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Bibliography on: Fecal Transplantation

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ESP: PubMed Auto Bibliography 18 Jul 2019 at 01:39 Created: 

Fecal Transplantation

Fecal Transplantion is a procedure in which fecal matter is collected from a tested donor, mixed with a saline or other solution, strained, and placed in a patient, by colonoscopy, endoscopy, sigmoidoscopy, or enema. The theory behind the procedure is that a normal gut microbial ecosystem is required for good health and that sometimes a benefucuial ecosystem can be destroyed, perhaps by antibiotics, allowing other bacteria, specifically Clostridium difficile to over-populate the colon, causing debilitating, sometimes fatal diarrhea. C. diff. is on the rise throughout the world. The CDC reports that approximately 347,000 people in the U.S. alone were diagnosed with this infection in 2012. Of those, at least 14,000 died. Fecal transplant has also had promising results with many other digestive or auto-immune diseases, including Irritable Bowel Syndrome, Crohn's Disease, and Ulcerative Colitis. It has also been used around the world to treat other conditions, although more research in other areas is needed. Fecal transplant was first documented in 4th century China, where the treatment was known as yellow soup.

Created with PubMed® Query: "(fecal OR faecal) (transplant OR transplantation)" OR "fecal microbiota transplant" NOT pmcbook NOT ispreviousversion

Citations The Papers (from PubMed®)

RevDate: 2019-07-17

Catho G, BD Huttner (2019)

Strategies for the eradication of extended-spectrum beta-lactamase or carbapenemase-producing Enterobacteriaceae intestinal carriage.

Expert review of anti-infective therapy [Epub ahead of print].

Introduction: Among the multidrug resistant pathogens, extended-spectrum beta-lactamase (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE) are currently considered the main threat due to the scarcity of therapeutic options and their rapid spread around the globe. In addition to developing new antibiotics and stopping transmission, recent research has focused on "decolonization" strategies to eradicate the carriage of ESBL-E/CPE before infection occurs. Areas covered: In this narrative review, we aim to describe the current evidence of decolonization strategies for ESBL-E or CPE intestinal carriage. We first define decolonization and highlight the issues related to the lack of standardized definition, then we summarize the available data on the natural history of colonization. Finally, we review the strategies assessed over the past 10 years for ESBL and CPE decolonization: oral antibiotics, probiotics and more recently fecal microbiota transplantation. We conclude by presenting the risks and uncertainties associated with these strategies. Expert opinion: The evidence available today is too low to recommend decolonization strategies for ESBL-E or CPE in routine clinical practice. The potential increase of resistance and the impact of microbiome manipulation should not be underestimated. Some of these decolonization strategies may nevertheless be effective, at least in temporarily suppressing colonization, which could be useful for specific populations such as high-risk patients. Effectiveness and long-term effects must be properly assessed through well-designed randomized controlled trials.

RevDate: 2019-07-17
CmpDate: 2019-07-17

Scanlan C, I Kerridge (2017)

Aesthetics, Ethics, and Fecal Microbiota Transplantations.

The American journal of bioethics : AJOB, 17(5):51-52.

RevDate: 2019-07-16
CmpDate: 2019-07-16

Lauro A, F Lacaille (2019)

Short bowel syndrome in children and adults: from rehabilitation to transplantation.

Expert review of gastroenterology & hepatology, 13(1):55-70.

INTRODUCTION: Short bowel syndrome (SBS) is a dramatic clinical condition in both children and adults; the residual bowel length is not sufficient to avoid intestinal failure, with subsequent malnutrition and growth retardation, and intravenous support is required to provide the nutrients normally coming from the intestine. Apart from the primary disease, the medical status can be worsened by complications of intestinal failure: if there are irreversible, the prognosis is poor unless a successful intestinal rehabilitation is achieved. Areas covered: The rescue of the remnant small bowel requires a multidisciplinary expertise to achieve digestive autonomy. The use of intestinal trophic factors has shown encouraging results in improving the intestinal adaptation process. Whenever the residual bowel length is inadequate, in a well-selected population weaning parenteral nutrition (PN) off could be attempted by surgery through lengthening procedures. A further subset of patients, with total and irreversible intestinal failure and severe complications on PN, may have an indication to intestinal transplantation. This procedure is still affected by poor long-term results. Expert commentary: Novel approaches developed through a multidisciplinary team work, such as manipulation of microbiota or tissue bioengineering, should be added to current therapies to treat successfully SBS.

RevDate: 2019-07-16
CmpDate: 2019-07-16

Hatton G, DL Shawcross (2019)

Is treating the gut microbiome the key to achieving better outcomes in cirrhosis?.

Expert review of gastroenterology & hepatology, 13(1):1-2.

RevDate: 2019-07-15

Lo GH (2019)

The transplantation of fecal microbiota for cirrhotic patients.

RevDate: 2019-07-15

Chen X, Li HY, Hu XM, et al (2019)

Current understanding of gut microbiota alterations and related therapeutic intervention strategies in heart failure.

Chinese medical journal [Epub ahead of print].

OBJECTIVE: The purpose of this review is to stress the complicated interactions between the microbiota and the development of heart failure. Moreover, the feasibility of modulating intestinal microbes and metabolites as novel therapeutic strategies is discussed.

DATA SOURCES: This study was based on data obtained from PubMed up to March 31, 2019. Articles were selected using the following search terms: "gut microbiota," "heart failure," "trimethylamine N-oxide (TMAO)," "short-chain fatty acid (SCFA)," "bile acid," "uremic toxin," "treatment," "diet," "probiotic," "prebiotic," "antibiotic," and "fecal microbiota transplantation."

RESULTS: Accumulated evidence has revealed that the composition of the gut microbiota varies obviously in people with heart failure compared to those with healthy status. Altered gut microbial communities contribute to heart failure through bacterial translocation or affecting multiple metabolic pathways, including the trimethylamine/TMAO, SCFA, bile acid, and uremic toxin pathways. Meanwhile, modulation of the gut microbiota through diet, pre/probiotics, fecal transplantation, and microbial enzyme inhibitors has become a potential therapeutic approach for many metabolic disorders. Specifically, a few studies have focused on the cardioprotective effects of probiotics on heart failure.

CONCLUSIONS: The composition of the gut microbiota in people with heart failure is different from those with healthy status. A reduction in SCFA-producing bacteria in patients with heart failure might be a notable characteristic for patients with heart failure. Moreover, an increase in the microbial potential to produce TMAO and lipopolysaccharides is prominent. More researches focused on the mechanisms of microbial metabolites and the clinical application of multiple therapeutic interventions is necessarily required.

RevDate: 2019-07-15

Allegretti JR, Z Kassam (2019)

Fecal Microbiota Transplantation in Patients With Primary Sclerosing Cholangitis: The Next Steps in This Promising Story.

The American journal of gastroenterology [Epub ahead of print].

RevDate: 2019-07-15

Sun L, Li J, Lan LL, et al (2019)

The effect of fecal microbiota transplantation on Hepatic myelopathy: A case report.

Medicine, 98(28):e16430.

RATIONALE: Hepatic myelopathy (HM), also known as portal-systemic myelopathy, is a rare neurological complication that occurs in patients with chronic liver disease. There is no easy and feasible treatment, liver transplantation is the only accepted therapy that may be effective for patients at early stage at present. The pathogenesis of the disease is not clear yet, and the prognosis is poor. Here we describe a reversible HM after fecal microbiota transplantation.

PATIENT CONCERNS: In this report, a middle-aged female patient with hepatitis B cirrhosis, occurred HM after transjugular intrahepatic portosystemic shunt, a progressive spastic paraparesis in both legs were the main symptoms.

DIAGNOSIS: The patient was diagnosed with HM.

INTERVENTIONS: The patient received 3 times of fecal microbiota transplantations (FMT).

OUTCOMES: The patient's muscle strength of both legs were increased at various degrees, the patient's condition improved from HM2 to HM1.

LESSONS: FMT may be another effective way to treat HM. It is cheaper, more operable, and simpler than the approved treatment and worthy of further research.

RevDate: 2019-07-15

Borody TJ, A Clancy (2019)

Fecal microbiota transplantation for ulcerative colitis-where to from here?.

Translational gastroenterology and hepatology, 4:48 pii:tgh-04-2019.06.04.

RevDate: 2019-07-14

Selvig D, Piceno Y, Terdiman J, et al (2019)

Fecal Microbiota Transplantation in Pouchitis: Clinical, Endoscopic, Histologic, and Microbiota Results from a Pilot Study.

Digestive diseases and sciences pii:10.1007/s10620-019-05715-2 [Epub ahead of print].

AIMS: This pilot study assessed the efficacy, safety, and microbiome dynamics of fecal microbiota transplantation (FMT) for patients with chronic pouchitis.

METHODS: A prospective open-label pilot study was performed at an academic center among pouchitis patients undergoing FMT. Patients received a minimum of a single FMT by pouchoscopy from healthy, screened donors. The primary outcome was clinical improvement in pouchitis assessed by patient survey at week 4. Secondary outcomes included decrease in total Pouchitis Disease Activity Index (PDAI) Score ≥ 3 at week 4, bowel movement frequency, ESR, CRP, fecal calprotectin, abdominal pain, and PDAI subscores including endoscopic and histologic changes. Stool samples were collected at baseline and 4 weeks post-FMT to assess bacterial microbiota using V4 16S rRNA sequencing.

RESULTS: Nineteen patients were enrolled; however, 1 patient was lost to follow-up. No patients had a major adverse event or escalation of therapy related to FMT. Total PDAI scores, endoscopic scores, and histologic scores did not decrease significantly post-FMT. However, there was a statistically significant improvement in bowel movement (BM) frequency (9.25-7.25 BM/day, p = 0.03) and trend for improvement in abdominal pain to improve post-FMT (p = 0.05). Bacterial microbiota profiling revealed no distinct community-level changes post-FMT, though a small number of specific bacterial taxa significantly differed in relative abundance.

CONCLUSIONS: A single FMT has a tolerable short-term safety profile and may be associated with a decrease in bowel movements in patients with chronic pouchitis; however, no robust endoscopic or histologic changes were observed.

RevDate: 2019-07-15
CmpDate: 2019-07-15

Aagaard K, E Hohmann (2019)

Regulating microbiome manipulation.

Nature medicine, 25(6):874-876.

RevDate: 2019-07-15
CmpDate: 2019-07-15

Lee S, Drennan K, Simons G, et al (2018)

The 'ins and outs' of faecal microbiota transplant for recurrent Clostridium difficile diarrhoea at Wits Donald Gordon Medical Centre, Johannesburg, South Africa.

South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde, 108(5):403-407.

BACKGROUND: Clostridium difficile-associated diarrhoea (CDAD) is a potentially life-threatening condition that is becoming increasingly common. A persistent burden of this infectious illness has been demonstrated over the past 4 years at Wits Donald Gordon Medical Centre (WDGMC), Johannesburg, South Africa, through implementation of active surveillance of hospital-acquired infections as part of the infection prevention and control programme. Oral treatment with metronidazole or vancomycin is recommended, but there is a major problem with symptomatic recurrence after treatment. Replacement of normal flora by the administration of donor stool through colonoscopy or nasogastric/duodenal routes is becoming increasingly popular.

OBJECTIVES: To identify risk factors for the development of CDAD in patients referred for faecal microbiota transplant (FMT) and evaluate the safety of administration of donor stool as an outpatient procedure, including via the nasogastric route.

METHODS: A retrospective record review of patients with recurrent CDAD referred for FMT at WDGMC between 1 January 2012 and 31 December 2016 was conducted.

RESULTS: Twenty-seven patients were identified, all of whom fulfilled the criteria for recurrent CDAD. One-third were aged >65 years, and the majority were female. The most common risk factors were prior exposure to antibiotics or proton-pump inhibitors and underlying inflammatory bowel disease. Three procedures were carried out as inpatients and 24 in the outpatient gastroenterology unit. At 4-week follow-up, all patients reported clinical resolution of their diarrhoea after a single treatment and there were no recurrences. The FMT procedure was associated with no morbidity (with particular reference to the risk of aspiration when administered via the nasogastric route) or mortality.

CONCLUSIONS: This case series confirms that FMT is a safe and effective therapy for recurrent CDAD. In most cases it can be administered via the nasogastric route in the outpatient department. We propose that the recently published South African Gastroenterology Society guidelines be reviewed with regard to recommendations for the route of administration of FMT and hospital admission. Meticulous prescription practice by clinicians practising in hospitals and outpatient settings, with particular attention to antimicrobials and chronic medication, is urgently required to prevent this debilitating and potentially life-threatening condition.

RevDate: 2019-07-15
CmpDate: 2019-07-15

Olesen SW, Leier MM, Alm EJ, et al (2018)

Searching for superstool: maximizing the therapeutic potential of FMT.

Nature reviews. Gastroenterology & hepatology, 15(7):387-388.

RevDate: 2019-07-13

Allegretti JR, Kassam Z, Mullish BH, et al (2019)

Effects of Fecal Microbiota Transplantation With Oral Capsules in Obese Patients.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association pii:S1542-3565(19)30739-6 [Epub ahead of print].

BACKGROUND & AIMS: Studies in mice have shown that the intestinal microbiota can contribute to obesity via the anorexigenic gut hormone glucagon-like peptide 1 (GLP1) and bile acids, which affect lipid metabolism. We performed a randomized, placebo-controlled pilot study of the effects of fecal microbiota transplantation (FMT) in obese, metabolically uncompromised patients.

METHODS: We performed a double-blind study of 22 obese patients (body mass index [BMI] ≥ 35kg/m2) without a diagnosis of diabetes, non-alcoholic steatohepatitis, or metabolic syndrome. Participants were randomly assigned (1:1) to groups that received FMT by capsules (induction dose of 30 capsules at week 4 and maintenance dose of 12 capsules at week 8) or placebo capsules. FMT capsules were derived from a single, lean donor (BMI, 17.5 kg/m2). Patients were followed through week 26; the primary outcome was safety. Stool and serum samples were collected from patients at baseline and at weeks 1, 4, 6, 8 and 12 after administration of the first dose of FMT or placebo and analyzed by 16S RNA gene sequencing. Stool and serum samples were analyzed for metabolomics by liquid chromatography-mass spectrometry. Additional outcomes were change in area under the curve for GLP1 at week 12.

RESULTS: We observed no significant differences in adverse events between patients who received FMT vs placebo. There was no increase in the area under the curve of GLP1 in either group. Patients who received FMT had sustained shifts in microbiomes associated with obesity toward those of the donor (P<.001). Patients who received FMT had a sustained decrease in stool levels of taurocholic acid (P<.05), compared with baseline; bile acid profiles began to more closely resemble those of the donor. We did not observe significant changes in mean BMI at week 12 in either group.

CONCLUSIONS: In a placebo-controlled pilot study, we found that FMT capsules (derived from a lean donor) were safe but did not reduce BMI in obese metabolically uncompromised patients. The FMT capsules were well tolerated and led to sustained changes in the intestinal microbiome and bile acid profiles that were similar to those of the lean donor.

RevDate: 2019-07-11

Campion D, Giovo I, Ponzo P, et al (2019)

Dietary approach and gut microbiota modulation for chronic hepatic encephalopathy in cirrhosis.

World journal of hepatology, 11(6):489-512.

Hepatic encephalopathy (HE) is a common and serious neuropsychiatric complication of cirrhosis, acute liver failure, and porto-systemic shunting. HE largely contributes to the morbidity of patients with liver disease, severely affecting the quality of life of both patients and their relatives and being associated with poor prognosis. Its presentation is largely variable, manifesting with a broad spectrum of cognitive abnormalities ranging from subtle cognitive impairment to coma. The pathogenesis of HE is complex and has historically been linked with hyperammonemia. However, in the last years, it has become evident that the interplay of multiple actors, such as intestinal dysbiosis, gut hyperpermeability, and neuroinflammation, is of crucial importance in its genesis. Therefore, HE can be considered a result of a dysregulated gut-liver-brain axis function, where cognitive impairment can be reversed or prevented by the beneficial effects induced by "gut-centric" therapies, such as non-absorbable disaccharides, non-absorbable antibiotics, probiotics, prebiotics, and fecal microbiota transplantation. In this context dietary modifications, by modulating the intestinal milieu, can also provide significant benefit to cirrhotic patients with HE. This review will provide a comprehensive insight into the mechanisms responsible for gut-liver-brain axis dysregulation leading to HE in cirrhosis. Furthermore, it will explore the currently available therapies and the most promising future treatments for the management of patients with HE, with a special focus on the dietary approach.

RevDate: 2019-07-11

Ni J, Huang R, Zhou H, et al (2019)

Analysis of the Relationship Between the Degree of Dysbiosis in Gut Microbiota and Prognosis at Different Stages of Primary Hepatocellular Carcinoma.

Frontiers in microbiology, 10:1458.

Gut microbiota dysbiosis is closely associated with primary hepatocellular carcinoma (HCC). Recent studies have evaluated the early diagnosis of primary HCC through analysis of gut microbiota dysbiosis. However, the relationship between the degree of dysbiosis and the prognosis of primary HCC remains unclear. Because primary HCC is accompanied by dysbiosis and dysbiosis usually increases the circulatory concentrations of endotoxin and other harmful bacterial substances, which further increases liver damage, we hypothesized that level of dysbiosis associated with primary HCC increases with the stage of cancer progression. To test this hypothesis, we introduced a more integrated index referred to as the degree of dysbiosis (Ddys); and we investigated Ddys of the gut microbiota with the development of primary HCC through high-throughput sequencing of 16S rRNA gene amplicons. Our results showed that compared with healthy individuals, patients with primary HCC showed increased pro-inflammatory bacteria in their fecal microbiota. The Ddys increased significantly in patients with primary HCC compared with that in healthy controls. Moreover, there was a tendency for the Ddys to increase with the development of primary HCC, although no significant difference was detected between different stages of primary HCC. Our findings provide important insights into the use of gut microbiota analysis during the treatment of primary HCC.

RevDate: 2019-07-12
CmpDate: 2019-07-12

Cammarota G, G Ianiro (2019)

FMT for ulcerative colitis: closer to the turning point.

Nature reviews. Gastroenterology & hepatology, 16(5):266-268.

RevDate: 2019-07-12
CmpDate: 2019-07-12

Thoma C (2019)

Bile salt hydrolases involved in the effectiveness of FMT for Clostridium difficile infection.

Nature reviews. Gastroenterology & hepatology, 16(4):198.

RevDate: 2019-07-11
CmpDate: 2019-07-11

Thomas H (2019)

FMT for drug-induced colitis.

Nature reviews. Gastroenterology & hepatology, 16(1):4.

RevDate: 2019-07-11
CmpDate: 2019-07-11

Adachi K, K Tamada (2018)

Microbial biomarkers for immune checkpoint blockade therapy against cancer.

Journal of gastroenterology, 53(9):999-1005.

Three major standard treatments, i.e., surgery, chemotherapy, and radiotherapy, were traditionally applied to the treatment of cancer and saved many patients. Meanwhile, clinical studies as well as basic research of immunotherapy are being actively conducted for intractable or advanced malignancies that cannot be cured by the conventional standard treatments. Remarkable therapeutic efficacies have been recently reported in clinical trials on some cancer types, and immunotherapy is now being recognized as the "fourth" standard therapy against cancer. In particular, immune checkpoint inhibitor therapy (ICI) has demonstrated the effectiveness of immunotherapy through large-scale randomized clinical trials, leading to the paradigm-shift in cancer treatment. Immune checkpoint molecules transduce co-inhibitory signals to immunocompetent cells including T cells, and crucially contribute to the formation of an immunosuppressive microenvironment in tumor tissues, which intrinsically confers the treatment resistance. Programmed death-1 (PD-1, CD279) is one of the typical immune checkpoint molecules. Anti-tumor therapies targeting PD-1 and its ligands had been developed and approved in many countries, and various studies utilizing clinical specimens are currently progressing. In this review, we provide an overview of the biomarkers based on the analysis of enteric microbiota that correlate with the clinical efficacy/inefficacy of PD-1-based therapy.

RevDate: 2019-07-10

Liu T, Song X, Khan S, et al (2019)

The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: an old story, yet mesmerizing.

International journal of cancer [Epub ahead of print].

The prevalence of colorectal cancer (CRC) dramatically increased worldwide in the last decade. Alterations of bile acid metabolism and gut microbiota have been reported to play vital roles in intestinal carcinogenesis. About trillions of bacteria inhabited in the human gut and maintained the balance of host metabolism. Bile acids are one of numerous metabolites that are synthesized in the liver and further metabolized by the gut microbiota, and are essential in maintaining the normal gut microbiota and lipid digestion. Multiple receptors such as FXR, GPBAR1, PXR, CAR and VDR act as sensors of bile acids have been reported. In this review, we mainly discussed interplay between bile acid metabolism and gut microbiota in intestinal carcinogenesis. We then summarized the critical role of bile acids receptors involving in CRC, and also addressed the rationale of multiple interventions for CRC management by regulating bile acids-microbiota axis such as probiotics, Metformin, ursodeoxycholic acid (UDCA) and fecal microbiota transplantation (FMT). Thus, by targeting the bile acids-microbiota axis may provide novel therapeutic modalities in CRC prevention and treatment. This article is protected by copyright. All rights reserved.

RevDate: 2019-07-10

Pianko MJ, Devlin SM, Littmann ER, et al (2019)

Minimal residual disease negativity in multiple myeloma is associated with intestinal microbiota composition.

Blood advances, 3(13):2040-2044.

Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity after upfront treatment have superior outcomes compared with those who remain MRD+ Recently, associations have been shown between specific commensal microbes and development of plasma cell disorders. Here, we report the association between intestinal microbiota composition and treatment outcome in MM. Microbiota composition of fecal samples collected from 34 MM patients after induction therapy and at the time of flow cytometry-based bone marrow MRD testing was determined by 16S ribosomal RNA sequencing. We observed a higher relative abundance of Eubacterium hallii in the 16 MRD- patients relative to the 18 MRD+ patients. No association was observed between microbial relative abundance and autologous stem cell transplantation history or MM paraprotein isotype. No differences in microbiota α diversity were observed between MRD- and MRD+ patients. The potential association of microbiota composition with treatment response in MM patients is an important parameter for additional correlative and clinical investigation.

RevDate: 2019-07-10
CmpDate: 2019-07-10

Dickson I (2018)

Therapy: FMT: the rules of engraftment.

Nature reviews. Gastroenterology & hepatology, 15(4):190-191.

RevDate: 2019-07-10
CmpDate: 2019-07-10

Dickson I (2018)

Therapy: Oral capsule FMT effective for C. difficile infection.

Nature reviews. Gastroenterology & hepatology, 15(2):68.

RevDate: 2019-07-10
CmpDate: 2019-07-10

Atreya R, B Siegmund (2018)

IBD in 2017: Development of therapy for and prediction of IBD - getting personal.

Nature reviews. Gastroenterology & hepatology, 15(2):72-74.

RevDate: 2019-07-10
CmpDate: 2019-07-10

Dickson I (2017)

Therapy: Bacteriophages important for FMT efficacy.

Nature reviews. Gastroenterology & hepatology, 14(7):386.

RevDate: 2019-07-05

Tian Y, Zhou Y, Huang S, et al (2019)

Fecal microbiota transplantation for ulcerative colitis: a prospective clinical study.

BMC gastroenterology, 19(1):116 pii:10.1186/s12876-019-1010-4.

BACKGROUND: Fecal microbiota transplantation may contribute to disease remission in ulcerative colitis; however, the factors that determine the effects of treatment remain unknown. The aim of the present study was to prospectively investigate the clinical efficacy of fecal microbiota transplantation in patients with ulcerative colitis and identify the bacterial signatures associated with clinical remission.

METHODS: A total of 20 patients with ulcerative colitis were included in this prospective and uncontrolled study. All patients underwent gastroscopy five times, once every 3 weeks. Clinical indices were used to assess the efficacy of fecal microbiota transplantation, as well as the Mayo score, a score used to evaluate the extent of intestinal mucosal lesions in patients with ulcerative colitis. The changes in intestinal flora were detected by 16S ribosomal RNA-sequencing, and the relationship between ulcerative colitis and intestinal flora was analyzed.

RESULTS: After treatment, clinical index scores for diarrhea, abdominal pain, and blood stool decreased significantly (p < 0.05). Erythrocyte sedimentation rate and C-reactive protein levels had not changed significantly; however, the clinical index score for intestinal mucosal lesions and the Mayo score decreased significantly. In addition, 16S ribosomal RNA-sequencing revealed that the intestinal flora in patients diagnosed with ulcerative colitis was different from that of donors.

CONCLUSION: Fecal microbiota transplantation has a potential therapeutic value for the treatment of ulcerative colitis as it changes the abundance of bacterial flora and improves the scores for diarrhea, abdominal pain, and mucous membrane lesions in patients with this disease.

TRIAL REGISTRATION: The clinical trial was retrospectively registered with ClinicalTrials.gov (NCT03016780) on January 11th, 2017.

RevDate: 2019-07-04
CmpDate: 2019-07-04

Vigvári S, Sipos D, Solt J, et al (2019)

Faecal microbiota transplantation for Clostridium difficile infection using a lyophilized inoculum from non-related donors: A case series involving 19 patients.

Acta microbiologica et immunologica Hungarica, 66(1):69-78.

Faecal microbiota transplantation (FMT) has been reported to be effective in treating relapsing of refractory Clostridium difficile infections, although some practical barriers are limiting its widespread use. In this study, our objective was to evaluate the rate of resolution of diarrhea following administration of lyophilized and resolved FMT via a nasogastric (NG) tube. We recruited 19 patients suffered from laboratory-confirmed C. difficile infection. Each of them was treated by lyophilized and resolved inoculum through a NG tube. One participant succumbed following the procedure due to unrelated diseases. Out of 18 cases, 15 patients reportedly experienced a resolution of the symptoms. One patient was treated with another course of antibiotics, and two of the non-responders were successfully retreated with another course of FMT utilizing a lyophilized inoculum. Notably, no significant adverse activities were observed. In accordance to our clinical experiences, a patient will likely benefit from FMT treatment including lyophilized inoculum.

RevDate: 2019-07-03

Bradley KC, Finsterbusch K, Schnepf D, et al (2019)

Microbiota-Driven Tonic Interferon Signals in Lung Stromal Cells Protect from Influenza Virus Infection.

Cell reports, 28(1):245-256.e4.

Type I interferon (IFNα/β) pathways are fine-tuned to elicit antiviral protection while minimizing immunopathology; however, the initiating stimuli, target tissues, and underlying mechanisms are unclear. Using models of physiological and dysregulated IFNα/β receptor (IFNAR1) surface expression, we show here that IFNAR1-dependent signals set the steady-state IFN signature in both hematopoietic and stromal cells. Increased IFNAR1 levels promote a lung environment refractory to early influenza virus replication by elevating the baseline interferon signature. Commensal microbiota drive the IFN signature specifically in lung stroma, as shown by antibiotic treatment and fecal transplantation. Bone marrow chimera experiments identify lung stromal cells as crucially important for early antiviral immunity and stroma-immune cell interaction for late antiviral resistance. We propose that the microbiota-driven interferon signature in lung epithelia impedes early virus replication and that IFNAR1 surface levels fine-tune this signature. Our findings highlight the interplay between bacterial and viral exposure, with important implications for antibiotic use.

RevDate: 2019-07-03

Martel B, G Saint-Lorant (2019)

[Pharmaceutical system of fecal microbiota transplantation: Heterogeneous practices].

Annales pharmaceutiques francaises pii:S0003-4509(19)30038-0 [Epub ahead of print].

OBJECTIVE: To describe current pharmaceutical practice in French hospitals regarding fecal microbiota transplantation in terms of prescription, preparation and compounding, as well as local legislation.

MATERIAL AND METHODS: A national survey was conducted at 28 French university hospital centers followed by the sending of a GoogleForm® questionnaire from June to August 2018 in the 16 respondent centers either performing or subcontracting fecal microbiota transplant.

RESULTS: All hospitals performing or subcontracting fecal transplant (n=16,%57) report prescription indication of recurrent Clostridium difficile infection treatment, and 6 of them also as part of a clinical trial protocol. In hospitals performing fecal transplant themselves (n=11), the number of pre-donation consultations with donors varies from one (n=6) to two (n=5). Fecal sample is collected at the donor's home in 45% of cases. Route of administration for transplant is either naso-gastric administration (n=4), rectal (n=4) or both (n=5). Fecal samples for transplant are compounded either in the hospital pharmacy (n=73%) or in the laboratory (27%). Thawing methods include refrigeration between 2-8°C (50%), room temperature (25%) and water bath (25%). Billing system and reporting to health authorities are highly heterogeneous from one hospital to another.

CONCLUSION: This survey shows significant pharmaceutical practice heterogeneity within French hospitals regarding fecal microbiota transplantation despite the existence of national and European recommendations.

RevDate: 2019-07-02

Morjaria S, Schluter J, Taylor BP, et al (2019)

Antibiotic-induced shifts in fecal microbiota density and composition during hematopoietic stem cell transplantation.

Infection and immunity pii:IAI.00206-19 [Epub ahead of print].

Background: Dramatic microbiota changes and loss of commensal anaerobic bacteria are associated with adverse outcomes in hematopoietic cell transplantation (HCT) recipients. In this study, we demonstrate these dynamic changes at high-resolution through daily stool sampling and assess the impact of individual antibiotics on those changes.Methods: We collected 272 longitudinal stool samples (with mostly daily frequency) from 18 patients undergoing HCT and determined their composition by multi-parallel 16S rRNA gene sequencing, as well as density of bacteria in stool by qPCR. We calculated microbiota volatility to quantify rapid shifts and developed a new dynamic systems inference method to assess the specific impact of antibiotics.Results: The greatest shifts in microbiota composition occurred between stem cell infusion and reconstitution of healthy immune cells. Piperacillin-tazobactam caused the most severe declines among obligate anaerobes.Conclusions: Our approach of daily sampling, bacterial density determination and dynamic systems modeling allowed us to infer the independent effects of specific antibiotics on the microbiota of HCT patients.

RevDate: 2019-07-02

Huang H, Xu H, Luo Q, et al (2019)

Fecal microbiota transplantation to treat Parkinson's disease with constipation: A case report.

Medicine, 98(26):e16163.

RATIONALE: Fecal microbiota transplantation (FMT) is recognized as an emerging treatment through reconstruction of gut microbiota. Parkinson's disease is a neurodegenerative disorder, which is accompanied by constipation. Here we first reported a patient with Parkinson's disease and constipation that were obviously relieved after FMT.

PATIENT CONCERNS: A 71-year-old male patient presented with 7 years of resting tremor, bradykinesia (first inflicted the upper limbs and subsequently spread to lower limbs), and intractable constipation (defecation needing more than 30 minutes).

DIAGNOSES: Parkinson's disease for 7 years; constipation >3 years.

INTERVENTIONS: The patient had used madopar, pramipexole, and amantadine for anti-Parkinson and showed partially mitigation while laxative therapy for constipation failed. Finally FMT was performed.

OUTCOMES: The patient successfully defecated within 5 minutes and maintained daily unobstructed defecation until the end of follow-up. The patient's tremor in legs almost disappeared at 1 week after FMT but recurred in the right lower extremity at 2 months after FMT.

LESSONS: Gut microbiota reconstruction may have therapeutic effects for Parkinson's disease patients, especially those who have gastrointestinal symptoms and limited treatment choices.

RevDate: 2019-07-01

Leshem A, Horesh N, E Elinav (2019)

Fecal Microbial Transplantation and Its Potential Application in Cardiometabolic Syndrome.

Frontiers in immunology, 10:1341.

Newly revealed links between inflammation, obesity, and cardiometabolic syndrome have created opportunities to try previously unexplored therapeutic modalities in these common and life-risking disorders. One potential modulator of these complex disorders is the gut microbiome, which was described in recent years to be altered in patients suffering from features of cardiometabolic syndrome and to transmit cardiometabolic phenotypes upon transfer into germ-free mice. As a result, there is great interest in developing new modalities targeting the altered commensal bacteria as a means of treatment for cardiometabolic syndrome. Fecal microbiota transplantation (FMT) is one such modality in which a disease-associated microbiome is replaced by a healthy microbiome configuration. So far clinical use of FMT has been overwhelmingly successful in recurrent Clostridium difficile infection and is being extensively studied in other microbiome-associated pathologies such as cardiometabolic syndrome. This review will focus on the rationale, promises and challenges in FMT utilization in human disease. In particular, it will overview the role of the gut microbiota in cardiometabolic syndrome and the rationale, experience, and prospects of utilizing FMT treatment as a potential preventive and curative treatment of metabolic human disease.

RevDate: 2019-07-01

Otrompke J (2019)

Digestive Disease Week 2019.

P & T : a peer-reviewed journal for formulary management, 44(7):428-429.

We review selected sessions on the questionable benefits of fecal microbiota transplant; intrahepatic cholestasis of pregnancy; weight-loss drugs in combination with intragastric balloon endoscopy; and beta blockers in pancreatic cancer.

RevDate: 2019-07-01
CmpDate: 2019-07-01

Stanisavljević S, Dinić M, Jevtić B, et al (2018)

Gut Microbiota Confers Resistance of Albino Oxford Rats to the Induction of Experimental Autoimmune Encephalomyelitis.

Frontiers in immunology, 9:942.

Albino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens. Subsequently, limited infiltration of the CNS occurs, yet without clinical sequels. It has recently become increasingly appreciated that gut-associated lymphoid tissues (GALT) and gut microbiota play an important role in regulation and propagation of encephalitogenic immune response. Therefore, modulation of AO gut microbiota by antibiotics was performed in this study. The treatment altered composition of gut microbiota in AO rats and led to a reduction in the proportion of regulatory T cells in Peyer's patches, mesenteric lymph nodes, and in lymph nodes draining the site of immunization. Upregulation of interferon-γ and interleukin (IL)-17 production was observed in the draining lymph nodes. The treatment led to clinically manifested EAE in AO rats with more numerous infiltrates and higher production of IL-17 observed in the CNS. Importantly, transfer of AO gut microbiota into EAE-prone Dark Agouti rats ameliorated the disease. These results clearly imply that gut microbiota is an important factor in AO rat resistance to EAE and that gut microbiota transfer is an efficacious way to treat CNS autoimmunity. These findings also support the idea that gut microbiota modulation has a potential as a future treatment of multiple sclerosis.

RevDate: 2019-06-29

Kelly CR, Fischer M, Grinspan A, et al (2019)

Patients Eligible for Trials of Microbe-based Therapeutics do not Represent the Population With Recurrent Clostridioides difficile Infection.

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association pii:S1542-3565(19)30725-6 [Epub ahead of print].

BACKGROUND & AIMS: Although there are many industry-funded trials of microbe-based therapeutics for Clostridioides (formerly Clostridium) difficile infection (CDI), not all patients are eligible for these trials, due to their strict enrollment criteria. Furthermore, given the widespread availability of fecal microbiota transplantation (FMT) and overwhelming evidence to support its efficacy, patients might refuse enrollment in trials with a placebo group. We analyzed willingness and eligibility of patients with recurrent CDI to participate in randomized controlled trials of microbe-based therapeutic agents.

METHODS: We performed a retrospective study of 199 patients referred to 4 tertiary referral centers for treatment of CDI from August 1, 2018 through January 31, 2019. We collected data on eligibility for FMT and enrollment in randomized controlled trials.

RESULTS: Of 130 patients deemed appropriate for FMT, 98 patients (75%) were ineligible for participation in a randomized controlled trial and 16 patients (17%) were eligible but refused to enroll. Immune compromise and inflammatory bowel diseases were the most common reasons for exclusion from trials CONCLUSIONS: Most patients with CDI who meet the guideline criteria for FMT are ineligible or unwilling to participate in randomized controlled trials of microbe-based therapeutics. Trial populations therefore do not represent the population of patients with CDI.

RevDate: 2019-06-28

Aron-Wisnewsky J, Clément K, M Nieuwdorp (2019)

Fecal Microbiota Transplantation: a Future Therapeutic Option for Obesity/Diabetes?.

Current diabetes reports, 19(8):51 pii:10.1007/s11892-019-1180-z.

PURPOSE OF REVIEW: The aim of this review is to summarize the current data available on the metabolic effects of fecal microbiota transplantation (FMT) including obesity and glucose metabolism in humans.

RECENT FINDINGS: Gut microbiota dysbiosis is a frequent characteristic observed in obesity and related metabolic diseases. Pieces of evidence mostly generated in mouse models suggest that rescuing this dysbiosis associates with improved metabolism. In humans, dietary or bariatric surgery interventions are often accompanied by complete or partial restoration of this dysbiosis together with weight reduction and metabolic amelioration. FMT is an interesting option to modify gut microbiota and has been associated with improved clinical outcomes, albeit only used in routine care for Clostridium difficile infection. However, there are only limited data on using FMT in the metabolic context. FMT from lean donors significantly improves insulin sensitivity in obese subjects with metabolic syndrome. However, there is a wide range of clinical responses. Interestingly in subjects with high microbial gene richness at baseline and when FMT donors that are metabolically compromised are used, no metabolic improvement is seen. Moreover, more studies evaluating the effect of FMT in patients with overt type 2 diabetes are warranted. Furthermore, interventions (in the receiver prior to FMT) aiming to enhance FMT response also need evaluation.

RevDate: 2019-06-28

Wang G, Huang S, Wang Y, et al (2019)

Bridging intestinal immunity and gut microbiota by metabolites.

Cellular and molecular life sciences : CMLS pii:10.1007/s00018-019-03190-6 [Epub ahead of print].

The gastrointestinal tract is the site of nutrient digestion and absorption and is also colonized by diverse, highly mutualistic microbes. The intestinal microbiota has diverse effects on the development and function of the gut-specific immune system, and provides some protection from infectious pathogens. However, interactions between intestinal immunity and microorganisms are very complex, and recent studies have revealed that this intimate crosstalk may depend on the production and sensing abilities of multiple bioactive small molecule metabolites originating from direct produced by the gut microbiota or by the metabolism of dietary components. Here, we review the interplay between the host immune system and the microbiota, how commensal bacteria regulate the production of metabolites, and how these microbiota-derived products influence the function of several major innate and adaptive immune cells involved in modulating host immune homeostasis.

RevDate: 2019-06-28
CmpDate: 2019-06-28

Mullish BH, HR Williams (2018)

Clostridium difficile infection and antibiotic-associated diarrhoea.

Clinical medicine (London, England), 18(3):237-241.

Antibiotic-associated diarrhoea is among the most common adverse events related to antibiotic use. Most cases are mild, but Clostridium difficile infection causes a spectrum of disease, ranging from occasional diarrhoea to colitis, toxic megacolon, and potentially death. Recent developments in our understanding of the biology of the gut microbiota have provided new insights into the pathogenesis of these conditions, and have revealed a role for manipulation of the gut microbiota as a novel therapeutic approach. This review will give an overview of the assessment of these conditions, before focusing on the rapidly developing area of their treatment.

RevDate: 2019-06-27

Chong PP, Chin VK, Looi CY, et al (2019)

The Microbiome and Irritable Bowel Syndrome - A Review on the Pathophysiology, Current Research and Future Therapy.

Frontiers in microbiology, 10:1136.

Irritable bowel syndrome (IBS) is a functional disorder which affects a large proportion of the population globally. The precise etiology of IBS is still unknown, although consensus understanding proposes IBS to be of multifactorial origin with yet undefined subtypes. Genetic and epigenetic factors, stress-related nervous and endocrine systems, immune dysregulation and the brain-gut axis seem to be contributing factors that predispose individuals to IBS. In addition to food hypersensitivity, toxins and adverse life events, chronic infections and dysbiotic gut microbiota have been suggested to trigger IBS symptoms in tandem with the predisposing factors. This review will summarize the pathophysiology of IBS and the role of gut microbiota in relation to IBS. Current methodologies for microbiome studies in IBS such as genome sequencing, metagenomics, culturomics and animal models will be discussed. The myriad of therapy options such as immunoglobulins (immune-based therapy), probiotics and prebiotics, dietary modifications including FODMAP restriction diet and gluten-free diet, as well as fecal transplantation will be reviewed. Finally this review will highlight future directions in IBS therapy research, including identification of new molecular targets, application of 3-D gut model, gut-on-a-chip and personalized therapy.

RevDate: 2019-06-26

Jørgensen SMD, Hvas CL, Dahlerup JF, et al (2019)

Banking feces: a new frontier for public blood banks?.

Transfusion [Epub ahead of print].

Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection and is potentially beneficial in other microbiota-related disorders. The provision of FMT in routine clinical practice requires an extensive infrastructure that is reliant on voluntary donors. Alongside an increasing demand for FMT, the logistic barriers of a large-scale donor-dependent operation and the difficulties among health authorities to regulate FMT limit the dissemination of sustainable FMT services. Blood centers are large organizations that handle a multitude of donor-dependent operations on a daily basis. Blood and feces share many of the same dependencies, and feces may present a new opportunity for the blood services to handle. In this paper, we describe how an FMT service may be established and embedded within the blood service infrastructure, and we explain the benefits of using blood donors as feces donors. We further explore the current indications of FMT, the challenges related to the lack of legislation, and the future perspectives for blood banks to meet a new and increasing demand.

RevDate: 2019-06-26

Xu Z, Liu T, Zhou Q, et al (2019)

Roles of Chinese Medicine and Gut Microbiota in Chronic Constipation.

Evidence-based complementary and alternative medicine : eCAM, 2019:9372563.

Chronic constipation is a common gastrointestinal dysfunction, but its aetiology and pathogenesis are still unclear. Interestingly, the compositions of the gut microbiota in constipation patients and healthy controls are different. Various studies reported the different gut microbiota alterations in constipation patients, but most studies indicated that constipation patients showed the decreased beneficial bacteria and the reduced species richness of gut bacteria. Besides, the alterations in the gut microbiota may lead to constipation and constipation-related symptoms and the regulation of gut microbiota has a positive effect on gut functional diseases such as constipation. Microbial treatment methods, such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation, can be used to regulate gut microbiota. Increasing evidences have suggested that Chinese medicine (CM) has a good therapeutic effect on chronic constipation. Chinese medicine is well known for its multitarget and multimode effects on diseases as well as less side effects. In previous studies, after the treatment of constipation with CM, the gut microbiota was restored, indicating that the gut microbiota might be the target or important way for CM to exert its efficacy. In this review, we summarized the effects of microbial treatment and CM on the gut microbiota of constipation patients and discussed the relationship between CM and gut microbiota.

RevDate: 2019-06-25

Singh T, Bedi P, Bumrah K, et al (2019)

Updates in Treatment of Recurrent Clostridium difficile Infection.

Journal of clinical medicine research, 11(7):465-471.

Recurrent Clostridium difficile infection (CDI) is a perpetual problem that leads to increased economic burden, higher healthcare cost, and significant morbidity and mortality. Its treatment remains a challenge. While various treatment approaches have been attempted with different levels of success, robust data establishing the superiority of one approach over the others is lacking. In this article, we review the current evidence pertaining to conventional pharmacological treatment as well as fecal microbiota transplantation (FMT) as a novel, rapidly emerging treatment modality for recurrent CDI.

RevDate: 2019-06-26
CmpDate: 2019-06-26

Biancheri P, Divekar D, AJM Watson (2018)

Could Fecal Transplantation Become Part of PD-1-Based Immunotherapy, Due to Effects of the Intestinal Microbiome?.

Gastroenterology, 154(6):1845-1847.

RevDate: 2019-06-24

Qi X, Zhang Y, Guo H, et al (2019)

Mechanism and intervention measures of iron side effects on the intestine.

Critical reviews in food science and nutrition [Epub ahead of print].

Excess oral iron in the intestinal tract usually produces reactive oxygen species via Fenton and Haber-Weiss reaction, so oxidative stress is triggered. Lipid peroxidation procedurally appears, ferroptosis, apoptosis and necrosis are often induced, subsequently, mitochondrial damage, endoplasmic reticulum dysfunction and even cell death occur. As a result, the intestinal epithelial cells are destroyed, leading to the incompleteness of intestinal mechanical barrier. Simultaneously, iron supplement can change the compositions and metabolic processes of intestinal microbes, and the intestinal inflammatory may be worsened. In principle, the easier dissociation of Fe2+ from oral iron supplements is, the more serious intestinal inflammation will occur. Fortunately, some interventions have been developed to alleviate these side effects. For instance, some antioxidants e.g. VE and ferulic acid have been used to prevent the formation of free radicals or to neutralize the formed free radicals. Furthermore, some new iron supplements with the ability of slow-releasing Fe2+, e.g. ferrous citrate liposome and EDTA iron sodium, have been successfully prepared. In order to recover the intestinal micro-ecological balance, probiotics and prebiotics, bacterial consortium transplantation, and fecal microbiota transplantation have been developed. This study is meaningful for us to develop safer oral iron supplements and to maintain intestinal micro-ecological health.

RevDate: 2019-06-24

Kellermayer R (2019)

Fecal microbiota transplantation: great potential with many challenges.

Translational gastroenterology and hepatology, 4:40 pii:tgh-04-2019.05.10.

In January of 2019, Samuel P. Costello and colleagues published a wonderfully executed, double blind placebo-controlled trial on fecal microbiota transplantation (FMT) versus autologous stool as placebo in mild to moderately active adult ulcerative colitis [UC: one type of inflammatory bowel disease (IBD)] patients. This review-commentary examines the current state of knowledge on human gut microbiome (live microbiota + their products and surrounding environment, i.e., fecal matter) and microbial therapeutics from a gastrointestinal (GI) clinician's standpoint. The varied forms of dysbiosis as the target of FMT, recipient donor and placebo considerations are also discussed in respect to randomized control trials in IBD [and the lack thereof in Crohn's disease (CD)] with this unconventional treatment modality.

RevDate: 2019-06-24
CmpDate: 2019-06-24

Papanicolas LE, Wesselingh SL, GB Rogers (2019)

Do we really understand how faecal microbiota transplantation works? Authors' reply.

EBioMedicine, 42:40.

RevDate: 2019-06-24
CmpDate: 2019-06-24

van der Sluis WB, Bouman MB, Mullender MG, et al (2019)

The effect of surgical fecal stream diversion of the healthy colon on the colonic microbiota.

European journal of gastroenterology & hepatology, 31(4):451-457.

OBJECTIVES: The intestinal microbiota plays an important role in intestinal health. After colonic diversion from the fecal stream, luminal nutrients for bacteria are expected to be depleted, inducing changes in microbial composition. In this study, we describe microbial changes in the healthy colon following surgical fecal stream diversion, studied in the surgically constructed sigmoid-derived neovagina.

METHODS: At various postoperative times after sigmoid vaginoplasty, rectal, neovaginal, and skin microbial swabs were obtained for microbial analysis by interspacer profiling, a PCR-based bacterial profiling technique. Differences in bacterial profiles, in terms of bacterial abundance and phylum diversity, were assessed. Microbial dissimilarities between anatomical locations were analyzed with principal coordinate analysis and partial least squares discriminant analysis.

RESULTS: Bacterial samples were obtained from 28 patients who underwent sigmoid vaginoplasty. By principal coordinate analysis, microbial profiles of samples from the sigmoid-derived neovagina were distinctively different from rectal samples. Partial least squares discriminant analysis showed that the most discriminative species derived from the phylum Bacteroidetes. The abundance and diversity of Bacteroidetes species were reduced following fecal stream diversion compared with rectal samples (median Shannon diversity index of 2.76 vs. 2.18, P<0.01). Similar abundance of Phyla Firmicutes, Actinobacteria, Fusobacteria, Verrucomicrobia, and Proteobacteria was observed.

CONCLUSION: By analyzing the microbiome of sigmoid-derived neovaginas, we studied the effects of fecal diversion on the microbial composition of the healthy intestine. Most changes were observed in the phylum Bacteroidetes, indicating that these bacteria are likely part of the diet-dependent (butyrate-producing) colonic microbiome. Bacteria of other phyla are likely to be part of the diet-independent microbiome.

RevDate: 2019-06-24
CmpDate: 2019-06-24

Weng MT, Chiu YT, Wei PY, et al (2019)

Microbiota and gastrointestinal cancer.

Journal of the Formosan Medical Association = Taiwan yi zhi, 118 Suppl 1:S32-S41.

Gut microbiota plays important roles in many diseases, including cancer. It may promote carcinogenesis by inducing oxidative stress, genotoxicity, host immune response disturbance, and chronic inflammation. Colorectal cancer, hepatocellular carcinoma, and gastric cancer are the major gastrointestinal tract cancers in Taiwan. The microbiota detected in patients with tubular adenoma and villous/tubulovillous polyps is different from that in healthy controls and patients with hyperplastic polyps. Normalization of the microbiota is observed in patients after colorectal cancer treatment. Furthermore, the liver is exposed to microbiota-associated molecular patterns (MAMPs), bacterial metabolites, and toxins, as it is anatomically connected to the gut via the portal vein. Patients with cirrhosis have significantly higher plasma endotoxin levels than healthy controls. Helicobacter pylori is a well-established risk factor for gastric cancer. Some nitrosating bacteria convert nitrogen compounds in gastric fluid to potentially carcinogenic N-nitroso compounds, which also contribute to gastric cancer development. Growing evidence demonstrates that gut microbiota promotes carcinogenesis. In this review, we discuss the mechanisms and types of microbiota changes involved in these gastrointestinal cancers and the future treatment choices.

RevDate: 2019-06-21

Xue H, Chen X, Chen K, et al (2019)

Anthocyanin Improves Glucose Homeostasis in Obese Mice via Beneficial Regulation of Intestinal Microbiota and Barrier Function (OR34-08-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz031.OR34-08-19.

Objectives: Anthocyanin (ACN) is a natural polyphenol with anti-diabetic effects. However, intact anthocyanin has low bioavailability and largely arrives unmetabolized in the colon, its mechanisms of action remain unclear. The intestinal microbiota dysbiosis and leaky gut contribute to the development of diet-induced type 2 diabetes. Therefore, we aim to investigate whether the anti-diabetic effects of anthocyanin were related to changes in the gut microbiota and epithelial barrier function.

Methods: Male C57Bl/6 N mice were randomly assigned into 4 groups and pair-fed either a chow or high fat/high sugar diet (HFHS, 45 kcal% fat, 17 kcal% sucrose) +/- 1.0% anthocyanin for 8 weeks. Indices of systemic inflammation, parameters of glucose homeostasis and intestinal barrier function were determined. The composition of the gut microbiota was assessed by analysing 16S rRNA gene sequences with Illumina pyrosequencing. To ascertain the involvement of the gut microbiota in the anti-diabetic effects of anthocyanin. A separate cohort of HFHS-fed C57Bl/6 N mice were oral gavage administered with fecal microbiota from chow-fed donors, HFHS-fed donors, HFHS + ACN-fed donors and heat-killed fecal microbial from HFHS + ACN-fed donors (HK-ACN) for 8 weeks, followed by the same examination.

Results: Relative to vehicle controls, ACN ingestion attenuated several effects of HFHS feeding, including glucose intolerance, insulin resistance and serum inflammatory markers. ACN ingestion reduced intestinal permeability and metabolic endotoxemia. These beneficial effects of ACN were associated with increased expression of genes involved in epithelial barrier function (ZO-1, occludin) and decreased inducible NO-synthase (iNOS) protein levels in ileum and colon of HFHS-fed mice. Gut microbiota analysis revealed that ACN ingestion induced profound alterations in the gut microbiome of HFHS-fed mice. Transplantation of the gut microbiome from ACN-fed mice, but not HFHS-fed or HK-ACN-fed mice, was sufficient to recapitulate the improvement in intestinal epithelial barrier function, systemic inflammation and glucose homeostasis observed with oral ACN treatment.

Conclusions: These findings indicate that ACN-mediated changes in the gut microbiota and epithelial barrier function may play a predominant role in the mechanism of action of anthocyanin.

Funding Sources: The State Key Program of National Natural Science Foundation of China [grant number 81730090].

RevDate: 2019-06-21

Shon WJ, Jung MH, Choi EY, et al (2019)

Sugar-sweetened Beverage and High Fat Diet Consumption Harmfully Alters Gut Microbiota and Promotes Gut Inflammation (P20-041-19).

Current developments in nutrition, 3(Suppl 1): pii:nzz040.P20-041-19.

Objectives: It is clear that epidemiologic trends document a dramatic increasing incidence of inflammatory bowel disease (IBD) paralleling global westernization. Despite strong tie among diets, gut microbiota (GM) and IBD, the exact mechanisms causing IBD remains incompletely understood. Here we hypothesized that changes in the gut immune system, in response to changes in gut microbiome induced "Westernized diet", would be sufficient to trigger IBD.

Methods: We set out to test this hypothesized by analyzing the changes in gut microbiota composition induced by feeding mice with High sugar-solution or/and High fat and demonstrated their causal roles through high-throughput microbiome analyses. We further assessed changes in inflammatory cell recruitment using flow cytometry, and performed transcriptomic profiling analyses of intestine tissue to identify altered gut microbiota deliver changes in intestinal innate immune and adaptive T cell homeostasis. Importantly, to identify the role of the microbiota in directing host immune responses, fecal microbiota transplantation (FMT) experiments were conducted.

Results: The microbiome analyses results showed that Prevotella, Betaproteobacteria, and Cytophaga, which are a well-known the most representative species in IBD, was significantly enriched only in the HF-Sugar group, suggesting that addition of high-sugar to high-fat diet may reshape the GM by favoring colonization of pathobionts. Also, transcriptome and FACS profiling results showed, among others, high sugar synergistically changes intestinal transcriptomic signature related Inflammatory/Immune Response induced by several pro-inflammatory cytokines and induces expansion of inflammatory DCs and T cells driven by the high fat diet. By using FMT, we prove that host immune traits can be regulated by altering the GM.

Conclusions: Together, our large-scale profiling analyses may uncover an interaction between dietary alterations causing IBD and gut microbiota and provide helpful information regarding the microbiota plays a critical role in programming the immune phenotypes of the host.

Funding Sources: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018R1D1A1B07048023).

RevDate: 2019-06-21

Burz SD, Abraham AL, Fonseca F, et al (2019)

A Guide for Ex Vivo Handling and Storage of Stool Samples Intended for Fecal Microbiota Transplantation.

Scientific reports, 9(1):8897 pii:10.1038/s41598-019-45173-4.

Owing to the growing recognition of the gut microbiota as a main partner of human health, we are expecting that the number of indications for fecal microbiota transplantation (FMT) will increase. Thus, there is an urgent need for standardization of the entire process of fecal transplant production. This study provides a complete standardized procedure to prepare and store live and ready-to-use transplants that meet the standard requirements of good practices to applied use in pharmaceutical industry. We show that, if time before transformation to transplants would exceed 24 hours, fresh samples should not be exposed to temperatures above 20 °C, and refrigeration at 4 °C can be a safe solution. Oxygen-free atmosphere was not necessary and simply removing air above collected samples was sufficient to preserve viability. Transplants prepared in maltodextrin-trehalose solutions, stored in a -80 °C standard freezer and then rapidly thawed at 37 °C, retained the best revivification potential as proven by 16S rRNA profiles, metabolomic fingerprints, and flow cytometry assays over a 3-month observation period. Maltodextrin-trehalose containing cryoprotectants were also efficient in preserving viability of lyophilized transplants, either in their crude or purified form, an option that can be attractive for fecal transplant biobanking and oral formulation.

RevDate: 2019-06-21

Frisbee AL, Saleh MM, Young MK, et al (2019)

IL-33 drives group 2 innate lymphoid cell-mediated protection during Clostridium difficile infection.

Nature communications, 10(1):2712 pii:10.1038/s41467-019-10733-9.

Clostridium difficile (C. difficile) incidence has tripled over the past 15 years and is attributed to the emergence of hypervirulent strains. While it is clear that C. difficile toxins cause damaging colonic inflammation, the immune mechanisms protecting from tissue damage require further investigation. Through a transcriptome analysis, we identify IL-33 as an immune target upregulated in response to hypervirulent C. difficile. We demonstrate that IL-33 prevents C. difficile-associated mortality and epithelial disruption independently of bacterial burden or toxin expression. IL-33 drives colonic group 2 innate lymphoid cell (ILC2) activation during infection and IL-33 activated ILC2s are sufficient to prevent disease. Furthermore, intestinal IL-33 expression is regulated by the microbiota as fecal microbiota transplantation (FMT) rescues antibiotic-associated depletion of IL-33. Lastly, dysregulated IL-33 signaling via the decoy receptor, sST2, predicts C. difficile-associated mortality in human patients. Thus, IL-33 signaling to ILC2s is an important mechanism of defense from C. difficile colitis.

RevDate: 2019-06-21
CmpDate: 2019-06-21

Falony G, Vandeputte D, Caenepeel C, et al (2019)

The human microbiome in health and disease: hype or hope.

Acta clinica Belgica, 74(2):53-64.

OBJECTIVES: The prognostic, diagnostic, and therapeutic potential of the human gut microbiota is widely recognised. However, translation of microbiome findings to clinical practice is challenging. Here, we discuss current knowledge and applications in the field.

METHODS: We revisit some recent advances in the field of faecal microbiome analyses with a focus on covariate analyses and ecological interpretation.

RESULTS: Population-level characterization of gut microbiota variation among healthy volunteers has allowed identifying microbiome covariates required for clinical studies. Currently, microbiome research is moving from relative to quantitative approaches that will shed a new light on microbiota-host interactions in health and disease.

CONCLUSIONS: Covariate characterization and technical advances increase reproducibility of microbiome research. Targeted in vitro/in vivo intervention studies will accelerate clinical implementation of microbiota findings.

RevDate: 2019-06-20

D'Haens GR, C Jobin (2019)

Fecal Microbial Transplantation For Diseases Beyond Recurrent Clostridium Difficile Infection.

Gastroenterology pii:S0016-5085(19)41017-2 [Epub ahead of print].

As microbiome research has moved from associative to mechanistic studies, the activities of specific microbes and their products have been investigated in development of inflammatory bowel diseases, cancer, metabolic syndrome, and neuropsychiatric disorders. Findings from microbiome research have already been applied to the clinic, such as in fecal microbiota transplantation (FMT) for treatment of recurrent Clostridium difficile infection. We review the evidence for associations between alterations in the intestinal microbiome and gastrointestinal diseases and findings from clinical trials of FMT. We discuss opportunities for treatment of other diseases with FMT, based on findings from small clinical and preclinical studies.

RevDate: 2019-06-20

Jagessar SAR, Long C, Cui B, et al (2019)

Improvement of Good's syndrome by fecal microbiota transplantation: the first case report.

The Journal of international medical research [Epub ahead of print].

RevDate: 2019-06-19

Foligné B, Plé C, Titécat M, et al (2019)

Contribution of the Gut Microbiota in P28GST-Mediated Anti-Inflammatory Effects: Experimental and Clinical Insights.

Cells, 8(6): pii:cells8060577.

An original immuno-regulatory strategy against inflammatory bowel diseases based on the use of 28 kDa glutathione S-transferase (P28GST), a unique schistosome protein, was recently proposed. Improvement of intestinal inflammation occurs through restoration of the immunological balance between pro-inflammatory T-helper 1 (Th1) responses and both T-helper 2 (Th2) and regulatory responses. However, detailed mechanisms explaining how P28GST prevents colitis and promotes gut homeostasis remain unknown. Considering the complex interplay between the adaptive and innate immune system and the intestinal microbiota, we raised the question of the possible role of the microbial ecosystem in the anti-inflammatory effects mediated by the helminth-derived P28GST protein. We first analyzed, by 16S rRNA sequencing, the bacterial profiles of mice fecal microbiota at several time points of the P28GST-immunomodulation period prior to trinitrobenzene sulfonic acid (TNBS)-colitis. The influence of gut microbiota in the P28GST-mediated anti-inflammatory effects was then assessed by fecal microbiota transplantation experiments from P28GST-immunized mice to either conventional or microbiota depleted naïve recipient mice. Finally, the experimental data were supplemented by the temporal fecal microbiota compositions of P28GST-treated Crohn's disease patients from a pilot clinical study (NCT02281916). The P28GST administration slightly modulated the diversity and composition of mouse fecal microbiota while it significantly reduced experimental colitis in mice. Fecal microbiota transplantation experiments failed to restore the P28GST-induced anti-inflammatory effects. In Crohn's disease patients, P28GST also induced slight changes in their overall fecal bacterial composition. Collectively, these results provide key elements in both the anti-inflammatory mechanisms and the safe therapeutic use of immunomodulation with such promising helminth-derived molecules.

RevDate: 2019-06-18

Reisinger EC, Ebbers M, M Löbermann (2019)

[Clostridium Difficile: Monoclonal Antibody Therapy and Vaccines].

Deutsche medizinische Wochenschrift (1946), 144(12):842-849.

Hospital-acquired Clostridium difficile infections have become much more frequent in recent years. Besides treatment with antibiotics and fecal microbiota transplant, new preventive strategies are available now. Bezlotoxumab is an antibody against toxin B and may reduce the risk of relapse by roughly 10 %. Several vaccine candidates against toxins A and B and surface-associated antigens were immunogenic and are tested in clinical trials to investigate the efficacy and safety.

RevDate: 2019-06-18

Kalinkovich A, G Livshits (2019)

A cross talk between dysbiosis and gut-associated immune system governs the development of inflammatory arthropathies.

Seminars in arthritis and rheumatism pii:S0049-0172(19)30170-2 [Epub ahead of print].

BACKGROUND: Emerging evidence suggests that dysbiosis, imbalanced gut microbial community, might be a key player in the development of various diseases, including inflammatory arthropathies, such as rheumatoid arthritis, spondyloarthritis (mainly, ankylosing spondylitis and psoriatic arthritis), and osteoarthritis. Yet, the underlying mechanisms and corresponding interactions remain poorly understood.

METHODS: We conducted a critical and extensive literature review to explore the association between dysbiosis and the development of inflammatory arthropathies. We also reviewed the literature to assess the perspectives that ameliorate inflammatory arthropathies by manipulating the microbiota with probiotics, prebiotics or fecal microbiota transplantation.

RESULTS: Some bacterial species (e.g. Prevotella, Citrobacter rodentium, Collinsella aerofaciens, Segmented filamentous bacteria) participate in the creation of the pro-inflammatory immune status, presumably via epitope mimicry, modification of self-antigens, enhanced cell apoptosis mechanisms, and destruction of tight junction proteins and intestinal barrier integrity, all leading to the development and maintainance of inflammatory arthropathies. Whether dysbiosis is an epiphenomenon or is an active driver of these disorders remains unclear, yet, recent observations clearly suggest that dysbiosis precedes and triggers their development implying a causative relationship between dysbiosis and inflammatory arthropathies. The underlying mechanisms include dysbiosis-mediated changes in the functional activity of the intestinal immune cell subsets, such as innate lymphoid cells, mucosa-associated invariant T cells, invariant natural killer T cells, T-follicular helper and T-regulatory cells. In turn, disturbed functionality of the gut-associated immune system is shown to promote the overgrowth of many bacteria, thus establishing a detrimental vicious circle of actively maintaining arthritis.

CONCLUSIONS: Analysis of the data described in the review supports the notion that a close, dynamic and tightly regulated cross talk between dysbiosis and the gut-associated immune system governs the development of inflammatory arthropathies.

RevDate: 2019-06-17

Ahamed R, Philips CA, P Augustine (2019)

Fecal Microbiota Transplantation for Primary Sclerosing Cholangitis-A Beautiful but Incomplete Story.

The American journal of gastroenterology [Epub ahead of print].

RevDate: 2019-06-17

Khoruts A, LJ Brandt (2019)

Fecal Microbiota Transplant: A Rose by Any Other Name.

The American journal of gastroenterology [Epub ahead of print].

RevDate: 2019-06-17

Wang B, Zhang L, Zhu SW, et al (2019)

Short chain fatty acids contribute to gut microbiota-induced promotion of colonic melatonin receptor expression.

Journal of biological regulators and homeostatic agents, 33(3):763-771.

RevDate: 2019-06-17

Smirnova DV, Zalomova LV, Zagainova AV, et al (2019)

Cryopreservation of the human gut microbiota: Current state and perspectives.

International journal of medical microbiology : IJMM pii:S1438-4221(18)30480-6 [Epub ahead of print].

The human intestinal microbiota is a complex ecosystem that consists of thousands of bacterial species that are responsible for human health and disease. The intestinal microbiota is a natural resource for production of therapeutic and preventive medicals, such as probiotics and fecal transplants. Modern lifestyles have resulted in the extinction of evolutionally selected microbial populations upon exposure to environmental factors. Therefore, it is very important to preserve the human gut microbiota to have the opportunity for timely restoration with minimal safety risks. Cryopreservation techniques that are suitable for the preservation of viable, mixed microbial communities and a biobanking approach are currently under development in different countries. However, the number of studies in this area is very limited. The variety of morphological and physiological characteristics of microbes in the microbiota, the different cryopreservation goals, and the criteria for the evaluation of cryopreservation effectiveness are the main challenges in the creation of a universal and standardized cryopreservation protocol. In this review, we summarized the current progress of the main cryopreservation techniques for gut microbiota communities and the methods for the assessment of the effectiveness of these techniques in the context of practical application.

RevDate: 2019-06-17
CmpDate: 2019-06-17

Stebegg M, Silva-Cayetano A, Innocentin S, et al (2019)

Heterochronic faecal transplantation boosts gut germinal centres in aged mice.

Nature communications, 10(1):2443 pii:10.1038/s41467-019-10430-7.

Ageing is a complex multifactorial process associated with a plethora of disorders, which contribute significantly to morbidity worldwide. One of the organs significantly affected by age is the gut. Age-dependent changes of the gut-associated microbiome have been linked to increased frailty and systemic inflammation. This change in microbial composition with age occurs in parallel with a decline in function of the gut immune system; however, it is not clear whether there is a causal link between the two. Here we report that the defective germinal centre reaction in Peyer's patches of aged mice can be rescued by faecal transfers from younger adults into aged mice and by immunisations with cholera toxin, without affecting germinal centre reactions in peripheral lymph nodes. This demonstrates that the poor germinal centre reaction in aged animals is not irreversible, and that it is possible to improve this response in older individuals by providing appropriate stimuli.

RevDate: 2019-06-17
CmpDate: 2019-06-17

Kuijper EJ, Vendrik KEW, MJGT Vehreschild (2019)

Manipulation of the microbiota to eradicate multidrug-resistant Enterobacteriaceae from the human intestinal tract.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 25(7):786-789.

RevDate: 2019-06-17
CmpDate: 2019-06-17

Selvanderan SP, Goldblatt F, Nguyen NQ, et al (2019)

Faecal microbiota transplantation for Clostridium difficile infection resulting in a decrease in psoriatic arthritis disease activity.

Clinical and experimental rheumatology, 37(3):514-515.

RevDate: 2019-06-17
CmpDate: 2019-06-17

Huttner BD, Galperine T, Kapel N, et al (2019)

'A five-day course of oral antibiotics followed by faecal transplantation to eradicate carriage of multidrug-resistant Enterobacteriaceae' - Author's reply.

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 25(7):914-915.

RevDate: 2019-06-17
CmpDate: 2019-06-17

Libertucci J, VB Young (2019)

The role of the microbiota in infectious diseases.

Nature microbiology, 4(1):35-45.

The human body is colonized by a diverse community of microorganisms collectively referred to as the microbiota. Here, we describe how the human microbiota influences susceptibility to infectious diseases using examples from the respiratory, gastrointestinal and female reproductive tract. We will discuss how interactions between the host, the indigenous microbiota and non-native microorganisms, including bacteria, viruses and fungi, can alter the outcome of infections. This Review Article will highlight the complex mechanisms by which the microbiota mediates colonization resistance, both directly and indirectly, against infectious agents. Strategies for the therapeutic modulation of the microbiota to prevent or treat infectious diseases will be discussed, and we will review potential therapies that directly target the microbiota, including prebiotics, probiotics, synbiotics and faecal microbiota transplantation.

RevDate: 2019-06-17
CmpDate: 2019-06-17

Meyers S, Shih J, Neher JO, et al (2018)

Clinical Inquiries: How effective and safe is fecal microbial transplant in preventing C difficile recurrence?.

The Journal of family practice, 67(6):386-388.

Fecal microbial transplant (fmt) is reasonably safe and effective. In patients who have had multiple Clostridium difficile infections (CDIs), fecal microbial transplant (FMT) results in a 65% to 80% cure rate with one treatment and 90% to 95% cure rate with repeated treatments compared with a 25% to 27% cure rate for antibiotics (strength of recommendation [SOR]: B, small open-label randomized controlled trials [RCTs]). Fresh and frozen donor feces, administered by either nasogastric tube or colonoscope, produce equal results (SOR B, RCTs). FMT has an overall adverse event rate of 30%, primarily involving abdominal discomfort, but also, rarely, severe infections (0.7%) and death (0.1%) (SOR: B, systematic review not limited to RCTs).

RevDate: 2019-06-15

Baron SA, Cassir N, Mékidèche T, et al (2019)

Successful treatment and digestive decolonization of a patient with osteitis caused by a Carbapenemase-producing Klebsiella pneumoniae isolate harboring both NDM-1 and OXA-48 enzymes.

Journal of global antimicrobial resistance pii:S2213-7165(19)30144-4 [Epub ahead of print].

OBJECTIVES: Carbapenem resistance in Klebsiella pneumoniae (CRKP) is an increasing problem worldwide and infections caused by this bacterium can be difficult to treat. Here we reported the case of a patient from Romania hospitalized in Bulgaria after an accident trauma that came in France for the treatment of an osteitis caused by a K. pneumoniae carrying both blaNDM-1 and blaOXA-48.

METHOD: The resistome of this extremely-drug-resistant bacterium was analyzed both with phenotypic (large antibiotic susceptibility testing) and genomic method (genome sequencing). The genetic environment of the two carbapenemases was studied.

RESULTS: K. pneumoniae ST307 carrying both a blaNDM-1 gene and a blaOXA-48 gene located on two different plasmids, an Inc L/M and an IncFII. Patient was successfully treated by a combination of intravenous colistin (9 MUI, then 4.5 MUI 2 times/day), intravenous fosfomycin (4 g 3 times/day) and oral doxycycline (100 mg 2 times/day) for 3 months. Fecal microbiota transplantation was successfully conducted for a stool carriage.

CONCLUSION: The ST307 type is becoming endemic in hospital environment and is frequently associated with carbapenem resistance. Treatment of infection caused by multi-drug resistant bacteria are a clinical challenge and the use of old antibiotics associated with a screening and decolonization of the reservoirs can be an efficient therapeutic alternative.

RevDate: 2019-06-15

Wortelboer K, Nieuwdorp M, H Herrema (2019)

Fecal microbiota transplantation beyond Clostridioides difficile infections.

EBioMedicine pii:S2352-3964(19)30375-5 [Epub ahead of print].

The importance of the commensal microbiota to human health and well-being has become increasingly evident over the past decades. From a therapeutic perspective, the popularity of fecal microbiota transplantation (FMT) to restore a disrupted microbiota and amend imbalances has increased. To date, most clinical experience with FMT originates from the treatment of recurrent or refractory Clostridioides difficile infections (rCDI), with resolution rates up to 90%. In addition to CDI, a role for the intestinal microbiome has been implicated in several disorders. FMT has been tested in several randomized controlled trials for the treatment of inflammatory bowel disease, irritable bowel disease and constipation with mixed results. FMT has also been explored for extra-gastrointestinal disorders such as metabolic syndrome, hepatic encephalopathy and graft-versus-host disease. With the exception of recurrent CDI, FMT is currently used in experimental settings only and should not yet be offered as standard care. In addition, it is critical to further standardize and optimize procedures for FMT preparation. This includes determination of active components of FMT to develop (personalized) approaches to treat disease.

RevDate: 2019-06-14

Wang JW, Wang YK, Zhang F, et al (2019)

Initial experience of fecal microbiota transplantation in gastrointestinal disease: A case series.

The Kaohsiung journal of medical sciences [Epub ahead of print].

Current studies have proven the strong association between gut microbiota dysbiosis and the pathogenesis of gastrointestinal diseases. Fecal microbiota transplantation (FMT) from a healthy donor is a promising therapeutic strategy to change and restore composition of the recipient's gut microbiota. Rapidly increasing clinical literatures confirmed the truth of the benefits of FMT on recurrent Clostridium difficile infection (rCDI) and inflammatory bowel disease. This article retrospectively reviewed nine cases (four cases had ulcerative colitis [UC], five cases had rCDI) who received FMT in Kaohsiung Medical University Hospital from April 2016 to November 2018. We summarized the procedure including donor selection, fecal materials preparation, transplantation delivery methods, and clinical outcomes. All of the four UC cases got clinical improvement and four rCDI cases achieved clinical remission after FMT. The other one rCDI case remained positive stool Toxin A+B result after FMT, and got remission after salvage treatment with fidaxomicin. FMT is considered to be a well-tolerated adjuvant treatment for UC and effective salvage treatment for rCDI in our initial experience. Multiple infusions of FMT in UC and rCDI might have exceptional clinical efficiency, and enteral tube insertion could be a useful method to reach this goal and make multiple sessions of FMT easier.

RevDate: 2019-06-13

Na SY, W Moon (2019)

Perspectives on Current and Novel Treatments for Inflammatory Bowel Disease.

Gut and liver pii:gnl19019 [Epub ahead of print].

New therapeutic strategies in inflammatory bowel disease (IBD) have shifted from symptom control towards treat-totarget algorithms in order to optimize treatment results. The treatment of IBD has evolved with the development of tumor necrosis factor-α inhibitors beyond the conventional therapies. In spite of their long-term effectiveness, many patients do not respond to or cannot sustain treatment with these drugs, which have various side effects. Therefore, the development of new drugs targeting specific pathways in the pathogenesis of IBD has become necessary. Some novel biologics and small molecule drugs have shown potential in IBD clinical trials, providing safe and effective results. In addition, clinicians are now trying to target the dysbiotic microbiome of patients with IBD using fecal microbiota transplantation. New tools such as stem cells have also been developed. The available therapeutic options for IBD are expanding rapidly. In the next few years, physicians will face an unprecedented number of options when choosing the best treatments for patients with IBD. This review provides an overview of recent advances in IBD treatment options.

RevDate: 2019-06-13

Ilan Y (2019)

Why targeting the microbiome is not so successful: can randomness overcome the adaptation that occurs following gut manipulation?.

Clinical and experimental gastroenterology, 12:209-217 pii:203823.

The microbiome is explored as a potential target for therapy of bowel and systemic diseases. Fecal microbiota transplantation (FMT) has demonstrated efficacy in Clostridium difficile infection. However, clinical results regarding other diseases are modest, despite the abundant research on the microbiome over the last decade. Both high rate variability of the microbiome and adaptation to gut manipulations may underlie the lack of ultimate effects of FMT, probiotics, prebiotics, synbiotics, and antibiotics, which are aimed at restoring a healthier microbiome. The present review discusses the inherent variability of the microbiome and multiple factors that affect its diversity, as possible causes of the adaptation of the gut microbiome to chronic manipulation. The potential use of randomness is proposed, as a means of overcoming the adaptation and of restoring some of the inherent variability, with the goal of improving the long-term efficacy of these therapies.

RevDate: 2019-06-13

Mazzawi T, Hausken T, Hov JR, et al (2019)

Clinical response to fecal microbiota transplantation in patients with diarrhea-predominant irritable bowel syndrome is associated with normalization of fecal microbiota composition and short-chain fatty acid levels.

Scandinavian journal of gastroenterology [Epub ahead of print].

Objectives: Irritable bowel syndrome (IBS) may be associated with disturbances in gut microbiota composition and functions. We recently performed a study of fecal microbiota transplantation (FMT) in diarrhea-predominant IBS (IBS-D) and found that IBS symptoms improved and the gut microbiota profile changed following FMT. We now aimed to explore the effects of FMT on the gut microenvironment in further detail by using 16S rRNA sequencing for more extended microbiota profiling and analyzing bacterial fermentation products (SCFAs: short chain fatty acids). Materials and methods: The study included 13 patients (four females and nine males) with IBS-D according to Rome III criteria and 13 healthy donors. Freshly donated feces were administered into duodenum via gastroscopy. The patients completed symptom and quality of life (QoL) questionnaires and delivered feces before and 1, 3, 12 and 20/28 weeks after FMT. Microbiota analysis was performed by sequencing 16S rRNA gene with Illumina Miseq technology. Fecal concentrations of SCFAs were analyzed by vacuum distillation followed by gas chromatography. Results: Several gut microbiota taxa and SCFAs were significantly different in the patients at baseline compared to their donors. These differences normalized by the third week following FMT in parallel with significant improvement in symptoms and QoL. Responders had different gut microbiota profile and SCFAs than nonresponders. Significant correlations were found between the gut microenvironment and IBS symptoms. No adverse effects were reported. Conclusions: FMT restores alterations of the gut microenvironment in IBS-D patients during the first 3 weeks and improves their symptoms for up to 28 weeks. ClinicalTrials.gov ID: NCT03333291.

RevDate: 2019-06-13
CmpDate: 2019-06-10

Zare A, Johansson AM, Karlsson E, et al (2018)

The gut microbiome participates in transgenerational inheritance of low-temperature responses in Drosophila melanogaster.

FEBS letters, 592(24):4078-4086.

Environmental perturbations induce transcriptional changes, some of which may be inherited even in the absence of the initial stimulus. Previous studies have focused on transfers through the germline although microbiota is also passed on to the offspring. Thus, we inspected the involvement of the gut microbiome in transgenerational inheritance of environmental exposures in Drosophila melanogaster. We grew flies in the cold versus control temperatures and compared their transcriptional patterns in both conditions as well as in their offspring. F2 flies grew in control temperature, while we controlled their microbiota acquisition from either F1 sets. Transcriptional status of some genes was conserved transgenerationally, and a subset of these genes, mainly expressed in the gut, was transcriptionally dependent on the acquired microbiome.

RevDate: 2019-06-13
CmpDate: 2019-06-10

Joshi T, Elderd BD, KC Abbott (2018)

No appendix necessary: Fecal transplants and antibiotics can resolve Clostridium difficile infection.

Journal of theoretical biology, 442:139-148.

The appendix has been hypothesized to protect the colon against Clostridium difficile infection (CDI) by providing a continuous source of commensal bacteria that crowd out the potentially unhealthy bacteria and/or by contributing to defensive immune dynamics. Here, a series of deterministic systems comprised of ordinary differential equations, which treat the system as an ecological community of microorganisms, model the dynamics of colon microbiome. The first model includes migration of commensal bacteria from the appendix to the gut, while the second model expands this to also include immune dynamics. Simulations and simple analytic techniques are used to explore dynamics under biologically relevant parameters values. Both models exhibited bistability with steady states of a healthy state and of fulminant CDI. However, we find that the appendix size was much too small for migration to affect the stability of the system. Both models affirm the use of fecal transplants in conjunction with antibiotic use for CDI treatment, while the second model also suggests that anti-inflammatory drugs may protect against CDI. Ultimately, in general neither the appendiceal migration rate of commensal microbiota nor the boost to antibody production could exert an appreciable impact on the stability of the system, thus failing to support the proposed protective role of the appendix against CDI.

RevDate: 2019-06-11

Costello SP, Conlon MA, JM Andrews (2019)

Fecal Microbiota Transplantation for Ulcerative Colitis-Reply.

JAMA, 321(22):2240-2241.

RevDate: 2019-06-11

Benech N, Kapel N, H Sokol (2019)

Fecal Microbiota Transplantation for Ulcerative Colitis.

JAMA, 321(22):2240.

RevDate: 2019-06-11

Smibert O, Satlin MJ, Nellore A, et al (2019)

Carbapenem-Resistant Enterobacteriaceae in Solid Organ Transplantation: Management Principles.

Current infectious disease reports, 21(7):26 pii:10.1007/s11908-019-0679-4.

PURPOSE OF REVIEW: Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as a worldwide problem. Given their degree of immunosuppression and the level of contact with the healthcare system, solid organ transplant (SOT) recipients are at a disproportionately higher risk of acquisition, colonization, and infection with CRE, and outcomes from infection tend to be worse compared to non-transplant patients. Therapeutic options are limited for CRE infections although several newer agents have recently been approved for use. How well these agents perform in the setting of immunosuppression and SOT is unclear. We sought to review the epidemiology of CRE in SOT and the management principles.

RECENT FINDINGS: CRE infections are becoming an increasing problem in SOT, and donor-derived infections present a challenge in the peri-transplant period. Newer treatments for CRE are emerging that are less toxic and potentially more effective than prior CRE-active agents, but supportive clinical data are limited. Newer beta-lactamase inhibitors have good activity against KPC carbapenemases, but they lack activity against metallo-beta-lactamases (e.g., NDM). Promising data is emerging with newer agents that have activity against most carbapenemases, but, again, clinical data is needed. Combination therapy in addition to optimal pharmacokinetic and pharmacodynamics may go some way to improve outcomes against these difficult-to-treat organisms. Other novel therapies that prevent the emergence of resistance (oral beta-lactamase inhibitors) and eradication of resistant Gram-negative colonization (fecal microbiota transplant) may eventually become part of a bundle approach to reduce CRE infections in the future. As in non-transplant patients, CRE infections in the transplant setting are challenging to treat and prevent. Infection prevention and control remains crucial to prevent widespread dissemination, and unique challenges exist with donor-derived CRE and how best to manage recipients in the peri-transplant period. Newer treatments are now in early-phase clinical studies, and in vitro activity data are supportive for several agents providing hope for improved outcomes with these typically difficult-to-treat and highly morbid infections in transplant recipients.

RevDate: 2019-06-10

Lam WC, Zhao C, Ma WJ, et al (2019)

The Clinical and Steroid-Free Remission of Fecal Microbiota Transplantation to Patients with Ulcerative Colitis: A Meta-Analysis.

Gastroenterology research and practice, 2019:1287493.

Background and Purpose: Since the first case of fecal microbiota transplantation for the treatment of ulcerative colitis was described in the year 1989, there have been an increment of case reports, case series, cohort studies, and randomized controlled trials (RCTs). In this study, we were going to investigate general clinical remission, clinical response, and steroid-free remission of fecal microbiota transplantation.

Methods: We searched Ovid Medline, Ovid EMBASE, and Cochrane Library, focusing prospective studies including randomized controlled trials and cohort studies. The outcomes were clinical remission, clinical response, steroid-free remission, and serious adverse events. We used RevMan 5.3 software for meta-analyses.

Key Results: A total of 4 RCTs and 2 cohort studies (340 cases from 5 countries) were included. We found that FMT might be more effective than placebo on clinical remission (OR, 3.85 [2.21, 6.7]; P < 0.001; I2 = 0%) and clinical response (OR, 2.75 [1.33, 5.67]; P = 0.006; I2 = 49%), but no statistical difference on steroid-free remission (OR, 2.08 [0.41, 10.5]; P = 0.37; I2 = 69%) and serious adverse events (OR, 2.0 [0.17, 22.97]; P = 0.44; I2 = 0%).

Conclusions and Inferences: Fecal microbiota transplantations were associated with significant clinical remission and response in ulcerative colitis patients while there was no significant difference found between FMT and placebo in steroid-free remission. Moreover, a common consensus on the route, volume, timing, preferred donor characteristics, and frequency of fecal administration is necessary to achieve remission.

RevDate: 2019-06-10

Lui RN, Wong SH, Lau LHS, et al (2019)

Faecal microbiota transplantation for treatment of recurrent or refractory Clostridioides difficile infection in Hong Kong.

Hong Kong medical journal = Xianggang yi xue za zhi [Epub ahead of print].

INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong.

METHODS: We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected.

RESULTS: A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported.

CONCLUSION: Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.

RevDate: 2019-06-07

Borody TJ, Eslick GD, RL Clancy (2019)

Fecal microbiota transplantation as a new therapy: from Clostridioides difficile infection to inflammatory bowel disease, irritable bowel syndrome, and colon cancer.

Current opinion in pharmacology, 49:43-51 pii:S1471-4892(19)30022-0 [Epub ahead of print].

Fecal microbiota transplantation (FMT) represents the most effective means of therapeutically manipulating the gastrointestinal microbiome. Originally employed as a treatment of last-resort in patients with life-threatening Clostridioides difficile infection (CDI), FMT gained widespread acceptance during the CDI epidemic, where it achieved resolution rates approaching 100%. Following our newfound appreciation for the role of the gut microbiome in both health and disease and owing to FMT's unique mechanism/s of action, FMT is rapidly advancing as an effective treatment for a number of conditions in which the gastrointestinal microbiome is thought to play a role. We review the role of FMT from its beginnings in CDI to its expansion into inflammatory bowel disease, irritable bowel syndrome, and colon cancer.

RevDate: 2019-06-10

Herfarth H, Barnes EL, Long MD, et al (2019)

Combined Endoscopic and Oral Fecal Microbiota Transplantation in Patients with Antibiotic-Dependent Pouchitis: Low Clinical Efficacy due to Low Donor Microbial Engraftment.

Inflammatory intestinal diseases, 4(1):1-6.

Background and Objective: A significant number of pouch patients develop antibiotic-dependent pouchitis (ADP). Microbial dysbiosis is thought to be a major driver of clinical symptoms in ADP. The objective of this proof of concept study was to evaluate safety, efficacy, and donor microbial engraftment of an intensified fecal microbiota transplant (FMT) consisting of a single endoscopic FMT followed by daily oral FMT for 2 weeks in patients with ADP.

Methods: We performed a prospective placebo-controlled double-blind FMT trial in patents with established ADP and planned to enroll 20 patients in this proof of concept study. In case of non-response, patients were offered an optional open label active FMT treatment. The endpoints were safety, clinical remission without need for antibiotics during 16 weeks of follow-up, quantitative changes of fecal calprotectin (FCP), and engraftment of donor FMT as determined by metagenomic sequencing of the V4 region of the 16S rRNA gene.

Results: Due to a lower than expected clinical remission rate and low FMT engraftment, enrollment in the study was stopped prematurely after 6 patients were included. All 6 patients enrolled in the placebo-controlled portion failed to respond and needed antibiotic rescue therapy shortly after FMT. FCP increased in the majority of patients in the setting of relapse after FMT. In the active open label FMT extension study 1 out of 5 patients achieved antibiotic-free clinical remission. FMT engraftment after active FMT was observed only in this single patient, whereas engraftment of donor FMT occurred in none of the other patients receiving active FMT, paralleling the lack of clinical response.

Conclusions: Low donor FMT engraftment resulted in low clinical efficacy of FMT in patients with ADP. Before embarking on larger clinical trials with FMT in patients with ADP or other forms of pouchitis, it is mandatory to explore approaches for superior FMT engraftment.

RevDate: 2019-06-07

Martínez N, Hidalgo-Cantabrana C, Delgado S, et al (2019)

Filling the gap between collection, transport and storage of the human gut microbiota.

Scientific reports, 9(1):8327 pii:10.1038/s41598-019-44888-8.

Stool collection devices minimizing the exposure of gut bacteria to oxygen are critical for the standardization of further microbiota-based studies, analysis and developments. The aim of this work was to evidence that keeping anaerobiosis has a deep impact on the viability and diversity of the fecal microbiota that is recovered in the laboratory. Recovering certain microbial populations, such as obligate anaerobic bacteria, is particularly critical if the purpose of the study is to envisage personalized therapeutic purposes, such as autologous Fecal Microbiota Transplant. In this study the same fecal specimens were sampled in conventional stool containers and GutAlive, a disposable device that minimizes exposure of the gut microbiota to oxygen. Samples from five healthy donors were analysed and 150 differential colonies were recovered and identified by 16S rRNA gene sequencing. Globally, GutAlive maintained extremely oxygen sensitive (EOS) populations that were lost in conventional stool containers, and thus viability of species such as as Akkermansia muciniphila, Faecalibacterium prausnitzii and a novel member of the Clostridiales order was kept. These obligate anaerobes were not recovered using the conventional stool collection device. In conclusion, the use of GutAlive for stool collection and transport optimized the viability and recovery of EOS bacteria in the lab by diminishing oxygen toxicity.

RevDate: 2019-06-06

Gurram B, PK Sue (2019)

Fecal microbiota transplantation in children: current concepts.

Current opinion in pediatrics [Epub ahead of print].

PURPOSE OF REVIEW: Administration of fecal material into the gastrointestinal tract, termed fecal microbiota transplantation (FMT), is increasingly recognized as an effective treatment option for recurrent Clostridium difficile infection (RCDI). The impact of FMT on host microbial communities and subsequent disease states has also been explored in recent years for conditions as varied as inflammatory bowel disease especially ulcerative colitis, metabolic diseases, such as diabetes, graft-versus-host disease in hematopoietic stem cell transplant recipients, and autism and autism spectrum disorders. The purpose of this article is to review the evidence for FMT as a treatment option in various pediatric illnesses.

RECENT FINDINGS: The rate of C. difficile infection is rising among children, and is associated with significant morbidity and disease, with recurrence in up to 20% of pediatric patients. Several randomized controlled trials evaluating the utility of FMT in RCDI in comparison to vancomycin have been published and demonstrate high rates of efficacy between 70 and 100%. In addition, the safety of FMT in the treatment of RCDI has been well described in the adult population, with several pediatric case series demonstrating similar rates of tolerability and adverse events. FMT in ulcerative colitis appears promising, especially with multiple infusions administered via the lower gastrointestinal tract. However, there are several limitations, including the lack of uniformity of protocols used, source of FMT, route of administration and the lack of standardization of concomitant therapies. The data on usage of FMT for other indications are preliminary and limited.

SUMMARY: FMT is recognized as an effective treatment option for RCDI and is increasing sought by parents. Although limited, pediatric studies to date on the use of FMT for RCDI demonstrate similar efficacy rates as in the adult population. FMT has been proposed as a treatment option for an increasing number of pediatric conditions, and additional studies are needed to delineate the efficacy of FMT outside of RCDI, as well as its short and long-term impacts on human health.

RevDate: 2019-06-05

Lee CH, Chai J, Hammond K, et al (2019)

Long-term durability and safety of fecal microbiota transplantation for recurrent or refractory Clostridioides difficile infection with or without antibiotic exposure.

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology pii:10.1007/s10096-019-03602-2 [Epub ahead of print].

Fecal microbiota transplant (FMT) is a safe and effective treatment for recurrent or refractory Clostridioides (Clostridium) difficile infection (RCDI) in the short term. However, there are a paucity of data on long-term durability and safety of FMT. The aim of this study is to determine the long-term efficacy and safety of FMT for RCDI. Ninety-four patients underwent FMT via retention enema for RCDI between 2008 and 2012 and completed a follow-up questionnaire 4 to 8 years following the last FMT. Of these, 32 were unreachable and 37 were deceased; 23 of the remaining 25 participants completed the survey. No CDI recurrences were reported in patients treated with FMT; 12 of the 23 participants (52.2%) received at least one course of non-CDI antibiotic(s). Nine participants (40.9%) received probiotics and 4 (17.4%) received both non-CDI antibiotics and probiotics. All 23 participants rated their overall health compared with pre-FMT. Current health was considered "much better" in 17 patients (73.9%); "somewhat better" in 3 patients (13.0%); and "about the same" in 3 patients (13.0%). A total of 11 participants (47.8%) reported an increase in weight of more than 5 kg (kg) post-FMT and 9 participants (39.1%) reported no change in weight (± 5 kg). Four of the 23 participants (17.4%) reported improvement or resolution (undifferentiated colitis, n = 1; Crohn's disease, n = 2; ulcerative colitis, n = 1) of pre-existing gastrointestinal condition following FMT. Eight of 23 participants (34.8%) experienced new medical condition(s) post-FMT. The long-term efficacy (48-96 months) of FMT for RCDI appears to be durable even after non-CDI antibiotic use. Thirty percent had improvement of their pre-existing medical conditions following FMT; 73.9% reported "much better" overall health following FMT.

RevDate: 2019-06-03

Yin GF, Li B, XM Fan (2019)

[Effects and mechanism of fecal transplantation on acute lung injury induced by lipopolysaccharide in rats].

Zhonghua yi xue za zhi, 99(20):1582-1587.

Objective: To investigate the effect of fecal microbiota transplantation (FMT) on acute lung injury (ALI) induced by lipopolysaccharide (LPS) and its regulatory mechanism. Methods: Fifteen rats were divided into control group, LPS group and LPS+FMT group by random number table method. LPS group and LPS+FMT group were intraperitoneally injected with LPS to generate rat ALI model. After 24 h of modeling, feces (10 ml/kg) were given to the LPS+FMT group twice a day, and the control group and LPS group were given the same amount of normal saline. The intervention lasted for 2 days. After 24 h of the last fecal microbiota transplantation, arterial blood gas analysis was performed in each group. Then rats were sacrificed and enzyme-linked immunosorbent (ELISA) method was used to detect intercellular adhesion molecule 1 (ICAM-1) content in the serum and bronchoalveolar lavage fluid (BALF). The lung wet-dry weight ratio (W/D) was evaluated; HE staining and lung tissue pathology scoring, immunohistochemical detection of nuclear factor-kappa B (NF-κB) predominate nuclear expression and expression of ICAM-1 of alveolar epithelial cells were conducted; Western blot was used to detect the expression of proteins related to the intracellular phosphatidylinositol kinase (PI3K)/protein kinase (AKT) signaling pathway. Samples of rat feces were collected and DNA was extracted. Polymerase chain reaction (PCR) products of the V3 and V4 regions of the 16S ribosomal RNA gene (16SrDNA) were sequenced at high throughput, and bioinformatics analysis was conducted on the microbial community based on the operational classification unit. Results: The lung W/D and lung histopathological score of the LPS group were significantly higher than those of the control group, while the arterial partial oxygen pressure (PaO(2)) of the LPS group was significantly lower than that of the control group [(79.2±5.89 vs 95.2±2.77) mmHg, 1 mmHg=0.133 kPa](all P<0.05). The results of intestinal flora sequencing revealed that the diversity index of LPS group was significantly higher than that of the control group, while the lactobacillus of LPS group rats was significantly lower than that of the control group. The content of ICAM-1 in serum, BALF and its relative expression on the cell membrane in the LPS group was significantly higher than that in the control group [(8.64±0.87) vs (7.40±0.32) ng/L; (0.941±0.035) vs (0.739±0.079) ng/L; (0.250±0.010) vs (0.076±0.010)] (all P<0.05). Moreover, the relative expression levels of phosphorylated P65 (p-P65), p-PI3K and p-AKT nucleoprotein in the LPS group were significantly higher than those in the control group (4.89±0.27 vs 3.28±0.13, 0.265±0.030 vs 0.036±0.013 and 0.444±0.040 vs 0.109±0.016) (all P<0.05). The above injury effect was reduced after fecal fungus transplantation. The lung W/D and lung pathological score of LPS+FMT group were significantly lower than those of LPS group, and PaO(2) of LPS+FMT group was significantly higher than that of LPS group [(88.0±3.53) mmHg]. The results of intestinal flora sequencing revealed that the diversity index of LPS+FMT group was significantly lower than that of LPS group, and the lactobacillus genus of LPS+FMT group was significantly higher than that of LPS group. ICAM-1 in the blood serum ((7.44±0.46) ng/L), BALF (0.834±0.040) ng/L) and its relative expression on alveolar epithelial cell membrane (0.173±0.030), the relative expression of p-P65, p-PI3K and p-AKT protein of NF-κB in alveolar epithelial cells was down-regulated ((2.99±0.28, 0.090±0.013 and 0.206±0.018) in LPS+FMT group than those of LPS group, the differences were statistically significant (all P<0.05). Conclusion: Fecal transplantation can alleviate lipopolysaccharide-induced acute lung injury in rats, and its regulatory effect may be related to inhibiting the activation of PI3K/AKT/NF-κB signaling pathway and reducing the expression of inflammatory factor ICAM-1.

RevDate: 2019-06-02

Kim KO, Schwartz MA, Lin OST, et al (2019)

Reducing Cost and Complexity of Fecal Microbiota Transplantation Using Universal Donors for Recurrent Clostridium difficile Infection.

Advances in therapy pii:10.1007/s12325-019-00974-x [Epub ahead of print].

INTRODUCTION: Fecal microbiota transplantation resolves recurrent Clostridium difficile infections in greater than 82% of patients. Highly screened, processed universal donor fecal material is available. We compared cost and scheduling efficiency of fecal microbiota transplantation by universal donors to patient-directed donors.

METHODS: Medical records from a prospectively maintained database of recurrent C. difficile patients who underwent fecal microbiota transplantation between 2012 and 2017 were reviewed retrospectively. Patient-directed donor stool was prepared in our microbiology laboratory using protocol-based screening. We transitioned to purchasing and using universal donor fecal material in 2015. Clinical outcomes, adverse events, time between consult to infusion, consultation fees, and material costs were compared. This was a retrospective comparison of two historical cohorts.

RESULTS: A total of 111 fecal microbiota transplantations were performed on 105 patients (56 from patient-directed donors and 55 from universal donors). Median recipient age was 66 years (18-96) with male to female ratio of 1:2.7, equivalent in both cohorts. Total consultation fees were significantly lower in the universal donor group owing to fewer infectious disease consultations. Costs for donor screening and stool preparation were lower in the universal donor cohort ($485.0 vs. $1189.90 ± 541.4, p < 0.001, 95% CI 559.9-849.9). Time from consultations to infusion was shorter in the universal donor cohort (18.9 ± 19.1 vs. 36.4 ± 23.3 days, p < 0.001, 95% CI 9.521-25.591). Recurrences within 8 weeks after fecal microbiota transplantation were equivalent (p = 0.354). Adverse events were equivalent.

CONCLUSIONS: Fecal microbiota transplantation using universal donors versus patient-directed donors for recurrent C. difficile showed comparable efficacy and short-term complications. The use of universal donors resulted in significant cost savings and scheduling efficiency.

RevDate: 2019-05-30

Ji J, Ge X, Chen Y, et al (2019)

Daphnetin ameliorates experimental colitis by modulating microbiota composition and Treg/Th17 balance.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology [Epub ahead of print].

Inflammatory bowel diseases (IBDs) are characterized by chronic pathologies associated with extensive gut dysbiosis and intestinal inflammation. Hence, endeavors to improve the inflammatory pathology by manipulating gut microbiota are ongoing. Daphnetin (DAPH) is a coumarin derivative extracted from Daphne odora var with anti-inflammatory and immune-regulatory properties that has been widely used in treating inflammatory disorders. Herein, we showed that DAPH remarkably alleviated experimental colitis by reducing colonic inflammation, improving colonic integrity, and reestablishing immune and metabolic homeostasis in the inflicted intestines. Our analysis showed that DAPH modified the composition of gut microbiota and altered the metabolic profiles in dextran sulfate sodium-treated mice. In particular, this agent significantly elevated the abundance of short-chain fatty acid (SCFA)-producing gut microbiota, causatively related with the enhanced development of Treg cells and the reduced proinflammatory Th17 cell differentiation. More critically, the protective effect of DAPH was shown to be transmissible among colitic mice through cohousing or fecal microbiota transplantation, further substantiating the importance of SCFA-producing gut microbiota in DAPH action. We thus for the first time reveal the potential of DAPH in resetting the gut microbiome and reestablishing immune homeostasis in colitic mice, which may have clinical implications for treating IBD.-Ji, J., Ge, X., Chen, Y., Zhu, B., Wu, Q., Zhang, J., Shan, J., Cheng, H., Shi, L. Daphnetin ameliorates experimental colitis by modulating microbiota composition and Treg/Th17 balance.

RevDate: 2019-06-10

Zeng W, Shen J, Bo T, et al (2019)

Cutting Edge: Probiotics and Fecal Microbiota Transplantation in Immunomodulation.

Journal of immunology research, 2019:1603758.

Probiotics are commensal or nonpathogenic microbes that confer beneficial effects on the host through several mechanisms such as competitive exclusion, antibacterial effects, and modulation of immune responses. Some probiotics have been found to regulate immune responses via immune regulatory mechanisms. T regulatory (Treg) cells, T helper cell balances, dendritic cells, macrophages, B cells, and natural killer (NK) cells can be considered as the most determinant dysregulated mediators in immunomodulatory status. Recently, fecal microbiota transplantation (FMT) has been defined as the transfer of distal gut microbial communities from a healthy individual to a patient's intestinal tract to cure some immune disorders (mainly inflammatory bowel diseases). The aim of this review was followed through the recent literature survey on immunomodulatory effects and mechanisms of probiotics and FMT and also efficacy and safety of probiotics and FMT in clinical trials and applications.

RevDate: 2019-05-30

Burrello C, Giuffrè MR, Macandog AD, et al (2019)

Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition.

Cells, 8(6): pii:cells8060517.

Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.

RevDate: 2019-05-25

Alagna L, Haak BW, A Gori (2019)

Fecal microbiota transplantation in the ICU: perspectives on future implementations.

Intensive care medicine pii:10.1007/s00134-019-05645-7 [Epub ahead of print].

RevDate: 2019-06-10

Cavuoto KM, Banerjee S, A Galor (2019)

Relationship between the microbiome and ocular health.

The ocular surface pii:S1542-0124(19)30028-X [Epub ahead of print].

The microbiome is important to the host as a whole, both in maintenance of health and in the pathophysiology of disease. The purpose of this review is to explore the relationship between the gut, ocular microbiome, and ocular disease states. We will also discuss how the microbiome can serve as a potential target for treatment, by methods such as modulation of diet, probiotics and fecal microbiota transplantation. The information discussed in the review has been gathered using literature published from 2004 to November 2018, as indexed in PubMed.

RevDate: 2019-05-24

Sharpton SR, Maraj B, Harding-Theobald E, et al (2019)

Gut microbiome-targeted therapies in nonalcoholic fatty liver disease: a systematic review, meta-analysis, and meta-regression.

The American journal of clinical nutrition pii:5498099 [Epub ahead of print].

BACKGROUND: Preclinical evidence suggests that modulation of the gut microbiome could represent a new therapeutic target in nonalcoholic fatty liver disease (NAFLD).

OBJECTIVES: The aim of this study was to evaluate the most current evidence for liver-specific and metabolic effects of microbiome-targeted therapies (MTTs) in persons with NAFLD.

METHODS: We searched multiple electronic databases for randomized controlled trials (RCTs) published from January 1, 2005 to December 1, 2018 that enrolled persons with NAFLD who received MTT rather than placebo or usual care. MTT was defined as antibiotics, probiotics, synbiotics, or fecal microbiota transplantation (FMT). Clinical outcomes were pooled with the use of random-effects models and heterogeneity was assessed with the I2 statistic. A random-effects meta-regression was performed to determine sources of heterogeneity in prevalence estimates between studies.

RESULTS: Twenty-one RCTs (1252 participants) were included; 9 evaluated probiotics and 12 evaluated synbiotics, with treatment duration ranging from 8 to 28 wk. No RCTs examined the efficacy of antibiotics or FMT. Probiotics/synbiotics were associated with a significant reduction in alanine aminotransferase activity [ALT, weighted mean difference (WMD): -11.23 IU/L; 95% CI: -15.02, -7.44 IU/L] and liver stiffness measurement (LSM) by elastography (reflecting inflammation and fibrosis) (WMD: -0.70 kPa; 95% CI: -1.00, -0.40 kPa), although analyses showed heterogeneity (I2 = 90.6% and I2 = 93.4%, respectively). Probiotics/synbiotics were also associated with increased odds of improvement in hepatic steatosis, as graded by ultrasound (OR: 2.40; 95% CI: 1.50, 3.84; I2 = 22.4%). No RCTs examined sequential liver biopsy findings. Probiotics (WMD: -1.84; 95% CI: -3.30, -0.38; I2 = 23.6%), but not synbiotics (WMD: -0.85; 95% CI: -2.17, 0.47; I2 = 96.6%), were associated with a significant reduction in body mass index.

CONCLUSIONS: The use of probiotics/synbiotics was associated with improvement in liver-specific markers of hepatic inflammation, LSM, and steatosis in persons with NAFLD. Although promising, given the heterogeneity in pooled analyses, additional well-designed RCTs are needed to define the efficacy of probiotics/synbiotics for treatment of NAFLD. This study was registered with PROSPERO as CRD42018091455.

RevDate: 2019-05-24

Li N, Wang Q, Wang Y, et al (2019)

Fecal microbiota transplantation from chronic unpredictable mild stress mice donors affects anxiety-like and depression-like behavior in recipient mice via the gut microbiota-inflammation-brain axis.

Stress (Amsterdam, Netherlands) [Epub ahead of print].

Recent studies have demonstrated that there are significant changes in the gut microbiota (GM) of humans with depression and animal models of depression and chronic stress. In our present study, we determined whether an alteration in GM is a decisive factor in anxiety-like and depression-like behavior and its impact on brain neurochemistry. An antibiotic cocktail was used to deplete the GM of mice before they were colonized, via fecal microbiota transplantation (FMT), by the GM of control mice or mice that had been exposed to chronic unpredictable mild stress (CUMS donors). The CUMS-donor group of mice and the mice that were colonized by their microbiota (the CUMS-recipient group) both showed higher levels of anxiety- and depression-like behavior compared to the controls. The GM community of the CUMS-donor and CUMS-recipient was distinctively different from the controls, with the CUMS group characterized by a lower relative abundance of Lactobacillus and a higher relative abundance of Akkermansia. Interestingly, FMT affected both behavior and neuroinflammation. Mice given the CUMS microbiota had significant elevations of interferon-γ (IFN-γ) and the tumor necrosis factor-alpha (TNF-α) in the hippocampus, which were accompanied by upregulated indoleamine 2,3-dioxygenase 1 (IDO1) in the hippocampus. These results suggest that GM modulates pro-inflammatory cytokines in the hippocampus through dysfunctional microbiota-gut-brain axis, exacerbating anxiety- and depression-like phenotypes. Key Points Chronic unpredictable mild stress increased anxiety- and depression-like behavior in mice. Mice colonized with gut microbiota (GM) from stressed mice showed similar behaviors. The GM composition of the donor and recipient mice was also comparable. Their relative pattern of two bacteria has been tied to neuroinflammatory activity. The results suggest a link between GM, brain function, and anxiety and depression.

RevDate: 2019-06-10

Yousi F, Kainan C, Junnan Z, et al (2019)

Evaluation of the effects of four media on human intestinal microbiota culture in vitro.

AMB Express, 9(1):69 pii:10.1186/s13568-019-0790-9.

The human intestinal microbiota has an important role in the maintenance of human health and disease pathogenesis. The aim of this research was to investigate the impact of four media on human intestinal microbiota metabolite and composition changes, we performed in vitro batch culture using intestinal microbiota samples from three fecal microbiota transplantation (FMT) donors. After 48 h culture, gut microbiota medium (GMM) had the highest production of acetic acid (73.00 ± 7.56 mM) and propionic acid (16.79 ± 1.59 mM), bacterial growth media (BGM) had the highest production of butyric acid (13.39 ± 0.56 mM). In addition, brain heart infusion (BHI) promoted (p < 0.05) the growth of Bacteroidetes, especially Bacteroides after 48 h, GMM resulted in a significant increase (p < 0.05) in Actinobacteria and increased the beneficial genus Bifidobacterium, fastidious anaerobe broth (FAB) increased Firmicutes population, and BGM promoted the growth of Escherichia-Shigella and Akkermansia. The results suggest that four media had different effects on the human intestinal microbiota metabolism and composition in vitro. These results may facilitate the culture of bacteria from the human intestinal microbiota.

RevDate: 2019-06-05

Yu F, Han W, Zhan G, et al (2019)

Abnormal gut microbiota composition contributes to cognitive dysfunction in streptozotocin-induced diabetic mice.

Aging, 11(10):3262-3279.

Both diabetes and Alzheimer's disease are age-related disorders, and numerous studies have demonstrated that patients with diabetes are at an increased risk of cognitive dysfunction (CD) and Alzheimer's disease, suggesting shared or interacting pathomechanisms. The present study investigated the role of abnormal gut microbiota in diabetes-induced CD and the potential underlying mechanisms. An intraperitoneal injection of streptozotocin administered for 5 consecutive days was used for establishing a diabetic animal model. Hierarchical cluster analysis of Morris water maze (MWM) performance indices (escape latency and target quadrant crossing) was adopted to classify the diabetic model mice into CD and Non-CD phenotypes. Both β-diversity and relative abundance of several gut bacteria significantly differed between the CD and Non-CD groups. Further, fecal bacteria transplantation from Non-CD mice, but not from CD mice, into the gut of pseudo-germ-free mice significantly improved host MWM performance, an effect associated with alterations in β-diversity and relative abundance of host gut bacteria. Collectively, these findings suggest that abnormal gut microbiota composition contributes to the onset of diabetes-induced CD and that improving gut microbiota composition is a potential therapeutic strategy for diabetes and related comorbidities.

RevDate: 2019-05-24

McSweeney B, Allegretti JR, Fischer M, et al (2019)

In search of stool donors: a multicenter study of prior knowledge, perceptions, motivators, and deterrents among potential donors for fecal microbiota transplantation.

Gut microbes [Epub ahead of print].

Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection. Stool donors are essential, but difficult to recruit and retain. We aimed to identify factors influencing willingness to donate stool. This multi-center study with a 32-item questionnaire targeted young adults and health care workers via social media and university email lists in Edmonton and Kingston, Canada; London and Nottingham, England; and Indianapolis and Boston, USA. Items included baseline demographics and FMT knowledge and perception. Investigated motivators and deterrents included economic compensation, screening process, time commitment, and stool donation logistics. Logistic regression and linear regression models estimated associations of study variables with self-assessed willingness to donate stool. 802 respondents completed our questionnaire: 387 (48.3%) age 21-30 years, 573 (71.4%) female, 323 (40%) health care workers. Country of residence, age and occupation were not associated with willingness to donate stool. Factors increasing willingness to donate were: already a blood donor (OR 1.64), male, altruism, economic benefit, knowledge of how FMT can help patients (OR 1.32), and positive attitudes towards FMT (OR 1.39). Factors decreasing willingness to donate were: stool collection unpleasant (OR 0.92), screening process invasive (OR 0.92), higher stool donation frequency, negative social perception of stool, and logistics of collection/transporting feces. We conclude that 1) blood donors and males are more willing to consider stool donation; 2) altruism, economic compensation, and positive feedback are motivators; and 3) screening process, high donation frequency, logistics of collection/transporting feces, lack of public awareness, and negative social perception are deterrents. Considering these variables could maximize donor recruitment and retention.

RevDate: 2019-06-10

Contreras GA, Munita JM, CA Arias (2019)

Novel Strategies for the Management of Vancomycin-Resistant Enterococcal Infections.

Current infectious disease reports, 21(7):22 pii:10.1007/s11908-019-0680-y.

PURPOSE OF REVIEW: Vancomycin-resistant enterococci (VRE) are important nosocomial pathogens that commonly affect critically ill patients. VRE have a remarkable genetic plasticity allowing them to acquire genes associated with antimicrobial resistance. Therefore, the treatment of deep-seated infections due to VRE has become a challenge for the clinician. The purpose of this review is to assess the current and future strategies for the management of recalcitrant deep-seated VRE infections and efforts for infection control in the hospital setting.

RECENT FINDINGS: Preventing colonization and decolonization of multidrug-resistant bacteria are becoming the most promising novel strategies to control and eradicate VRE from the hospital environment. Fecal microbiota transplantation (FMT) has shown remarkable results on treating colonization and infection due to Clostridiodes difficille and VRE, as well as to recover the integrity of the gut microbiota under antibiotic pressure. Initial reports have shown the efficacy of FMT on reestablishing patient microbiota diversity in the gut and reducing the dominance of VRE in the gastrointestinal tract. In addition, the use of bacteriophages may be a promising strategy in eradicating VRE from the gut of patients. Until these strategies become widely available in the hospital setting, the implementation of infection control measures and stewardship programs are paramount for the control of this pathogen and each program should provide recommendations for the proper use of antibiotics and develop strategies that help to detect populations at risk of VRE colonization, prevent and control nosocomial transmission of VRE, and develop educational programs for all healthcare workers addressing the epidemiology of VRE and the potential impact of these pathogens on the cost and outcomes of patients. In terms of antibiotic strategies, daptomycin has become the standard of care for the management of deep-seated infections due to VRE. However, recent evidence indicates that the efficacy of this antibiotic is limited, and higher (10-12 mg/kg) doses and/or combination with β-lactams is needed for therapeutic success. Clinical data to support the best use of daptomycin against VRE are urgently needed. This review provides an overview of recent developments regarding the prevention, treatment, control, and eradication of VRE in the hospital setting. We aim to provide an update of the most recent therapeutic strategies to treat deep-seated infections due to VRE.

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ESP Quick Facts

ESP Origins

In the early 1990's, Robert Robbins was a faculty member at Johns Hopkins, where he directed the informatics core of GDB — the human gene-mapping database of the international human genome project. To share papers with colleagues around the world, he set up a small paper-sharing section on his personal web page. This small project evolved into The Electronic Scholarly Publishing Project.

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In 1995, Robbins became the VP/IT of the Fred Hutchinson Cancer Research Center in Seattle, WA. Soon after arriving in Seattle, Robbins secured funding, through the ELSI component of the US Human Genome Project, to create the original ESP.ORG web site, with the formal goal of providing free, world-wide access to the literature of classical genetics.

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Although the methods of molecular biology can seem almost magical to the uninitiated, the original techniques of classical genetics are readily appreciated by one and all: cross individuals that differ in some inherited trait, collect all of the progeny, score their attributes, and propose mechanisms to explain the patterns of inheritance observed.

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Usage of the site grew rapidly and has remained high. Faculty began to use the site for their assigned readings. Other on-line publishers, ranging from The New York Times to Nature referenced ESP materials in their own publications. Nobel laureates (e.g., Joshua Lederberg) regularly used the site and even wrote to suggest changes and improvements.

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When the site began, no journals were making their early content available in digital format. As a result, ESP was obliged to digitize classic literature before it could be made available. For many important papers — such as Mendel's original paper or the first genetic map — ESP had to produce entirely new typeset versions of the works, if they were to be available in a high-quality format.

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With the development of methods for adding typeset side notes to PDF files, the ESP project now plans to add annotated versions of some classical papers to its holdings. We also plan to add new reference and pedagogical material. We have already started providing regularly updated, comprehensive bibliographies to the ESP.ORG site.

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Selected Bibliographies

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