; Aged ; Allografts ; *Bacteroidetes/classification/genetics ; Disease-Free Survival ; Female ; *Firmicutes/classification/genetics ; *Gastrointestinal Microbiome ; *Graft vs Host Disease/genetics/microbiology/mortality ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Survival Rate ; }, abstract = {Post-transplant microbial diversity in the gastrointestinal tract is closely associated with clinical outcomes following allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the impact of the fecal microbiota before allo-HSCT. We analyzed fecal samples approximately 2 weeks before conditioning among 107 allo-HSCT recipients between 2013 and 2015. Microbial analysis was performed using 16S rRNA gene sequencing. Operational taxonomic unit-based microbial diversity was estimated by calculating the Shannon index. Patients were classified into three groups based on the diversity index: low (<2), intermediate (2, 3), and high (>3) diversity (18 (16.8%), 48 (44.9%), and 41 (38.3%) patients, respectively). There were no significant differences in the 20-month overall survival, cumulative incidence of relapse, and non-relapse mortality among three groups. The cumulative incidence of grade II to IV acute graft-versus-host disease (aGVHD) was similar among the three groups (low 55.6%; intermediate 35.4%; high 48.8%, p = 0.339, at day 100). Furthermore, we found no differences in the cumulative incidence of grade II to IV acute gastrointestinal GVHD among the three groups (low 38.9%; intermediate 21.3%; high 24.4%, p = 0.778, at day 100). Regarding the composition of microbiota before allo-HSCT, aGVHD patients showed a significantly higher abundance of phylum Firmicutes (p < 0.01) and a lower tendency for Bacteroidetes (p = 0.106) than non-aGVHD patients. Maintenance of Bacteroidetes throughout allo-HSCT may be a strategy to prevent aGVHD.}, } @article {pmid28728967, year = {2017}, author = {Galloway-Peña, J and Brumlow, C and Shelburne, S}, title = {Impact of the Microbiota on Bacterial Infections during Cancer Treatment.}, journal = {Trends in microbiology}, volume = {25}, number = {12}, pages = {992-1004}, doi = {10.1016/j.tim.2017.06.006}, pmid = {28728967}, issn = {1878-4380}, mesh = {Bacterial Infections/*complications ; Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Humans ; Microbiota/*immunology ; Neoplasms/*complications/*drug therapy ; }, abstract = {Patients being treated for cancer are at high risk for infectious complications, generally due to colonizing organisms that gain access to sterile sites via disrupted epithelial barriers. There is an emerging understanding that the ability of bacterial pathogens, including multidrug-resistant organisms, to colonize and subsequently infect humans is largely dependent on protective bacterial species present in the microbiome. Thus, herein we review recent studies demonstrating strong correlations between the microbiome of the oncology patient and infections occurring during chemotherapy. An increased knowledge of the interplay between potential pathogens, protective commensals, and the host immune system may facilitate the development of novel biomarkers or therapeutics that could help ameliorate the toll that infections take during the treatment of cancer.}, } @article {pmid28723262, year = {2017}, author = {Qazi, T and Amaratunga, T and Barnes, EL and Fischer, M and Kassam, Z and Allegretti, JR}, title = {The risk of inflammatory bowel disease flares after fecal microbiota transplantation: Systematic review and meta-analysis.}, journal = {Gut microbes}, volume = {8}, number = {6}, pages = {574-588}, doi = {10.1080/19490976.2017.1353848}, pmid = {28723262}, issn = {1949-0984}, mesh = {Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/*adverse effects ; Feces/microbiology ; Humans ; Inflammatory Bowel Diseases/*epidemiology/*etiology ; Risk ; Symptom Flare Up ; Treatment Outcome ; }, abstract = {Several studies have suggested worsening in inflammatory bowel disease (IBD) activity following fecal microbiota transplantation (FMT). We aimed to assess the risk of worsening in IBD activity following FMT. An electronic search was conducted using MEDLINE (1946-June 2016), EMBASE (1954-June 2016) and Cochrane Central Register of Controlled Trials (2016). Studies in which FMT was provided to IBD patients for IBD management or (Clostridium difficile infection) CDI treatment were included. The primary outcome was the rate of worsening in IBD activity.

RESULTS: Twenty-nine studies with 514 FMT-treated IBD patients were included. Range of follow up was 4 weeks to 3 y. The pooled rate of IBD worsening was 14.9% (95% CI 10-21%). Heterogeneity was detected: I2 D 52.1%, Cochran Q test D 58.1, p D 0.01. A priori subgroup analyses were performed. Although not significant, the pooled rate of worsening in IBD activity following FMT for CDI (22.7% (95% CI: 13-36%)) was higher compared with FMT for IBD (11.1% (95% CI 7-17%)). Rates of worsening in IBD after lower GI FMT delivery revealed a higher rate of worsening in IBD activity (16.5% (95% CI: 11-24%)) compared with upper GI delivery (5.6% (95% CI: 2-16%)). Rates of worsening in high quality studies and randomized controls trials (RCTS) suggested a marginal risk of worsening in IBD activity (4.6%, (95% CI: 1.8-11%). Rates of IBD worsening are overall marginal across high quality RCTS. It is unknown if the FMT itself led to the worsening of IBD in this small fraction or if this represents alternative etiologies.}, } @article {pmid28721078, year = {2017}, author = {Chong, Y and Shimoda, S and Miyake, N and Aoki, T and Ito, Y and Kamimura, T and Shimono, N}, title = {Incomplete recovery of the fecal flora of hematological patients with neutropenia and repeated fluoroquinolone prophylaxis.}, journal = {Infection and drug resistance}, volume = {10}, number = {}, pages = {193-199}, doi = {10.2147/IDR.S133333}, pmid = {28721078}, issn = {1178-6973}, abstract = {BACKGROUND: Routine fluoroquinolone prophylaxis in neutropenic patients with hematological malignancies is still controversial, because of antibiotic resistance concerns. The recovery of the fecal microbiota to the initial composition in patients receiving multiple courses of quinolone prophylaxis and repeated chemotherapy has not been evaluated.

METHODS: We prospectively examined the changes in the fecal bacterial composition before and after levofloxacin prophylaxis. A sequential observation of bacterial resistance in patients receiving multiple prophylactic courses was also conducted.

RESULTS: In this trial, 68 cases, including (35 with the first course and 33 with the second and subsequent courses) were registered. The disappearance of quinolone-susceptible (QS) Entero-bacteriaceae and dominant emergence of quinolone-resistant (QR) coagulase negative staphylococci (CNS) and QR Enterococci were observed after the first prophylaxis. The detection of QS Enterobacteriaceae was recovered before the second and subsequent courses to a level of the initial composition (28/35 samples, 80.0% before the first course vs 23/33 samples, 69.7% before the second and subsequent courses, P=0.41). In contrast, the detection rate of QR CNS and Enterococci significantly increased at the second and subsequent courses, even before prophylaxis (8/35 samples, 22.9% before the first course vs 20/33 samples, 60.6% before the second and subsequent courses, P=0.003). The incomplete recovery of the initial bacterial composition was associated with a prophylactic interval of within 30 days. Of the patients receiving multiple prophylactic courses, six had QR Escherichia coli, including extended-spectrum β-lactamase (ESBL) producers, at the first course, and four (66.3%) of the six patients had persistent detection of QR E. coli at the second course.

CONCLUSION: In patients receiving multiple courses of prophylactic quinolone, along with a common chemotherapy schedule, newly emergent resistant bacteria could be frequently persistent in their fecal flora.}, } @article {pmid28719392, year = {2017}, author = {Volkmann, ER}, title = {Intestinal microbiome in scleroderma: recent progress.}, journal = {Current opinion in rheumatology}, volume = {29}, number = {6}, pages = {553-560}, doi = {10.1097/BOR.0000000000000429}, pmid = {28719392}, issn = {1531-6963}, mesh = {Gastrointestinal Microbiome/*immunology ; Homeostasis/immunology ; Humans ; Inflammation/immunology/microbiology ; Scleroderma, Systemic/*microbiology ; Symbiosis/immunology ; }, abstract = {PURPOSE OF REVIEW: Our evolving understanding of how gut microbiota affects immune function and homeostasis has led many investigators to explore the potentially pathologic role of gut microbiota in autoimmune diseases. This review will discuss the rapidly advancing field of microbiome research in systemic sclerosis (SSc), an incurable autoimmune disease with significant gastrointestinal morbidity and mortality.

RECENT FINDINGS: Recent reports have identified common perturbations in gut microbiota across different SSc cohorts. Compared with healthy controls, patients with SSc have decreased abundance of beneficial commensal genera (e.g. Faecalibacterium, Clostridium and Bacteroides) and increased abundance of pathbiont genera (e.g. Fusobacterium, Prevotella and Erwinia). Certain genera may protect against (e.g. Bacteroides, Clostridium, and Lactobacillus), or conversely exacerbate (e.g. Fusobacterium and Prevotella) gastrointestinal symptoms in SSc. These genera represent potential targets to avert or treat gastrointestinal dysfunction in SSc.

SUMMARY: Emerging evidence suggests that alterations in gut microbiota exist in the SSc disease state; however, future basic and clinical studies are needed to ascertain the mechanism by which these alterations perpetuate inflammation and fibrosis in SSc. Therapeutic trials are also needed to investigate whether dietary interventions or fecal transplantation can restore the gut microbial balance and improve health outcomes in SSc. VIDEO ABSTRACT: http://links.lww.com/COR/A38.}, } @article {pmid28714946, year = {2017}, author = {Innes, AJ and Mullish, BH and Fernando, F and Adams, G and Marchesi, JR and Apperley, JF and Brannigan, E and Davies, F and Pavlů, J}, title = {Faecal microbiota transplant: a novel biological approach to extensively drug-resistant organism-related non-relapse mortality.}, journal = {Bone marrow transplantation}, volume = {52}, number = {10}, pages = {1452-1454}, doi = {10.1038/bmt.2017.151}, pmid = {28714946}, issn = {1476-5365}, mesh = {Allografts ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage ; Asparaginase/administration & dosage ; *Bacteria/growth & development/isolation & purification ; Daunorubicin/administration & dosage ; *Drug Resistance, Bacterial ; Fatal Outcome ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; *Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Methotrexate/administration & dosage ; Middle Aged ; *Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*therapy ; Prednisolone/administration & dosage ; Vincristine/administration & dosage ; }, } @article {pmid28714344, year = {2018}, author = {Barfield, E and Small, L and Navallo, L and Solomon, A}, title = {Going to the Bank: Fecal Microbiota Transplantation in Pediatrics.}, journal = {Clinical pediatrics}, volume = {57}, number = {4}, pages = {481-483}, doi = {10.1177/0009922817721159}, pmid = {28714344}, issn = {1938-2707}, } @article {pmid28714089, year = {2017}, author = {Mullish, BH and McDonald, JAK and Thursz, MR and Marchesi, JR}, title = {Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial.}, journal = {Hepatology (Baltimore, Md.)}, volume = {66}, number = {4}, pages = {1354-1355}, doi = {10.1002/hep.29369}, pmid = {28714089}, issn = {1527-3350}, mesh = {*Fecal Microbiota Transplantation ; Feces ; *Hepatic Encephalopathy ; Humans ; Microbiota ; }, } @article {pmid28714029, year = {2017}, author = {Yang, M and Fukui, H and Eda, H and Kitayama, Y and Hara, K and Kodani, M and Tomita, T and Oshima, T and Watari, J and Miwa, H}, title = {Involvement of gut microbiota in the association between gastrointestinal motility and 5‑HT expression/M2 macrophage abundance in the gastrointestinal tract.}, journal = {Molecular medicine reports}, volume = {16}, number = {3}, pages = {3482-3488}, doi = {10.3892/mmr.2017.6955}, pmid = {28714029}, issn = {1791-3004}, mesh = {Animals ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Gastrointestinal Motility ; Gastrointestinal Tract/cytology/*microbiology/*physiology ; Germ-Free Life ; Intestinal Mucosa/metabolism ; Lectins, C-Type/metabolism ; Macrophages/*metabolism ; Male ; Mannose-Binding Lectins/metabolism ; Mice, Inbred ICR ; Organ Specificity ; Receptors, Cell Surface/metabolism ; Serotonin/*metabolism ; Time Factors ; }, abstract = {Serotonin (5‑hydroxytryptamine; 5‑HT) may be a key player in gastrointestinal (GI) motility and the GI immune system. In the present study, the effect of gut microbiota on the association between GI motility, and 5‑HT expression and macrophage abundance in the GI tract was examined. Germ‑free (GF) mice (6 weeks old) were orally administered a fecal bacterial suspension prepared from specific pathogen‑free mice and their GI tissues were evaluated 4 weeks later. The expression of 5‑HT and mannose receptor (MR) was examined by immunohistochemistry, and GI transit time (GITT) was measured by administration of carmine red solution. The numbers of 5‑HT‑positive endocrine cells and muscularis MR‑positive macrophages were significantly increased in the upper GI and colon of GF mice subjected to fecal transplantation (FT) compared with control GF mice without FT. GITT was significantly decreased in GF mice subjected to FT compared with GF mice without FT, and negatively correlated with the numbers of 5‑HT‑positive cells in the upper GI and muscularis MR‑positive macrophages throughout the GI tract. The numbers of 5‑HT‑positive endocrine cells and muscularis MR‑positive macrophages were significantly correlated throughout the GI tract. The present results suggest that the gut microbiota is involved in the association between accelerated GI motility and induction of the 5‑HT/muscularis MR‑positive macrophage axis in the GI tract.}, } @article {pmid28711782, year = {2017}, author = {Blum, HE}, title = {The human microbiome.}, journal = {Advances in medical sciences}, volume = {62}, number = {2}, pages = {414-420}, doi = {10.1016/j.advms.2017.04.005}, pmid = {28711782}, issn = {1898-4002}, mesh = {Bacteria ; *Bacterial Physiological Phenomena ; Biodiversity ; *Disease ; Humans ; *Microbiota ; }, abstract = {Until recently, human microbiology was based on the identification of single microbes, such as bacteria, fungi and viruses, frequently isolated from patients with acute or chronic infections. Novel culture-independent molecular biochemical analyses (genomics, transcriptomics, proteomics, metabolomics) allow today to detect and classify the diverse microorganisms in a given ecosystem (microbiota), such as the gastrointestinal tract, the skin, the airway system, the urogenital tract and others, and to assess all genomes in these ecosystems (microbiome) as well as their gene products. These analyses revealed that each individual has its own microbiota that plays a role in health and disease. In addition, they greatly contributed to the recent advances in the understanding of the pathogenesis of a wide range of human diseases. It is to be expected that these new insights will translate into diagnostic, therapeutic and preventive measures in the context of personalized/precision medicine.}, } @article {pmid28708089, year = {2017}, author = {Uebanso, T and Kano, S and Yoshimoto, A and Naito, C and Shimohata, T and Mawatari, K and Takahashi, A}, title = {Effects of Consuming Xylitol on Gut Microbiota and Lipid Metabolism in Mice.}, journal = {Nutrients}, volume = {9}, number = {7}, pages = {}, doi = {10.3390/nu9070756}, pmid = {28708089}, issn = {2072-6643}, mesh = {Animals ; Anti-Bacterial Agents/administration & dosage ; Bacteria/classification/genetics ; DNA, Bacterial/analysis ; *Diet ; Diet, High-Fat ; Drinking ; Dyslipidemias/drug therapy/etiology ; Electrophoresis/methods ; Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Glucose Tolerance Test ; Lipid Metabolism/*drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Sequence Analysis, DNA ; *Sweetening Agents ; Xylitol/administration & dosage/*pharmacology/therapeutic use ; }, abstract = {The sugar alcohol xylitol inhibits the growth of some bacterial species including Streptococcus mutans. It is used as a food additive to prevent caries. We previously showed that 1.5-4.0 g/kg body weight/day xylitol as part of a high-fat diet (HFD) improved lipid metabolism in rats. However, the effects of lower daily doses of dietary xylitol on gut microbiota and lipid metabolism are unclear. We examined the effect of 40 and 200 mg/kg body weight/day xylitol intake on gut microbiota and lipid metabolism in mice. Bacterial compositions were characterized by denaturing gradient gel electrophoresis and targeted real-time PCR. Luminal metabolites were determined by capillary electrophoresis electrospray ionization time-of-flight mass spectrometry. Plasma lipid parameters and glucose tolerance were examined. Dietary supplementation with low- or medium-dose xylitol (40 or 194 mg/kg body weight/day, respectively) significantly altered the fecal microbiota composition in mice. Relative to mice not fed xylitol, the addition of medium-dose xylitol to a regular and HFD in experimental mice reduced the abundance of fecal Bacteroidetes phylum and the genus Barnesiella, whereas the abundance of Firmicutes phylum and the genus Prevotella was increased in mice fed an HFD with medium-dose dietary xylitol. Body composition, hepatic and serum lipid parameters, oral glucose tolerance, and luminal metabolites were unaffected by xylitol consumption. In mice, 40 and 194 mg/kg body weight/day xylitol in the diet induced gradual changes in gut microbiota but not in lipid metabolism.}, } @article {pmid28707337, year = {2017}, author = {Quraishi, MN and Widlak, M and Bhala, N and Moore, D and Price, M and Sharma, N and Iqbal, TH}, title = {Systematic review with meta-analysis: the efficacy of faecal microbiota transplantation for the treatment of recurrent and refractory Clostridium difficile infection.}, journal = {Alimentary pharmacology & therapeutics}, volume = {46}, number = {5}, pages = {479-493}, doi = {10.1111/apt.14201}, pmid = {28707337}, issn = {1365-2036}, support = {EME/13/179/01//Department of Health/United Kingdom ; }, mesh = {Clostridium Infections/*therapy ; Clostridium difficile/*isolation & purification ; Cross Infection ; Diarrhea/etiology ; Fecal Microbiota Transplantation/*methods ; Humans ; Randomized Controlled Trials as Topic ; Treatment Outcome ; Vancomycin/therapeutic use ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is the commonest nosocomial cause of diarrhoea. Faecal microbiota transplantation (FMT) is an approved treatment for recurrent or refractory CDI but there is uncertainty about its use.

AIM: To evaluate the efficacy of FMT in treating recurrent and refractory CDI and investigate outcomes from modes of delivery and preparation.

METHODS: A systematic review and meta-analysis was performed. MEDLINE, EMBASE, CINAHL, Cochrane Library, trial registers and conference proceedings were searched. Studies on FMT in recurrent and refractory CDI were included. The primary outcome was clinical resolution with subgroup analyses of modes of delivery and preparation. Random effects meta-analyses were used to combine data.

RESULTS: Thirty seven studies were included; seven randomised controlled trials and 30 case series. FMT was more effective than vancomycin (RR: 0.23 95%CI 0.07-0.80) in resolving recurrent and refractory CDI. Clinical resolution across all studies was 92% (95%CI 89%-94%). A significant difference was observed between lower GI and upper GI delivery of FMT 95% (95%CI 92%-97%) vs 88% (95%CI 82%-94%) respectively (P=.02). There was no difference between fresh and frozen FMT 92% (95%CI 89%-95%) vs 93% (95%CI 87%-97%) respectively (P=.84). Administering consecutive courses of FMT following failure of first FMT resulted in an incremental effect. Donor screening was consistent but variability existed in recipient preparation and volume of FMT. Serious adverse events were uncommon.

CONCLUSION: Faecal microbiota transplantation is an effective treatment for recurrent and refractory Clostridium difficile infection, independent of preparation and route of delivery.}, } @article {pmid28702022, year = {2017}, author = {Ji, SK and Yan, H and Jiang, T and Guo, CY and Liu, JJ and Dong, SZ and Yang, KL and Wang, YJ and Cao, ZJ and Li, SL}, title = {Preparing the Gut with Antibiotics Enhances Gut Microbiota Reprogramming Efficiency by Promoting Xenomicrobiota Colonization.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {1208}, doi = {10.3389/fmicb.2017.01208}, pmid = {28702022}, issn = {1664-302X}, abstract = {Gut microbiota plays multiple important roles in intestinal and physiological homeostasis, and using fecal microbiota transplantation (FMT) to reprogram gut microbiota has demonstrated promise for redressing intestinal and physiological disorders. This study tested the alterations in reprogramming efficiency caused by different gut preparation procedures and explored the associated underlying mechanisms. We prepared the guts of mice for FMT by administering one of the three most-clinically used pretreatments [antibiotics, bowel cleansing (BC) solution, or no pretreatment], and we found that preparing the gut with antibiotics induced a more efficient modification of the gut bacterial community than was induced by either of the other two pretreatment types. The increased efficiency of antibiotic treatment appeared to occur via increasing the xenomicrobiota colonization. Further analysis demonstrated that antibiotic treatment of mice induced intestinal microbiota disruption, mostly by expelling antibiotic-sensitive bacteria, while the indigenous microbiota was maintained after treatment with a BC solution or in the absence of pretreatment. The amount of antibiotic-resistant bacteria increased shortly after antibiotics usage but subsequently decreased after FMT administration. Together, these results suggest that FMT relied on the available niches in the intestinal mucosa and that preparing the gut with antibiotics facilitated xenomicrobiota colonization in the intestinal mucosa, which thus enhanced the overall gut microbiota reprogramming efficiency.}, } @article {pmid28695658, year = {2017}, author = {Laffin, M and Madsen, KL}, title = {Fecal Microbial Transplantation in Inflammatory Bowel Disease: A Movement Too Big to Be Ignored.}, journal = {Clinical pharmacology and therapeutics}, volume = {102}, number = {4}, pages = {588-590}, doi = {10.1002/cpt.747}, pmid = {28695658}, issn = {1532-6535}, mesh = {Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; Inflammatory Bowel Diseases/*therapy ; Randomized Controlled Trials as Topic ; Remission Induction/*methods ; Treatment Outcome ; }, abstract = {The development of new therapies for inflammatory bowel disease is plagued by high costs, potential side effects, and variable levels of effectiveness. Fecal microbial transplant in inflammatory bowel diseases can offer an alternative to traditionally developed pharmacologic therapies and has demonstrated the ability to induce disease remission in randomized control trials. However, questions remain about the ultimate role of this therapy in disease management, including long term safety, and the optimal composition of transplanted stool.}, } @article {pmid28685630, year = {2017}, author = {Khajah, MA}, title = {The potential role of fecal microbiota transplantation in the treatment of inflammatory Bowel disease.}, journal = {Scandinavian journal of gastroenterology}, volume = {52}, number = {11}, pages = {1172-1184}, doi = {10.1080/00365521.2017.1347812}, pmid = {28685630}, issn = {1502-7708}, mesh = {Animals ; Dysbiosis/microbiology/therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*microbiology/*therapy ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of an unknown etiology. Its pathogenesis involves an interplay of infectious, genetic, environmental, and immunological factors. The current therapeutic options have various limitations in terms of cost, side effect profile, and the development of drug resistance and dependence. Therefore, there is a need to develop future therapeutic options which are safe and effective to control the inflammatory process. This review focuses in a method for the administration of fecal matters (which contains a mixture of various commensals) from a healthy donor to the inflamed colon called fecal microbiota transplantation (FMT) aiming to correct the underlying dysbiosis in the gut as one of the major driving force for the inflammatory process. IBD patients have reduced number of protective (e.g., clostridia and bacteroids) and increased number of pathogenic (e.g., adhesive invasive E. coli and mycobacterium avium paratuberculosis) commensals, and this method is aimed to shift these changes in the gut. Recent studies from animal models and clinical trials suggest promising effects of this method in treating patients with IBD, but more studies are urgently needed to confirm its efficacy and safety, since the etiology of this chronic inflammatory disease is not fully understood and caution should be taken when transplanting fecal matters between individuals which might transfer other infectious organisms and diseases.}, } @article {pmid28684845, year = {2017}, author = {He, Z and Li, P and Zhu, J and Cui, B and Xu, L and Xiang, J and Zhang, T and Long, C and Huang, G and Ji, G and Nie, Y and Wu, K and Fan, D and Zhang, F}, title = {Multiple fresh fecal microbiota transplants induces and maintains clinical remission in Crohn's disease complicated with inflammatory mass.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {4753}, doi = {10.1038/s41598-017-04984-z}, pmid = {28684845}, issn = {2045-2322}, abstract = {The ancient Chinese medical literature, as well as our prior clinical experience, suggests that fecal microbiota transplantation (FMT) could treat the inflammatory mass. We aimed to evaluate the efficacy and safety of multiple fresh FMTs for Crohn's disease (CD) complicated with intraabdominal inflammatory mass. The "one-hour FMT protocol" was followed in all patients. Twenty-five patients were diagnosed with CD and related inflammatory mass by CT or MRI. All patients received the initial FMT followed by repeated FMTs every 3 months. The primary endpoint was clinical response (improvement and remission) and sustained clinical remission at 12 months. Secondary endpoints were improvement in size of phegmon/abscess based upon cross-sectional imaging and safety of FMT. 68.0% (17/25) and 52.0% (13/25) of patients achieved clinical response and clinical remission at 3 months post the initial FMT, respectively. The proportion of patients at 6 months, 12 months and 18 months achieving sustained clinical remission with sequential FMTs was 48.0% (12/25), 32.0% (8/25) and 22.7% (5/22), respectively. 9.5% (2/21) of patients achieved radiological healing and 71.4% (15/21) achieved radiological improvement. No severe adverse events related to FMT were observed. This pragmatic study suggested that sequential fresh FMTs might be a promising, safe and effective therapy to induce and maintain clinical remission in CD with intraabdominal inflammatory mass.}, } @article {pmid28682224, year = {2017}, author = {Debré, P}, title = {[Challenges set by the microbiota].}, journal = {Biologie aujourd'hui}, volume = {211}, number = {1}, pages = {19-28}, doi = {10.1051/jbio/2017012}, pmid = {28682224}, issn = {2105-0686}, mesh = {Animals ; Digestion/physiology ; Disease/*etiology ; Dysbiosis/diet therapy/etiology/microbiology ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Tract/immunology/microbiology ; Humans ; Immune System/physiology ; Microbiota/*physiology ; Prebiotics/administration & dosage ; Probiotics/administration & dosage ; Symbiosis/physiology ; }, abstract = {The microbiota designates the various flora of commensal microbes of living species. Most research in human focusing mainly on the intestinal microbiota, we will limit ourselves to its description and role in physiology and pathology. The intestinal microbiota acts on digestion and the immune system. It seems responsible, at least in part, for obesity, digestive cancers, several autoimmune and allergic pathologies, and pathologies of the nervous system. The role of prebiotics, probiotics, xenobiotics and stool transplantations will be discussed.}, } @article {pmid28677158, year = {2017}, author = {Shen, Z and Zhu, C and Quan, Y and Yuan, W and Wu, S and Yang, Z and Luo, W and Tan, B and Wang, X}, title = {Update on intestinal microbiota in Crohn's disease 2017: Mechanisms, clinical application, adverse reactions, and outlook.}, journal = {Journal of gastroenterology and hepatology}, volume = {32}, number = {11}, pages = {1804-1812}, doi = {10.1111/jgh.13861}, pmid = {28677158}, issn = {1440-1746}, mesh = {Clostridium Infections/therapy ; Crohn Disease/immunology/*microbiology/*therapy ; Dysbiosis ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Probiotics/administration & dosage ; }, abstract = {The pathogenesis of Crohn's disease (CD) is complex, and it is thought to be associated with the environment, immune, hereditary, microbe, and other factors. If the balance between the host and the intestinal microbes in CD patients was broken, immune-inflammatory response of susceptible individuals might be triggered. Probiotics could improve the intestinal microbial flora balance and treat human effectively. There are several new mechanisms that might explain the role of probiotics. Fecal microbiota transplantation (FMT) is becoming more and more attractive in treating a large amount of digestive system diseases that are related to the dysbiosis of intestinal microbiota. FMT has been widely used in recurrent Clostridium difficile infection. More and more attention has been paid on the clinical application of FMT in CD, while the exact mechanism is still a mystery. So in this review, we explore the mechanism, clinical application, and adverse reactions of intestinal microbiota in CD so that we can use the tool to cure more diseases. Enteric microbiota leads to new therapeutic strategies for CD.}, } @article {pmid28675277, year = {2016}, author = {Frossard, JL and Moradpour, D}, title = {.}, journal = {Revue medicale suisse}, volume = {12}, number = {528}, pages = {1403}, pmid = {28675277}, issn = {1660-9379}, mesh = {*Fecal Microbiota Transplantation ; }, } @article {pmid28672320, year = {2017}, author = {Gupta, A and Khanna, S}, title = {Fecal Microbiota Transplantation.}, journal = {JAMA}, volume = {318}, number = {1}, pages = {102}, doi = {10.1001/jama.2017.6466}, pmid = {28672320}, issn = {1538-3598}, mesh = {*Fecal Microbiota Transplantation/adverse effects ; Humans ; }, } @article {pmid28672282, year = {2017}, author = {Ma, GK and Brensinger, CM and Wu, Q and Lewis, JD}, title = {Increasing Incidence of Multiply Recurrent Clostridium difficile Infection in the United States: A Cohort Study.}, journal = {Annals of internal medicine}, volume = {167}, number = {3}, pages = {152-158}, doi = {10.7326/M16-2733}, pmid = {28672282}, issn = {1539-3704}, mesh = {Adolescent ; Adult ; Clostridium Infections/*epidemiology/therapy ; *Clostridium difficile ; Fecal Microbiota Transplantation ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Recurrence ; Retrospective Studies ; Risk Factors ; United States/epidemiology ; Young Adult ; }, abstract = {Background: Clostridium difficile infection (CDI), the most common health care-associated infection, often recurs. Fecal microbiota transplantation is increasingly used to treat multiply recurrent CDI (mrCDI).

Objective: To determine whether the incidence of mrCDI is increasing in proportion to CDI and to identify risk factors for mrCDI.

Design: Retrospective cohort study.

Setting: United States.

Participants: 38 911 718 commercially insured patients in the OptumInsight Clinformatics Database, of whom 45 341 developed CDI.

Measurements: Age- and sex-standardized incidence rates for CDI and mrCDI.

Results: From 2001 to 2012, the annual incidence of CDI and mrCDI per 1000 person-years increased by 42.7% (from 0.4408 to 0.6289 case) and 188.8% (from 0.0107 to 0.0309 case), respectively. The increase in mrCDI incidence was independent of known risk factors for CDI. Those who developed mrCDI were older (median age, 56.0 vs. 49.0 years; adjusted odds ratio [aOR] per 10-year increase in age, 1.25 [95% CI, 1.21 to 1.29]) and were more likely to be female (63.8% vs. 58.7%; aOR, 1.24 [CI, 1.11 to 1.38]) and to have used antibiotics (72.3% vs. 58.8%; aOR, 1.79 [CI, 1.59 to 2.01]), proton-pump inhibitors (24.6% vs. 18.2%; aOR, 1.14 [CI, 1.01 to 1.29]), or corticosteroids (18.3% vs. 13.7%; aOR, 1.15 [CI, 1.00 to 1.32]) within 90 days of CDI diagnosis. Chronic kidney disease (10.4% vs. 5.6%; aOR, 1.49 [CI, 1.24 to 1.80]) and diagnosis in a nursing home (2.1% vs. 0.6%; aOR, 1.99 [CI, 1.34 to 2.93]) were also associated with increased risk for mrCDI.

Limitation: The primary analyses included only commercially insured patients in the United States.

Conclusion: Relative to CDI, mrCDI incidence has disproportionately increased, indicating a rising demand for mrCDI therapies.

Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases and National Institute of Allergy and Infectious Diseases.}, } @article {pmid28656322, year = {2017}, author = {Thaiss, CA and Elinav, E}, title = {The remedy within: will the microbiome fulfill its therapeutic promise?.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {95}, number = {10}, pages = {1021-1027}, doi = {10.1007/s00109-017-1563-z}, pmid = {28656322}, issn = {1432-1440}, mesh = {Animals ; Clostridium Infections/microbiology/*therapy ; *Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {The last decade of research has witnessed a tremendous upsurge in our understanding of the intestinal microbiome and its role in a large range of human diseases, which has incited hopes for a rapid clinical utilization of the new insights for the development of microbiome-based therapies. Nonetheless, only a single microbiome-targeted therapy has so far found its way into clinical routine: fecal microbiota transplantation for patients suffering from recurrent Clostridium difficile infections. Herein, we discuss the current hopes, advances, challenges, and obstacles for translating basic microbiome research into therapeutic applications for a larger number of diseases and provide an outline of how such clinical applications might emerge.}, } @article {pmid28652796, year = {2017}, author = {Lane, ER and Zisman, TL and Suskind, DL}, title = {The microbiota in inflammatory bowel disease: current and therapeutic insights.}, journal = {Journal of inflammation research}, volume = {10}, number = {}, pages = {63-73}, doi = {10.2147/JIR.S116088}, pmid = {28652796}, issn = {1178-7031}, abstract = {Inflammatory bowel disease is a heterogeneous group of chronic disorders that result from the interaction of the intestinal immune system with the gut microbiome. Until recently, most investigative efforts and therapeutic breakthroughs were centered on understanding and manipulating the altered mucosal immune response that characterizes these diseases. However, more recent studies have highlighted the important role of environmental factors, and in particular the microbiota, in disease onset and disease exacerbation. Advances in genomic sequencing technology and bioinformatics have facilitated an explosion of investigative inquiries into the composition and function of the intestinal microbiome in health and disease and have advanced our understanding of the interplay between the gut microbiota and the host immune system. The gut microbiome is dynamic and changes with age and in response to diet, antibiotics and other environmental factors, and these alterations in the microbiome contribute to disease onset and exacerbation. Strategies to manipulate the microbiome through diet, probiotics, antibiotics or fecal microbiota transplantation may potentially be used therapeutically to influence modulate disease activity. This review will characterize the factors involved in the development of the intestinal microbiome and will describe the typical alterations in the microbiota that are characteristic of inflammatory bowel disease. Additionally, this manuscript will summarize the early but promising literature on the role of the gut microbiota in the pathogenesis of inflammatory bowel disease with implications for utilizing this data for diagnostic or therapeutic application in the clinical management of patients with these diseases.}, } @article {pmid28652664, year = {2017}, author = {Halkjær, SI and Boolsen, AW and Günther, S and Christensen, AH and Petersen, AM}, title = {Can fecal microbiota transplantation cure irritable bowel syndrome?.}, journal = {World journal of gastroenterology}, volume = {23}, number = {22}, pages = {4112-4120}, doi = {10.3748/wjg.v23.i22.4112}, pmid = {28652664}, issn = {2219-2840}, mesh = {Fecal Microbiota Transplantation/adverse effects ; Feces/*microbiology ; Humans ; Intestines/*microbiology ; Irritable Bowel Syndrome/diagnosis/microbiology/*therapy ; Remission Induction ; Treatment Outcome ; }, abstract = {AIM: To verify the utility of treatment with fecal microbiota transplantation (FMT) in patients with irritable bowel syndrome (IBS).

METHODS: We searched EMBASE, Cochrane Library and PubMed in March, 2017. The reviewed literature was based on two systematic searches in each of the databases. The MeSH terms used were IBS and fecal microbiota transplantation and the abbreviations IBS and FMT. Reference lists from the articles were reviewed to identify additional pertinent articles.

RESULTS: A total of six conference abstracts, one case report, one letter to the editor, and one clinical review were included. In the final analysis, treatment of 48 patients was evaluated. Treatment revealed an improvement in 58% of cases. The varying structure of the nine included studies must be taken into consideration.

CONCLUSION: Data on FMT and IBS are too limited to draw sufficient conclusions. Standardized double blinded randomized clinical trials need to be carried out to evaluate the effect of FMT on IBS.}, } @article {pmid28649413, year = {2017}, author = {Kumar, R and Yi, N and Zhi, D and Eipers, P and Goldsmith, KT and Dixon, P and Crossman, DK and Crowley, MR and Lefkowitz, EJ and Rodriguez, JM and Morrow, CD}, title = {Identification of donor microbe species that colonize and persist long term in the recipient after fecal transplant for recurrent Clostridium difficile.}, journal = {NPJ biofilms and microbiomes}, volume = {3}, number = {}, pages = {12}, doi = {10.1038/s41522-017-0020-7}, pmid = {28649413}, issn = {2055-5008}, support = {P30 AI027767/AI/NIAID NIH HHS/United States ; P30 CA013148/CA/NCI NIH HHS/United States ; UL1 TR001417/TR/NCATS NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation has been shown to be an effective treatment for patients with recurrent C. difficile colitis. Although fecal microbiota transplantation helps to re-establish a normal gut function in patients, the extent of the repopulation of the recipient microbial community varies. To further understand this variation, it is important to determine the fate of donor microbes in the patients following fecal microbiota transplantation. We have developed a new method that utilizes the unique single nucleotide variants of gut microbes to accurately identify microbes in paired fecal samples from the same individual taken at different times. Using this method, we identified transplant donor microbes in seven recipients 3-6 months after fecal microbiota transplantation; in two of these fecal microbiota transplantation, we were able to identify donor microbes that persist in recipients up to 2 years post-fecal microbiota transplantation. Our study provides new insights into the dynamics of the reconstitution of the gastrointestinal microbe community structure following fecal microbiota transplantation.}, } @article {pmid28646951, year = {2017}, author = {Chen, B and Avinashi, V and Dobson, S}, title = {Fecal microbiota transplantation for recurrent clostridium difficile infection in children.}, journal = {The Journal of infection}, volume = {74 Suppl 1}, number = {}, pages = {S120-S127}, doi = {10.1016/S0163-4453(17)30202-5}, pmid = {28646951}, issn = {1532-2742}, mesh = {Adolescent ; Child ; Child, Preschool ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/adverse effects/*methods/*utilization ; Humans ; Infant ; *Secondary Prevention ; Treatment Outcome ; Young Adult ; }, abstract = {Fecal microbiota transplantation (FMT) is a relatively simple, promising treatment for recurrent Clostridium difficile infection. While there are a wide variety of approaches including mode of delivery, the results are nonetheless encouraging, even amongst younger children. Experience with FMT in the pediatric population is increasing, showing similar success compared to adults. This article will provide an overview of C. difficile infection along with review of the rationale, methods and complications of FMT including the current experience of FMT in children.}, } @article {pmid28637803, year = {2017}, author = {Fischer, DD and Kandasamy, S and Paim, FC and Langel, SN and Alhamo, MA and Shao, L and Chepngeno, J and Miyazaki, A and Huang, HC and Kumar, A and Rajashekara, G and Saif, LJ and Vlasova, AN}, title = {Protein Malnutrition Alters Tryptophan and Angiotensin-Converting Enzyme 2 Homeostasis and Adaptive Immune Responses in Human Rotavirus-Infected Gnotobiotic Pigs with Human Infant Fecal Microbiota Transplant.}, journal = {Clinical and vaccine immunology : CVI}, volume = {24}, number = {8}, pages = {}, doi = {10.1128/CVI.00172-17}, pmid = {28637803}, issn = {1556-679X}, support = {R01 AI099451/AI/NIAID NIH HHS/United States ; }, mesh = {*Adaptive Immunity ; Animals ; B-Lymphocytes/immunology ; Diarrhea/virology ; Fecal Microbiota Transplantation ; Germ-Free Life ; Homeostasis ; Humans ; Immunoglobulin A/immunology ; Infant ; Microbiota ; Peptidyl-Dipeptidase A/blood/*metabolism ; Protein Deficiency/*complications ; Rotavirus/immunology/isolation & purification/physiology ; Rotavirus Infections/*complications/immunology/metabolism ; Sus scrofa ; T-Lymphocytes/immunology ; Tryptophan/blood/*metabolism ; }, abstract = {Malnutrition leads to increased morbidity and is evident in almost half of all deaths in children under the age of 5 years. Mortality due to rotavirus diarrhea is common in developing countries where malnutrition is prevalent; however, the relationship between malnutrition and rotavirus infection remains unclear. In this study, gnotobiotic pigs transplanted with the fecal microbiota of a healthy 2-month-old infant were fed protein-sufficient or -deficient diets and infected with virulent human rotavirus (HRV). After human rotavirus infection, protein-deficient pigs had decreased human rotavirus antibody titers and total IgA concentrations, systemic T helper (CD3+ CD4+) and cytotoxic T (CD3+ CD8+) lymphocyte frequencies, and serum tryptophan and angiotensin I-converting enzyme 2. Additionally, deficient-diet pigs had impaired tryptophan catabolism postinfection compared with sufficient-diet pigs. Tryptophan supplementation was tested as an intervention in additional groups of fecal microbiota-transplanted, rotavirus-infected, sufficient- and deficient-diet pigs. Tryptophan supplementation increased the frequencies of regulatory (CD4+ or CD8+ CD25+ FoxP3+) T cells in pigs on both the sufficient and the deficient diets. These results suggest that a protein-deficient diet impairs activation of the adaptive immune response following HRV infection and alters tryptophan homeostasis.}, } @article {pmid28630433, year = {2017}, author = {Sun, LY and Yang, YS and Qu, W and Zhu, ZJ and Wei, L and Ye, ZS and Zhang, JR and Sun, XY and Zeng, ZG}, title = {Gut microbiota of liver transplantation recipients.}, journal = {Scientific reports}, volume = {7}, number = {1}, pages = {3762}, doi = {10.1038/s41598-017-03476-4}, pmid = {28630433}, issn = {2045-2322}, abstract = {The characteristics of intestinal microbial communities may be affected by changes in the pathophysiology of patients with end-stage liver disease. Here, we focused on the characteristics of intestinal fecal microbial communities in post-liver transplantation (LT) patients in comparison with those in the same individuals pre-LT and in healthy individuals. The fecal microbial communities were analyzed via MiSeq-PE250 sequencing of the V4 region of 16S ribosomal RNA and were then compared between groups. We found that the gut microbiota of patients with severe liver disease who were awaiting LT was significantly different from that of healthy controls, as represented by the first principal component (p = 0.0066). Additionally, the second principal component represented a significant difference in the gut microbiota of patients between pre-LT and post-LT surgery (p = 0.03125). After LT, there was a significant decrease in the abundance of certain microbial species, such as Actinobacillus, Escherichia, and Shigella, and a significant increase in the abundance of other microbial species, such as Micromonosporaceae, Desulfobacterales, the Sarcina genus of Eubacteriaceae, and Akkermansia. Based on KEGG profiles, 15 functional modules were enriched and 21 functional modules were less represented in the post-LT samples compared with the pre-LT samples. Our study demonstrates that fecal microbial communities were significantly altered by LT.}, } @article {pmid28628918, year = {2017}, author = {Mizuno, S and Masaoka, T and Naganuma, M and Kishimoto, T and Kitazawa, M and Kurokawa, S and Nakashima, M and Takeshita, K and Suda, W and Mimura, M and Hattori, M and Kanai, T}, title = {Bifidobacterium-Rich Fecal Donor May Be a Positive Predictor for Successful Fecal Microbiota Transplantation in Patients with Irritable Bowel Syndrome.}, journal = {Digestion}, volume = {96}, number = {1}, pages = {29-38}, doi = {10.1159/000471919}, pmid = {28628918}, issn = {1421-9867}, mesh = {Adult ; Bifidobacterium/*isolation & purification ; Colonoscopy ; Dysbiosis/etiology/microbiology/psychology/*therapy ; Fecal Microbiota Transplantation/*adverse effects ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Intestines/microbiology ; Irritable Bowel Syndrome/complications/microbiology/psychology/*therapy ; Japan ; *Living Donors ; Male ; Middle Aged ; Treatment Outcome ; }, abstract = {BACKGROUND/AIMS: Dysbiosis is associated with various systemic disorders including irritable bowel syndrome (IBS). Fecal microbiota transplantation (FMT) might restore intestinal microbial balance. The study aimed to determine the safety and efficacy of FMT in IBS patients, as well as also positive predictors for FMT.

METHODS: This was a single-arm, open-label study. Eligible patients were diagnosed based on Rome III Diagnostic Criteria. Fecal materials were administered to the patient via colonoscopy. The primary end point was a change in the Bristol stool form scale at 4 weeks after FMT. Recovery to types 3-4 was considered a clinical response. The secondary end point was a change in intestinal microbiota and psychological status using the Hamilton Rating Scale.

RESULTS: Ten patients were enrolled. Six patients achieved a clinical response. The diversity of patients 4 weeks after FMT increased significantly compared with patients before FMT, and that of responding patients was significantly higher than non-responder patients. The abundance of Bifidobacterium in effective donors was significantly higher than in ineffective donors and patients. Psychological status of all patients was significantly improved after FMT.

CONCLUSIONS: FMT for patients with IBS is safe, and relatively effective. Bifidobacterium-rich fecal donor may be a positive predictor for successful FMT. Key Summary: (1) Dysbiosis is associated with various gastrointestinal disorders including IBS. (2) FMT has potential to restore intestinal microbial balance. (3) We showed that FMT improved stool form and psychological status of IBS patients. (4) Bifidobacterium-rich donor efficiently induced symbiosis in IBS patients.}, } @article {pmid28626231, year = {2017}, author = {Sommer, F and Anderson, JM and Bharti, R and Raes, J and Rosenstiel, P}, title = {The resilience of the intestinal microbiota influences health and disease.}, journal = {Nature reviews. Microbiology}, volume = {15}, number = {10}, pages = {630-638}, doi = {10.1038/nrmicro.2017.58}, pmid = {28626231}, issn = {1740-1534}, mesh = {Dysbiosis/*microbiology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Homeostasis/*physiology ; Humans ; Inflammatory Bowel Diseases/*microbiology ; Intestines/*microbiology/physiology ; }, abstract = {The composition of the intestinal microbiota varies among individuals and throughout development, and is dependent on host and environmental factors. However, although the microbiota is constantly exposed to environmental challenges, its composition and function in an individual are stable against perturbations, as microbial communities are resilient and resistant to change. The maintenance of a beneficial microbiota requires a homeostatic equilibrium within microbial communities, and also between the microorganisms and the intestinal interface of the host. The resilience of the healthy microbiota protects us from dysbiosis-related diseases, such as inflammatory bowel disease (IBD) or metabolic disorder. By contrast, a resilient dysbiotic microbiota may cause disease. In this Opinion article, we propose that microbial resilience has a key role in health and disease. We will discuss the concepts and mechanisms of microbial resilience against dietary, antibiotic or bacteriotherapy-induced perturbations and the implications for human health.}, } @article {pmid28624575, year = {2017}, author = {Botschuijver, S and Roeselers, G and Levin, E and Jonkers, DM and Welting, O and Heinsbroek, SEM and de Weerd, HH and Boekhout, T and Fornai, M and Masclee, AA and Schuren, FHJ and de Jonge, WJ and Seppen, J and van den Wijngaard, RM}, title = {Intestinal Fungal Dysbiosis Is Associated With Visceral Hypersensitivity in Patients With Irritable Bowel Syndrome and Rats.}, journal = {Gastroenterology}, volume = {153}, number = {4}, pages = {1026-1039}, doi = {10.1053/j.gastro.2017.06.004}, pmid = {28624575}, issn = {1528-0012}, mesh = {Abdominal Pain/*microbiology/physiopathology/prevention & control/psychology ; Adult ; Animals ; Antifungal Agents/pharmacology ; Anxiety, Separation/psychology ; Behavior, Animal ; Case-Control Studies ; Cell Degranulation/drug effects ; Cell Line ; Disease Models, Animal ; Dysbiosis ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Fungi/drug effects/*growth & development ; *Gastrointestinal Microbiome/drug effects ; Humans ; Hyperalgesia/*microbiology/physiopathology/prevention & control/psychology ; Intestines/innervation/metabolism/*microbiology ; Irritable Bowel Syndrome/*microbiology/physiopathology/prevention & control/psychology ; Male ; Mast Cells/drug effects/metabolism ; Maternal Deprivation ; Middle Aged ; Pain Measurement ; Pain Perception ; Pain Threshold ; Protein Kinase Inhibitors/pharmacology ; Rats, Long-Evans ; Syk Kinase/antagonists & inhibitors/metabolism ; beta-Glucans/pharmacology ; }, abstract = {BACKGROUND & AIMS: Visceral hypersensitivity is one feature of irritable bowel syndrome (IBS). Bacterial dysbiosis might be involved in the activation of nociceptive sensory pathways, but there have been few studies of the role of the mycobiome (the fungal microbiome) in the development of IBS. We analyzed intestinal mycobiomes of patients with IBS and a rat model of visceral hypersensitivity.

METHODS: We used internal transcribed spacer 1-based metabarcoding to compare fecal mycobiomes of 18 healthy volunteers with those of 39 patients with IBS (with visceral hypersensitivity or normal levels of sensitivity). We also compared the mycobiomes of Long-Evans rats separated from their mothers (hypersensitive) with non-handled (normally sensitive) rats. We investigated whether fungi can cause visceral hypersensitivity using rats exposed to fungicide (fluconazole and nystatin). The functional relevance of the gut mycobiome was confirmed in fecal transplantation experiments: adult maternally separated rats were subjected to water avoidance stress (to induce visceral hypersensitivity), then given fungicide and donor cecum content via oral gavage. Other rats subjected to water avoidance stress were given soluble β-glucans, which antagonize C-type lectin domain family 7 member A (CLEC7A or DECTIN1) signaling via spleen-associated tyrosine kinase (SYK), a SYK inhibitor to reduce visceral hypersensitivity, or vehicle (control). The sensitivity of mast cells to fungi was tested with mesenteric windows (ex vivo) and the human mast cell line HMC-1.

RESULTS: α diversity (Shannon index) and mycobiome signature (stability selection) of both groups of IBS patients differed from healthy volunteers, and the mycobiome signature of hypersensitive patients differed from that of normally sensitive patients. We observed mycobiome dysbiosis in rats that had been separated from their mothers compared with non-handled rats. Administration of fungicide to hypersensitive rats reduced their visceral hypersensitivity to normal levels of sensitivity. Administration of cecal mycobiomes from rats that had been separated from their mothers (but not non-handled mycobiome) restored hypersensitivity to distension. Administration of soluble β-glucans or a SYK inhibitor reduced visceral hypersensitivity, compared with controls. Particulate β-glucan (a DECTIN-1 agonist) induced mast cell degranulation in mesenteric windows and HMC-1 cells responded to fungal antigens by release of histamine.

CONCLUSIONS: In an analysis of patients with IBS and controls, we associated fungal dysbiosis with IBS. In studies of rats, we found fungi to promote visceral hypersensitivity, which could be reduced by administration of fungicides, soluble β-glucans, or a SYK inhibitor. The intestinal fungi might therefore be manipulated for treatment of IBS-related visceral hypersensitivity.}, } @article {pmid28617055, year = {2017}, author = {Panés, J and Alfaro, I}, title = {New treatment strategies for ulcerative colitis.}, journal = {Expert review of clinical immunology}, volume = {13}, number = {10}, pages = {963-973}, doi = {10.1080/1744666X.2017.1343668}, pmid = {28617055}, issn = {1744-8409}, mesh = {Adrenal Cortex Hormones/*therapeutic use ; Aminosalicylic Acids/*therapeutic use ; Antibodies, Monoclonal/*therapeutic use ; Colitis, Ulcerative/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Quality of Life ; }, abstract = {INTRODUCTION: Therapeutic strategies in ulcerative colitis are evolving. A personalized and optimal use of available drugs and the integration of new drug classes are the cornerstones underpinning the new treatment paradigms. Areas covered: A structured literature search in Medline and PubMed, Cochrane meta-analyses, and abstracts of international congresses has been performed to review therapeutic approaches to ulcerative colitis. The primary therapeutic objective of therapy is to achieve clinical remission since persistence of active disease, even if mild, leads to a significant reduction in quality of life. Current treatment paradigms of ulcerative colitis are based on the use of 5-aminosalycilates, corticosteroids, thiopurines, TNF-α inhibitors and α4ß7 integrin blockers. The main determinants for drug class selection are disease extension, disease severity, and previous drug history. New drug classes that will likely become available in the foreseeable future include inhibitors of Janus kinases, modulators of sphingosine-1-phosphate receptors, SMAD-7 antisense oligonucleotides, interleukin-12/23 blockers, and fecal microbiota transplantation. Expert commentary: Increasing therapeutic options for ulcerative colitis make predictors of response highly relevant. While these are not available, judicious use of therapies, avoidance of underdosing, or persistent therapy when criteria for drug failure are met are essential.}, } @article {pmid28612983, year = {2017}, author = {Costello, SP and Soo, W and Bryant, RV and Jairath, V and Hart, AL and Andrews, JM}, title = {Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis.}, journal = {Alimentary pharmacology & therapeutics}, volume = {46}, number = {3}, pages = {213-224}, doi = {10.1111/apt.14173}, pmid = {28612983}, issn = {1365-2036}, mesh = {Colitis, Ulcerative/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces ; Humans ; Randomized Controlled Trials as Topic ; Remission Induction ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is emerging as a novel therapy for ulcerative colitis (UC). Interpretation of efficacy of FMT for UC is complicated by differences among studies in blinding, FMT administration procedures, intensity of therapy and donor stool processing methods.

AIM: To determine whether FMT is effective and safe for the induction of remission in active UC.

METHODS: Medline (Ovid), Embase and the Cochrane Library were searched from inception through February 2017. Original studies reporting remission rates following FMT for active UC were included. All study designs were included in the systematic review and a meta-analysis performed including only randomised controlled trials (RCTs).

RESULTS: There were 14 cohort studies and four RCTs that used markedly different protocols. In the meta-analysis of RCTs, clinical remission was achieved in 39 of 140 (28%) patients in the donor FMT groups compared with 13 of 137 (9%) patients in the placebo groups; odds ratio 3.67 (95% CI: 1.82-7.39, P<.01). Clinical response was achieved in 69 of 140 (49%) donor FMT patients compared to 38 of 137 (28%) placebo patients; odds ratio 2.48 (95% CI: 1.18-5.21, P=.02). In cohort studies, 39 of 168 (24%; 95% CI: 11%-40%) achieved clinical remission.

CONCLUSIONS: Despite variation in processes, FMT appears to be effective for induction of remission in UC, with no major short-term safety signals. Further studies are needed to better define dose frequency and preparation methods, and to explore its feasibility, efficacy and safety as a maintenance agent.}, } @article {pmid28609775, year = {2017}, author = {Biedermann, L}, title = {Vancomycin in Very-Early Onset Inflammatory Bowel Disease-Dysbiosis: Fight Fire with Fire?.}, journal = {Digestion}, volume = {95}, number = {4}, pages = {327-328}, doi = {10.1159/000477088}, pmid = {28609775}, issn = {1421-9867}, mesh = {Age Factors ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Dysbiosis/etiology/microbiology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Humans ; Inflammatory Bowel Diseases/etiology/microbiology/*therapy ; Treatment Outcome ; Vancomycin/pharmacology/*therapeutic use ; }, } @article {pmid28609252, year = {2017}, author = {de Groot, PF and Frissen, MN and de Clercq, NC and Nieuwdorp, M}, title = {Fecal microbiota transplantation in metabolic syndrome: History, present and future.}, journal = {Gut microbes}, volume = {8}, number = {3}, pages = {253-267}, doi = {10.1080/19490976.2017.1293224}, pmid = {28609252}, issn = {1949-0984}, support = {//CIHR/Canada ; }, mesh = {Animals ; Atherosclerosis/microbiology/therapy ; Clostridium Infections/therapy ; Disease Models, Animal ; Fecal Microbiota Transplantation/*trends ; Feces/microbiology ; Gastrointestinal Microbiome ; *Host-Pathogen Interactions ; Humans ; Inflammation/therapy ; Inflammatory Bowel Diseases/microbiology/therapy ; Insulin Resistance ; Intestines/microbiology ; Metabolic Syndrome/microbiology/*therapy ; Non-alcoholic Fatty Liver Disease/microbiology/therapy ; Randomized Controlled Trials as Topic ; }, abstract = {The history of fecal microbiota transplantation (FMT) dates back even to ancient China. Recently, scientific studies have been looking into FMT as a promising treatment of various diseases, while in the process teaching us about the interaction between the human host and its resident microbial communities. Current research focuses mainly on Clostridium difficile infections, however interest is rising in other areas such as inflammatory bowel disease (IBD) and the metabolic syndrome. With regard to the latter, the intestinal microbiota might be causally related to the progression of insulin resistance and diabetes. FMT in metabolic syndrome has proven to be an intriguing method to study the role of the gut microbiota and open the way to new therapies by dissecting in whom insulin resistance is driven by microbiota. In this article we review the history of FMT, the present evidence on its role in the pathophysiology of metabolic syndrome and its efficacy, limitations and future prospects.}, } @article {pmid28609251, year = {2017}, author = {Weingarden, AR and Vaughn, BP}, title = {Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease.}, journal = {Gut microbes}, volume = {8}, number = {3}, pages = {238-252}, doi = {10.1080/19490976.2017.1290757}, pmid = {28609251}, issn = {1949-0984}, mesh = {Animals ; Clostridium Infections/therapy ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Helminthiasis/therapy ; Humans ; Inflammatory Bowel Diseases/*therapy ; Intestines/microbiology ; Randomized Controlled Trials as Topic ; Treatment Outcome ; }, abstract = {Inflammatory bowel disease (IBD) is a complex set of diseases that lead to chronic inflammation in the gastrointestinal tract. Although the etiology of IBD is not fully understood, it is well-known that the intestinal microbiota is associated with the development and maintenance of IBD. Manipulation of the gut microbiota, therefore, may represent a target for IBD therapy. Fecal microbiota transplantation (FMT), where fecal microbiota from a healthy donor is transplanted into a patient's GI tract, is already a successful therapy for Clostridium difficile infection. FMT is currently being explored as a potential therapy for IBD as well. In this review, the associations between the gut microbiota and IBD and the emerging data on FMT for IBD will be discussed.}, } @article {pmid28602517, year = {2017}, author = {Tang, G and Yin, W and Liu, W}, title = {Is frozen fecal microbiota transplantation as effective as fresh fecal microbiota transplantation in patients with recurrent or refractory Clostridium difficile infection: A meta-analysis?.}, journal = {Diagnostic microbiology and infectious disease}, volume = {88}, number = {4}, pages = {322-329}, doi = {10.1016/j.diagmicrobio.2017.05.007}, pmid = {28602517}, issn = {1879-0070}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Clostridium Infections/*microbiology/*therapy ; Clostridium difficile/pathogenicity ; Fecal Microbiota Transplantation/methods ; Feces/*microbiology ; Female ; Freezing ; Humans ; Male ; Microbiota/physiology ; Middle Aged ; Recurrence ; Treatment Outcome ; Young Adult ; }, abstract = {Fecal microbiota transplantation (FMT) is a remarkably efficacious therapy for recurrent or refractory Clostridium difficile infection (CDI), but not standardized. This work is to determine whether frozen FMT is as effective as fresh FMT. Meta-analysis showed that frozen FMT was as effective as fresh FMT, both pooled first effective rate (65.0% (95% CI 57.0-73.0%) vs. 65.0% (95% CI 57.0-73.0%), P=0.962) and pooled second effective rate (95.0% (95% CI 91.0-99.0%) vs. 95.0% (95% CI 92.0-99.0%), P=0.880). In conclusion, among patients with recurrent or refractory CDI, frozen FMT is as effective as fresh FMT. Considering potential advantages of performing frozen FMT, it is a reasonable option to select frozen FMT.}, } @article {pmid28596693, year = {2017}, author = {He, Z and Cui, BT and Zhang, T and Li, P and Long, CY and Ji, GZ and Zhang, FM}, title = {Fecal microbiota transplantation cured epilepsy in a case with Crohn's disease: The first report.}, journal = {World journal of gastroenterology}, volume = {23}, number = {19}, pages = {3565-3568}, doi = {10.3748/wjg.v23.i19.3565}, pmid = {28596693}, issn = {2219-2840}, mesh = {Crohn Disease/*complications/*therapy ; Epilepsy/*complications/*therapy ; *Fecal Microbiota Transplantation ; Feces ; Female ; Gastrointestinal Microbiome ; Humans ; Intestines/microbiology/physiopathology ; Quality of Life ; Recurrence ; Remission Induction ; Seizures ; Treatment Outcome ; Young Adult ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising strategy that involves reconstruction of gut microbiota. Recently, it has been considered as a treatment of Crohn's disease (CD) and certain neurological diseases. Here, to the best of our knowledge, we report the first case that used FMT to achieve remission of intestinal and neurological symptoms in a girl with CD and a 17-year history of epilepsy. During the 20 mo of follow-up, FMT has proved its efficacy in preventing relapse of seizures after withdrawing the antiepileptic drugs. Furthermore, this finding highlights the role of microbiota-gut-brain axis and inspires a novel treatment for epilepsy through remodeling gut microbiota.}, } @article {pmid28595295, year = {2017}, author = {Dinh, A and Duran, C and Bouchand, F and Salomon, J and Davido, B}, title = {Fecal Microbiota Transplantation Is a New Effective Weapon to Fight Multidrug-Resistant Bacteria, but Harmonization and More Data Are Needed.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {65}, number = {8}, pages = {1425-1426}, doi = {10.1093/cid/cix538}, pmid = {28595295}, issn = {1537-6591}, } @article {pmid28592766, year = {2017}, author = {Kakihana, K}, title = {Fecal microbiota transplantation for acute graft-versus-host disease of the gut.}, journal = {[Rinsho ketsueki] The Japanese journal of clinical hematology}, volume = {58}, number = {5}, pages = {499-505}, doi = {10.11406/rinketsu.58.499}, pmid = {28592766}, issn = {0485-1439}, mesh = {Acute Disease ; Animals ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Graft vs Host Disease/*therapy ; Humans ; Intestinal Diseases/microbiology/*therapy ; }, abstract = {Advances in microbial analysis have provided new insights into the complex interactions between the host and gut microbiota. An imbalance in the gut microbiota (dysbiosis) is associated with various disorders and their pathogenesis. Furthermore, in allogeneic stem cell transplantation, increasing evidence indicates that the gut microbiota is closely associated with acute graft-versus-host disease (GVHD) and transplant outcomes, suggesting that its manipulation could be a new treatment strategy for this acute condition. We conducted a feasibility study of fecal microbiota transplantation (FMT) for acute GVHD of the gut in four human transplant recipients. No severe adverse events that were obviously attributable to FMT were observed. All patients responded to FMT: three patients showed a complete response and one a partial response. Our results indicate that FMT could be a new treatment option for acute GVHD of the gut. However, the use of FMT in treating acute GVHD is in the initial stages of clinical application. FMT has limitations that need to be addressed, such as safety and determination of the optimal donor screening or the treatment protocol. Further evaluation is thus warranted.}, } @article {pmid28589214, year = {2017}, author = {Solbach, P and Dersch, P and Bachmann, O}, title = {[Individualized treatment strategies for Clostridium difficile infections].}, journal = {Der Internist}, volume = {58}, number = {7}, pages = {675-681}, doi = {10.1007/s00108-017-0268-2}, pmid = {28589214}, issn = {1432-1289}, mesh = {Aminoglycosides/therapeutic use ; Anti-Bacterial Agents/adverse effects/*therapeutic use ; Clostridium Infections/*drug therapy/mortality ; *Clostridium difficile ; Fecal Microbiota Transplantation ; Female ; Humans ; Metronidazole/*therapeutic use ; Recurrence ; Secondary Prevention ; Vancomycin/*therapeutic use ; }, abstract = {Upon hospitalization, up to 15.5% of patients are already colonized with a toxigenic Clostridium difficile strain (TCD). The rate of asymptomatic colonization is 0-3% in healthy adults and up to 20-40% in hospitalized patients. The incidence and mortality of C. difficile infection (CDI) has significantly increased during recent years. Mortality lies between 3 and 14%. CDI is generally caused by intestinal dysbiosis, which can be triggered by various factors, including antibiotics or immune suppressants. If CDI occurs, ongoing antibiotic therapy should be discontinued. The choice of treatment is guided by the clinical situation: Mild courses of CDI should be treated with metronidazole. Oral vancomycin is suitable as a first-line therapy of mild CDI occurring during pregnancy and lactation, as well as in cases of intolerance or allergy to metronidazole. Severe courses should be treated with vancomycin. Recurrence should be treated with vancomycin or fidaxomicin. Multiple recurrences should be treated with vancomycin or fidaxomicin; if necessary, a vancomycin taper regimen may also be used. An alternative is fecal microbiota transplant (FMT), with healing rates of more than 80%. Bezlotoxumab is the first available monoclonal antibody which neutralizes the C. difficile toxin B, and in combination with an antibiotic significantly reduces the rate of a new C. difficile infection compared to placebo. A better definition of clinical and microbiota-associated risk factors and the ongoing implementation of molecular diagnostics are likely to lead to optimized identification of patients at risk, and an increasing individualization of prophylactic and therapeutic approaches.}, } @article {pmid28588566, year = {2017}, author = {Tidjani Alou, M and Million, M and Traore, SI and Mouelhi, D and Khelaifia, S and Bachar, D and Caputo, A and Delerce, J and Brah, S and Alhousseini, D and Sokhna, C and Robert, C and Diallo, BA and Diallo, A and Parola, P and Golden, M and Lagier, JC and Raoult, D}, title = {Gut Bacteria Missing in Severe Acute Malnutrition, Can We Identify Potential Probiotics by Culturomics?.}, journal = {Frontiers in microbiology}, volume = {8}, number = {}, pages = {899}, doi = {10.3389/fmicb.2017.00899}, pmid = {28588566}, issn = {1664-302X}, abstract = {Severe acute malnutrition is the world-leading cause of children under-five's death. Recent metagenomics studies have established a link between gut microbiota and severe acute malnutrition, describing an immaturity with a striking depletion in oxygen-sensitive prokaryotes. Amoxicillin and therapeutic diet cure most of the children with severe acute malnutrition but an irreversible disruption of the gut microbiota is suspected in the refractory and most severe cases. In these cases, therapeutic diet may be unable to reverse the microbiota alteration leading to persistent impaired development or death. In addition, as enteric sepsis is a major cause of death in this context, identification of missing gut microbes to be tested as probiotics (live bacteria that confer a benefit to the host) to restore rapidly the healthy gut microbiota and prevent the gut pathogenic invasion is of foremost importance. In this study, stool samples of malnourished patients with kwashiorkor and healthy children were collected from Niger and Senegal and analyzed by culturomics and metagenomics. We found a globally decreased diversity, a decrease in the hitherto unknown diversity (new species isolation), a depletion in oxygen-sensitive prokaryotes including Methanobrevibacter smithii and an enrichment in potentially pathogenic Proteobacteria, Fusobacteria and Streptococcus gallolyticus. A complex of 12 species identified only in healthy children using culturomics and metagenomics were identified as probiotics candidates, providing a possible, defined, reproducible, safe, and convenient alternative to fecal transplantation to restore a healthy gut microbiota in malnourished children. Microbiotherapy based on selected strains has the potential to improve the current treatment of severe acute malnutrition and prevent relapse and death by reestablishing a healthy gut microbiota.}, } @article {pmid28586116, year = {2017}, author = {Bajaj, JS and Kassam, Z and Fagan, A and Gavis, EA and Liu, E and Cox, IJ and Kheradman, R and Heuman, D and Wang, J and Gurry, T and Williams, R and Sikaroodi, M and Fuchs, M and Alm, E and John, B and Thacker, LR and Riva, A and Smith, M and Taylor-Robinson, SD and Gillevet, PM}, title = {Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial.}, journal = {Hepatology (Baltimore, Md.)}, volume = {66}, number = {6}, pages = {1727-1738}, doi = {10.1002/hep.29306}, pmid = {28586116}, issn = {1527-3350}, support = {I01 CX001076/CX/CSRD VA/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R21 TR002024/TR/NCATS NIH HHS/United States ; }, mesh = {Aged ; Cognition ; *Fecal Microbiota Transplantation ; Female ; Hepatic Encephalopathy/*therapy ; Humans ; Male ; Metabolome ; Microbiota ; Middle Aged ; Treatment Outcome ; }, abstract = {Recurrent hepatic encephalopathy (HE) is a leading cause of readmission despite standard of care (SOC) associated with microbial dysbiosis. Fecal microbiota transplantation (FMT) may improve dysbiosis; however, it has not been studied in HE. We aimed to define whether FMT using a rationally derived stool donor is safe in recurrent HE compared to SOC alone. An open-label, randomized clinical trial with a 5-month follow-up in outpatient men with cirrhosis with recurrent HE on SOC was conducted with 1:1 randomization. FMT-randomized patients received 5 days of broad-spectrum antibiotic pretreatment, then a single FMT enema from the same donor with the optimal microbiota deficient in HE. Follow-up occurred on days 5, 6, 12, 35, and 150 postrandomization. The primary outcome was safety of FMT compared to SOC using FMT-related serious adverse events (SAEs). Secondary outcomes were adverse events, cognition, microbiota, and metabolomic changes. Participants in both arms were similar on all baseline criteria and were followed until study end. FMT with antibiotic pretreatment was well tolerated. Eight (80%) SOC participants had a total of 11 SAEs compared to 2 (20%) FMT participants with SAEs (both FMT unrelated; P = 0.02). Five SOC and no FMT participants developed further HE (P = 0.03). Cognition improved in the FMT, but not the SOC, group. Model for End-Stage Liver Disease (MELD) score transiently worsened postantibiotics, but reverted to baseline post-FMT. Postantibiotics, beneficial taxa, and microbial diversity reduction occurred with Proteobacteria expansion. However, FMT increased diversity and beneficial taxa. SOC microbiota and MELD score remained similar throughout.

CONCLUSION: FMT from a rationally selected donor reduced hospitalizations, improved cognition, and dysbiosis in cirrhosis with recurrent HE. (Hepatology 2017;66:1727-1738).}, } @article {pmid28583769, year = {2018}, author = {Allegretti, JR and Kassam, Z and Osman, M and Budree, S and Fischer, M and Kelly, CR}, title = {The 5D framework: a clinical primer for fecal microbiota transplantation to treat Clostridium difficile infection.}, journal = {Gastrointestinal endoscopy}, volume = {87}, number = {1}, pages = {18-29}, doi = {10.1016/j.gie.2017.05.036}, pmid = {28583769}, issn = {1097-6779}, mesh = {*Clostridium difficile ; Contraindications, Procedure ; Directive Counseling ; *Donor Selection ; Enterocolitis, Pseudomembranous/diagnosis/*therapy ; Fecal Microbiota Transplantation/*adverse effects/methods ; Humans ; Patient Discharge ; Patient Education as Topic ; Patient Participation ; *Patient Selection ; }, } @article {pmid28576475, year = {2017}, author = {Yoshioka, K and Kakihana, K and Doki, N and Ohashi, K}, title = {Gut microbiota and acute graft-versus-host disease.}, journal = {Pharmacological research}, volume = {122}, number = {}, pages = {90-95}, doi = {10.1016/j.phrs.2017.05.028}, pmid = {28576475}, issn = {1096-1186}, mesh = {Acute Disease ; Animals ; Dysbiosis/*complications/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Graft vs Host Disease/etiology/*microbiology/therapy ; Humans ; Probiotics/therapeutic use ; Stem Cell Transplantation/adverse effects ; }, abstract = {Although allogeneic stem cell transplantation (allo-SCT) is a potentially curative treatment for various hematological diseases, acute graft-versus-host disease (GVHD) is a major cause of morbidity and mortality, and its management is clinically important. Advances in biological techniques have led to great progress in understanding the complex interactions between the host and the gut microbiota. The gut microbiota clearly modulates the immune response and is associated with the pathogenesis of various disorders. Also in allo-SCT, both preclinical and clinical results indicate that the gut microbiota is closely associated with the development of acute GVHD and transplant outcomes. These results led to the idea that improvement in quantitative and/or qualitative abnormalities of microbiota (dysbiosis) may be a new treatment strategy for acute GVHD. Evaluations of therapies targeting the gut microbiota such as probiotics or fecal microbiota transplantation have just begun. Furthermore, intervention in the gut microbiota with a nutritional approach including prebiotics, postbiotics, and antibiotics selection may also be another promising treatment option for acute GVHD.}, } @article {pmid28575220, year = {2017}, author = {Patron, RL and Hartmann, CA and Allen, S and Griesbach, CL and Kosiorek, HE and DiBaise, JK and Orenstein, R}, title = {Vancomycin Taper and Risk of Failure of Fecal Microbiota Transplantation in Patients With Recurrent Clostridium difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {65}, number = {7}, pages = {1214-1217}, doi = {10.1093/cid/cix511}, pmid = {28575220}, issn = {1537-6591}, abstract = {We retrospectively analyzed a cohort of 109 subjects treated for recurrent Clostridium difficile infection with fecal microbiota transplantation (FMT) at a tertiary referral center between 2011 and 2014 to determine risk factors for FMT failure. In a multivariate analysis, failure to use an oral vancomycin taper preceding FMT was associated with a significant risk of FMT failure (odds ratio, 0.15; 95% confidence interval, .007-.40).}, } @article {pmid28572754, year = {2017}, author = {Gaci, N and Chaudhary, PP and Tottey, W and Alric, M and Brugère, JF}, title = {Functional amplification and preservation of human gut microbiota.}, journal = {Microbial ecology in health and disease}, volume = {28}, number = {1}, pages = {1308070}, doi = {10.1080/16512235.2017.1308070}, pmid = {28572754}, issn = {0891-060X}, abstract = {Background: The availability of fresh stool samples is a prerequisite in most gut microbiota functional studies. Objective: Strategies for amplification and long-term gut microbiota preservation from fecal samples would favor sample sharing, help comparisons and reproducibility over time and between laboratories, and improve the safety and ethical issues surrounding fecal microbiota transplantations. Design: Taking advantage of in vitro gut-simulating systems, we amplified the microbial repertoire of a fresh fecal sample and assessed the viability and resuscitation of microbes after preservation with some common intracellular and extracellular acting cryoprotective agents (CPAs), alone and in different combinations. Preservation efficiencies were determined after 3 and 6 months and compared with the fresh initial microbiota diversity and metabolic activity, using the chemostat-based Environmental Control System for Intestinal Microbiota (ECSIM) in vitro model of the gut environment. Microbial populations were tested for fermentation gas, short-chain fatty acids, and composition of amplified and resuscitated microbiota, encompassing methanogenic archaea. Results: Amplification of the microbial repertoire from a fresh fecal sample was achieved with high fidelity. Dimethylsulfoxide, alone or mixed with other CPAs, showed the best efficiency for functional preservation, and the duration of preservation had little effect. Conclusions: The amplification and resuscitation of fecal microbiota can be performed using specialized in vitro gut models. Correct amplification of the initial microbes should ease the sharing of clinical samples and improve the safety of fecal microbiota transplantation. Abbreviations: CDI, Clostridium difficile infection; CPA, cryoprotective agent; D, DMSO, dimethylsulfoxide; FMT, fecal microbiota transplantation; G, glycerol; IBD, inflammatory bowel disease; P, PEG-4000, polyethylene glycol 4000 g.mol-1; SCFA, short-chain fatty acid; SNR, signal-to-noise ratio.}, } @article {pmid28572645, year = {2017}, author = {Youngster, I and Gerding, DN}, title = {Editorial: Making Fecal Microbiota Transplantation Easier to Swallow: Freeze-Dried Preparation for Recurrent Clostridium difficile Infections.}, journal = {The American journal of gastroenterology}, volume = {112}, number = {6}, pages = {948-950}, doi = {10.1038/ajg.2017.91}, pmid = {28572645}, issn = {1572-0241}, mesh = {Clostridium Infections/microbiology ; *Clostridium difficile ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Microbiota ; }, abstract = {Fecal microbiota transplant (FMT) has emerged as an effective and increasingly popular therapy for recurrent Clostridium difficile infections in patients that have failed standard antimicrobial treatment. Patient access to FMT is hampered by the logistics of manufacturing, storing, and delivering the inocula. An observational study describes the development and clinical efficacy of freeze-dried FMT capsules for oral administration. While awaiting the emergence of defined bacterial therapeutics for Clostridium difficile infections, this refinement of FMT is an encouraging step toward simplifying FMT treatment. Randomized controlled trials are required to further establish the efficacy and safety of lyophilized FMT.}, } @article {pmid28569200, year = {2017}, author = {Yamazaki, Y and Kawarai, S and Morita, H and Kikusui, T and Iriki, A}, title = {Faecal transplantation for the treatment of Clostridium difficile infection in a marmoset.}, journal = {BMC veterinary research}, volume = {13}, number = {1}, pages = {150}, doi = {10.1186/s12917-017-1070-z}, pmid = {28569200}, issn = {1746-6148}, mesh = {Animals ; Callithrix/*microbiology ; Clostridium Infections/therapy/*veterinary ; *Clostridium difficile ; Fecal Microbiota Transplantation/*veterinary ; Male ; Monkey Diseases/*microbiology/therapy ; Treatment Outcome ; }, abstract = {BACKGROUND: The common marmoset has been used as an experimental animal for various purposes. Because its average weight ranges from 250 to 500 g, weight loss quickly becomes critical for sick animals. Therefore, effective and non-stressful treatment for chronic diseases, including diarrhoea, is essential.

CASE PRESENTATION: We report a case in which faecal microbiota transplantation (FMT) led to immediate recovery from chronic and recurrent diarrhoea caused by Clostridium difficile infection. A male common marmoset experienced chronic diarrhoea after antibiotic treatments. The animal experienced severe weight loss, and a faecal sample was confirmed to be C. difficile-positive but was negative for protozoa. Metronidazole was partially effective at the first administration but not after the recurrence of the clinical signs. Then, oral FMT was administered to the subject by feeding fresh faeces from healthy individuals mixed with the marmoset's usual food. We monitored the faeces by categorization into four groups: normal, loose, diarrhoea, and watery. After the first day of FMT treatment, the marmoset underwent a remarkable recovery from diarrhoea, and after the fourth day of treatment, a test for C. difficile was negative. The clinical signs did not recur. The marmoset recovered from sinusitis and bilateral dacryocystitis, which also did not recur, as a by-product of the improvement in its general health caused by the cessation of diarrhoea after the FMT.

CONCLUSION: This is the first reported case of successful treatment of a marmoset using oral FMT. As seen in human patients, FMT was effective for the treatment of recurrent C. difficile infection in a captive marmoset.}, } @article {pmid28569156, year = {2017}, author = {Ma, Y and Yang, J and Cui, B and Xu, H and Xiao, C and Zhang, F}, title = {How Chinese clinicians face ethical and social challenges in fecal microbiota transplantation: a questionnaire study.}, journal = {BMC medical ethics}, volume = {18}, number = {1}, pages = {39}, doi = {10.1186/s12910-017-0200-2}, pmid = {28569156}, issn = {1472-6939}, mesh = {*Attitude of Health Personnel ; Awareness ; *Bioethical Issues ; China ; Clostridium Infections/*therapy ; Emotions ; *Fecal Microbiota Transplantation/ethics/psychology ; Gastroenterologists ; Gastroenterology ; Humans ; Informed Consent ; *Physician-Patient Relations ; *Physicians ; Privacy ; Surveys and Questionnaires ; Tissue Donors ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is reportedly the most effective therapy for relapsing Clostridium Difficile infection (CDI) and a potential therapeutic option for many diseases. It also poses important ethical concerns. This study is an attempt to assess clinicians' perception and attitudes towards ethical and social challenges raised by fecal microbiota transplantation.

METHODS: A questionnaire was developed which consisted of 20 items: four items covered general aspects, nine were about ethical aspects such as informed consent and privacy issues, four concerned social and regulatory issues, and three were about an FMT bank. This was distributed to participants at the Second China gastroenterology and FMT conference in May 2015. Basic descriptive statistical analyses and simple comparative statistical tests were performed.

RESULTS: Nearly three quarters of the 100 respondents were gastro-enterologist physicians. 89% of all respondents believed FMT is a promising treatment modality for some diseases and 88% of whom chose clinical efficacy as the primary reason for recommending FMT. High expectation from patients and pressure on clinicians (33%) was reported as the most frequent reasons for not recommending FMT. The clinicians who had less familiarity with FMT reported significantly more worry related to the dignity and psychological impact of FMT compared to those who have high familiarity with FMT (51.6% vs 27.8%, p = 0.021).More than half of the respondents (56.1%) were concerned about the commercialization of FMT, although almost one in five respondents did not see this as a problem.

CONCLUSIONS: We found most respondents have positive attitudes towards FMT but low awareness of published evidence. Informed consent for vulnerable patients, privacy and protection of donors were perceived as the most challenging ethical aspects of FMT. This study identified areas of limited knowledge and ways of addressing ethical issues and indicates the need to devise the education and training for clinicians on FMT.}, } @article {pmid28560232, year = {2017}, author = {Chiriac, MT and Mahapatro, M and Neurath, MF and Becker, C}, title = {The Microbiome in Visceral Medicine: Inflammatory Bowel Disease, Obesity and Beyond.}, journal = {Visceral medicine}, volume = {33}, number = {2}, pages = {153-162}, doi = {10.1159/000470892}, pmid = {28560232}, issn = {2297-4725}, abstract = {It has become increasingly evident over the past two decades that the microbiota plays a nurturing role in the development of the immune system. This appears to be important since the amplitude of immune responses has a crucial regulatory function in homeostasis and the prevention of unwanted inflammation. Hence, a malfunctioning gut flora has been shown to play a key role in visceral medicine. Strong evidence demonstrates for example that intestinal inflammation can develop as a result of a dysregulated microbiota, deficient antimicrobial responses, and aberrant bacterial translocation into the bowel wall. In healthy individuals, the bacterial translocation is blocked by a single layer of highly specialized intestinal epithelial cells which forms a strong barrier that lines the gut wall. This structure is responsible for an efficient absorption of nutrients while keeping the luminal flora at bay. In susceptible individuals, for yet incompletely understood reasons, either defective epithelial barrier function or dysregulated microbial composition or microbial pathogens drive intestinal inflammation. Many therapeutic strategies focusing on the modulation of the microbiota have been proposed recently but future research including prospective human studies and gnotobiotic mouse models are still needed to evaluate the contribution and potential therapeutic value of individual bacteria to human health.}, } @article {pmid28559695, year = {2017}, author = {Iacob, T and Ţăţulescu, DF and Dumitraşcu, DL}, title = {Therapy of the postinfectious irritable bowel syndrome: an update.}, journal = {Clujul medical (1957)}, volume = {90}, number = {2}, pages = {133-138}, doi = {10.15386/cjmed-752}, pmid = {28559695}, issn = {1222-2119}, abstract = {After acute infectious gastroenteritis, up to thirty percent of patients present prolonged gastrointestinal symptoms and a part of those affected patients can have the diagnostic criteria for postinfectious irritable bowel syndrome. Treatment is symptom directed rather than curative and includes agents prescribed for the treatment of irritable bowel syndrome in general. Prophylaxis or early treatment of acute bacterial diarrhea may reduce the risk of postinfectious irritable bowel syndrome development by reducing the occurrence, duration, and severity of the chronic inflammation and mucosal alterations (all these believed to play an important role in disease persistence). Probiotic treatment is effective in restoring the intestinal microbiota in patients with irritable bowel syndrome and in animal models there are improvements of postinfectious irritable bowel syndrome. Fecal microbiota transplantation seems to be one of the most effective methods of treating the postinfectious irritable bowel syndrome (with recurrent episodes) caused by Clostridium difficile.}, } @article {pmid28557822, year = {2017}, author = {de Clercq, NC and Frissen, MN and Groen, AK and Nieuwdorp, M}, title = {Gut Microbiota and the Gut-Brain Axis: New Insights in the Pathophysiology of Metabolic Syndrome.}, journal = {Psychosomatic medicine}, volume = {79}, number = {8}, pages = {874-879}, doi = {10.1097/PSY.0000000000000495}, pmid = {28557822}, issn = {1534-7796}, mesh = {Animals ; *Brain/metabolism ; *Gastrointestinal Microbiome ; Humans ; Metabolic Syndrome/immunology/*metabolism/microbiology ; *Signal Transduction ; }, abstract = {OBJECTIVE: Emerging preclinical evidence has shown that the bidirectional signaling between the gastrointestinal (GI) tract and the brain, the so-called gut-brain axis, plays an important role in both host metabolism and behavior. In this review, we discuss the potential mechanisms of the brain-gut axis in relation to the pathophysiology of metabolic syndrome.

METHODS: A selective literature review was conducted to evaluate GI and brain interactions.

RESULTS: Evidence suggests reduced microbial diversity in obesity and metabolic dysregulation. However, findings of microbiota composition in obese individuals are inconsistent, and the investigation of causality between gut microbiota and energy homeostasis is complex because multiple variables contribute to the gut microbiota composition. The microbial metabolites short chain fatty acids are found to exert numerous physiologic effects, including energy homeostasis through the regulation of GI hormones such as cholecystokinin, glucagon-like peptide 1, peptide tyrosine-tyrosine, and leptin. Preclinical studies show that modifying rodents' microbiota through fecal transplantation results in alterations of these GI hormones and subsequently an altered metabolism and behavior. However, whether and to what extent preclinical findings translate to human metabolism is unclear.

CONCLUSIONS: One of the major limitations and challenges in this field of research is interindividual variability of the microbiome. Future research needs to combine recent insights gained into tracking the dynamics of the microbiome as well as the metabolic responses. Furthermore, advanced mapping of the human microbiome is required to investigate the metabolic implications of the gut-brain axis to develop targeted interventions for obesity and metabolic syndrome.}, } @article {pmid28550391, year = {2018}, author = {Arab, JP and Martin-Mateos, RM and Shah, VH}, title = {Gut-liver axis, cirrhosis and portal hypertension: the chicken and the egg.}, journal = {Hepatology international}, volume = {12}, number = {Suppl 1}, pages = {24-33}, doi = {10.1007/s12072-017-9798-x}, pmid = {28550391}, issn = {1936-0541}, support = {R01 DK59615//National Institute of Diabetes and Digestive and Kidney Diseases/ ; P30 DK084567//National Institute of Diabetes and Digestive and Kidney Diseases/ ; R01 AA021171//National Institute on Alcohol Abuse and Alcoholism/ ; AASLD/Lifer Clinical and Translational Research Fellowship in Liver Diseases//American Association for the Study of Liver Diseases/ ; }, mesh = {Adrenergic beta-Antagonists/therapeutic use ; Bacterial Infections/complications ; Bacterial Translocation/genetics ; Bile Acids and Salts/metabolism ; Endotoxemia/etiology/metabolism ; Fecal Microbiota Transplantation/adverse effects/methods ; Gastrointestinal Microbiome/*drug effects/genetics ; Hepatic Encephalopathy/complications/microbiology ; Humans ; Hypertension, Portal/*etiology/metabolism/microbiology ; Intestines/metabolism/*microbiology ; Lipopolysaccharide Receptors/metabolism ; Liver/*metabolism ; Liver Cirrhosis/*complications/metabolism/therapy ; Liver Diseases/metabolism/*physiopathology ; Non-alcoholic Fatty Liver Disease/complications/prevention & control/therapy ; Peritonitis/microbiology ; Probiotics/therapeutic use ; Receptors, Cytoplasmic and Nuclear/metabolism ; }, abstract = {The term gut-liver axis is used to highlight the close anatomical and functional relationship between the intestine and the liver. The intestine has a highly specialized epithelial membrane which regulates transport across the mucosa. Due to dysbiosis, impairment of the intestinal barrier and altered immunity status, bacterial products can reach the liver through the portal vein, where they are recognized by specific receptors, activate the immune system and lead to a proinflammatory response. Gut microbiota and bacterial translocation play an important role in the pathogenesis of chronic liver diseases, including alcoholic and non-alcoholic fatty liver disease, cirrhosis, and its complications, such as portal hypertension, spontaneous bacterial peritonitis and hepatic encephalopaty. The gut microbiota also plays a critical role as a modulator of bile acid metabolism which can also influence intestinal permeability and portal hypertension through the farnesoid-X receptor. On the other hand, cirrhosis and portal hypertension affect the microbiota and increase translocation, leading to a "chicken and egg" situation, where translocation increases portal pressure, and vice versa. A myriad of therapies targeting gut microbiota have been evaluated specifically in patients with chronic liver disease. Further studies targeting intestinal microbiota and its possible hemodynamic and metabolic effects are needed. This review summarizes the current knowledge about the role of gut microbiota in the pathogenesis of chronic liver diseases and portal hypertension.}, } @article {pmid28547076, year = {2017}, author = {Longhi, MS and Moss, A and Jiang, ZG and Robson, SC}, title = {Purinergic signaling during intestinal inflammation.}, journal = {Journal of molecular medicine (Berlin, Germany)}, volume = {95}, number = {9}, pages = {915-925}, doi = {10.1007/s00109-017-1545-1}, pmid = {28547076}, issn = {1432-1440}, support = {P01 HL087203/HL/NHLBI NIH HHS/United States ; R01 DK108894//National Institutes of Health/ ; R01 HL094400, P01HL107152, P01 HL087203//National Institutes of Health/ ; R01 AI132389/AI/NIAID NIH HHS/United States ; R01 HL094400/HL/NHLBI NIH HHS/United States ; R01 DK108894/DK/NIDDK NIH HHS/United States ; P01 HL107152/HL/NHLBI NIH HHS/United States ; }, mesh = {Adenosine/metabolism ; Animals ; Antigens, CD/metabolism ; Apyrase/metabolism ; Biomarkers ; Dysbiosis ; Exosomes/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; Inflammatory Bowel Diseases/etiology/*metabolism/pathology/therapy ; Lymphocytes/immunology/metabolism ; Macrophages/immunology/metabolism ; Purines/*metabolism ; Receptors, Aryl Hydrocarbon/metabolism ; *Signal Transduction ; }, abstract = {Inflammatory bowel disease (IBD) is a devastating disease that is associated with excessive inflammation in the intestinal tract in genetically susceptible individuals and potentially triggered by microbial dysbiosis. This illness markedly predisposes patients to thrombophilia and chronic debility as well as bowel, lymphatic, and liver cancers. Development of new therapies is needed to re-establish long-term immune tolerance in IBD patients without increasing the risk of opportunistic infections and cancer. Aberrant purinergic signaling pathways have been implicated in disordered thromboregulation and immune dysregulation, as noted in the pathogenesis of IBD and other gastrointestinal/hepatic autoimmune diseases. Expression of CD39 on endothelial or immune cells allows for homeostatic integration of hemostasis and immunity, which are disrupted in IBD. Our focus in this review is on novel aspects of the functions of CD39 and related NTPDases in IBD. Regulated CD39 activity allows for scavenging of extracellular nucleotides, the maintenance of P2-receptor integrity and coordination of adenosinergic signaling responses. CD39 together with CD73, serves as an integral component of the immunosuppressive machinery of dendritic cells, myeloid cells, T and B cells. Genetic inheritance and environental factors closely regulate the levels of expression and phosphohydrolytic activity of CD39, both on immune cells and released microparticles. Purinergic mechanisms associated with T regulatory and supressor T helper type 17 cells modulate disease activity in IBD, as can be modeled in experimental colitis. As a recent example, upregulation of CD39 is dependent upon ligation of the aryl hydrocarbon receptor (AHR), as with natural ligands such as bilirubin and 2-(1' H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). Decreased expression of CD39 and/or dysfunctional AHR signaling, however, abrogates the protective effects of immunosuppressive AHR ligands. These factors could also serve as biomarkers of disease activity in IBD. Heightened thrombosis, inflammation, and immune disturbances as seen in IBD appear to be associated with aberrant purinergic signaling. Ongoing development of therapeutic strategies augmenting CD39 ectonucleotidase bioactivity via cytokines or AHR ligands offers promise for management of thrombophilia, disordered inflammation, and aberrant immune reactivity in IBD.}, } @article {pmid28546791, year = {2017}, author = {Gianotti, RJ and Moss, AC}, title = {Fecal Microbiota Transplantation: From Clostridium difficile to Inflammatory Bowel Disease.}, journal = {Gastroenterology & hepatology}, volume = {13}, number = {4}, pages = {209-213}, pmid = {28546791}, issn = {1554-7914}, abstract = {Fecal microbiota transplantation (FMT) has evolved from a case report in the medical literature to the basis of major innovations in the treatment of Clostridium difficile infection (CDI) and, potentially, inflammatory bowel disease (IBD). In the clinical setting, FMT was noted to significantly lower the risk of recurrent CDI, likely by increasing microbial diversity and altering the metabolic environment in the intestinal tract of recipients. In parallel, advances in the ability to quantify and characterize microbial communities in fecal samples led to the association of IBD with a state of intestinal dysbiosis. Consequently, a number of case series and randomized, controlled trials have evaluated FMT in treating active ulcerative colitis or Crohn's disease. Unlike in CDI, the efficacy of FMT in the treatment of IBD appears to be influenced by a number of factors, including donor microbial profiles, inflammatory burden, and the microbial diversity of the recipient. The therapeutic potential of the microbiome has led to a number of biotechnology and pharmaceutical companies isolating specific strains from healthy stool for use as targeted therapies for IBD in clinical trials. Ongoing studies are likely to determine the missing link between the efficacy of FMT and its impact on microbial communities and mucosal inflammation.}, } @article {pmid28546789, year = {2017}, author = {Lichtenstein, GR}, title = {Fecal Microbiota Transplantation: An Update.}, journal = {Gastroenterology & hepatology}, volume = {13}, number = {4}, pages = {203}, pmid = {28546789}, issn = {1554-7914}, } @article {pmid28545829, year = {2017}, author = {Kang, Y and Cai, Y}, title = {Gut microbiota and hepatitis-B-virus-induced chronic liver disease: implications for faecal microbiota transplantation therapy.}, journal = {The Journal of hospital infection}, volume = {96}, number = {4}, pages = {342-348}, doi = {10.1016/j.jhin.2017.04.007}, pmid = {28545829}, issn = {1532-2939}, mesh = {Dysbiosis/*therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Hepatitis B, Chronic/*complications/*therapy ; Humans ; }, abstract = {Hepatitis B is one of the most common infectious diseases globally. It has been estimated that there are 350 million chronic hepatitis B virus (HBV) carriers worldwide. The liver is connected to the small intestine by the bile duct, which carries bile formed in the liver to the intestine. Nearly all of the blood that leaves the stomach and intestines must pass through the liver. Human intestines contain a wide diversity of microbes, collectively termed the 'gut microbiota'. Gut microbiota play a significant role in host metabolic processes and host immune modulation, and influence host development and physiology (organ development). Altered gut microbiota is a common complication in liver disease. Changes in intestinal microbiota seem to play an important role in induction and promotion of HBV-induced chronic liver disease progression, and specific species among the intestinal commensal bacteria may play either a pathogenic or a protective role in the development of HBV-induced chronic liver disease. Thus, the gut microbiome may represent fertile targets for prevention or management of HBV-induced chronic liver disease. Faecal microbiota transplantation (FMT) may be a useful therapy for HBV-related disease in the future. However, the data available in this field remain limited, and relevant scientific work has only just commenced. New technologies have enabled systematic studies of gut microbiota, and provided more realistic information about its composition and pathological variance. This review summarizes the cutting edge of research into the relationship between gut microbiota and HBV-induced chronic liver disease, and the future prospects of FMT therapy.}, } @article {pmid28545248, year = {2017}, author = {Wang, JH and Kim, BS and Han, K and Kim, H}, title = {Ephedra-Treated Donor-Derived Gut Microbiota Transplantation Ameliorates High Fat Diet-Induced Obesity in Rats.}, journal = {International journal of environmental research and public health}, volume = {14}, number = {6}, pages = {}, doi = {10.3390/ijerph14060555}, pmid = {28545248}, issn = {1660-4601}, mesh = {Adipose Tissue ; Animals ; Blood Glucose/analysis ; Body Weight ; Cecum/microbiology ; Chemokine CCL2 ; Cytokines/genetics ; Diet, High-Fat ; *Ephedra ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/drug effects ; Gene Expression ; Insulin/blood ; Insulin Resistance ; Liver ; Male ; Metabolic Diseases/blood/*therapy ; Obesity/blood/*therapy ; Plant Extracts/*pharmacology ; Rats, Sprague-Dawley ; }, abstract = {Changes in gut microbiota (GM) are closely associated with metabolic syndrome, obesity, type 2 diabetes and so on. Several medicinal herbs, including Ephedra sinica (Es), have anti-obesity effects that ameliorate metabolic disorders. Therefore, in this study we evaluated whether Es maintains its anti-obesity effect through Es-altered gut microbiota (EsM) transplantation. GM was isolated from cecal contents of Es treated and untreated rats following repeated transplants into obese rats via oral gavage over three weeks. High-fat-diet (HFD)-induced obese rats transplanted with EsM lost significant body weight, epididymal fat, and perirenal fat weight, but no remarkable changes were observed in abdominal fat, liver, cecum weight and food efficiency ratio. In addition, treatment with EsM also significantly lowered the fasting blood glucose, serum insulin level, and insulin resistance index. Meanwhile, EsM transplantation significantly reduced gene expression of proinflammatory cytokines interleukin-1 and monocyte chemotactic protein-1. Rats treated with EsM also showed changed GM composition, especially blautia, roseburia and clostridium, significantly reduced the level of endotoxin and markedly increased the acetic acid in feces. Overall, our results demonstrated that EsM ameliorates HFD-induced obesity and related metabolic disorders, like hyperglycemia and insulin resistance, and is strongly associated with modulating the distribution of GM, enterogenous endotoxin and enteral acetic acid.}, } @article {pmid28543188, year = {2017}, author = {Chitrala, KN and Guan, H and Singh, NP and Busbee, B and Gandy, A and Mehrpouya-Bahrami, P and Ganewatta, MS and Tang, C and Chatterjee, S and Nagarkatti, P and Nagarkatti, M}, title = {CD44 deletion leading to attenuation of experimental autoimmune encephalomyelitis results from alterations in gut microbiome in mice.}, journal = {European journal of immunology}, volume = {47}, number = {7}, pages = {1188-1199}, doi = {10.1002/eji.201646792}, pmid = {28543188}, issn = {1521-4141}, support = {R01 AI129788/AI/NIAID NIH HHS/United States ; R01 MH094755/MH/NIMH NIH HHS/United States ; R01 ES019313/ES/NIEHS NIH HHS/United States ; P20 GM103641/GM/NIGMS NIH HHS/United States ; P01 AT003961/AT/NCCIH NIH HHS/United States ; R01 AT006888/AT/NCCIH NIH HHS/United States ; R01 AI123947/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteroidetes/genetics/immunology/isolation & purification ; Disease Models, Animal ; Dysbiosis ; Encephalomyelitis, Autoimmune, Experimental/*immunology/physiopathology ; Fatty Acids, Volatile/immunology ; Fecal Microbiota Transplantation ; Feces/microbiology ; Firmicutes/genetics/immunology/isolation & purification ; Gastrointestinal Microbiome/genetics/*immunology ; Gene Deletion ; Hyaluronan Receptors/*genetics/*immunology ; Metagenomics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Propionates/metabolism ; RNA, Ribosomal, 16S ; }, abstract = {Dysbiosis in gut microbiome has been shown to be associated with inflammatory and autoimmune diseases. Previous studies from our laboratory demonstrated the pivotal role played by CD44 in the regulation of EAE, a murine model of multiple sclerosis. In the current study, we determined whether these effects resulted from an alteration in gut microbiota and the short-chain fatty acid (SCFA) production in CD44 knockout (CD44KO) mice. Fecal transfer from naïve CD44KO but not C57BL/6 wild type (CD44WT) mice, into EAE-induced CD44WT mice, led to significant amelioration of EAE. High-throughput bacterial 16S rRNA gene sequencing, followed by clustering sequences into operational taxonomic units (OTUs) and biochemical analysis, revealed that EAE-induced CD44KO mice showed significant diversity, richness, and evenness when compared to EAE-induced CD44WT mice at the phylum level, with dominant Bacteroidetes (68.5%) and low Firmicutes (26.8%). Further, data showed a significant change in the abundance of SCFAs, propionic acid, and i-butyric acid in EAE-CD44KO compared to EAE-CD44WT mice. In conclusion, our results demonstrate that the attenuation of EAE seen following CD44 gene deletion in mice may result from alterations in the gut microbiota and SCFAs. Furthermore, our studies also demonstrate that the phenotype of gene knock-out animals may be shaped by gut microbiota.}, } @article {pmid28542111, year = {2017}, author = {Nanayakkara, D and Nanda, N}, title = {Clostridium difficile infection in solid organ transplant recipients.}, journal = {Current opinion in organ transplantation}, volume = {22}, number = {4}, pages = {314-319}, doi = {10.1097/MOT.0000000000000430}, pmid = {28542111}, issn = {1531-7013}, mesh = {Clostridium Infections/*etiology/pathology ; Clostridium difficile/*pathogenicity ; Humans ; Organ Transplantation/*adverse effects/mortality ; Risk Factors ; Survival Analysis ; Transplant Recipients ; }, abstract = {PURPOSE OF REVIEW: Clostridium difficile infection (CDI) is a major healthcare-associated infection that causes significant morbidity and an economic impact in the United States. In this review, we provide an overview of Clostridium difficile infection in solid organ transplant recipients with an emphasis on recent literature.

RECENT FINDINGS: C. difficile in solid organ transplant population has unique risk factors. Fecal microbiota transplantation has shown favorable results in treatment of recurrent C. difficile in this population. Preliminary data from animal studies suggests excellent efficacy with immunization against C. difficile toxins.

SUMMARY: Over the last decade, number of individuals receiving solid organ transplants has increased exponentially making peri-transplant complications a common occurrence.C. difficile is a frequent cause of morbidity in solid organ transplant recipients. Early and accurate diagnosis of C. difficile requires a stepwise approach. Differentiating between asymptomatic carriage and infection is a diagnostic challenge. Microbial diversity is inversely proportional to risk of C. difficile infection. Antimicrobial stewardship programs help to retain microbial diversity in individuals susceptible to CDI. Recurrent or relapsing C. difficile infection require fecal microbiota transplantation for definitive cure.}, } @article {pmid28541799, year = {2017}, author = {Vujkovic-Cvijin, I and Rutishauser, RL and Pao, M and Hunt, PW and Lynch, SV and McCune, JM and Somsouk, M}, title = {Limited engraftment of donor microbiome via one-time fecal microbial transplantation in treated HIV-infected individuals.}, journal = {Gut microbes}, volume = {8}, number = {5}, pages = {440-450}, doi = {10.1080/19490976.2017.1334034}, pmid = {28541799}, issn = {1949-0984}, support = {P30 AI027763/AI/NIAID NIH HHS/United States ; T32 AI007334/AI/NIAID NIH HHS/United States ; T32 AI060530/AI/NIAID NIH HHS/United States ; R21 DK104664/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Dysbiosis/*therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; HIV Infections/*complications ; Humans ; Male ; Middle Aged ; Treatment Outcome ; }, abstract = {Many HIV-infected individuals on antiretroviral therapy (ART) exhibit persistent systemic inflammation, which predicts morbidity and mortality. ART-treated subjects concurrently exhibit marked compositional alterations in the gut bacterial microbiota and the degree of dysbiosis correlates with systemic inflammation. Whether interventions to modulate the microbiome can affect systemic inflammation is unknown. An open-label fecal microbial transplantation (FMT) was delivered by colonoscopy to asymptomatic HIV-infected ART-suppressed individuals without antibiotic pre-treatment. Stool was assessed before and after FMT for engraftment of donor microbes, and peripheral blood was assayed for immune activation biomarkers. Six participants received FMT and 2 participants served as controls. No serious adverse effects occurred during 24 weeks of follow-up. At baseline, HIV-infected individuals exhibited microbiota profiles distinct from uninfected donors. During the 8 weeks post-FMT, recipients demonstrated partial engraftment of the donor microbiome (P < 0.05). Recipient microbiota remained significantly distant from donors, unlike that observed following FMT for treatment of C. difficile infection. Systemic inflammatory markers showed no significant change post-FMT. FMT was well-tolerated in ART-treated, HIV-infected individuals. Engraftment was detectable but modest, and appeared to be limited to specific bacterial taxa. Whether antibiotic conditioning can enhance engraftment and the capacity of microbiota to modulate inflammation remains to be investigated.}, } @article {pmid28540921, year = {2017}, author = {Suez, J and Elinav, E}, title = {The path towards microbiome-based metabolite treatment.}, journal = {Nature microbiology}, volume = {2}, number = {}, pages = {17075}, doi = {10.1038/nmicrobiol.2017.75}, pmid = {28540921}, issn = {2058-5276}, mesh = {Bacteria/*metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Microbial Interactions ; Prebiotics/administration & dosage ; Precision Medicine/methods ; Probiotics/*therapeutic use ; }, abstract = {The increasing evidence pointing towards the involvement of the gut microbiome in multiple diseases, as well as its plasticity, renders it a desirable potential therapeutic target. Nevertheless, classical therapies based on the consumption of live probiotic bacteria, or their enrichment by prebiotics, exhibit limited efficacy. Recently, a novel therapeutic approach has been suggested based on metabolites secreted, modulated or degraded by the microbiome. As many of the host-microorganism interactions pertaining to human health are mediated by metabolites, this approach may be able to provide therapeutic efficacy while overcoming caveats of current microbiome-targeting therapies, such as colonization resistance and inter-individual variation in microbial composition. In this Perspective, we will discuss the evidence that supports pursuing the metabolite-based therapeutic approach as well as issues critical for its implementation. In a broader context, we will discuss how recent advances in microbiome research may improve and refine current treatment modalities, and the potential of combining them with metabolite-based interventions as a means of achieving a person-specific, integrated and efficient therapy.}, } @article {pmid28540475, year = {2017}, author = {Witte, T and Pieper, DH and Heidrich, B}, title = {[Intestinal microbiota in individualized therapies].}, journal = {Der Internist}, volume = {58}, number = {7}, pages = {682-686}, doi = {10.1007/s00108-017-0259-3}, pmid = {28540475}, issn = {1432-1289}, mesh = {Animals ; *Clostridium difficile ; Enterocolitis, Pseudomembranous/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; }, abstract = {During recent years, the analysis of the human microbiota has been receiving more and more scientific focus. Deep sequencing analysis enables characterization of microbial communities in different environments without the need of culture-based methods. Hereby, information about microbial communities is increasing enormously. Numerous studies in humans and animal models revealed the important role of the microbiome in emergence and natural course of diseases such as autoimmune diseases and metabolic disorders, e. g., the metabolic syndrome. The identification of causalities between the intestinal microbiota composition and function, and diseases in humans and animal models can help to develop individualized therapies targeting the microbiome and its modification. Nowadays, it is established that several factors influence the composition of the microbiota. Diet it is one of the major factors shaping the microbiota and the use of pro- and prebiotica may induce changes in the microbial community. Fecal microbiome transfer is the first approach targeting the intestinal microbiota which is implemented in the clinical routine for patients with therapy-refractory infections with Clostridium difficile. Herewith, the recipient's microbiota can be changed permanently and the patient can be cured from the infection.}, } @article {pmid28539351, year = {2018}, author = {Zuo, T and Wong, SH and Lam, K and Lui, R and Cheung, K and Tang, W and Ching, JYL and Chan, PKS and Chan, MCW and Wu, JCY and Chan, FKL and Yu, J and Sung, JJY and Ng, SC}, title = {Bacteriophage transfer during faecal microbiota transplantation in Clostridium difficile infection is associated with treatment outcome.}, journal = {Gut}, volume = {67}, number = {4}, pages = {634-643}, doi = {10.1136/gutjnl-2017-313952}, pmid = {28539351}, issn = {1468-3288}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*therapeutic use ; *Bacteriophages ; Case-Control Studies ; Clostridium Infections/*therapy ; *Fecal Microbiota Transplantation ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Vancomycin/*therapeutic use ; }, abstract = {OBJECTIVE: Faecal microbiota transplantation (FMT) is effective for the treatment of recurrent Clostridium difficile infection (CDI). Studies have shown bacterial colonisation after FMT, but data on viral alterations in CDI are scarce. We investigated enteric virome alterations in CDI and the association between viral transfer and clinical outcome in patients with CDI.

DESIGN: Ultra-deep metagenomic sequencing of virus-like particle preparations and bacterial 16S rRNA sequencing were performed on stool samples from 24 subjects with CDI and 20 healthy controls. We longitudinally assessed the virome and bacterial microbiome changes in nine CDI subjects treated with FMT and five treated with vancomycin. Enteric virome alterations were assessed in association with treatment response.

RESULTS: Subjects with CDI demonstrated a significantly higher abundance of bacteriophage Caudovirales and a lower Caudovirales diversity, richness and evenness compared with healthy household controls. Significant correlations were observed between bacterial families Proteobacteria, Actinobacteria and Caudovirales taxa in CDI. FMT treatment resulted in a significant decrease in the abundance of Caudovirales in CDI. Cure after FMT was observed when donor-derived Caudovirales contigs occupied a larger fraction of the enteric virome in the recipients (p=0.024). In treatment responders, FMT was associated with alterations in the virome and the bacterial microbiome, while vancomycin treatment led to alterations in the bacterial community alone.

CONCLUSIONS: In a preliminary study, CDI is characterised by enteric virome dysbiosis. Treatment response in FMT was associated with a high colonisation level of donor-derived Caudovirales taxa in the recipient. Caudovirales bacteriophages may play a role in the efficacy of FMT in CDI.

TRIAL REGISTRATION NUMBER: NCT02570477.}, } @article {pmid28536285, year = {2017}, author = {Kang, C and Wang, B and Kaliannan, K and Wang, X and Lang, H and Hui, S and Huang, L and Zhang, Y and Zhou, M and Chen, M and Mi, M}, title = {Gut Microbiota Mediates the Protective Effects of Dietary Capsaicin against Chronic Low-Grade Inflammation and Associated Obesity Induced by High-Fat Diet.}, journal = {mBio}, volume = {8}, number = {3}, pages = {}, doi = {10.1128/mBio.00470-17}, pmid = {28536285}, issn = {2150-7511}, mesh = {Animals ; Anti-Obesity Agents/*administration & dosage ; Capsaicin/*administration & dosage ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Diet, High-Fat ; Disease Models, Animal ; Dysbiosis/complications ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; Inflammation/complications ; Mice ; Obesity/*prevention & control ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Metabolic endotoxemia originating from dysbiotic gut microbiota has been identified as a primary mediator for triggering the chronic low-grade inflammation (CLGI) responsible for the development of obesity. Capsaicin (CAP) is the major pungent bioactivator in chili peppers and has potent anti-obesity functions, yet the mechanisms linking this effect to gut microbiota remain obscure. Here we show that mice fed a high-fat diet (HFD) supplemented with CAP exhibit lower levels of metabolic endotoxemia and CLGI associated with lower body weight gain. High-resolution responses of the microbiota were examined by 16S rRNA sequencing, short-chain fatty acid (SCFA) measurements, and phylogenetic reconstruction of unobserved states (PICRUSt) analysis. The results showed, among others, that dietary CAP induced increased levels of butyrate-producing Ruminococcaceae and Lachnospiraceae, while it caused lower levels of members of the lipopolysaccharide (LPS)-producing family S24_7. Predicted function analysis (PICRUSt) showed depletion of genes involved in bacterial LPS synthesis in response to CAP. We further identified that inhibition of cannabinoid receptor type 1 (CB1) by CAP also contributes to prevention of HFD-induced gut barrier dysfunction. Importantly, fecal microbiota transplantation experiments conducted in germfree mice demonstrated that dietary CAP-induced protection against HFD-induced obesity is transferrable. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block the CAP-induced protective phenotype against obesity, further suggesting the role of microbiota in this context. Together, our findings uncover an interaction between dietary CAP and gut microbiota as a novel mechanism for the anti-obesity effect of CAP acting through prevention of microbial dysbiosis, gut barrier dysfunction, and chronic low-grade inflammation.IMPORTANCE Metabolic endotoxemia due to gut microbial dysbiosis is a major contributor to the pathogenesis of chronic low-grade inflammation (CLGI), which primarily mediates the development of obesity. A dietary strategy to reduce endotoxemia appears to be an effective approach for addressing the issue of obesity. Capsaicin (CAP) is the major pungent component in red chili (genus Capsicum). Little is known about the role of gut microbiota in the anti-obesity effect of CAP. High-throughput 16S rRNA gene sequencing revealed that CAP significantly increased butyragenic bacteria and decreased LPS-producing bacteria (e.g., members of the S24-7 family) and LPS biosynthesis. By using antibiotics and microbiota transplantation, we prove that gut microbiota plays a causal role in dietary CAP-induced protective phenotype against high-fat-diet-induced CLGI and obesity. Moreover, CB1 inhibition was partially involved in the beneficial effect of CAP. Together, these data suggest that the gut microbiome is a critical factor for the anti-obesity effects of CAP.}, } @article {pmid28531908, year = {2017}, author = {Bafeta, A and Yavchitz, A and Riveros, C and Batista, R and Ravaud, P}, title = {Methods and Reporting Studies Assessing Fecal Microbiota Transplantation: A Systematic Review.}, journal = {Annals of internal medicine}, volume = {167}, number = {1}, pages = {34-39}, doi = {10.7326/M16-2810}, pmid = {28531908}, issn = {1539-3704}, mesh = {Clostridium Infections/therapy ; Clostridium difficile ; *Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/therapy ; *Research Design ; }, abstract = {Background: Fecal microbiota transplantation (FMT) could be a novel treatment option for several chronic diseases associated with altered gut microbiota.

Purpose: To examine the conduct and reporting of studies assessing FMT.

Data Sources: Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science from inception to 31 January 2017.

Study Selection: Two reviewers independently examined titles and abstracts to identify all English-language reports of human clinical studies assessing the safety or efficacy of FMT.

Data Extraction: Three reviewers independently assessed study types and characteristics and the reporting of important methodological components of the FMT intervention.

Data Synthesis: Most (84%) of the 85 published reports found addressed the use of FMTs for Clostridium difficile infection or inflammatory bowel disease, and most (87%) were non-randomized controlled trials. Important methodological components that were not reported in published studies included the following: eligibility criteria for donors (47%), materials used for collecting stools and the period of collection (96%), methods used for conservation of stools (76%), the amount and type of stools used (for example, fresh or frozen), and duration of stool conservation (67%). Many (58%) did not report an analysis of microbiota composition.

Limitations: Lack of universal consensus regarding the most important methodological components of FMT and inability to assess the actual conduct of studies and whether the publication process affected the completeness of reporting.

Conclusion: Key components of FMT interventions, which are necessary to replicate and understand study findings about efficacy and safety, are poorly reported.

Primary Funding Source: No specific funding.}, } @article {pmid28531905, year = {2017}, author = {Young, VB}, title = {Treatment With Fecal Microbiota Transplantation: The Need for Complete Methodological Reporting for Clinical Trials.}, journal = {Annals of internal medicine}, volume = {167}, number = {1}, pages = {61-62}, doi = {10.7326/M17-1157}, pmid = {28531905}, issn = {1539-3704}, support = {U01 AI124255/AI/NIAID NIH HHS/United States ; U19 AI116482/AI/NIAID NIH HHS/United States ; }, mesh = {Clinical Trials as Topic/*standards ; Clostridium Infections/*therapy ; *Clostridium difficile ; *Fecal Microbiota Transplantation ; Humans ; Research Design/standards ; }, } @article {pmid28530702, year = {2017}, author = {Wu, H and Esteve, E and Tremaroli, V and Khan, MT and Caesar, R and Mannerås-Holm, L and Ståhlman, M and Olsson, LM and Serino, M and Planas-Fèlix, M and Xifra, G and Mercader, JM and Torrents, D and Burcelin, R and Ricart, W and Perkins, R and Fernàndez-Real, JM and Bäckhed, F}, title = {Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug.}, journal = {Nature medicine}, volume = {23}, number = {7}, pages = {850-858}, doi = {10.1038/nm.4345}, pmid = {28530702}, issn = {1546-170X}, mesh = {Animals ; Bile Acids and Salts/metabolism ; DNA, Bacterial/*analysis ; Diabetes Mellitus, Type 2/*drug therapy/microbiology ; Double-Blind Method ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation ; Feces/chemistry/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Germ-Free Life ; Glucose Tolerance Test ; Humans ; Hypoglycemic Agents/*therapeutic use ; In Vitro Techniques ; Male ; Metagenomics ; Metformin/*therapeutic use ; Mice ; Middle Aged ; }, abstract = {Metformin is widely used in the treatment of type 2 diabetes (T2D), but its mechanism of action is poorly defined. Recent evidence implicates the gut microbiota as a site of metformin action. In a double-blind study, we randomized individuals with treatment-naive T2D to placebo or metformin for 4 months and showed that metformin had strong effects on the gut microbiome. These results were verified in a subset of the placebo group that switched to metformin 6 months after the start of the trial. Transfer of fecal samples (obtained before and 4 months after treatment) from metformin-treated donors to germ-free mice showed that glucose tolerance was improved in mice that received metformin-altered microbiota. By directly investigating metformin-microbiota interactions in a gut simulator, we showed that metformin affected pathways with common biological functions in species from two different phyla, and many of the metformin-regulated genes in these species encoded metalloproteins or metal transporters. Our findings provide support for the notion that altered gut microbiota mediates some of metformin's antidiabetic effects.}, } @article {pmid28529928, year = {2017}, author = {Ekmekciu, I and von Klitzing, E and Fiebiger, U and Neumann, C and Bacher, P and Scheffold, A and Bereswill, S and Heimesaat, MM}, title = {The Probiotic Compound VSL#3 Modulates Mucosal, Peripheral, and Systemic Immunity Following Murine Broad-Spectrum Antibiotic Treatment.}, journal = {Frontiers in cellular and infection microbiology}, volume = {7}, number = {}, pages = {167}, doi = {10.3389/fcimb.2017.00167}, pmid = {28529928}, issn = {2235-2988}, mesh = {Adaptive Immunity/*immunology ; Animals ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; B-Lymphocytes ; Bacteria/classification/*drug effects/*immunology ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Colon ; Cytokines/metabolism ; Dendritic Cells/immunology ; Drug Combinations ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects/*immunology ; Immunity, Innate/*immunology ; Immunohistochemistry ; Intestinal Mucosa/immunology/microbiology ; Intestines/immunology/microbiology ; Lymph Nodes ; Mice ; Mice, Inbred C57BL ; Probiotics/pharmacology/*therapeutic use ; Spleen ; T-Lymphocytes/immunology ; T-Lymphocytes, Regulatory ; }, abstract = {There is compelling evidence linking the commensal intestinal microbiota with host health and, in turn, antibiotic induced perturbations of microbiota composition with distinct pathologies. Despite the attractiveness of probiotic therapy as a tool to beneficially alter the intestinal microbiota, its immunological effects are still incompletely understood. The aim of the present study was to assess the efficacy of the probiotic formulation VSL#3 consisting of eight distinct bacterial species (including Streptococcus thermophilus, Bifidobacterium breve, B. longum, B. infantis, Lactobacillus acidophilus, L. plantarum, L. paracasei, and L. delbrueckii subsp. Bulgaricus) in reversing immunological effects of microbiota depletion as compared to reassociation with a complex murine microbiota. To address this, conventional mice were subjected to broad-spectrum antibiotic therapy for 8 weeks and perorally reassociated with either VSL#3 bacteria or a complex murine microbiota. VSL#3 recolonization resulted in restored CD4+ and CD8+ cell numbers in the small and large intestinal lamina propria as well as in B220+ cell numbers in the former, whereas probiotic intervention was not sufficient to reverse the antibiotic induced changes of respective cell populations in the spleen. However, VSL#3 application was as efficient as complex microbiota reassociation to attenuate the frequencies of regulatory T cells, activated dendritic cells and memory/effector T cells in the small intestine, colon, mesenteric lymph nodes, and spleen. Whereas broad-spectrum antibiotic treatment resulted in decreased production of cytokines such as IFN-γ, IL-17, IL-22, and IL-10 by CD4+ cells in respective immunological compartments, VSL#3 recolonization was sufficient to completely recover the expression of the anti-inflammatory cytokine IL-10 without affecting pro-inflammatory mediators. In summary, the probiotic compound VSL#3 has an extensive impact on mucosal, peripheral, and systemic innate as well as adaptive immunity, exerting beneficial anti-inflammatory effects in intestinal as well as systemic compartments. Hence, VSL#3 might be considered a therapeutic immunomodulatory tool following antibiotic therapy.}, } @article {pmid28529025, year = {2017}, author = {Terveer, EM and van Beurden, YH and Goorhuis, A and Seegers, JFML and Bauer, MP and van Nood, E and Dijkgraaf, MGW and Mulder, CJJ and Vandenbroucke-Grauls, CMJE and Verspaget, HW and Keller, JJ and Kuijper, EJ}, title = {How to: Establish and run a stool bank.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {23}, number = {12}, pages = {924-930}, doi = {10.1016/j.cmi.2017.05.015}, pmid = {28529025}, issn = {1469-0691}, mesh = {Biological Specimen Banks/*organization & administration/standards ; *Fecal Microbiota Transplantation ; *Feces ; Humans ; Netherlands ; }, abstract = {BACKGROUND: Since 2013, several stool banks have been developed following publications reporting on clinical success of 'faecal microbiota transplantation' (FMT) for recurrent Clostridium difficile infections (CDI). However, protocols for donor screening, faecal suspension preparation, and transfer of the faecal suspension differ between countries and institutions. Moreover, no European consensus exists regarding the legislative aspects of the faecal suspension product. Internationally standardized recommendations about the above mentioned aspects have not yet been established.

OBJECTIVE: In 2015, the Netherlands Donor Feces Bank (NDFB) was founded with the primary aim of providing a standardized product for the treatment of patients with recurrent CDI in the Netherlands. Standard operation procedures for donor recruitment, donor selection, donor screening, and production, storage, and distribution of frozen faecal suspensions for FMT were formulated.

RESULTS AND DISCUSSION: Our experience summarized in this review addresses current donor recruitment and screening, preparation of the faecal suspension, transfer of the faecal microbiota suspension, and the experiences and follow-up of the patients treated with donor faeces from the NDFB.}, } @article {pmid28526488, year = {2017}, author = {Wiest, R and Albillos, A and Trauner, M and Bajaj, JS and Jalan, R}, title = {Targeting the gut-liver axis in liver disease.}, journal = {Journal of hepatology}, volume = {67}, number = {5}, pages = {1084-1103}, doi = {10.1016/j.jhep.2017.05.007}, pmid = {28526488}, issn = {1600-0641}, mesh = {Disease Management ; Fecal Microbiota Transplantation/methods ; Gastrointestinal Microbiome/*physiology ; Humans ; *Liver Diseases/microbiology/physiopathology/therapy ; }, abstract = {The gut-liver axis is widely implicated in the pathogenesis of liver diseases, where it is increasingly the focus of clinical research. Recent studies trialling an array of therapeutic and preventative strategies have yielded promising results. Considering these strategies, the armamentarium for targeting the gut-liver axis will continue to expand. Further clinical trials, translated from our current knowledge of the gut-liver axis, promise an exciting future in liver treatment.}, } @article {pmid28522956, year = {2017}, author = {Bak, SH and Choi, HH and Lee, J and Kim, MH and Lee, YH and Kim, JS and Cho, YS}, title = {Fecal microbiota transplantation for refractory Crohn's disease.}, journal = {Intestinal research}, volume = {15}, number = {2}, pages = {244-248}, doi = {10.5217/ir.2017.15.2.244}, pmid = {28522956}, issn = {1598-9100}, abstract = {Approximately one-third of patients with Crohn's disease do not respond to conventional treatments, and some experience significant adverse effects, such as serious infections and lymphoma, and many patients require surgery due to complications. Increasing evidence suggests that specific changes in the composition of gut microbiota, termed as dysbiosis, are a common feature in patients with inflammatory bowel disease (IBD). Dysbiosis can lead to activation of the mucosal immune system, resulting in chronic inflammation and the development of mucosal lesions. Recently, fecal microbiota transplantation, aimed at modifying the composition of gut microbiota to overcome dysbiosis, has become a potential alternative therapeutic option for IBD. Herein, we present a patient with Crohn's colitis in whom biologic therapy failed previously, but clinical remission and endoscopic improvement was achieved after a single fecal microbiota transplantation infusion.}, } @article {pmid28522941, year = {2017}, author = {Eun, CS}, title = {Is there a potential role of fecal microbiota transplantation in the treatment of inflammatory bowel disease?.}, journal = {Intestinal research}, volume = {15}, number = {2}, pages = {145-146}, doi = {10.5217/ir.2017.15.2.145}, pmid = {28522941}, issn = {1598-9100}, } @article {pmid30225401, year = {2017}, author = {Tariq, R and Weatherly, RM and Kammer, PP and Pardi, DS and Khanna, S}, title = {Experience and Outcomes at a Specialized Clostridium difficile Clinical Practice.}, journal = {Mayo Clinic proceedings. Innovations, quality & outcomes}, volume = {1}, number = {1}, pages = {49-56}, doi = {10.1016/j.mayocpiqo.2017.05.002}, pmid = {30225401}, issn = {2542-4548}, abstract = {Objective: To report our experience with and outcomes among patients referred to a specialized Clostridium difficile clinical practice.

Patients and Methods: We retrospectively identified consecutive patients referred for Clostridium difficile infection (CDI) management from January 1, 2013, through May 30, 2015. Data were collected for demographic characteristics, CDI history, final diagnoses, and management.

Results: Overall, 211 patients (median age, 65 years; 66.4% women) were included. The most common indications for referral were recurrent CDI in 199 patients (94.3%), first CDI episode in 5 patients (2.4%), and chronic diarrhea in 7 patients (3.3%). After evaluation, the diagnoses were recurrent CDI in 127 patients (60.2%), resolved CDI in 36 patients (17.1%), first-episode CDI in 5 patients (2.4%), and non-CDI in 43 patients (20.4%). The most common non-CDI diagnoses were postinfection irritable bowel syndrome (PI-IBS) in 32 patients (15.2% overall), inflammatory bowel disease (n=3), small intestinal bacterial overgrowth (n=2), microscopic colitis (n=1), and asymptomatic C difficile colonization (n=2). Two patients had diabetic gastroparesis and food intolerances, and 1 had chronic constipation with overflow diarrhea. Of 127 patients with recurrent CDI, 30 (23.6%) received antibiotics; of these 30, 12 had antibiotic treatment failure and received fecal microbiota transplantation (FMT) for recurrent CDI. Among 97 patients (76.4%) who underwent FMT, 85 (87.6%) were cured after the first FMT, 5 were cured after the second FMT, and 7 were treated with antibiotics for FMT failure, with resolution of symptoms.

Conclusion: A substantial proportion of patients referred for CDI subsequently received alternative diagnoses; PI-IBS was the most common. Patients being referred for recurrent CDI should be evaluated carefully for alternative diagnoses.}, } @article {pmid28513974, year = {2017}, author = {Alrabaa, S and Jariwala, R and Zeitler, K and Montero, J}, title = {Fecal microbiota transplantation outcomes in immunocompetent and immunocompromised patients: A single-center experience.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {19}, number = {4}, pages = {}, doi = {10.1111/tid.12726}, pmid = {28513974}, issn = {1399-3062}, mesh = {Aged ; Clostridium Infections/microbiology/*surgery ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Humans ; Immunocompromised Host ; Male ; Middle Aged ; Risk Factors ; Treatment Outcome ; }, abstract = {BACKGROUND: Clostridium difficile infection (CDI) is a major infectious disease focus for which fecal microbiota transplantation (FMT) has been used with success in various patient populations.

METHODS: We conducted a retrospective study of FMT in immunocompetent and immunocompromised patients to review outcomes at our center, with a focus on identifying risk factors for FMT failure in solid organ transplant (SOT) patients. FMT was conducted using universal banked frozen stool via naso-duodenal tube in patients with recurrent CDI of 3 or more episodes per our institutional protocol.

RESULTS: Thirteen patients were included in the analysis, 6 who were immunocompetent and 7 who were immunocompromised. Of these, 6 patients had a history of SOT and were primarily abdominal organ recipients. All immunocompetent patients experienced success with FMT, while 3 immunocompromised SOT patients experienced failure. Two patients who failed FMT had a second FMT, which was successful in one patient and failed in the second patient. No adverse events were noted with FMT administration. A predictor of FMT failure was antimicrobial exposure pre-FMT.

CONCLUSIONS: This study highlights the safe use of FMT for recurrent CDI with variable efficacy in immunocompromised patients. Antimicrobial exposure prior to FMT was an identified risk factor for FMT failure. The use of sequential FMT in SOT patients may be considered but ultimately requires further investigation.}, } @article {pmid28506317, year = {2017}, author = {Khanna, S and Vazquez-Baeza, Y and González, A and Weiss, S and Schmidt, B and Muñiz-Pedrogo, DA and Rainey, JF and Kammer, P and Nelson, H and Sadowsky, M and Khoruts, A and Farrugia, SL and Knight, R and Pardi, DS and Kashyap, PC}, title = {Changes in microbial ecology after fecal microbiota transplantation for recurrent C. difficile infection affected by underlying inflammatory bowel disease.}, journal = {Microbiome}, volume = {5}, number = {1}, pages = {55}, doi = {10.1186/s40168-017-0269-3}, pmid = {28506317}, issn = {2049-2618}, support = {K08 DK100638/DK/NIDDK NIH HHS/United States ; P30 DK084567/DK/NIDDK NIH HHS/United States ; R03 DK111850/DK/NIDDK NIH HHS/United States ; UL1 TR000135/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacteria/*classification/genetics ; Clostridium Infections/complications/microbiology/*therapy ; Clostridium difficile/physiology ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*complications/microbiology ; Male ; Middle Aged ; Sequence Analysis, DNA ; Young Adult ; }, abstract = {BACKGROUND: Gut microbiota play a key role in maintaining homeostasis in the human gut. Alterations in the gut microbial ecosystem predispose to Clostridium difficile infection (CDI) and gut inflammatory disorders such as inflammatory bowel disease (IBD). Fecal microbiota transplantation (FMT) from a healthy donor can restore gut microbial diversity and pathogen colonization resistance; consequently, it is now being investigated for its ability to improve inflammatory gut conditions such as IBD. In this study, we investigated changes in gut microbiota following FMT in 38 patients with CDI with or without underlying IBD.

RESULTS: There was a significant change in gut microbial composition towards the donor microbiota and an overall increase in microbial diversity consistent with previous studies after FMT. FMT was successful in treating CDI using a diverse set of donors, and varying degrees of donor stool engraftment suggesting that donor type and degree of engraftment are not drivers of a successful FMT treatment of CDI. However, patients with underlying IBD experienced an increased number of CDI relapses (during a 24-month follow-up) and a decreased growth of new taxa, as compared to the subjects without IBD. Moreover, the need for IBD therapy did not change following FMT. These results underscore the importance of the existing gut microbial landscape as a decisive factor to successfully treat CDI and potentially for improvement of the underlying pathophysiology in IBD.

CONCLUSIONS: FMT leads to a significant change in microbial diversity in patients with recurrent CDI and complete resolution of symptoms. Stool donor type (related or unrelated) and degree of engraftment are not the key for successful treatment of CDI by FMT. However, CDI patients with IBD have higher proportion of the original community after FMT and lack of improvement of their IBD symptoms and increased episodes of CDI on long-term follow-up.}, } @article {pmid28506071, year = {2017}, author = {Gravito-Soares, M and Gravito-Soares, E and Portela, F and Ferreira, M and Sofia, C}, title = {Fecal microbiota transplantation in recurrent Clostridium difficile infection in a patient with concomitant inflammatory bowel disease.}, journal = {Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva}, volume = {109}, number = {6}, pages = {473-476}, doi = {10.17235/reed.2017.4819/2016}, pmid = {28506071}, issn = {1130-0108}, mesh = {Clostridium Infections/*microbiology/*therapy ; Clostridium difficile ; Colitis, Ulcerative/microbiology/therapy ; Enterocolitis, Pseudomembranous/*microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Inflammatory Bowel Diseases/*microbiology/*therapy ; Male ; Middle Aged ; Recurrence ; }, abstract = {The use of fecal microbiota transplantation in recurrent Clostridium difficile infection and coexistent inflammatory bowel disease remains unclear. A 61-year-old man with ulcerative pancolitis was diagnosed with a third recurrence of Clostridium difficile infection, previously treated with metronidazole, vancomycin and fidaxomicin. Fecal microbiota transplantation of an unrelated healthy donor was performed by the lower route. After a twelve month follow-up, the patient remains asymptomatic without Clostridium difficile infection relapses or inflammatory bowel disease flare-ups. Fecal microbiota transplantation is relatively simple to perform, well-tolerated, safe and effective in recurrent Clostridium difficile infection with ulcerative pancolitis, as an alternative in case of antibiotic therapy failure.}, } @article {pmid28503135, year = {2017}, author = {Li, Q and Han, Y and Dy, ABC and Hagerman, RJ}, title = {The Gut Microbiota and Autism Spectrum Disorders.}, journal = {Frontiers in cellular neuroscience}, volume = {11}, number = {}, pages = {120}, doi = {10.3389/fncel.2017.00120}, pmid = {28503135}, issn = {1662-5102}, abstract = {Gastrointestinal (GI) symptoms are a common comorbidity in patients with autism spectrum disorder (ASD), but the underlying mechanisms are unknown. Many studies have shown alterations in the composition of the fecal flora and metabolic products of the gut microbiome in patients with ASD. The gut microbiota influences brain development and behaviors through the neuroendocrine, neuroimmune and autonomic nervous systems. In addition, an abnormal gut microbiota is associated with several diseases, such as inflammatory bowel disease (IBD), ASD and mood disorders. Here, we review the bidirectional interactions between the central nervous system and the gastrointestinal tract (brain-gut axis) and the role of the gut microbiota in the central nervous system (CNS) and ASD. Microbiome-mediated therapies might be a safe and effective treatment for ASD.}, } @article {pmid28502839, year = {2017}, author = {Ianiro, G and Sanguinetti, M and Gasbarrini, A and Cammarota, G}, title = {Predictors of failure after single faecal microbiota transplantation in patients with recurrent Clostridium difficile infection: results from a 3-year cohort study: authors' reply.}, journal = {Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases}, volume = {23}, number = {11}, pages = {891}, doi = {10.1016/j.cmi.2017.05.005}, pmid = {28502839}, issn = {1469-0691}, mesh = {*Clostridium Infections ; Clostridium difficile ; Cohort Studies ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Humans ; Recurrence ; }, } @article {pmid28501333, year = {2017}, author = {Gundacker, ND and Tamhane, A and Walker, JB and Morrow, CD and Rodriguez, JM}, title = {Comparative effectiveness of faecal microbiota transplant by route of administration.}, journal = {The Journal of hospital infection}, volume = {96}, number = {4}, pages = {349-352}, doi = {10.1016/j.jhin.2017.05.004}, pmid = {28501333}, issn = {1532-2939}, mesh = {Adult ; Aged ; Aged, 80 and over ; Fecal Microbiota Transplantation/*methods ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Prospective Studies ; Treatment Outcome ; }, abstract = {The optimal route of delivery for faecal microbiota transplant (FMT) is unknown. This observational single-centre study analysed the two-week cure rates for all patients who received FMT from 2013 to 2016 according to route of delivery. Overall, nasogastric delivery of FMT was less effective than lower endoscopic delivery. When patients were stratified by illness severity, nasogastric delivery achieved similar cure rates in healthier individuals, whereas lower endoscopic delivery was preferred for relatively ill individuals. Nasogastric delivery may be less effective than lower endoscopic delivery; however, when taking the cost, preparation and potential risk into account, this difference may not be clinically significant for patients with mild disease.}, } @article {pmid28495755, year = {2017}, author = {Shi, J and Wang, Y and He, J and Li, P and Jin, R and Wang, K and Xu, X and Hao, J and Zhang, Y and Liu, H and Chen, X and Wu, H and Ge, Q}, title = {Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {31}, number = {8}, pages = {3695-3709}, doi = {10.1096/fj.201700034R}, pmid = {28495755}, issn = {1530-6860}, mesh = {Animals ; Bacteria/*classification/genetics ; Colon/*pathology ; Dysbiosis ; Epithelial Cells/physiology ; Feces/chemistry ; Female ; Homeostasis ; Immunoglobulin A/chemistry ; Intestinal Mucosa/*microbiology/pathology ; Mice ; Mice, Inbred C57BL ; Microbiota/*physiology ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Random Allocation ; *Weightlessness Simulation ; }, abstract = {Exposure to microgravity leads to alterations in multiple systems, but microgravity-related changes in the gastrointestinal tract and its clinical significance have not been well studied. We used the hindlimb unloading (HU) mouse model to simulate a microgravity condition and investigated the changes in intestinal microbiota and colonic epithelial cells. Compared with ground-based controls (Ctrls), HU affected fecal microbiota composition with a profile that was characterized by the expansion of Firmicutes and decrease of Bacteroidetes. The colon epithelium of HU mice showed decreased goblet cell numbers, reduced epithelial cell turnover, and decreased expression of genes that are involved in defense and inflammatory responses. As a result, increased susceptibility to dextran sulfate sodium-induced epithelial injury was observed in HU mice. Cohousing of Ctrl mice with HU mice resulted in HU-like epithelial changes in Ctrl mice. Transplantation of feces from Ctrl to HU mice alleviated these epithelial changes in HU mice. Results indicate that HU changes intestinal microbiota, which leads to altered colonic epithelial cell homeostasis, impaired barrier function, and increased susceptibility to colitis. We further demonstrate that alteration in gastrointestinal motility may contribute to HU-associated dysbiosis. These animal results emphasize the necessity of evaluating astronauts' intestinal homeostasis during distant space travel.-Shi, J., Wang, Y., He, J., Li, P., Jin, R., Wang, K., Xu, X., Hao, J., Zhang, Y., Liu, H., Chen, X., Wu, H., Ge, Q. Intestinal microbiota contributes to colonic epithelial changes in simulated microgravity mouse model.}, } @article {pmid28491142, year = {2017}, author = {van Beurden, YH and Nieuwdorp, M and van de Berg, PJEJ and Mulder, CJJ and Goorhuis, A}, title = {Current challenges in the treatment of severe Clostridium difficile infection: early treatment potential of fecal microbiota transplantation.}, journal = {Therapeutic advances in gastroenterology}, volume = {10}, number = {4}, pages = {373-381}, doi = {10.1177/1756283X17690480}, pmid = {28491142}, issn = {1756-283X}, abstract = {Fecal microbiota transplantation (FMT) is a very effective treatment for recurrent Clostridium difficile infection (CDI). Less is known about the application of FMT as a curative treatment of severe or complicated CDI. In this review, we present and discuss evidence supporting the curative use of FMT in severe or complicated CDI. We performed a literature search in PubMed and Embase for studies on the curative use of FMT in severe or complicated CDI. In addition, we describe a patient with severe CDI not responding to initial antibiotic treatment, who was successfully treated with curative FMT. We found 23 reports (12 case reports; 11 case series) about FMT as treatment for severe or complicated CDI. The patients described all had severe or complicated CDI, did not respond to conventional CDI antibiotic treatment and received FMT as last resort treatment. Patients were treated with (sequential) FMT, whether or not followed by additional antibiotic treatment for CDI. FMT, with or without additional antibiotic CDI treatment, appears to be a promising curative treatment option in patients with severe and complicated CDI, or only complicated CDI, who do not respond sufficiently to conventional antibiotic treatment. Treatment with FMT should be considered in these patients before proceeding to emergency bowel surgery.}, } @article {pmid28486648, year = {2017}, author = {Paramsothy, S and Paramsothy, R and Rubin, DT and Kamm, MA and Kaakoush, NO and Mitchell, HM and Castaño-Rodríguez, N}, title = {Faecal Microbiota Transplantation for Inflammatory Bowel Disease: A Systematic Review and Meta-analysis.}, journal = {Journal of Crohn's & colitis}, volume = {11}, number = {10}, pages = {1180-1199}, doi = {10.1093/ecco-jcc/jjx063}, pmid = {28486648}, issn = {1876-4479}, mesh = {Colitis, Ulcerative/therapy ; Crohn Disease/therapy ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/*therapy ; Treatment Outcome ; }, abstract = {Background: Faecal microbiota transplantation [FMT] has been investigated as a potential treatment for inflammatory bowel dise