@article {pmid33628361, year = {2021}, author = {Du, D and Tang, W and Zhou, C and Sun, X and Wei, Z and Zhong, J and Huang, Z}, title = {Fecal Microbiota Transplantation Is a Promising Method to Restore Gut Microbiota Dysbiosis and Relieve Neurological Deficits after Traumatic Brain Injury.}, journal = {Oxidative medicine and cellular longevity}, volume = {2021}, number = {}, pages = {5816837}, doi = {10.1155/2021/5816837}, pmid = {33628361}, issn = {1942-0994}, abstract = {Background: Traumatic brain injury (TBI) can induce persistent fluctuation in the gut microbiota makeup and abundance. The present study is aimed at determining whether fecal microbiota transplantation (FMT) can rescue microbiota changes and ameliorate neurological deficits after TBI in rats.

Methods: A controlled cortical impact (CCI) model was used to simulate TBI in male Sprague-Dawley rats, and FMT was performed for 7 consecutive days. 16S ribosomal RNA (rRNA) sequencing of fecal samples was performed to analyze the effects of FMT on gut microbiota. Modified neurological severity score and Morris water maze were used to evaluate neurobehavioral functions. Metabolomics was used to screen differential metabolites from the rat serum and ipsilateral brains. The oxidative stress indices were measured in the brain.

Results: TBI induced significance changes in the gut microbiome, including the alpha- and beta-bacterial diversity, as well as the microbiome composition at 8 days after TBI. On the other hand, FMT could rescue these changes and relieve neurological deficits after TBI. Metabolomics results showed that the level of trimethylamine (TMA) in feces and the level of trimethylamine N-oxide (TMAO) in the ipsilateral brain and serum was increased after TBI, while FMT decreased TMA levels in the feces, and TMAO levels in the ipsilateral brain and serum. Antioxidant enzyme methionine sulfoxide reductase A (MsrA) in the ipsilateral hippocampus was decreased after TBI but increased after FMT. In addition, FMT elevated SOD and CAT activities and GSH/GSSG ratio and diminished ROS, GSSG, and MDA levels in the ipsilateral hippocampus after TBI.

Conclusions: FMT can restore gut microbiota dysbiosis and relieve neurological deficits possibly through the TMA-TMAO-MsrA signaling pathway after TBI.}, } @article {pmid32635373, year = {2020}, author = {Johnson, D and Letchumanan, V and Thurairajasingam, S and Lee, LH}, title = {A Revolutionizing Approach to Autism Spectrum Disorder Using the Microbiome.}, journal = {Nutrients}, volume = {12}, number = {7}, pages = {}, pmid = {32635373}, issn = {2072-6643}, support = {Project No. PVC-ECR-2016, Biotek Abadi - Vote No. GBA-808138 and GBA-808813//PVC Award Grant & External Industry Grant/ ; }, mesh = {Autism Spectrum Disorder/*microbiology/therapy ; Diet/methods ; Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Microbiota/*physiology ; Mouth/microbiology ; Prebiotics ; Probiotics/therapeutic use ; Vagina/microbiology ; }, abstract = {The study of human microbiota and health has emerged as one of the ubiquitous research pursuits in recent decades which certainly warrants the attention of both researchers and clinicians. Many health conditions have been linked to the gut microbiota which is the largest reservoir of microbes in the human body. Autism spectrum disorder (ASD) is one of the neurodevelopmental disorders which has been extensively explored in relation to gut microbiome. The utilization of microbial knowledge promises a more integrative perspective in understanding this disorder, albeit being an emerging field in research. More interestingly, oral and vaginal microbiomes, indicating possible maternal influence, have equally drawn the attention of researchers to study their potential roles in the etiopathology of ASD. Therefore, this review attempts to integrate the knowledge of microbiome and its significance in relation to ASD including the hypothetical aetiology of ASD and its commonly associated comorbidities. The microbiota-based interventions including diet, prebiotics, probiotics, antibiotics, and faecal microbial transplant (FMT) have also been explored in relation to ASD. Of these, diet and probiotics are seemingly promising breakthrough interventions in the context of ASD for lesser known side effects, feasibility and easier administration, although more studies are needed to ascertain the actual clinical efficacy of these interventions. The existing knowledge and research gaps call for a more expanded and resolute research efforts in establishing the relationship between autism and microbiomes.}, } @article {pmid33625548, year = {2021}, author = {Wang, J and Li, X and Wu, X and Wang, Z and Zhang, C and Cao, G and Liu, S and Yan, T}, title = {Gut microbiota alterations associated with antibody-mediated rejection after kidney transplantation.}, journal = {Applied microbiology and biotechnology}, volume = {}, number = {}, pages = {}, pmid = {33625548}, issn = {1432-0614}, support = {No. 32000650//National Natural Science Foundation of China/ ; No. 192102310036//Henan Provincial Scientific and Technological Research Project/ ; No. 201702191//Henan Provincial Medical Scientific and Technological Research Project/ ; }, abstract = {Antibody-mediated rejection (AMR) has become the major challenge for kidney transplantation, and the efficacy of existing therapies was limited to prevent AMR. Increasing evidences have demonstrated the link between gut microbiota alterations and allograft outcome. However, there has been no comprehensive analysis to profile the gut microbiota associated with AMR after kidney transplantation. We performed this study to characterize the gut microbiota possibly associated with AMR. Fecal specimens were collected from 24 kidney transplantation recipients with AMR and 29 controls. DNA extracted from the specimens was processed for 16S rRNA gene sequencing using Illumina MiSeq. Gut microbial community of recipients with AMR was significantly different from that of controls based on unweighted (P = 0.001) and weighted (P = 0.02) UniFrac distances, and the bacterial richness (observed species: P = 0.0448; Chao1 index: P = 0.0450; ACE index: P = 0.0331) significantly decreased in the AMR group. LEfSe showed that 1 phylum, 5 classes, 7 families, and 10 genera were increased, whereas 1 class, 2 order, 3 families, and 4 genera were decreased in the AMR group. Specific taxa such as Clostridiales could be potentially used as biomarkers to distinguish the recipients with AMR from the controls (AUC = 0.77). PICRUSt analysis illustrated that 16 functional pathways were with significantly different abundances in the AMR and control groups. Our findings provide a foundation for further investigation on the role of gut microbiota in AMR after kidney transplantation, and potentially support novel diagnostic biomarkers and therapeutic options for AMR. KEY POINTS: • Gut microbial community of kidney recipients with AMR was different from that of controls. • Clostridiales is a potential marker to distinguish recipients with AMR from controls.}, } @article {pmid33623056, year = {2021}, author = {Berland, M and Cadiou, J and Levenez, F and Galleron, N and Quinquis, B and Thirion, F and Gauthier, F and Le Chatelier, E and Plaza Oñate, F and Schwintner, C and Rabot, S and Lepage, P and Ehrlich, D and Doré, J and Juste, C}, title = {High engraftment capacity of frozen ready-to-use human fecal microbiota transplants assessed in germ-free mice.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {4365}, pmid = {33623056}, issn = {2045-2322}, abstract = {The number of indications for fecal microbiota transplantation is expected to rise, thus increasing the needs for production of readily available frozen or freeze-dried transplants. Using shotgun metagenomics, we investigated the capacity of two novel human fecal microbiota transplants prepared in maltodextrin-trehalose solutions (abbreviated MD and TR for maltodextrin:trehalose, 3:1, w/w, and trehalose:maltodextrin 3:1, w/w, respectively), to colonize a germ-free born mouse model. Gavage with frozen-thawed MD or TR suspensions gave the taxonomic profiles of mouse feces that best resembled those obtained with the fresh inoculum (Spearman correlations based on relative abundances of metagenomic species around 0.80 and 0.75 for MD and TR respectively), while engraftment capacity of defrosted NaCl transplants most diverged (Spearman correlations around 0.63). Engraftment of members of the family Lachnospiraceae and Ruminoccocaceae was the most challenging in all groups of mice, being improved with MD and TR transplants compared to NaCl, but still lower than with the fresh preparation. Improvement of engraftment of this important group in maintaining health represents a challenge that could benefit from further research on fecal microbiota transplant manufacturing.}, } @article {pmid33620078, year = {2021}, author = {Sheh, A}, title = {The Gastrointestinal Microbiota of the Common Marmoset (Callithrix jacchus).}, journal = {ILAR journal}, volume = {}, number = {}, pages = {}, doi = {10.1093/ilar/ilaa025}, pmid = {33620078}, issn = {1930-6180}, abstract = {The microbiota is heavily involved in both health and disease pathogenesis, but defining a normal, healthy microbiota in the common marmoset has been challenging. The aim of this review was to systematically review recent literature involving the gastrointestinal microbiome of common marmosets in health and disease. Twelve sources were included in this review. The gut microbiome composition was reviewed across institutions worldwide, and taxonomic shifts between healthy individuals were described. Unlike the human gut microbiome, which is dominated by Firmicutes and Bacteroidetes, the marmoset gut microbiome shows great plasticity across institutions, with 5 different phyla described as dominant in different healthy cohorts. Genera shared across institutions include Anaerobiospirillum, Bacteroides, Bifidobacterium, Collinsella, Fusobacterium, Megamonas, Megasphaera, Phascolarctobacterium, and Prevotella. Shifts in the abundance of Prevotella or Bifidobacterium or invasion by pathogens like Clostridium perfringens may be associated with disease. Changes in microbial composition have been described in healthy and diseased marmosets, but factors influencing the severe changes in microbial composition have not been established. Multi-institutional, prospective, and longitudinal studies that utilize multiple testing methodologies are required to determine sources of variability in the reporting of marmoset microbiomes. Furthermore, methods of microbial manipulation, whether by diet, enrichment, fecal microbiome transplantation, etc, need to be established to modulate and maintain robust and resilient microbiome communities in marmoset colonies and reduce the incidence of idiopathic gastrointestinal disease.}, } @article {pmid33617596, year = {2021}, author = {Rungue, M and Melo, V and Martins, D and Campos, PC and Leles, G and Galvão, I and Mendes, V and Aganetti, M and Pedersen, Á and Assis, NRG and Santos, R and Cassali, GD and Godard, ALB and Martins, FS and Oliveira, SC and Vieira, AT}, title = {NLRP6-associated host microbiota composition impacts in the intestinal barrier to systemic dissemination of Brucella abortus.}, journal = {PLoS neglected tropical diseases}, volume = {15}, number = {2}, pages = {e0009171}, doi = {10.1371/journal.pntd.0009171}, pmid = {33617596}, issn = {1935-2735}, abstract = {Brucella abortus is a Gram-negative bacterium responsible for a worldwide zoonotic infection-Brucellosis, which has been associated with high morbidity rate in humans and severe economic losses in infected livestock. The natural route of infection is through oral and nasal mucosa but the invasion process through host gut mucosa is yet to be understood. Studies have examined the role of NLRP6 (NOD-like receptor family pyrin domain-containing-6 protein) in gut homeostasis and defense against pathogens. Here, we investigated the impact of gut microbiota and NLRP6 in a murine model of Ba oral infection. Nlrp6-/- and wild-type (WT) mice were infected by oral gavage with Ba and tissues samples were collected at different time points. Our results suggest that Ba oral infection leads to significant alterations in gut microbiota. Moreover, Nlrp6-/- mice were more resistant to infection, with decreased CFU in the liver and reduction in gut permeability when compared to the control group. Fecal microbiota transplantation from WT and Nlrp6-/- into germ-free mice reflected the gut permeability phenotype from the donors. Additionally, depletion of gut microbiota by broad-spectrum-antibiotic treatment prevented Ba replication in WT while favoring bacterial growth in Nlrp6-/-. Finally, we observed higher eosinophils in the gut and leukocytes in the blood of infected Nlrp6-/- compared to WT-infected mice, which might be associated to the Nlrp6-/- resistance phenotype. Altogether, these results indicated that gut microbiota composition is the major factor involved in the initial stages of pathogen host replication and partially also by the resistance phenotype observed in Nlrp6 -/- mice regulating host inflammation against Ba infection.}, } @article {pmid33617526, year = {2021}, author = {Henson, MA}, title = {Computational modeling of the gut microbiota reveals putative metabolic mechanisms of recurrent Clostridioides difficile infection.}, journal = {PLoS computational biology}, volume = {17}, number = {2}, pages = {e1008782}, doi = {10.1371/journal.pcbi.1008782}, pmid = {33617526}, issn = {1553-7358}, abstract = {Approximately 30% of patients who have Clostridioides difficile infection (CDI) will suffer at least one incident of reinfection. While the underlying causes of CDI recurrence are poorly understood, interactions between C. difficile and commensal gut bacteria are thought to play an important role. In this study, an in silico pipeline was used to process 16S rRNA gene amplicon sequence data of 225 stool samples from 93 CDI patients into sample-specific models of bacterial community metabolism. Clustered metabolite production rates generated from post-diagnosis samples generated a high Enterobacteriaceae abundance cluster containing disproportionately large numbers of recurrent samples and patients. This cluster was predicted to have significantly reduced capabilities for secondary bile acid synthesis but elevated capabilities for aromatic amino acid catabolism. When applied to 16S sequence data of 40 samples from fecal microbiota transplantation (FMT) patients suffering from recurrent CDI and their stool donors, the community modeling method generated a high Enterobacteriaceae abundance cluster with a disproportionate large number of pre-FMT samples. This cluster also was predicted to exhibit reduced secondary bile acid synthesis and elevated aromatic amino acid catabolism. Collectively, these in silico predictions suggest that Enterobacteriaceae may create a gut environment favorable for C. difficile spore germination and/or toxin synthesis.}, } @article {pmid33615992, year = {2021}, author = {Pham, VT and Fehlbaum, S and Seifert, N and Richard, N and Bruins, MJ and Sybesma, W and Rehman, A and Steinert, RE}, title = {Effects of colon-targeted vitamins on the composition and metabolic activity of the human gut microbiome- a pilot study.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-20}, doi = {10.1080/19490976.2021.1875774}, pmid = {33615992}, issn = {1949-0984}, abstract = {An increasing body of evidence has shown that gut microbiota imbalances are linked to diseases. Currently, the possibility of regulating gut microbiota to reverse these perturbations by developing novel therapeutic and preventive strategies is being extensively investigated. The modulatory effect of vitamins on the gut microbiome and related host health benefits remain largely unclear. We investigated the effects of colon-delivered vitamins A, B2, C, D, and E on the gut microbiota using a human clinical study and batch fermentation experiments, in combination with cell models for the assessment of barrier and immune functions. Vitamins C, B2, and D may modulate the human gut microbiome in terms of metabolic activity and bacterial composition. The most distinct effect was that of vitamin C, which significantly increased microbial alpha diversity and fecal short-chain fatty acids compared to the placebo. The remaining vitamins tested showed similar effects on microbial diversity, composition, and/or metabolic activity in vitro, but in varying degrees. Here, we showed that vitamins may modulate the human gut microbiome. Follow-up studies investigating targeted delivery of vitamins to the colon may help clarify the clinical significance of this novel concept for treating and preventing dysbiotic microbiota-related human diseases. Trial registration: ClinicalTrials.gov, NCT03668964. Registered 13 September 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03668964.}, } @article {pmid33613491, year = {2021}, author = {Qi, R and Zhang, Z and Wang, J and Qiu, X and Wang, Q and Yang, F and Huang, J and Liu, Z}, title = {Introduction of Colonic and Fecal Microbiota From an Adult Pig Differently Affects the Growth, Gut Health, Intestinal Microbiota and Blood Metabolome of Newborn Piglets.}, journal = {Frontiers in microbiology}, volume = {12}, number = {}, pages = {623673}, doi = {10.3389/fmicb.2021.623673}, pmid = {33613491}, issn = {1664-302X}, abstract = {Microbiota transplantation is a rapid and effective method for changing and reshaping the intestinal microbiota and metabolic profile in humans and animals. This study compared the different influences of the introduction of fecal microbes and colonic microbes from a fat, adult pig in newborn pigs. Both colonic microbiota transplantation (CMT) and fecal microbiota transplantation (FMT) promoted growth and improved gut functions in suckling pigs up to weaning. FMT was more beneficial for body weight gain and body fat deposition in piglets, while CMT was more beneficial for intestinal health and mucosal immunity. 16S rDNA sequence analysis indicated that both CMT and FMT significantly increased the abundances of beneficial or functional bacteria, such as Lactobacillus and Prevotella_2 genera, in the piglets, and reduced the abundances of harmful bacteria, such as Escherichia-Shigella. Blood metabolome analysis showed that transplantation, especially FMT, enhanced lipid metabolism in piglets. In addition, while CMT also changed amino acid metabolism and increased anti-inflammatory metabolites such as 3-indoleacetic acid and 3-indolepropionic acid in piglets, FMT did not. Of note, FMT damaged the intestinal barrier of piglets to a certain extent and increased the levels of inflammatory factors in the blood that are potentially harmful to the health of pigs. Taken together, these results suggested that intestinal and fecal microbiota transplantations elicited similar but different physiological effects on young animals, so the application of microbiota transplantation in animal production requires the careful selection and evaluation of source bacteria.}, } @article {pmid32843743, year = {2021}, author = {Khoruts, A and Staley, C and Sadowsky, MJ}, title = {Faecal microbiota transplantation for Clostridioides difficile: mechanisms and pharmacology.}, journal = {Nature reviews. Gastroenterology & hepatology}, volume = {18}, number = {1}, pages = {67-80}, pmid = {32843743}, issn = {1759-5053}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; *Clostridioides difficile/metabolism/pathogenicity/physiology ; Clostridium Infections/etiology/*physiopathology/*therapy ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Recurrence ; Treatment Outcome ; }, abstract = {Faecal microbiota transplantation (FMT) has emerged as a remarkably successful treatment for recurrent Clostridioides difficile infection that cannot be cured with antibiotics alone. Understanding the complex biology and pathogenesis of C. difficile infection, which we discuss in this Perspective, is essential for understanding the potential mechanisms by which FMT cures this disease. Although FMT has already entered clinical practice, different microbiota-based products are currently in clinical trials and are vying for regulatory approval. However, all these therapeutics belong to an entirely new class of agents that require the development of a new branch of pharmacology. Characterization of microbiota therapeutics uses novel and rapidly evolving technologies and requires incorporation of microbial ecology concepts. Here, we consider FMT within a pharmacological framework, including its essential elements: formulation, pharmacokinetics and pharmacodynamics. From this viewpoint, multiple gaps in knowledge become apparent, identifying areas that require systematic research. This knowledge is needed to help clinical providers use microbiota therapeutics appropriately and to facilitate development of next-generation microbiota products with improved safety and efficacy. The discussion here is limited to FMT as a representative of microbiota therapeutics and recurrent C. difficile as the indication; however, consideration of the intrinsic basic principles is relevant to this entire class of microbiota-based therapeutics.}, } @article {pmid33609647, year = {2021}, author = {Gunaratnam, S and Millette, M and McFarland, LV and DuPont, HL and Lacroix, M}, title = {Potential role of probiotics in reducing Clostridioides difficile virulence: Interference with quorum sensing systems.}, journal = {Microbial pathogenesis}, volume = {}, number = {}, pages = {104798}, doi = {10.1016/j.micpath.2021.104798}, pmid = {33609647}, issn = {1096-1208}, abstract = {Opportunistic pathogenic bacteria may cause disease after the normally protective microbiome is disrupted (typically by antibiotic exposure). Clostridioides difficile is one such pathogen having a severe impact on healthcare facilities and increasing costs of medical care. The search for new therapeutic strategies that are not reliant on additional antibiotic exposures are currently being explored. One such strategy is to disrupt the production of C. difficile virulence factors by interfering with quorum sensing (QS) systems. QS has been well studied in other bacteria, but our understanding in C. difficile is not so well understood. Some probiotic strains or combinations of strains have been shown to be effective in the treatment or primary prevention of C. difficile infections and may possess multiple mechanisms of action. One mechanism of probiotics might be the inhibition of QS, but their role has not been clearly defined yet. A literature search was conducted using standard databases (PubMed, Google Scholar) from database inception to August 2020. The objective of this paper is to update our understanding of how QS leads to toxin production by C. difficile, which is important in pathogenesis, and how QS inhibitors or probiotics may disrupt this pathway. We found two main QS systems for C. difficile (Agr and Lux systems) that are involved in C. difficile pathogenesis by regulating toxin production, motility and adherence. Probiotics and other QS inhibitors targeting QS systems may represent important new directions of therapy and prevention of CDI.}, } @article {pmid33609303, year = {2021}, author = {Barrow, F and Khan, S and Fredrickson, G and Wang, H and Dietsche, K and Parthiban, P and Robert, S and Kaiser, T and Winer, S and Herman, A and Adeyi, O and Mouzaki, M and Khoruts, A and Hogquist, KA and Staley, C and Winer, DA and Revelo, XS}, title = {Microbiota-Driven Activation of Intrahepatic B Cells Aggravates Nonalcoholic Steatohepatitis through Innate and Adaptive Signaling.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep.31755}, pmid = {33609303}, issn = {1527-3350}, abstract = {BACKGROUND AND AIMS: Nonalcoholic steatohepatitis (NASH) is rapidly becoming the leading cause of liver failure and indication for liver transplantation. Hepatic inflammation is a key feature of NASH but the immune pathways involved in this process are poorly understood. B lymphocytes are cells of the adaptive immune system that are critical regulators of immune responses. However, the role of B cells in the pathogenesis of NASH and the potential mechanisms leading to their activation in the liver are unclear.

APPROACH AND RESULTS: In this study, we report that NASH livers accumulate B cells with elevated pro-inflammatory cytokine secretion and antigen-presentation ability. Single-cell and bulk RNA sequencing of intrahepatic B cells from mice with NASH unveiled a transcriptional landscape that reflects their pro-inflammatory function. Accordingly, B cell-deficiency ameliorated NASH progression and adoptively transferring B cells from NASH livers recapitulates the disease. Mechanistically, B cell activation during NASH involves signaling through the innate adaptor myeloid differentiation primary response protein 88 (MyD88) as B cell-specific deletion of MyD88 reduced hepatic T cell-mediated inflammation and fibrosis, but not steatosis. In addition, activation of intrahepatic B cells implicates B cell receptor signaling, delineating a synergy between innate and adaptive mechanisms of antigen recognition. Furthermore, fecal microbiota transplantation of human NAFLD gut microbiotas into recipient mice promoted the progression of NASH by increasing the accumulation and activation of intrahepatic B cells, suggesting that gut microbial factors drive the pathogenic function of B cells during NASH.

CONCLUSION: Our findings reveal that a gut microbiota-driven activation of intrahepatic B cells leads to hepatic inflammation and fibrosis during the progression of NASH via innate and adaptive immune mechanisms.}, } @article {pmid33608575, year = {2021}, author = {Kazemian, N and Ramezankhani, M and Sehgal, A and Khalid, FM and Kalkhoran, AHZ and Narayan, A and Wong, GK and Kao, D and Pakpour, S}, title = {Author Correction: The trans-kingdom battle between donor and recipient gut microbiome influences fecal microbiota transplantation outcome.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {4546}, doi = {10.1038/s41598-021-82644-z}, pmid = {33608575}, issn = {2045-2322}, } @article {pmid33607299, year = {2021}, author = {Wang, B and Zhu, S and Liu, Z and Wei, H and Zhang, L and He, M and Pei, F and Zhang, J and Sun, Q and Duan, L}, title = {Increased Expression of Colonic Mucosal Melatonin in Patients with Irritable Bowel Syndrome Correlated with Gut Dysbiosis.}, journal = {Genomics, proteomics & bioinformatics}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.gpb.2020.06.013}, pmid = {33607299}, issn = {2210-3244}, abstract = {Dysregulation of the gut microbiota/gut hormone axis contributes to the pathogenesis of irritable bowel syndrome (IBS). Melatonin plays a beneficial role in gut motility and immunity. However, altered expression of local mucosal melatonin in IBS and its relationship with the gut microbiota remain unclear. Therefore, we aimed to detect the colonic melatonin levels and microbiota profiles in patients with diarrhea-predominant IBS (IBS-D) and explore their relationship in germ-free (GF) rats and BON-1 cells. Thirty-two IBS-D patients and twenty-eight healthy controls (HC) were recruited. Fecal specimens from IBS-D patients and HC were separately transplanted into GF rats by gavage. The levels of colon mucosal melatonin were assessed by immunohistochemical methods, and fecal microbiota communities were analyzed using 16S rDNA sequencing. The effect of butyrate on melatonin synthesis in BON-1 cells was evaluated by ELISA. Melatonin levels were significantly increased and negatively correlated with visceral sensitivity in IBS-D patients. GF rats inoculated with fecal microbiota from IBS-D patients had high colonic melatonin levels. Butyrate-producing Clostridium cluster XIVa species, such as Roseburia species and Lachnospira species, were positively related to colonic mucosal melatonin expression. Butyrate significantly increased melatonin secretion in BON-1 cells. Increased melatonin expression may be an adaptive protective mechanism in the development of IBS-D. Moreover, some Clostridium cluster XIVa species could increase melatonin expression via butyrate production. Modulation of the gut hormone/gut microbiota axis offers a promising target of interest for IBS in the future.}, } @article {pmid33606488, year = {2021}, author = {Gupta, S and Mullish, BH and Allegretti, JR}, title = {Fecal Microbiota Transplantation: The Evolving Risk Landscape.}, journal = {The American journal of gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.14309/ajg.0000000000001075}, pmid = {33606488}, issn = {1572-0241}, abstract = {Fecal microbiota transplantation (FMT) has been recommended in clinical guidelines for the treatment of recurrent Clostridioides difficile infection (CDI). However, it is considered investigational by most regulatory agencies. As the adoption of FMT has increased from a small group of CDI experts alone to more widespread use, there has been a corresponding increase in concern regarding potential risk. FMT is largely considered a safe procedure although risks described range from mild gastrointestinal symptoms to serious infection. Currently, there is variability in how "FMT" is characterized specifically regarding testing approach, which, in turn, impacts the risk profile. This has been highlighted by the rare cases of multidrug-resistant organisms, Shiga toxin-producing Escherichia and enteropathogenic E. coli, recently reported, where these organisms were not screened. These cases have prompted additional screening mandates from the US Food and Drug Administration (FDA), which has maintained its policy of enforcement discretion for the use of FMT for CDI not responding to standard therapy. Here, we examine the evolving risk landscape of FMT.}, } @article {pmid33605497, year = {2021}, author = {Zhang, LT and Westblade, LF and Iqbal, F and Taylor, MR and Chung, A and Satlin, MJ and Magruder, M and Edusei, E and Albakry, S and Botticelli, B and Robertson, A and Alston, T and Dadhania, DM and Lubetzky, M and Hirota, SA and Greenway, SC and Lee, JR}, title = {Gut microbiota profiles and fecal beta-glucuronidase activity in kidney transplant recipients with and without post-transplant diarrhea.}, journal = {Clinical transplantation}, volume = {}, number = {}, pages = {e14260}, doi = {10.1111/ctr.14260}, pmid = {33605497}, issn = {1399-0012}, abstract = {Post-transplant diarrhea is a common complication after solid organ transplantation and is frequently attributed to the widely prescribed immunosuppressant mycophenolate mofetil (MMF). Given recent work identifying the relationship between MMF toxicity and gut bacterial β-glucuronidase activity, we evaluated the relationship between gut microbiota composition, fecal β-glucuronidase activity, and post-transplant diarrhea. We recruited 97 kidney transplant recipients and profiled the gut microbiota in 273 fecal specimens using 16S rRNA gene sequencing. We further characterized fecal β-glucuronidase activity in a subset of this cohort. Kidney transplant recipients with post-transplant diarrhea had decreased gut microbial diversity and decreased relative gut abundances of 12 genera when compared to those without post-transplant diarrhea (adjusted P value<0.15, Wilcoxon rank sum test). Among the kidney transplant recipients with post-transplant diarrhea, those with higher fecal β-glucuronidase activity had a more prolonged course of diarrhea (≥7 days) compared to patients with lower fecal β-glucuronidase activity (91% vs 40%, P=0.02, Fisher's exact test). Our data reveal post-transplant diarrhea as a complex phenomenon with decreased gut microbial diversity and commensal gut organisms. This study further links commensal bacterial metabolism with an important clinical outcome measure, suggesting fecal β-glucuronidase activity could be a novel biomarker for gastrointestinal-related MMF toxicity.}, } @article {pmid33602945, year = {2021}, author = {Serrano-Villar, S and Talavera-Rodríguez, A and Gosalbes, MJ and Madrid, N and Pérez-Molina, JA and Elliott, RJ and Navia, B and Lanza, VF and Vallejo, A and Osman, M and Dronda, F and Budree, S and Zamora, J and Gutiérrez, C and Manzano, M and Vivancos, MJ and Ron, R and Martínez-Sanz, J and Herrera, S and Ansa, U and Moya, A and Moreno, S}, title = {Fecal microbiota transplantation in HIV: A pilot placebo-controlled study.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {1139}, pmid = {33602945}, issn = {2041-1723}, abstract = {Changes in the microbiota have been linked to persistent inflammation during treated HIV infection. In this pilot double-blind study, we study 30 HIV-infected subjects on antiretroviral therapy (ART) with a CD4/CD8 ratio < 1 randomized to either weekly fecal microbiota capsules or placebo for 8 weeks. Stool donors were rationally selected based on their microbiota signatures. We report that fecal microbiota transplantation (FMT) is safe, not related to severe adverse events, and attenuates HIV-associated dysbiosis. FMT elicits changes in gut microbiota structure, including significant increases in alpha diversity, and a mild and transient engraftment of donor's microbiota during the treatment period. The greater engraftment seems to be achieved by recent antibiotic use before FMT. The Lachnospiraceae and Ruminococcaceae families, which are typically depleted in people with HIV, are the taxa more robustly engrafted across time-points. In exploratory analyses, we describe a significant amelioration in the FMT group in intestinal fatty acid-binding protein (IFABP), a biomarker of intestinal damage that independently predicts mortality. Gut microbiota manipulation using a non-invasive and safe strategy of FMT delivery is feasible and deserves further investigation. Trial number: NCT03008941.}, } @article {pmid33598642, year = {2021}, author = {Hua, H and Zhang, Y and Zhao, F and Chen, K and Wu, T and Liu, Q and Huang, S and Zhang, A and Jia, Z}, title = {Celastrol inhibits intestinal lipid absorption by reprofiling the gut microbiota to attenuate high-fat diet-induced obesity.}, journal = {iScience}, volume = {24}, number = {2}, pages = {102077}, pmid = {33598642}, issn = {2589-0042}, abstract = {Celastrol, a compound extracted from traditional Chinese medicine, has been reported as a potent anti-obesity agent with controversial mechanisms. Here both C57BL/6J and leptin-deficient (ob/ob) mice fed a high-fat diet (HFD) displayed body weight loss after celastrol therapy, opposing the previous viewpoint that celastrol improves obesity by sensitizing leptin signaling. More importantly, celastrol downregulated lipid transporters in the intestine, increased lipid excretion in feces, and reduced body weight gain in HFD mice. Meanwhile, analysis of gut microbiota revealed that celastrol altered the gut microbiota composition in HFD-fed mice, and modulating gut microbiota by antibiotics or fecal microbiota transplantation blocked the celastrol effect on intestinal lipid transport and body weight gain, suggesting a critical role of the gut microbiota composition in mediating the anti-obesity role of celastrol under HFD. Together, the findings revealed that celastrol reduces intestinal lipid absorption to antagonize obesity by resetting the gut microbiota profile under HFD feeding.}, } @article {pmid33598269, year = {2021}, author = {Zeng, J and Peng, L and Zheng, W and Huang, F and Zhang, N and Wu, D and Yang, Y}, title = {Fecal microbiota transplantation for rheumatoid arthritis: A case report.}, journal = {Clinical case reports}, volume = {9}, number = {2}, pages = {906-909}, pmid = {33598269}, issn = {2050-0904}, abstract = {No previous case of using fecal microbiota transplantation (FMT) to treat rheumatoid arthritis (RA) has been reported. We report a case of a patient with refractory RA successfully treated with FMT indicating that FMT may have a good therapeutic effect on RA.}, } @article {pmid32675558, year = {2020}, author = {SahBandar, IN and Chew, GM and Corley, MJ and Pang, APS and Tsai, N and Hanks, N and Khadka, VS and Klatt, NR and Hensley-McBain, T and Somsouk, M and Vujkovic-Cvijin, I and Chow, DC and Shikuma, CM and Ndhlovu, LC}, title = {Changes in gastrointestinal microbial communities influence HIV-specific CD8+ T-cell responsiveness to immune checkpoint blockade.}, journal = {AIDS (London, England)}, volume = {34}, number = {10}, pages = {1451-1460}, pmid = {32675558}, issn = {1473-5571}, support = {R56 AI083112/AI/NIAID NIH HHS/United States ; R21 AI122393/AI/NIAID NIH HHS/United States ; R21 DK104664/DK/NIDDK NIH HHS/United States ; R01 DK112254/DK/NIDDK NIH HHS/United States ; DP1 DA037979/DA/NIDA NIH HHS/United States ; U54 GM104944/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Anti-HIV Agents/therapeutic use ; CD8-Positive T-Lymphocytes/*drug effects ; Fecal Microbiota Transplantation ; Female ; Fusobacteria/isolation & purification ; *Gastrointestinal Microbiome ; HIV Infections/drug therapy/*microbiology ; Humans ; Immune Checkpoint Inhibitors/*therapeutic use ; Male ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Sexual and Gender Minorities ; }, abstract = {OBJECTIVES: The aim of this study was to examine the relationship between gut microbial communities in HIV-infected individuals on suppressive antiretroviral therapy (cART), and the peripheral HIV-Gag-specific CD8 T-cell responses before and after ex-vivo immune checkpoint blockade (ICB).

DESIGN: Thirty-four HIV-seropositive, 10 HIV-seronegative and 12 HIV-seropositive receiving faecal microbiota transplant (FMT) participants were included. Gut microbial communities, peripheral and gut associated negative checkpoint receptors (NCRs) and peripheral effector functions were assessed.

METHODS: Bacterial 16s rRNA sequencing for gut microbiome study and flow-based assays for peripheral and gut NCR and their cognate ligand expression, including peripheral HIV-Gag-specific CD8 T-cell responses before and after ex-vivo anti-PD-L1 and anti-TIGIT ICB were performed.

RESULTS: Fusobacteria abundance was significantly higher in HIV-infected donors compared to uninfected controls. In HIV-infected participants receiving Fusobacteria-free FMT, Fusobacteria persisted up to 24 weeks in stool post FMT. PD-1 TIGIT and their ligands were expanded in mucosal vs. peripheral T cells and dendritic cells, respectively. PD-L1 and TIGIT blockade significantly increased the magnitude of peripheral anti-HIV-Gag-specific CD8 T-cell responses. Higher gut Fusobacteria abundance was associated with lower magnitude of peripheral IFN-γ+ HIV-Gag-specific CD8 T-cell responses following ICB.

CONCLUSION: The gut colonization of Fusobacteria in HIV infection is persistent and may influence anti-HIV T-cell immunity to PD-1 or TIGIT blockade. Strategies modulating Fusobacteria colonization may elicit a favourable mucosal immune landscape to enhance the efficacy of ICB for HIV cure.}, } @article {pmid32133003, year = {2020}, author = {Rogala, AR and Oka, A and Sartor, RB}, title = {Strategies to Dissect Host-Microbial Immune Interactions That Determine Mucosal Homeostasis vs. Intestinal Inflammation in Gnotobiotic Mice.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {214}, pmid = {32133003}, issn = {1664-3224}, support = {P40 OD010995/OD/NIH HHS/United States ; P01 DK094779/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/immunology ; Disease Models, Animal ; Fecal Microbiota Transplantation/methods ; Gastroenteritis/*immunology/microbiology ; Gastrointestinal Microbiome/immunology ; *Germ-Free Life ; Homeostasis/*immunology ; Host Microbial Interactions/*immunology ; Humans ; Inflammatory Bowel Diseases/immunology/microbiology ; Intestinal Mucosa/*immunology ; Mice ; }, abstract = {When identifying the key immunologic-microbial interactions leading to either mucosal homeostasis in normal hosts or intestinal inflammatory responses in genetically susceptible individuals, it is important to not only identify microbial community correlations but to also define the functional pathways involved. Gnotobiotic rodents are a very effective tool for this purpose as they provide a highly controlled environment in which to identify the function of complex intestinal microbiota, their individual components, and metabolic products. Herein we review specific strategies using gnotobiotic mice to functionally evaluate the role of various intestinal microbiota in host responses. These studies include basic comparisons between host responses in germ-free (GF), specific-pathogen-free or conventionally raised wild-type mice or those with underlying genetic susceptibilities to intestinal inflammation. We also discuss what can be learned from studies in which GF mice are colonized with single wild-type or genetically-modified microbial isolates to examine the functions of individual bacteria and their targeted bacterial genes, or colonized by multiple defined isolates to determine interactions between members of defined consortia. Additionally, we discuss studies to identify functions of complex microbial communities from healthy or diseased human or murine hosts via fecal transplant into GF mice. Finally, we conclude by suggesting ways to improve studies of immune-microbial interactions using gnotobiotic mice.}, } @article {pmid33595467, year = {2021}, author = {Shivaji, S}, title = {A systematic review of gut microbiome and ocular inflammatory diseases: Are they associated?.}, journal = {Indian journal of ophthalmology}, volume = {69}, number = {3}, pages = {535-542}, doi = {10.4103/ijo.IJO_1362_20}, pmid = {33595467}, issn = {1998-3689}, abstract = {The primary focus of this review was to establish the possible association of dysbiotic changes in the gut bacterial microbiomes with both intestinal and extra-intestinal diseases with emphasis on ocular diseases such as bacterial keratitis, fungal keratitis, uveitis, age-related macular degeneration, and ocular mucosal diseases. For this particular purpose, a systematic search was conducted using PubMed and Google Scholar for publications related to gut microbiome and human health (using the keywords: gut microbiome, ocular disease, dysbiosis, keratitis, uveitis, and AMD). The predictions are that microbiome studies would help to unravel dysbiotic changes in the gut bacterial microbiome at the taxonomic and functional level and thus form the basis to mitigate inflammatory diseases of the eye by using nutritional supplements or fecal microbiota transplantation.}, } @article {pmid33595259, year = {2021}, author = {Li, S and Guo, H and Xu, X and Hua, R and Zhao, Q and Li, J and Lv, J and Li, J}, title = {Therapeutic Methods for Gut Microbiota Modification in Lipopolysaccharide-Associated Encephalopathy.}, journal = {Shock (Augusta, Ga.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/SHK.0000000000001758}, pmid = {33595259}, issn = {1540-0514}, abstract = {OBJECTIVE: To compare the efficacy of four therapeutic methods to modify gut microbiota dysbiosis and brain dysfunction in septic rats.

METHODS: Rats were treated with fecal microbiota transplantation, prebiotics, probiotics, and synbiotics after exposure to lipopolysaccharide. The diversity and composition of gut microbiota, electroencephalogram values, and the concentrations of TNF-α, IL-1β, and IL-6 in the cortex were analyzed.

RESULTS: Fecal microbiota transplantation was the most efficacious method to restore intestinal microbial diversity and exert the best corrective effects in modulating microbial composition in septic rats. More interestingly, fecal microbiota transplantation exerted the best protective effects in brain dysfunction in septic rats.

CONCLUSION: Among the four methods, fecal microbiota transplantation was the most useful method to modify the dysbiosis of intestinal microbiota and improve brain function in septic rats. These findings reveal the protective consequence of microbiota modification, and the findings suggest opportunities to improve brain function in sepsis.}, } @article {pmid33593430, year = {2021}, author = {Langdon, A and Schwartz, DJ and Bulow, C and Sun, X and Hink, T and Reske, KA and Jones, C and Burnham, CD and Dubberke, ER and Dantas, G and , }, title = {Microbiota restoration reduces antibiotic-resistant bacteria gut colonization in patients with recurrent Clostridioides difficile infection from the open-label PUNCH CD study.}, journal = {Genome medicine}, volume = {13}, number = {1}, pages = {28}, pmid = {33593430}, issn = {1756-994X}, support = {1U1CI000033 301/CC/CDC HHS/United States ; R01AI123394//National Institute of Allergy and Infectious Diseases/ ; R01HD092414//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; TL1 TR000449/NH/NIH HHS/United States ; St. Jude Fellowship in Basic Research//Pediatric Infectious Diseases Society/ ; T32 HG000045/HG/NHGRI NIH HHS/United States ; }, abstract = {BACKGROUND: Once antibiotic-resistant bacteria become established within the gut microbiota, they can cause infections in the host and be transmitted to other people and the environment. Currently, there are no effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent Clostridioides difficile infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non-C. difficile multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and resistome, as well as multidrug-resistant organism carriage, after delivery to patients suffering from recurrent CDI.

METHODS: An open-label, multi-center clinical trial in 11 centers in the USA for the safety and efficacy of RBX2660 on recurrent CDI was conducted. Fecal specimens from 29 of these subjects with recurrent CDI who received either one (N = 16) or two doses of RBX2660 (N = 13) were analyzed secondarily. Stool samples were collected prior to and at intervals up to 6 months post-therapy and analyzed in three ways: (1) 16S rRNA gene sequencing for microbiota taxonomic composition, (2) whole metagenome shotgun sequencing for functional pathways and antibiotic resistome content, and (3) selective and differential bacterial culturing followed by isolate genome sequencing to longitudinally track multidrug-resistant organisms.

RESULTS: Successful prevention of CDI recurrence with RBX2660 correlated with taxonomic convergence of patient microbiota to the donor microbiota as measured by weighted UniFrac distance. RBX2660 dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae in the 2 months after administration. Fecal antibiotic resistance gene carriage decreased in direct relationship to the degree to which donor microbiota engrafted.

CONCLUSIONS: Microbiota-based therapeutics reduce resistance gene abundance and resistant organisms in the recipient gut microbiome. This approach could potentially reduce the risk of infections caused by resistant organisms within the patient and the transfer of resistance genes or pathogens to others.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT01925417 ; registered on August 19, 2013.}, } @article {pmid33593429, year = {2021}, author = {Moshkelgosha, S and Verhasselt, HL and Masetti, G and Covelli, D and Biscarini, F and Horstmann, M and Daser, A and Westendorf, AM and Jesenek, C and Philipp, S and Diaz-Cano, S and Banga, JP and Michael, D and Plummer, S and Marchesi, JR and Eckstein, A and Ludgate, M and Berchner-Pfannschmidt, U and , }, title = {Modulating gut microbiota in a mouse model of Graves' orbitopathy and its impact on induced disease.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {45}, pmid = {33593429}, issn = {2049-2618}, support = {GA 612116//FP7 People: Marie-Curie Actions IAPP/ ; }, abstract = {BACKGROUND: Graves' disease (GD) is an autoimmune condition in which autoantibodies to the thyrotropin receptor (TSHR) cause hyperthyroidism. About 50% of GD patients also have Graves' orbitopathy (GO), an intractable disease in which expansion of the orbital contents causes diplopia, proptosis and even blindness. Murine models of GD/GO, developed in different centres, demonstrated significant variation in gut microbiota composition which correlated with TSHR-induced disease heterogeneity. To investigate whether correlation indicates causation, we modified the gut microbiota to determine whether it has a role in thyroid autoimmunity. Female BALB/c mice were treated with either vancomycin, probiotic bacteria, human fecal material transfer (hFMT) from patients with severe GO or ddH2O from birth to immunization with TSHR-A subunit or beta-galactosidase (βgal; age ~ 6 weeks). Incidence and severity of GD (TSHR autoantibodies, thyroid histology, thyroxine level) and GO (orbital fat and muscle histology), lymphocyte phenotype, cytokine profile and gut microbiota were analysed at sacrifice (~ 22 weeks).

RESULTS: In ddH2O-TSHR mice, 84% had pathological autoantibodies, 67% elevated thyroxine, 77% hyperplastic thyroids and 70% orbital pathology. Firmicutes were increased, and Bacteroidetes reduced relative to ddH2O-βgal; CCL5 was increased. The random forest algorithm at the genus level predicted vancomycin treatment with 100% accuracy but 74% and 70% for hFMT and probiotic, respectively. Vancomycin significantly reduced gut microbiota richness and diversity compared with all other groups; the incidence and severity of both GD and GO also decreased; reduced orbital pathology correlated positively with Akkermansia spp. whilst IL-4 levels increased. Mice receiving hFMT initially inherited their GO donors' microbiota, and the severity of induced GD increased, as did the orbital brown adipose tissue volume in TSHR mice. Furthermore, genus Bacteroides, which is reduced in GD patients, was significantly increased by vancomycin but reduced in hFMT-treated mice. Probiotic treatment significantly increased CD25+ Treg cells in orbital draining lymph nodes but exacerbated induced autoimmune hyperthyroidism and GO.

CONCLUSIONS: These results strongly support a role for the gut microbiota in TSHR-induced disease. Whilst changes to the gut microbiota have a profound effect on quantifiable GD endocrine and immune factors, the impact on GO cellular changes is more nuanced. The findings have translational potential for novel, improved treatments. Video abstract.}, } @article {pmid31611297, year = {2020}, author = {Olsson, LM and Poitou, C and Tremaroli, V and Coupaye, M and Aron-Wisnewsky, J and Bäckhed, F and Clément, K and Caesar, R}, title = {Gut microbiota of obese subjects with Prader-Willi syndrome is linked to metabolic health.}, journal = {Gut}, volume = {69}, number = {7}, pages = {1229-1238}, pmid = {31611297}, issn = {1468-3288}, mesh = {Adult ; Animals ; Case-Control Studies ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome/genetics/physiology ; Glucose/metabolism ; Humans ; Male ; Mice ; Obesity/complications/metabolism/*microbiology ; Prader-Willi Syndrome/complications/metabolism/*microbiology ; RNA, Ribosomal, 16S/genetics ; }, abstract = {OBJECTIVE: The gut microbiota has been implicated in the aetiology of obesity and associated comorbidities. Patients with Prader-Willi syndrome (PWS) are obese but partly protected against insulin resistance. We hypothesised that the gut microbiota of PWS patients differs from that of non-genetically obese controls and correlate to metabolic health. Therefore, here we used PWS as a model to study the role of gut microbiota in the prevention of metabolic complications linked to obesity.

DESIGN: We conducted a case-control study with 17 adult PWS patients and 17 obese subjects matched for body fat mass index, gender and age. The subjects were metabolically characterised and faecal microbiota was profiled by 16S ribosomal RNA gene sequencing. The patients' parents were used as a non-obese control group. Stool samples from two PWS patients and two obese controls were used for faecal microbiota transplantations in germ-free mice to examine the impact of the microbiota on glucose metabolism.

RESULTS: The composition of the faecal microbiota in patients with PWS differed from that of obese controls, and was characterised by higher phylogenetic diversity and increased abundance of several taxa such as Akkermansia, Desulfovibrio and Archaea, and decreased abundance of Dorea. Microbial taxa prevalent in the PWS microbiota were associated with markers of insulin sensitivity. Improved insulin resistance of PWS was partly transmitted by faecal microbiota transplantations into germ-free mice.

CONCLUSION: The gut microbiota of PWS patients is similar to that of their non-obese parents and might play a role for the protection of PWS patients from metabolic complications.}, } @article {pmid33159374, year = {2021}, author = {Marcella, C and Cui, B and Kelly, CR and Ianiro, G and Cammarota, G and Zhang, F}, title = {Systematic review: the global incidence of faecal microbiota transplantation-related adverse events from 2000 to 2020.}, journal = {Alimentary pharmacology & therapeutics}, volume = {53}, number = {1}, pages = {33-42}, doi = {10.1111/apt.16148}, pmid = {33159374}, issn = {1365-2036}, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is an effective treatment in C. difficile infection (CDI) and is currently being investigated in other diseases. There is concern around the safety of FMT and that side effects or complications may be under-reported in the medical literature.

AIM: To evaluate the safety of FMT by summarising the overall reported Adverse Events (AEs) over a 20-year period METHODS: We searched EMBASE, MEDLINE, and Cochrane Library databases, and CNKI and Wanfang Data from January 2000 to April 2020. All original studies reporting FMT-related AEs were considered for inclusion. FMT-related AEs were further classified as delivery-related or microbiota-related.

RESULTS: Based on the inclusion criteria, 129 studies, which included 4241 patients (5688 FMT courses), were finally eligible. The most common indication for FMT was CDI. Overall, FMT-related AEs were observed in 19% of FMT procedures. The most frequently reported FMT-related AEs were diarrhoea (10%) and abdominal discomfort/pain/cramping (7%). FMT-related serious adverse events (SAEs), including infections and deaths, have been reported in 1.4% of patients who underwent FMT (0.99% microbiota-related SAEs). Four of five FMT-related deaths were reported in patients receiving FMT via the upper gastrointestinal route. Importantly, all reported FMT-related SAEs were in patients with mucosal barrier injury.

CONCLUSION: Most FMT-related AEs were mild or moderate and self-limiting. Although FMT appears to be highly safe, its methodology should be improved to reduce both delivery-related AEs and, microbiota-related AEs.}, } @article {pmid32900719, year = {2020}, author = {Benech, N and Leboucher, G and Monard, C and Ferry, T}, title = {Septic shock due to refractory severe clostridioides difficile colitis rapidly resolving after faecal microbiota transplantation.}, journal = {BMJ case reports}, volume = {13}, number = {9}, pages = {}, doi = {10.1136/bcr-2020-234329}, pmid = {32900719}, issn = {1757-790X}, } @article {pmid32843418, year = {2020}, author = {Costello, SP and Day, A and Yao, CK and Bryant, RV}, title = {Faecal microbiota transplantation (FMT) with dietary therapy for acute severe ulcerative colitis.}, journal = {BMJ case reports}, volume = {13}, number = {8}, pages = {}, pmid = {32843418}, issn = {1757-790X}, abstract = {A 19-year-old man presented with acute severe ulcerative colitis. He was taking azathioprine (therapeutic metabolites) and sulphasalazine as well as infliximab with a therapeutic drug level. On day 3 of hydrocortisone therapy, he met day Oxford criteria with >8 bloody stools per day and was given faecal microbiota transplantation and subsequently commenced on dietary therapy combining several strategies-(1) increased intake of fermentable fibres, (2) reduced intake of overall and sulfur-containing protein and (3) restriction of sulfate and sulfite food additives. At week 8 assessment, he was in clinical and endoscopic remission and remained in clinical and endoscopic remission at 12 months.}, } @article {pmid32690735, year = {2020}, author = {Jiménez-Jorge, S and Labrador-Herrera, G and Rosso-Fernández, CM and Rodríguez-Torres, N and Pachón-Ibáñez, ME and Smani, Y and Márquez-Malaver, FJ and Limón Ramos, C and Solano, C and Vázquez-López, L and Kwon, M and Mora Barrios, JM and Aguilar-Guisado, M and Espigado, I and , }, title = {Assessing the impact on intestinal microbiome and clinical outcomes of antibiotherapy optimisation strategies in haematopoietic stem cell transplant recipients: study protocol for the prospective multicentre OptimBioma study.}, journal = {BMJ open}, volume = {10}, number = {7}, pages = {e034570}, pmid = {32690735}, issn = {2044-6055}, abstract = {INTRODUCTION: Haematopoietic stem cell transplantation (HSCT) is a life-saving treatment for a number of haematological diseases. Graft versus host disease (GVHD) is its main complication and hampers survival. There is strong evidence that intestinal microbiota diversity of the recipient may increase the risk of GVHD worsening survival. Antibiotic regimens used during the early phase of the transplant may influence clinical outcomes by reducing intestinal microbiota diversity. Present guidelines of European Conference on Infections in Leukaemia exhort to optimising antibiotic use in haematological patients including HSCT recipients. The present study aims to investigate if, in HSCT recipients, the optimisation of antibacterial use may preserve intestinal microbiota composition reducing the incidence and severity of acute GVHD and improving relevant clinical outcomes.

METHODS AND ANALYSIS: This is a prospective longitudinal observational study of two cohorts of HSCT recipients: (1) the intervention cohort includes patients treated in centres in which a predefined strategy of antibiotherapy optimisation is implemented, with the objective of optimising and reducing antibiotic administration according to clinical criteria and (2) the control cohort includes patients treated in centres in which a classic permissive strategy of antibiotic prophylaxis and treatment is used. Adult patient receiving a first HSCT as a treatment for any haematological condition are included. Clinical variables are prospectively recorded and up to five faecal samples are collected for microbiota characterisation at prestablished peritransplant time points. Patients are followed since the preconditioning phase throughout 1-year post-transplant and four follow-up visits are scheduled. Faecal microbiota composition and diversity will be compared between both cohorts along with acute GVHD incidence and severity, severe infections rate, mortality and overall and disease-free survival.

ETHICS AND DISSEMINATION: The study was approved between 2017 and 2018 by the Ethical Committees of participant centres. Study results will be disseminated through peer-reviewed journals and national and international scientific conferences.

TRIAL REGISTRATION NUMBER: NCT03727113.}, } @article {pmid32044317, year = {2020}, author = {Aron-Wisnewsky, J and Warmbrunn, MV and Nieuwdorp, M and Clément, K}, title = {Nonalcoholic Fatty Liver Disease: Modulating Gut Microbiota to Improve Severity?.}, journal = {Gastroenterology}, volume = {158}, number = {7}, pages = {1881-1898}, doi = {10.1053/j.gastro.2020.01.049}, pmid = {32044317}, issn = {1528-0012}, abstract = {Gut microbiota plays a role in the pathophysiology of metabolic diseases, which include nonalcoholic fatty liver diseases, through the gut-liver axis. To date, clinical guidelines recommend a weight loss goal of 7%-10% to improve features of nonalcoholic fatty liver diseases. Because this target is not easily achieved by all patients, alternative therapeutic options are currently being evaluated. This review focuses on therapeutics that aim to modulate the gut microbiota and the gut-liver axis. We discuss how probiotics, prebiotics, synbiotic, fecal microbiota transfer, polyphenols, specific diets, and exercise interventions have been found to modify gut microbiota signatures; improve nonalcoholic fatty liver disease outcomes; and detail, when available, the different mechanisms by which these beneficial outcomes might occur. Apart from probiotics that have already been tested in human randomized controlled trials, most of these potential therapeutics have been studied in animals. Their efficacy still warrants confirmation in humans using appropriate design.}, } @article {pmid32035985, year = {2020}, author = {Park, HK and Choi, Y and Lee, DH and Kim, S and Lee, JM and Choi, SW and Lee, HR and Rho, M and Park, HS}, title = {Altered gut microbiota by azithromycin attenuates airway inflammation in allergic asthma.}, journal = {The Journal of allergy and clinical immunology}, volume = {145}, number = {5}, pages = {1466-1469.e8}, doi = {10.1016/j.jaci.2020.01.044}, pmid = {32035985}, issn = {1097-6825}, } @article {pmid33580895, year = {2021}, author = {Wilmes, L and Collins, JM and O'Riordan, KJ and O'Mahony, SM and Cryan, JF and Clarke, G}, title = {Of bowels, brain and behavior: A role for the gut microbiota in psychiatric comorbidities in irritable bowel syndrome.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {}, number = {}, pages = {e14095}, doi = {10.1111/nmo.14095}, pmid = {33580895}, issn = {1365-2982}, support = {SFI/12/RC/2273_P2/SFI_/Science Foundation Ireland/Ireland ; //Horizon 2020 (848228 - DISCOvERIE)/ ; }, abstract = {BACKGROUND: The gastrointestinal microbiota has emerged as a key regulator of gut-brain axis signalling with important implications for neurogastroenterology. There is continuous bidirectional communication between the gut and the brain facilitated by neuronal, endocrine, metabolic, and immune pathways. The microbiota influences these signalling pathways via several mechanisms. Studies have shown compositional and functional alterations in the gut microbiota in stress-related psychiatric disorders. Gut microbiota reconfigurations are also a feature of irritable bowel syndrome (IBS), a gut-brain axis disorder sharing high levels of psychiatric comorbidity including both anxiety and depression. It remains unclear how the gut microbiota alterations in IBS align with both core symptoms and these psychiatric comorbidities.

METHODS: In this review, we highlight common and disparate features of these microbial signatures as well as the associated gut-brain axis signalling pathways. Studies suggest that patients with either IBS, depression or anxiety, alone or comorbid, present with alterations in gut microbiota composition and harbor immune, endocrine, and serotonergic system alterations relevant to the common pathophysiology of these comorbid conditions.

KEY RESULTS: Research has illustrated the utility of fecal microbiota transplantation in animal models, expanding the evidence base for a potential causal role of disorder-specific gut microbiota compositions in symptom set expression. Moreover, an exciting study by Constante and colleagues in this issue highlights the possibility of counteracting this microbiota-associated aberrant behavioral phenotype with a probiotic yeast, Saccharomyces boulardii CNCM I-745.

CONCLUSIONS AND INFERENCES: Such data highlights the potential for therapeutic targeting of the gut microbiota as a valuable strategy for the management of comorbid psychiatric symptoms in IBS.}, } @article {pmid33579424, year = {2021}, author = {Golonka, RM and Vijay-Kumar, M}, title = {Atypical immunometabolism and metabolic reprogramming in liver cancer: Deciphering the role of gut microbiome.}, journal = {Advances in cancer research}, volume = {149}, number = {}, pages = {171-255}, doi = {10.1016/bs.acr.2020.10.004}, pmid = {33579424}, issn = {2162-5557}, abstract = {Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related mortality worldwide. Much recent research has delved into understanding the underlying molecular mechanisms of HCC pathogenesis, which has revealed to be heterogenous and complex. Two major hallmarks of HCC include: (i) a hijacked immunometabolism and (ii) a reprogramming in metabolic processes. We posit that the gut microbiota is a third component in an entanglement triangle contributing to HCC progression. Besides metagenomic studies highlighting the diagnostic potential in the gut microbiota profile, recent research is pinpointing the gut microbiota as an instigator, not just a mere bystander, in HCC. In this chapter, we discuss mechanistic insights on atypical immunometabolism and metabolic reprogramming in HCC, including the examination of tumor-associated macrophages and neutrophils, tumor-infiltrating lymphocytes (e.g., T-cell exhaustion, regulatory T-cells, natural killer T-cells), the Warburg effect, rewiring of the tricarboxylic acid cycle, and glutamine addiction. We further discuss the potential involvement of the gut microbiota in these characteristics of hepatocarcinogenesis. An immediate highlight is that microbiota metabolites (e.g., short chain fatty acids, secondary bile acids) can impair anti-tumor responses, which aggravates HCC. Lastly, we describe the rising 'new era' of immunotherapies (e.g., immune checkpoint inhibitors, adoptive T-cell transfer) and discuss for the potential incorporation of gut microbiota targeted therapeutics (e.g., probiotics, fecal microbiota transplantation) to alleviate HCC. Altogether, this chapter invigorates for continuous research to decipher the role of gut microbiome in HCC from its influence on immunometabolism and metabolic reprogramming.}, } @article {pmid33578974, year = {2021}, author = {Lee, JJ and Yong, D and Suk, KT and Kim, DJ and Woo, HJ and Lee, SS and Kim, BS}, title = {Alteration of Gut Microbiota in Carbapenem-Resistant Enterobacteriaceae Carriers during Fecal Microbiota Transplantation According to Decolonization Periods.}, journal = {Microorganisms}, volume = {9}, number = {2}, pages = {}, doi = {10.3390/microorganisms9020352}, pmid = {33578974}, issn = {2076-2607}, support = {2019R1I1A3A01060465//Ministry of Education, Korea/ ; 2020R1A6A1A03043026//Ministry of Education, Korea/ ; NRF-2017M3A9F3043837//Ministry of Science, ICT and Future Planning/ ; HURF-2015-32//Hallym University/ ; }, abstract = {Fecal microbiota transplantation (FMT) has been suggested as an alternative therapeutic option to decolonize carbapenem-resistant Enterobacteriaceae (CRE). However, the analysis of gut microbiota alteration in CRE carriers during FMT is still limited. Here, gut microbiota changes in CRE carriers were evaluated during FMT according to decolonization periods. The decolonization of 10 CRE carriers was evaluated after FMT, using serial consecutive rectal swab cultures. Alterations of gut microbiota before and after FMT (56 serial samples) were analyzed using high-throughput sequencing. The decolonization rates of CRE carriers were 40%, 50%, and 90% within 1, 3 and 5 months after initial FMT, respectively. Gut microbiota significantly changed after FMT (p = 0.003). Microbiota alteration was different between the early decolonization carriers (EDC) and late decolonization carriers (LDC). Microbiota convergence in carriers to donors was detected in EDC within 4 weeks, and keystone genera within the Bacteroidetes were found in the gut microbiota of EDC before FMT. The relative abundance of Klebsiella was lower in EDC than in LDC, before and after FMT. Our results indicate that FMT is a potential option for CRE decolonization. The gut microbiota of CRE carriers could be used to predict decolonization timing after FMT, and determine repeated FMT necessity.}, } @article {pmid33578830, year = {2021}, author = {Heo, G and Lee, Y and Im, E}, title = {Interplay between the Gut Microbiota and Inflammatory Mediators in the Development of Colorectal Cancer.}, journal = {Cancers}, volume = {13}, number = {4}, pages = {}, doi = {10.3390/cancers13040734}, pmid = {33578830}, issn = {2072-6694}, support = {2019R1A2C1010536//National Research Foundation of Korea/ ; }, abstract = {Inflammatory mediators modulate inflammatory pathways during the development of colorectal cancer. Inflammatory mediators secreted by both immune and tumor cells can influence carcinogenesis, progression, and tumor metastasis. The gut microbiota, which colonize the entire intestinal tract, especially the colon, are closely linked to colorectal cancer through an association with inflammatory mediators such as tumor necrosis factor, nuclear factor kappa B, interleukins, and interferons. This association may be a potential therapeutic target, since therapeutic interventions targeting the gut microbiota have been actively investigated in both the laboratory and in clinics and include fecal microbiota transplantation and probiotics.}, } @article {pmid33577875, year = {2021}, author = {Fujimoto, K and Kimura, Y and Allegretti, JR and Yamamoto, M and Zhang, YZ and Katayama, K and Tremmel, G and Kawaguchi, Y and Shimohigoshi, M and Hayashi, T and Uematsu, M and Yamaguchi, K and Furukawa, Y and Akiyama, Y and Yamaguchi, R and Crowe, SE and Ernst, PB and Miyano, S and Kiyono, H and Imoto, S and Uematsu, S}, title = {Functional Restoration of Bacteriomes and Viromes by Fecal Microbiota Transplantation.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2021.02.013}, pmid = {33577875}, issn = {1528-0012}, abstract = {BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI). However, the overall mechanisms underlying FMT success await comprehensive elucidation, and the safety of FMT has recently become a serious concern because of the occurrence of drug-resistant bacteremia transmitted by FMT. We investigated whether functional restoration of the bacteriomes and viromes by FMT could be an indicator of successful FMT.

METHODS: The human intestinal bacteriomes and viromes from nine patients with rCDI who had undergone successful FMT and their donors were analyzed. Prophage-based and CRISPR spacer-based host bacteria-phage associations in samples from recipients before and after FMT and in donor samples were examined. The gene functions of intestinal microorganisms affected by FMT were evaluated.

RESULTS: Metagenomic sequencing of both the viromes and bacteriomes revealed that FMT does change the characteristics of intestinal bacteriomes and viromes in recipients after FMT compared with those before FMT. In particular, many Proteobacteria, the fecal abundance of which was high before FMT, were eliminated, and the proportion of Microviridae increased in recipients. Most temperate phages also behaved in parallel with the host bacteria that were altered by FMT. Furthermore, the identification of bacterial and viral gene functions before and after FMT revealed that some distinctive pathways, including fluorobenzoate degradation and secondary bile acid biosynthesis, were significantly represented.

CONCLUSIONS: The coordinated action of phages and their host bacteria restored the recipients' intestinal flora. These findings show that the restoration of intestinal microflora functions reflects the success of FMT.}, } @article {pmid33575297, year = {2021}, author = {Saha, S and Khanna, S}, title = {Stool banking for fecal microbiota transplantation: ready for prime time?.}, journal = {Hepatobiliary surgery and nutrition}, volume = {10}, number = {1}, pages = {110-112}, pmid = {33575297}, issn = {2304-3881}, } @article {pmid33575288, year = {2021}, author = {Sheng, L and Jena, PK and Hu, Y and Wan, YY}, title = {Age-specific microbiota in altering host inflammatory and metabolic signaling as well as metabolome based on the sex.}, journal = {Hepatobiliary surgery and nutrition}, volume = {10}, number = {1}, pages = {31-48}, pmid = {33575288}, issn = {2304-3881}, abstract = {Background: Metabolism is sex-different, and the direct link between gut microbiota and aging-associated metabolic changes needs to be established in both sexes.

Methods: Gene expression, metabolic and inflammatory signaling, gut microbiota profile, and metabolome were studied during aging and after fecal microbiota transplantation (FMT) in mice of both sexes.

Results: Our data revealed young female mice and aged male mice were the most insulin sensitive and resistant group, respectively. In addition, aging reduced sex difference in insulin sensitivity. Such age- and sex-dependent metabolic phenotypes were accompanied by shifted gut microbiota profile and altered abundance of bacterial genes that produce butyrate, propionate, and bile acids. After receiving feces from the aged males (AFMT), the most insulin-resistant group, recipients of both sexes had increased hepatic inflammation and serum endotoxin. However, AFMT only increased insulin resistance in female mice and abolished sex difference in insulin sensitivity. Additionally, such changes were accompanied by narrowed sex difference in metabolome. Metabolomics data revealed that age-associated insulin resistance in males was accompanied by increased sugar alcohols and dicarboxylic acids as well as reduced aromatic and branched-chain amino acids. Further, receiving feces from the young females (YFMT), the most insulin-sensitive group, reduced body weight and fasting blood glucose in male recipients and improved insulin sensitivity in females, leading to enhanced sex differences in insulin sensitivity and metabolome.

Conclusions: Aging systemically affected inflammatory and metabolic signaling based on the sex. Gut microbiome is age and sex-specific, which affects inflammation and metabolism in a sex-dependent manner.}, } @article {pmid33573867, year = {2020}, author = {Ciernikova, S and Kasperova, B and Drgona, L and Smolkova, B and Stevurkova, V and Mego, M}, title = {Targeting the gut microbiome: An emerging trend in hematopoietic stem cell transplantation.}, journal = {Blood reviews}, volume = {}, number = {}, pages = {100790}, doi = {10.1016/j.blre.2020.100790}, pmid = {33573867}, issn = {1532-1681}, abstract = {Mounting evidence has demonstrated the critical role of the gut microbiome in different cancer treatment modalities showing intensive crosstalk between microbiota and the host immune system. In cancer patients receiving hematopoietic stem cell transplantation (HSCT), conditioning regimens including chemotherapy, radiotherapy, and immunosuppressive therapy, as well as antimicrobial prophylaxis, result in intestinal barrier disruption and massive changes in microbiota composition. According to clinical studies, a drastic loss of microbial diversity during HSCT is associated with enhanced pro-inflammatory immune response and an increased risk of transplant-related complications such as graft-versus-host disease (GvHD) and mortality. In this review, we outline the current understanding of the role of microbiota diversity in the patient response to cancer therapies and highlight the impact of changes in the gut microbiome on clinical outcomes in post-HSCT patients. Moreover, the therapeutic implications of microbiota modulation by probiotics, prebiotics, and fecal microbiota transplantation (FMT) in hematologic cancer patients receiving HSCT are discussed.}, } @article {pmid33571456, year = {2021}, author = {Ianiro, G and Mullish, BH and Hvas, CL and Segal, JP and Kuijper, EJ and Costello, SP and Kelly, CR and Allegretti, JR and Fischer, M and Iqbal, TH and Satokari, R and Kao, D and van Prehn, J and Ng, SC and Bibbò, S and Baunwall, SMD and Quraishi, MN and Sokol, H and Zhang, F and Keller, J and Masucci, L and Quaranta, G and Kassam, Z and Sanguinetti, M and Tilg, H and Gasbarrini, A and Cammarota, G}, title = {SARS-CoV-2 vaccines and donor recruitment for FMT.}, journal = {The lancet. Gastroenterology & hepatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/S2468-1253(21)00032-7}, pmid = {33571456}, issn = {2468-1253}, } @article {pmid33571442, year = {2021}, author = {Rebeck, ON and Dantas, G and Schwartz, DJ}, title = {Improving ICI outcomes with a little help from my microbial friends.}, journal = {Cell host & microbe}, volume = {29}, number = {2}, pages = {155-157}, doi = {10.1016/j.chom.2021.01.012}, pmid = {33571442}, issn = {1934-6069}, abstract = {Gut microbiome composition correlates with responsiveness to immune checkpoint inhibitor therapy. In a recent study in Science, Baruch et al. manipulated gut microbiome composition in patients with refractory metastatic melanoma using fecal microbiota transplants. Fecal microbiota transplant was safe and partially effective in inducing remission in refractory patients.}, } @article {pmid33570405, year = {2021}, author = {Huang, Y and Yang, Q and Mi, X and Qiu, L and Tao, X and Zhang, Z and Xia, J and Wu, Q and Wei, H}, title = {Ripened Pu-erh Tea Extract Promotes Gut Microbiota Resilience against Dextran Sulfate Sodium Induced Colitis.}, journal = {Journal of agricultural and food chemistry}, volume = {}, number = {}, pages = {}, doi = {10.1021/acs.jafc.0c07537}, pmid = {33570405}, issn = {1520-5118}, abstract = {Ripened Pu-erh tea (RPT) has been shown to be an effective natural ingredient to defend against experimentally induced colitis. We hypothesized that RPT would alleviate dextran sulfate sodium (DSS) induced colitis via modulating intestinal microbiota. The effect of RPT on mice gut microbiota was evaluated using 16S rRNA gene amplicon sequencing, broad-spectrum antibiotic (ABX) treatment, and fecal microbiota transplantation (FMT). Pretreatment with RPT enhanced intestinal barrier function, reduced colonic and serum proinflammatory cytokine and macrophage infiltration, and preserved the resilience of gut microbiota in mice during a DSS challenge. Administration of either RPT-regulated or healthy control-derived gut microbiota showed similar protection against colitis, and such protection could not be recapitulated with fecal microbiota from ABX-treated mice, suggesting a key role of protective consortium in the disease protection. Mechanistically, cecal contents of short-chain fatty acids (SCFAs) and colonic peroxisome proliferator activated receptor-γ (PPAR-γ) expression in colitis mice increased significantly by RPT intervention. Collectively, RPT treatment improved DSS-induced colitis by partially reversing the dysbiosis state of gut microbiota, which might be associated with an increase in SCFA level and PPAR-γ expression.}, } @article {pmid33569665, year = {2021}, author = {Wada, A and Higashiyama, M and Kurihara, C and Ito, S and Tanemoto, R and Mizoguchi, A and Nishii, S and Inaba, K and Sugihara, N and Hanawa, Y and Horiuchi, K and Shibuya, N and Akiyama, M and Okada, Y and Watanabe, C and Komoto, S and Tomita, K and Takei, F and Hokari, R}, title = {Protective Effect of Luminal Uric Acid Against Indomethacin-Induced Enteropathy: Role of Antioxidant Effect and Gut Microbiota.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, pmid = {33569665}, issn = {1573-2568}, abstract = {BACKGROUND: Uric acid (UA) has anti- and pro-inflammatory properties. We previously revealed that elevated serum UA levels provide protection against murine small intestinal injury probably via luminal UA secreted in the small intestine. Luminal UA may act as an antioxidant, preventing microbiota vulnerability to oxidative stress. However, whether luminal UA is increased under hyperuricemia and plays a protective role in a dose-dependent manner as well as the mechanism by which luminal UA exerts its protective effects on enteropathy remains unknown.

METHODS: Inosinic acid (IMP) (1000 mg/kg, i.p.) was administered to obtain high serum UA (HUA) and moderate serum UA (500 mg/kg IMP, i.p.) mice. UA concentrations and levels of oxidative stress markers in the serum and intestine were measured. Mice received indomethacin (20 mg/kg, i.p.) to evaluate the effects of UA on indomethacin-induced enteropathy. Reactive oxygen species (ROS) on the ileal mucosa were analyzed. The fecal microbiota of HUA mice was transplanted to investigate its effect on indomethacin-induced enteropathy.

RESULTS: IMP increased luminal UA dose-dependently, with higher levels of luminal antioxidant markers. Indomethacin-induced enteropathy was significantly ameliorated in both UA-elevated groups, with decreased indomethacin-induced luminal ROS. The microbiota of HUA mice showed a significant increase in α-diversity and a significant difference in β-diversity from the control. Fecal microbiota transplantation from HUA mice ameliorated indomethacin-induced enteropathy.

CONCLUSIONS: The protective role of luminal UA in intestinal injury is likely exerted via oxidative stress elimination and microbiota composition modulation, preferably for gut immunity. Therefore, enhancing anaerobic conditions using antioxidants is a potential therapeutic target.}, } @article {pmid33567176, year = {2021}, author = {Janket, SJ and Conte, HA and Diamandis, EP}, title = {Inappropriate extrapolations abound in fecal microbiota research.}, journal = {Clinical chemistry and laboratory medicine}, volume = {}, number = {}, pages = {}, doi = {10.1515/cclm-2020-1862}, pmid = {33567176}, issn = {1437-4331}, } @article {pmid33564705, year = {2020}, author = {Gouveia, C and Palos, C and Pereira, P and Roque Ramos, L and Cravo, M}, title = {Fecal Microbiota Transplant in a Patient Infected with Multidrug-Resistant Bacteria: A Case Report.}, journal = {GE Portuguese journal of gastroenterology}, volume = {28}, number = {1}, pages = {56-61}, pmid = {33564705}, issn = {2341-4545}, abstract = {Introduction: There has been a growing interest in fecal microbiota transplantation (FMT) as a way to manipulate gut microbiota, with potential benefit in patients infected with multidrug-resistant (MDR) bacteria.

Case Presentation: We present the case of an 87-year-old male with recurrent ascending cholangitis due to biliary atony and impaired biliary drainage after multiple biliary sphincterotomies and two papillary balloon dilations. In this context, a choledochoduodenostomy was performed, but the patient kept on having repeated episodes of acute cholangitis, resulting in multiple hospitalizations, every other week, with need of multiple broad-spectrum antibiotic courses, which led to bacteremias with MDR microorganisms. Several therapeutic strategies such as prophylactic antibiotics (including rifaximin), pre- and probiotics, prokinetics, and ursodeoxycholic acid were unsuccessfully attempted. After multidisciplinary case discussion, an FMT was proposed, with the aim of manipulating gut microbiota and decreasing MDR bacteremias. We first performed FMT via colonoscopy in September 2018, after which the patient still had 3 more hospitalizations for acute cholangitis, but isolated bacteria in blood cultures were resistant only to amoxicillin and clavulanic acid. Considering this apparent change in the microbial resistance profile, we performed a second FMT in January 2019 via the upper gastrointestinal route. During the next 4 months, the patient remained well. In April 2019, the patient relapsed again with three more episodes of cholangitis, for which we repeated the FMT via upper gastrointestinal endoscopy. No readmissions were observed during the next 4 months. All three FMTs were performed without complications.

Discussion and Conclusion: FMT seems to be a safe procedure and was effective in decreasing hospital admissions and changing the profile of MDR bacteria previously isolated from blood cultures.}, } @article {pmid33563907, year = {2020}, author = {Chen, H and Chen, Z and Shen, L and Wu, X and Ma, X and Lin, D and Zhang, M and Ma, X and Liu, Y and Wang, Z and Zhang, Y and Kuang, Z and Lu, Z and Li, X and Ma, L and Lin, X and Si, L and Chen, X}, title = {Fecal microbiota transplantation from patients with autoimmune encephalitis modulates Th17 response and relevant behaviors in mice.}, journal = {Cell death discovery}, volume = {6}, number = {1}, pages = {75}, pmid = {33563907}, issn = {2058-7716}, support = {81971141//National Natural Science Foundation of China (National Science Foundation of China)/ ; }, abstract = {The significance of the microbiota-gut-brain axis has been increasingly recognized as a major modulator of autoimmunity. Here, we aim to characterize the gut microbiota of a large cohort of treatment-naïve anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis patients relative to that of healthy controls (HCs). Relative to HCs, anti-NMDAR encephalitis patients had a decreased microbiome alpha-diversity index, marked disturbances of gut microbial composition and intestinal permeability damage. Disturbed microbiota in anti-NMDAR encephalitis patients might be linked with different clinical characteristics. Imputed KEGG analysis revealed perturbations of functional modules in the gut microbiomes of anti-NMDAR encephalitis. Compared to HCs, microbiota-depleted mice receiving fecal microbiota transplantation (FMT) from anti-NMDAR encephalitis patients had hypersensitivity and cognitive impairment. Furthermore, anti-NMDAR encephalitis FMT mice showed altered T cells in the spleen and small intestine lamina propria with an increased Th17 cells. Overall, this study first suggests that the anti-NMDAR encephalitis microbiome itself can influence neurologic, Th17 response and behavioral function. The gut microbiota is a potential therapeutic target for anti-NMDAR encephalitis.}, } @article {pmid33558654, year = {2021}, author = {Zhang, JD and Liu, J and Zhu, SW and Fang, Y and Wang, B and Jia, Q and Hao, HF and Kao, JY and He, QH and Song, LJ and Liu, F and Zhu, BL and Owyang, C and Duan, LP}, title = {Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation.}, journal = {Acta pharmacologica Sinica}, volume = {}, number = {}, pages = {}, pmid = {33558654}, issn = {1745-7254}, abstract = {Accumulating evidence shows that agents targeting gut dysbiosis are effective for improving symptoms of irritable bowel syndrome (IBS). However, the potential mechanisms remain unclear. In this study we investigated the effects of berberine on the microbiota-gut-brain axis in two rat models of visceral hypersensitivity, i.e., specific pathogen-free SD rats subjected to chronic water avoidance stress (WAS) and treated with berberine (200 mg· kg-1 ·d-1, ig, for 10 days) as well as germ-free (GF) rats subjected to fecal microbiota transplantation (FMT) from a patient with IBS (designated IBS-FMT) and treated with berberine (200 mg· kg-1 ·d-1, ig, for 2 weeks). Before the rats were sacrificed, visceral sensation and depressive behaviors were evaluated. Then colonic tryptase was measured and microglial activation in the dorsal lumbar spinal cord was assessed. The fecal microbiota was profiled using 16S rRNA sequencing, and short chain fatty acids (SCFAs) were measured. We showed that berberine treatment significantly alleviated chronic WAS-induced visceral hypersensitivity and activation of colonic mast cells and microglia in the dorsal lumbar spinal cord. Transfer of fecal samples from berberine-treated stressed donors to GF rats protected against acute WAS. FMT from a patient with IBS induced visceral hypersensitivity and pro-inflammatory phenotype in microglia, while berberine treatment reversed the microglial activation and altered microbial composition and function and SCFA profiles in stools of IBS-FMT rats. We demonstrated that berberine did not directly influence LPS-induced microglial activation in vitro. In both models, several SCFA-producing genera were enriched by berberine treatment, and positively correlated to the morphological parameters of microglia. In conclusion, activation of microglia in the dorsal lumbar spinal cord was involved in the pathogenesis of IBS caused by dysregulation of the microbiota-gut-brain axis, and the berberine-altered gut microbiome mediated the modulatory effects of the agent on microglial activation and visceral hypersensitivity, providing a potential option for the treatment of IBS.}, } @article {pmid33557941, year = {2021}, author = {Liu, F and Ye, S and Zhu, X and He, X and Wang, S and Li, Y and Lin, J and Wang, J and Lin, Y and Ren, X and Li, Y and Deng, Z}, title = {Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patients.}, journal = {Journal of medical case reports}, volume = {15}, number = {1}, pages = {60}, pmid = {33557941}, issn = {1752-1947}, support = {81970156//National Natural Science foundation of China/ ; 81970118//National Natural Science foundation of China/ ; }, abstract = {BACKGROUND: To investigate the potential beneficial effect of fecal microbiota transplantation (FMT) on gastrointestinal symptoms, gut dysbiosis and immune status in discharged COVID-19 patients.

CASE PRESENTATION: A total of 11 COVID-19 patients were recruited in April, 2020, about one month on average after they were discharged from the hospital. All subjects received FMT for 4 consecutive days by oral capsule administrations with 10 capsules for each day. In total, 5 out of 11 patients reported to be suffered from gastrointestinal symptoms, which were improved after FMT. After FMT, alterations of B cells were observed, which was characterized as decreased naive B cell (P = 0.012) and increased memory B cells (P = 0.001) and non-switched B cells (P = 0.012).The microbial community richness indicated by operational taxonomic units number, observed species and Chao1 estimator was marginally increased after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteria (9.2%). FMT can partially restore the gut dysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteria (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium had significantly increased after FMT.

CONCLUSIONS: After FMT, altered peripheral lymphocyte subset, restored gut microbiota and alleviated gastrointestinal disorders were observe, suggesting that FMT may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.}, } @article {pmid33557125, year = {2021}, author = {Pession, A and Zama, D and Muratore, E and Leardini, D and Gori, D and Guaraldi, F and Prete, A and Turroni, S and Brigidi, P and Masetti, R}, title = {Fecal Microbiota Transplantation in Allogeneic Hematopoietic Stem Cell Transplantation Recipients: A Systematic Review.}, journal = {Journal of personalized medicine}, volume = {11}, number = {2}, pages = {}, doi = {10.3390/jpm11020100}, pmid = {33557125}, issn = {2075-4426}, support = {GR-2013-02357136//Ministero della Salute/ ; }, abstract = {The disruption of gut microbiota eubiosis has been linked to major complications in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Various strategies have been developed to reduce dysbiosis and related complications. Fecal microbiota transplantation (FMT) consists of the infusion of fecal matter from a healthy donor to restore impaired intestinal homeostasis, and could be applied in the allo-HSCT setting. We conducted a systematic review of studies addressing the use of FMT in allo-HSCT patients. In the 23 papers included in the qualitative synthesis, FMT was used for the treatment of recurrent Clostridioides difficile infections or as a therapeutic strategy for steroid-resistant gut aGvHD. FMT was also performed with a preventive aim (e.g., to decolonize from antibiotic-resistant bacteria). Additional knowledge on the biological mechanisms underlying clinical findings is needed in order to employ FMT in clinical practice. There is also concern regarding the administration of microbial consortia in immune-compromised patients with altered gut permeability. Therefore, the safety profile and efficacy of the procedure must be determined to better assess the role of FMT in allo-HSCT recipients.}, } @article {pmid33556916, year = {2021}, author = {Wu, L and Yan, Q and Chen, F and Cao, C and Wang, S}, title = {Bupleuri radix extract ameliorates impaired lipid metabolism in high-fat diet-induced obese mice via gut microbia-mediated regulation of FGF21 signaling pathway.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {135}, number = {}, pages = {111187}, doi = {10.1016/j.biopha.2020.111187}, pmid = {33556916}, issn = {1950-6007}, abstract = {BACKGROUND: Obesity and its comorbidities are associated with abnormal lipid metabolism and gut microbiota dysbiosis. Bupleuri Radix is a medicinal plant used in traditional Chinese medicine with the prevention and treatment of obesity-related diseases. In this study, we aim to validate the regulation of Bupleuri Radix Extract (BupE) on lipid metabolism in obese mice, and try to find out the potential active components and reveal the underlying mechanisms.

METHODS: Ingredients in BupE, their circulating metabolites in mice and fecal biotransformation products were analyzed by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS). Western blotting, RT-PCR and ELISA were used for tests of objective genes and proteins. 16 s rRNA sequencing was performed to examine intestinal bacteria composition and microbes' functional changes were predicted with PICRUSt software. An absolute quantification method was set up via the construction of recombinant plasmid for the assays of intestinal flora. Specific microbial strains were cultured in anaerobic conditions and oral administrated to mice for intestinal mono-colonization.

RESULTS: BupE attenuated obesity, liver steatosis, and dyslipidemia in HFD-fed mice by up-regulating the expression of FGF21 in liver and white adipose tissue (WAT) as well as the downstream proteins of FGF21 signal pathway including β-klotho, GLUT1 and PGC-1α, etc. UPLC/Q-TOF-MS fingerprints showed no compounds from BupE or their metabolites or biotransformation products were detected in rodent serum samples. High-throughput pyrosequencing data indicated that BupE reversed obesity-induced constructional and functional alterations of intestinal flora. Two bacterial strains, Bacteroides acidifaciens (B. acidifaciens) and Ruminococcus gnavus (R. gnavus), were separated and identified from the feces of obese mice and by intestinal mono-colonization they were verified to intervene in the anti-obesity effects of BupE on mice.

CONCLUSION: These data suggest that BupE protects against diet-induced obesity and counteracts metabolic syndrome features consistent with a mechanism involving the gut-liver axis that boosts hepatic FGF21 secretion and consequent down-stream proteins expression relating to lipid metabolism. And in this gut-liver axis, intestinal microbes such as B.acidifaciens and R.gnavus play an indispensable role.}, } @article {pmid33556154, year = {2021}, author = {Jung, HJ and Sorbara, MT and Pamer, EG}, title = {TAM mediates adaptation of carbapenem-resistant Klebsiella pneumoniae to antimicrobial stress during host colonization and infection.}, journal = {PLoS pathogens}, volume = {17}, number = {2}, pages = {e1009309}, doi = {10.1371/journal.ppat.1009309}, pmid = {33556154}, issn = {1553-7374}, abstract = {Gram-negative pathogens, such as Klebsiella pneumoniae, remodel their outer membrane (OM) in response to stress to maintain its integrity as an effective barrier and thus to promote their survival in the host. The emergence of carbapenem-resistant K. pneumoniae (CR-Kp) strains that are resistant to virtually all antibiotics is an increasing clinical problem and OM impermeability has limited development of antimicrobial agents because higher molecular weight antibiotics cannot access sites of activity. Here, we demonstrate that TAM (translocation and assembly module) deletion increases CR-Kp OM permeability under stress conditions and enhances sensitivity to high-molecular weight antimicrobials. SILAC-based proteomic analyses revealed mis-localization of membrane proteins in the TAM deficient strain. Stress-induced sensitization enhances clearance of TAM-deficient CR-Kp from the gut lumen following fecal microbiota transplantation and from infection sites following pulmonary or systemic infection. Our study suggests that TAM, as a regulator of OM permeability, represents a potential target for development of agents that enhance the effectiveness of existing antibiotics.}, } @article {pmid33554953, year = {2021}, author = {Sofi, MH and Wu, Y and Ticer, T and Schutt, S and Bastian, D and Choi, HJ and Tian, L and Mealer, C and Liu, C and Westwater, C and Armeson, KE and Alekseyenko, AV and Yu, XZ}, title = {A single strain of Bacteroides fragilis protects gut integrity and reduces GVHD.}, journal = {JCI insight}, volume = {6}, number = {3}, pages = {}, doi = {10.1172/jci.insight.136841}, pmid = {33554953}, issn = {2379-3708}, abstract = {Graft-versus-host disease (GVHD) is a pathological process caused by an exaggerated donor lymphocyte response to host antigens after allogeneic hematopoietic cell transplantation (allo-HCT). Donor T cells undergo extensive clonal expansion and differentiation, which culminate in damage to recipient target organs. Damage to the gastrointestinal tract is a main contributor to morbidity and mortality. The loss of diversity among intestinal bacteria caused by pretransplant conditioning regimens leads to an outgrowth of opportunistic pathogens and exacerbated GVHD after allo-HCT. Using murine models of allo-HCT, we found that an increase of Bacteroides in the intestinal microbiota of the recipients was associated with reduced GVHD in mice given fecal microbial transplantation. Administration of Bacteroides fragilis through oral gavage increased gut microbiota diversity and beneficial commensal bacteria and significantly ameliorated acute and chronic GVHD development. Preservation of gut integrity following B. fragilis exposure was likely attributed to increased short chain fatty acids, IL-22, and regulatory T cells, which in turn improved gut tight junction integrity and reduced inflammatory cytokine production of pathogenic T cells. The current study provides a proof of concept that a single strain of commensal bacteria can be a safe and effective means to protect gut integrity and ameliorate GVHD after allo-HCT.}, } @article {pmid33554105, year = {2021}, author = {Jeevarathinam, AS and Guo, F and Williams, T and Smolen, JA and Hyde, JA and McShane, MJ and de Figueiredo, P and Alge, DL}, title = {Enzyme functionalized microgels enable precise regulation of dissolved oxygen and anaerobe culture.}, journal = {Materials today. Bio}, volume = {9}, number = {}, pages = {100092}, pmid = {33554105}, issn = {2590-0064}, abstract = {Anaerobes are a major constituent of the gut microbiome and profoundly influence the overall health of humans. However, the lack of a simple, cost-effective, and scalable system that mimics the anaerobic conditions of the human gut is hindering research on the gut microbiome and the development of therapeutics. Here, we address this gap by using glucose oxidase and catalase containing gelatin microparticles (GOx-CAT-GMPs) to precisely regulate dissolved oxygen concentration [O2] via GOx-mediated consumption of oxygen. Fluorescence images generated using conjugated polymer afterglow nanoparticles showed that [O2] can be tuned from 257.9 ​± ​6.2 to 0.0 ​± ​4.0 ​μM using GOx-CAT-GMPs. Moreover, when the obligate anaerobe Bacteroides thetaiotaomicron was inoculated in media containing GOx-CAT-GMPs, bacterial growth under ambient oxygen was comparable to control conditions in an anaerobic chamber (5.4 ​× ​105 and 8.8 ​× ​105 colony forming units mL-1, respectively). Finally, incorporating GOx-CAT-GMPs into a bioreactor that permitted continuous radial diffusion of oxygen and glucose generated a gut-mimetic [O2] gradient of 132.4 ​± ​2.6 ​μM in the outer ring of the reactor to 7.9 ​± ​1.7 ​μM at the core. Collectively, these results indicate that GOx-CAT-GMPs are highly effective oxygen-regulating materials. These materials can potentially be leveraged to advance gut microbiome research and fecal microbiota transplantation, particularly in low-resource settings.}, } @article {pmid33553973, year = {2021}, author = {Bajaj, JS and Shamsaddini, A and Fagan, A and Sterling, RK and Gavis, E and Khoruts, A and Fuchs, M and Lee, H and Sikaroodi, M and Gillevet, PM}, title = {Fecal Microbiota Transplant in Cirrhosis Reduces Gut Microbial Antibiotic Resistance Genes: Analysis of Two Trials.}, journal = {Hepatology communications}, volume = {5}, number = {2}, pages = {258-271}, pmid = {33553973}, issn = {2471-254X}, abstract = {Antibiotic resistance leads to poor outcomes in cirrhosis. Fecal microbiota transplant (FMT) is associated with reduction in antibiotic resistance gene (ARG) burden in patients without cirrhosis; however, the impact in cirrhosis is unclear. We aimed to study the effect of capsule and enema FMT on ARG abundance in fecal samples, which were collected during two published FMT trials in patients with cirrhosis on rifaximin, lactulose, and proton pump inhibitors. ARGs were identified using metagenomics and mapped against the Comprehensive Antibiotic Resistance Database. Changes in ARG abundance were studied within/between groups. The capsule FMT trial involved a one-time FMT or placebo capsule administration with stool collection at baseline and week 4 postintervention. Antibiotics+enema FMT included preprocedure antibiotics followed by FMT enema versus standard-of-care (SOC). Stool was collected at baseline, postantibiotics, and day 7/15 postintervention. Both trials included 20 patients each. There was no safety/infection signal linked to FMT. In the capsule trial, beta-lactamase (OXY/LEN) expression decreased post-FMT versus baseline. Compared to placebo, patients who were post-FMT had lower abundance of vancomycin (VanH), beta-lactamase (ACT), and rifamycin ARGs; the latter was associated with cognitive improvement. No changes were seen within patients treated with placebo. In the antibiotics+enema trial for postantibiotics at day 7 versus baseline, there was an increase in vancomycin and beta-lactamase ARGs, which decreased at day 15. However, quinolone resistance increased at day 15 versus baseline. Between SOC and FMT, day 7 had largely lower ARG (CfxA beta-lactamase, VanW, and VanX) that continued at day 15 (cepA beta-lactamase, VanW). No changes were seen within the SOC group. Conclusion: Despite differences in routes of administration and preintervention antibiotics, we found that ARG abundance is largely reduced after FMT compared to pre-FMT baseline and non-FMT groups in decompensated cirrhosis.}, } @article {pmid33553045, year = {2020}, author = {Mohammadi, SO and Yadegar, A and Kargar, M and Mirjalali, H and Kafilzadeh, F}, title = {The impact of Helicobacter pylori infection on gut microbiota-endocrine system axis; modulation of metabolic hormone levels and energy homeostasis.}, journal = {Journal of diabetes and metabolic disorders}, volume = {19}, number = {2}, pages = {1855-1861}, pmid = {33553045}, issn = {2251-6581}, abstract = {The gut microbiota is a complex ecosystem that is involved in the development and preservation of the immune system, energy homeostasis and nutritional status of the host. The crosstalk between gut microbiota and the host cells modulates host physiology and metabolism through different mechanisms. Helicobacter pylori (H. pylori) is known to reside in the gastric mucosa, induce inflammation, and alter both gastric and intestinal microbiota resulting in a broad spectrum of diseases, in particular metabolic syndrome-related disorders. Infection with H. pylori have been shown to affect production level and physiological regulation of the gut metabolic hormones such as ghrelin and leptin which are involved in food intake, energy expenditure and body mass. In this study, we reviewed and discussed data from the literature and follow-up investigations that links H. pylori infection to alterations of the gut microbiota and metabolic hormone levels, which can exert broad influences on host metabolism, energy homeostasis, behavior, appetite, growth, reproduction and immunity. Also, we discussed the strong potential of fecal microbiota transplantation (FMT) as an innovative and promising investigational treatment option for homeostasis of metabolic hormone levels to overcome H. pylori-associated metabolic syndrome-related disorders.}, } @article {pmid33549144, year = {2021}, author = {Strati, F and Pujolassos, M and Burrello, C and Giuffrè, MR and Lattanzi, G and Caprioli, F and Troisi, J and Facciotti, F}, title = {Antibiotic-associated dysbiosis affects the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in experimental colitis models.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {39}, pmid = {33549144}, issn = {2049-2618}, abstract = {BACKGROUND: The gut microbiota plays a central role in host physiology and in several pathological mechanisms in humans. Antibiotics compromise the composition and functions of the gut microbiota inducing long-lasting detrimental effects on the host. Recent studies suggest that the efficacy of different clinical therapies depends on the action of the gut microbiota. Here, we investigated how different antibiotic treatments affect the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in an experimental colitis model and in ex vivo experiments with human intestinal biopsies.

RESULTS: Murine fecal donors were pre-treated with different antibiotics, i.e., vancomycin, streptomycin, and metronidazole before FMT administration to colitic animals. The analysis of the gut microbiome, fecal metabolome, and the immunophenotyping of colonic lamina propria immune cells revealed that antibiotic pre-treatment significantly influences the capability of the microbiota to control intestinal inflammation. Streptomycin and vancomycin-treated microbiota failed to control intestinal inflammation and were characterized by the blooming of pathobionts previously associated with IBD as well as with metabolites related to the presence of oxidative stress and metabolism of simple sugars. On the contrary, the metronidazole-treated microbiota retained its ability to control inflammation co-occurring with the enrichment of Lactobacillus and of innate immune responses involving iNKT cells. Furthermore, ex vivo cultures of human intestinal lamina propria mononuclear cells and iNKT cell clones from IBD patients with vancomycin pre-treated sterile fecal water showed a Th1/Th17 skewing in CD4+ T-cell populations; metronidazole, on the other hand, induced the polarization of iNKT cells toward the production of IL10.

CONCLUSIONS: Diverse antibiotic regimens affect the ability of the gut microbiota to control intestinal inflammation in experimental colitis by altering the microbial community structure and microbiota-derived metabolites. Video Abstract.}, } @article {pmid33549047, year = {2021}, author = {Xu, F and Li, N and Wang, C and Xing, H and Chen, D and Wei, Y}, title = {Clinical efficacy of fecal microbiota transplantation for patients with small intestinal bacterial overgrowth: a randomized, placebo-controlled clinic study.}, journal = {BMC gastroenterology}, volume = {21}, number = {1}, pages = {54}, pmid = {33549047}, issn = {1471-230X}, abstract = {BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is characterized by the condition that bacteria overgrowth in the small intestine. Fecal microbiota transplantation (FMT) has been applied as an effective tool for reestablishing the structure of gut microbiota. However, whether FMT could be applied as a routine SIBO treatment has not been investigated.

METHODS: In this trial, 55 SIBO patients were enrolled. All participants were randomized in two groups, and were given FMT capsule or placebo capsules once a week for 4 consecutive weeks. Measurements including the lactulose hydrogen breath test gastrointestinal symptoms, as well as fecal microbiota diversity were assessed before and after FMT therapy.

RESULTS: Gastrointestinal symptoms significantly improved in SIBO patients after treatment with FMT compared to participants in placebo group. The gut microbiota diversity of FMT group had a significant increase, while placebo group showed none.

CONCLUSIONS: This study suggests that applying FMT for patients with SIBO can alleviate gastrointestinal symptoms, indicating that FMT may be a promising and novel therapeutic regimen for SIBO. Trial registry This study was retrospectively registered with the Chinese Clinical Trial registry on 2019.7.10 (ID: ChiCTR1900024409, http://www.chictr.org.cn).}, } @article {pmid33546192, year = {2021}, author = {Parker, KD and Maurya, AK and Ibrahim, H and Rao, S and Hove, PR and Kumar, D and Kant, R and Raina, B and Agarwal, R and Kuhn, KA and Raina, K and Ryan, EP}, title = {Dietary Rice Bran-Modified Human Gut Microbial Consortia Confers Protection against Colon Carcinogenesis Following Fecal Transfaunation.}, journal = {Biomedicines}, volume = {9}, number = {2}, pages = {}, doi = {10.3390/biomedicines9020144}, pmid = {33546192}, issn = {2227-9059}, support = {5R01CA201112/NH/NIH HHS/United States ; }, abstract = {Rice bran, removed from whole grain rice for white rice milling, has demonstrated efficacy for the control and suppression of colitis and colon cancer in multiple animal models. Dietary rice bran intake was shown to modify human stool metabolites as a result of modifications to metabolism by gut microbiota. In this study, human stool microbiota from colorectal cancer (CRC) survivors that consumed rice bran daily was examined by fecal microbiota transplantation (FMT) for protection from azoxymethane and dextran sodium sulfate (AOM/DSS) induced colon carcinogenesis in germ-free mice. Mice transfaunated with rice bran-modified microbiota communities (RMC) harbored fewer neoplastic lesions in the colon and displayed distinct enrichment of Flavonifractor and Oscillibacter associated with colon health, and the depletion of Parabacteroides distasonis correlated with increased tumor burden. Two anti-cancer metabolites, myristoylcarnitine and palmitoylcarnitine were increased in the colon of RMC transplanted mice. Trimethylamine-N-oxide (TMAO) and tartarate that are implicated in CRC development were reduced in murine colon tissue after FMT with rice bran-modified human microbiota. Findings from this study show that rice bran modified gut microbiota from humans confers protection from colon carcinogenesis in mice and suggests integrated dietary-FMT intervention strategies should be tested for colorectal cancer control, treatment, and prevention.}, } @article {pmid33546191, year = {2021}, author = {Plaza-Díaz, J and Solis-Urra, P and Aragón-Vela, J and Rodríguez-Rodríguez, F and Olivares-Arancibia, J and Álvarez-Mercado, AI}, title = {Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis.}, journal = {Biomedicines}, volume = {9}, number = {2}, pages = {}, doi = {10.3390/biomedicines9020145}, pmid = {33546191}, issn = {2227-9059}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).}, } @article {pmid33542131, year = {2021}, author = {Davar, D and Dzutsev, AK and McCulloch, JA and Rodrigues, RR and Chauvin, JM and Morrison, RM and Deblasio, RN and Menna, C and Ding, Q and Pagliano, O and Zidi, B and Zhang, S and Badger, JH and Vetizou, M and Cole, AM and Fernandes, MR and Prescott, S and Costa, RGF and Balaji, AK and Morgun, A and Vujkovic-Cvijin, I and Wang, H and Borhani, AA and Schwartz, MB and Dubner, HM and Ernst, SJ and Rose, A and Najjar, YG and Belkaid, Y and Kirkwood, JM and Trinchieri, G and Zarour, HM}, title = {Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients.}, journal = {Science (New York, N.Y.)}, volume = {371}, number = {6529}, pages = {595-602}, doi = {10.1126/science.abf3363}, pmid = {33542131}, issn = {1095-9203}, support = {R01 CA228181/CA/NCI NIH HHS/United States ; R01 CA222203/CA/NCI NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; }, abstract = {Anti-programmed cell death protein 1 (PD-1) therapy provides long-term clinical benefits to patients with advanced melanoma. The composition of the gut microbiota correlates with anti-PD-1 efficacy in preclinical models and cancer patients. To investigate whether resistance to anti-PD-1 can be overcome by changing the gut microbiota, this clinical trial evaluated the safety and efficacy of responder-derived fecal microbiota transplantation (FMT) together with anti-PD-1 in patients with PD-1-refractory melanoma. This combination was well tolerated, provided clinical benefit in 6 of 15 patients, and induced rapid and durable microbiota perturbation. Responders exhibited increased abundance of taxa that were previously shown to be associated with response to anti-PD-1, increased CD8+ T cell activation, and decreased frequency of interleukin-8-expressing myeloid cells. Responders had distinct proteomic and metabolomic signatures, and transkingdom network analyses confirmed that the gut microbiome regulated these changes. Collectively, our findings show that FMT and anti-PD-1 changed the gut microbiome and reprogrammed the tumor microenvironment to overcome resistance to anti-PD-1 in a subset of PD-1 advanced melanoma.}, } @article {pmid33542126, year = {2021}, author = {Woelk, CH and Snyder, A}, title = {Modulating gut microbiota to treat cancer.}, journal = {Science (New York, N.Y.)}, volume = {371}, number = {6529}, pages = {573-574}, doi = {10.1126/science.abg2904}, pmid = {33542126}, issn = {1095-9203}, mesh = {Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Immunotherapy ; *Melanoma ; *Microbiota ; }, } @article {pmid33537709, year = {2021}, author = {Kim, M and Huda, MN and Bennett, BJ}, title = {Sequence Meets Function-Microbiota And Cardiovascular Disease.}, journal = {Cardiovascular research}, volume = {}, number = {}, pages = {}, doi = {10.1093/cvr/cvab030}, pmid = {33537709}, issn = {1755-3245}, abstract = {The discovery that gut-microbiota plays a profound role in human health has opened a new avenues of basic and clinical research. Application of ecological approaches where the Bacterial 16S rRNA gene is queried has provided a number of candidate bacteria associated with coronary artery disease and hypertension. We examine the associations between gut microbiota and a variety of CVD including atherosclerosis, coronary artery disease and blood pressure. These approaches are associative in nature and there is now increasing interest in identifying the mechanisms underlying these associations. We discuss three potential mechanisms including: gut permeability and endotoxemia, increased immune system activation, and microbial derived metabolites. In addition to discussing these potential mechanisms we highlight current studies manipulating the gut microbiota or microbial metabolites to move beyond sequenced based association studies. The goal of these mechanistic studies is to determine the mode of action by which the gut microbiota may affect disease susceptibility and severity. Importantly, the gut microbiota appears to have a significant effect on host metabolism and CVD by producing metabolites entering the host circulatory system such as short chain fatty acids (SCFAs) and trimethylamine N-Oxide (TMAO). Therefore, the intersection of metabolomics and microbiota research may yield novel targets to reduce disease susceptibility. Finally, we discuss approaches to demonstrate causality such as specific diet changes, inhibition of microbial pathways and fecal microbiota transplant.}, } @article {pmid33537028, year = {2020}, author = {Gill, T and Rosenbaum, JT}, title = {Putative Pathobionts in HLA-B27-Associated Spondyloarthropathy.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {586494}, pmid = {33537028}, issn = {1664-3224}, abstract = {Spondyloarthritis (SpA) is a group of immune mediated inflammatory diseases with a strong association to the major histocompatibility (MHC) class I molecule, HLA-B27. Although the association between HLA-B27 and AS has been known for almost 50 years, the mechanisms underlying disease pathogenesis are elusive. Over the years, three hypotheses have been proposed to explain HLA-B27 and disease association: 1) HLA B27 presents arthritogenic peptides and thus creates a pathological immune response; 2) HLA-B27 misfolding causes endoplasmic reticulum (ER) stress which activates the unfolded protein response (UPR); 3) HLA-B27 dimerizes on the cell surface and acts as a target for natural killer (NK) cells. None of these hypotheses explains SpA pathogenesis completely. Evidence supports the hypothesis that HLA-B27-related diseases have a microbial pathogenesis. In animal models of various SpAs, a germ-free environment abrogates disease development and colonizing these animals with gut commensal microbes can restore disease manifestations. The depth of microbial influence on SpA development has been realized due to our ability to characterize microbial communities in the gut using next-generation sequencing approaches. In this review, we will discuss various putative pathobionts in the pathogenesis of HLA-B27-associated diseases. We pursue whether a single pathobiont or a disruption of microbial community and function is associated with HLA-B27-related diseases. Furthermore, rather than a specific pathobiont, metabolic functions of various disease-associated microbes might be key. While the use of germ-free models of SpA have facilitated understanding the role of microbes in disease development, future studies with animal models that mimic diverse microbial communities instead of mono-colonization are indispensable. We discuss the causal mechanisms underlying disease pathogenesis including the role of these pathobionts on mucin degradation, mucosal adherence, and gut epithelial barrier disruption and inflammation. Finally, we review the various uses of microbes as therapeutic modalities including pre/probiotics, diet, microbial metabolites and fecal microbiota transplant. Unravelling these complex host-microbe interactions will lead to the development of new targets/therapies for alleviation of SpA and other HLA-B27 associated diseases.}, } @article {pmid33536363, year = {2021}, author = {Seo, HS and Chin, HS and Kim, YH and Moon, HS and Kim, K and Nguyen, LP and Yong, D}, title = {Laboratory Aspects of Donor Screening for Fecal Microbiota Transplantation at a Korean Fecal Microbiota Bank.}, journal = {Annals of laboratory medicine}, volume = {41}, number = {4}, pages = {424-428}, doi = {10.3343/alm.2021.41.4.424}, pmid = {33536363}, issn = {2234-3814}, abstract = {Fecal microbiota transplantation (FMT) is a widely accepted alternative therapy for Clostridioides difficile infection and other gastrointestinal disorders. Thorough donor screening is required as a safety control measure to minimize transmission of infectious agents in FMT. We report the donor screening process and outcomes at a fecal microbiota bank in Korea. From August 2017 to June 2020, the qualification of 62 individuals as FMT donors was evaluated using clinical assessment and laboratory tests. Forty-six (74%) candidates were excluded after clinical assessment; high body mass index (>25) was the most common reason for exclusion, followed by atopy, asthma, and allergy history. Four of the remaining 16 (25%) candidates failed to meet laboratory test criteria, resulting in a 19% qualification rate. FMT donor re-qualification was conducted monthly as an additional safety control measure, and only three (5%) candidates were eligible for repeated donation. As high prevalence of multidrug-resistant organisms (55%) and Helicobacter pylori (44%) were detected in qualified donors during the screening, a urea breath test was added to the existing protocol. The present results emphasize the importance of implementing a donor re-qualification system to minimize risk factors not identified during initial donor screening.}, } @article {pmid33535557, year = {2021}, author = {Parisi, A and Porzio, G and Pulcini, F and Cannita, K and Ficorella, C and Mattei, V and Delle Monache, S}, title = {What Is Known about Theragnostic Strategies in Colorectal Cancer.}, journal = {Biomedicines}, volume = {9}, number = {2}, pages = {}, doi = {10.3390/biomedicines9020140}, pmid = {33535557}, issn = {2227-9059}, abstract = {Despite the paradigmatic shift occurred in recent years for defined molecular subtypes in the metastatic setting treatment, colorectal cancer (CRC) still remains an incurable disease in most of the cases. Therefore, there is an urgent need for new tools and biomarkers for both early tumor diagnosis and to improve personalized treatment. Thus, liquid biopsy has emerged as a minimally invasive tool that is capable of detecting genomic alterations from primary or metastatic tumors, allowing the prognostic stratification of patients, the detection of the minimal residual disease after surgical or systemic treatments, the monitoring of therapeutic response, and the development of resistance, establishing an opportunity for early intervention before imaging detection or worsening of clinical symptoms. On the other hand, preclinical and clinical evidence demonstrated the role of gut microbiota dysbiosis in promoting inflammatory responses and cancer initiation. Altered gut microbiota is associated with resistance to chemo drugs and immune checkpoint inhibitors, whereas the use of microbe-targeted therapies including antibiotics, pre-probiotics, and fecal microbiota transplantation can restore response to anticancer drugs, promote immune response, and therefore support current treatment strategies in CRC. In this review, we aim to summarize preclinical and clinical evidence for the utilization of liquid biopsy and gut microbiota in CRC.}, } @article {pmid33534360, year = {2021}, author = {Ruan, W and Kellermayer, R}, title = {Alternative Diagnoses in Pediatric Fecal Microbiota Transplant Referral Patients.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1097/MPG.0000000000003060}, pmid = {33534360}, issn = {1536-4801}, abstract = {ABSTRACT: The incidence of Clostridioides difficile infection (CDI) has been increasing in the United States. About 10-20% recur after initial treatment, with increasing recurrence following subsequent treatment courses. This sequence can lead to recurrent CDI (rCDI), refractory to conventional therapeutics resulting in the most common indication for fecal microbiota transplantation (FMT). FMT is the most effective microbial therapeutic to date and can cure rCDI in 80-90% of cases. There is growing concern, however, for pathogen transmission through FMT, underscoring the importance of careful recipient selection. In adults referred for FMT with a tentative diagnosis of rCDI, alternative diagnoses were recognized in 25% of patients, but such observation in children is lacking. In this single-center retrospective study, alternative diagnoses (for example constipation/overflow diarrhea, inflammatory bowel disease) were found in 13 (22.4%) of 58 children who were referred for FMT evaluation for rCDI. Of the patients who were diagnosed with rCDI, 16 (27.6%) did not require FMT.}, } @article {pmid33533699, year = {2020}, author = {Durham, SH and Le, P and Cassano, AT}, title = {Navigating changes in Clostridioides difficile prevention and treatment.}, journal = {Journal of managed care & specialty pharmacy}, volume = {26}, number = {12-a Suppl}, pages = {S3-S23}, doi = {10.18553/jmcp.2020.26.12-a.s3}, pmid = {33533699}, issn = {2376-1032}, abstract = {Clostridioides difficile (C. difficile, previously known as Clostridium difficile) infections are a major health care concern. The Centers for Disease Control and Prevention (CDC) estimates that C. difficile causes almost half a million illnesses in the United States yearly, and approximately 1 in 5 patients with a C. difficile infection (CDI) will experience 1 or more recurrent infections. The incidence of infection has risen dramatically in recent years, and infection severity has increased due to the emergence of hypervirulent strains. There have been noteworthy advances in the development of CDI prevention and treatment, including a growth in the understanding of the role a patient's gut microbiome plays. The 2017 Infectious Diseases Society of America (IDSA) guidelines made a significant change in treatment recommendations for first time CDI episodes by recommending the use of oral vancomycin or fidaxomicin in place of metronidazole as a first-line treatment. The guidelines also included detailed recommendations on the use of fecal microbiota transplant (FMT) in those patients who experience 3 or more recurrent CDI episodes. A number of novel therapies for the treatment of CDI are in various stages of development. Treatments currently in phase 3 trials include the antibiotic ridinilazole, the microbiome products SER-109 and RBX2660, and a vaccine. All of these agents have shown promise in phase 1 and 2 trials. Additionally, several other antibiotic and microbiome candidates are currently in phase 1 or phase 2 trials. A qualitative review and evaluation of the literature on the cost-effectiveness of treatments for CDI in the U.S. setting was conducted, and the summary provided herein. Due to the higher cost of newer agents, cost-effectiveness evaluations will continue to be critical in clinical decision making for CDI. This paper reviews the updated CDI guidelines for prevention and treatment, the role of the microbiome in new and recurrent infections, pipeline medications, and comparative effectiveness research (CER) data on these treatments. DISCLOSURES: Durham and Le have nothing to disclose. Cassano reports consulting fees from Baxter Healthcare. Peer reviewers Drs. Ami Gopalan and Mark Rubin and Ms. Kathleen Jarvis have nothing to disclose. Planners Dr. Christine L. Cooper and Ms. Susan Yarbrough have nothing to disclose.}, } @article {pmid33532747, year = {2020}, author = {Shin, W and Ambrosini, YM and Shin, YC and Wu, A and Min, S and Koh, D and Park, S and Kim, S and Koh, H and Kim, HJ}, title = {Robust Formation of an Epithelial Layer of Human Intestinal Organoids in a Polydimethylsiloxane-Based Gut-on-a-Chip Microdevice.}, journal = {Frontiers in medical technology}, volume = {2}, number = {}, pages = {}, pmid = {33532747}, issn = {2673-3129}, support = {F99 CA245801/CA/NCI NIH HHS/United States ; }, abstract = {Polydimethylsiloxane (PDMS) is a silicone polymer that has been predominantly used in a human organ-on-a-chip microphysiological system. The hydrophobic surface of a microfluidic channel made of PDMS often results in poor adhesion of the extracellular matrix (ECM) as well as cell attachment. The surface modification by plasma or UV/ozone treatment in a PDMS-based device produces a hydrophilic surface that allows robust ECM coating and the reproducible attachment of human intestinal immortalized cell lines. However, these surface-activating methods have not been successful in forming a monolayer of the biopsy-derived primary organoid epithelium. Several existing protocols to grow human intestinal organoid cells in a PDMS microchannel are not always reproducibly operative due to the limited information. Here, we report an optimized methodology that enables robust and reproducible attachment of the intestinal organoid epithelium in a PDMS-based gut-on-a-chip. Among several reported protocols, we optimized a method by performing polyethyleneimine-based surface functionalization followed by the glutaraldehyde cross linking to activate the PDMS surface. Moreover, we discovered that the post-functionalization step contributes to provide uniform ECM deposition that allows to produce a robust attachment of the dissociated intestinal organoid epithelium in a PDMS-based microdevice. We envision that our optimized protocol may disseminate an enabling methodology to advance the integration of human organotypic cultures in a human organ-on-a-chip for patient-specific disease modeling.}, } @article {pmid33531483, year = {2021}, author = {Littmann, ER and Lee, JJ and Denny, JE and Alam, Z and Maslanka, JR and Zarin, I and Matsuda, R and Carter, RA and Susac, B and Saffern, MS and Fett, B and Mattei, LM and Bittinger, K and Abt, MC}, title = {Host immunity modulates the efficacy of microbiota transplantation for treatment of Clostridioides difficile infection.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {755}, pmid = {33531483}, issn = {2041-1723}, support = {R00 AI125786/AI/NIAID NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation (FMT) is a successful therapeutic strategy for treating recurrent Clostridioides difficile infection. Despite remarkable efficacy, implementation of FMT therapy is limited and the mechanism of action remains poorly understood. Here, we demonstrate a critical role for the immune system in supporting FMT using a murine C. difficile infection system. Following FMT, Rag1 heterozygote mice resolve C. difficile while littermate Rag1-/- mice fail to clear the infection. Targeted ablation of adaptive immune cell subsets reveal a necessary role for CD4+ Foxp3+ T-regulatory cells, but not B cells or CD8+ T cells, in FMT-mediated resolution of C. difficile infection. FMT non-responsive mice exhibit exacerbated inflammation, impaired engraftment of the FMT bacterial community and failed restoration of commensal bacteria-derived secondary bile acid metabolites in the large intestine. These data demonstrate that the host's inflammatory immune status can limit the efficacy of microbiota-based therapeutics to treat C. difficile infection.}, } @article {pmid33531405, year = {2021}, author = {Haifer, C and Paramsothy, S and Borody, TJ and Clancy, A and Leong, RW and Kaakoush, NO}, title = {Long-Term Bacterial and Fungal Dynamics following Oral Lyophilized Fecal Microbiota Transplantation in Clostridioides difficile Infection.}, journal = {mSystems}, volume = {6}, number = {1}, pages = {}, pmid = {33531405}, issn = {2379-5077}, abstract = {Oral lyophilized fecal microbiota transplantation (FMT) is effective in recurrent Clostridioides difficile infection (CDI); however, limited data exist on its efficacy in primary CDI and long-term microbial engraftment. Patients with primary or recurrent CDI were prospectively enrolled to receive oral FMT. Changes in the bacterial and fungal communities were characterized prior to and up to 6 months following treatment. A total of 37 patients with CDI (15 primary, 22 recurrent) were treated with 6 capsules each containing 0.35-g lyophilized stool extract. A total of 33 patients (89%) had sustained CDI cure, of whom 3 required a second course. There were no safety signals identified. FMT significantly increased bacterial diversity and shifted composition toward donor profiles in responders but not in nonresponders, with robust donor contribution observed to 6 months following FMT (P < 0.001). Responders showed consistent decreases in Enterobacteriaceae and increases in Faecalibacterium sp. to levels seen in donors. Mycobiome profiling revealed an association with FMT failure and increases in one Penicillium taxon, as well as coexclusion relationships between Candida sp. and bacterial taxa enriched in both donors and responders. Primary CDI was associated with more robust changes in the bacterial community than those with recurrent disease. Oral FMT leads to durable microbial engraftment in patients with primary and recurrent CDI, with several microbial taxa being associated with therapy outcome. Novel coexclusion relationships between bacterial and fungal species support the clinical relevance of transkingdom dynamics.IMPORTANCEClostridioides difficile infection (CDI) is a substantial health concern worldwide, complicated by patterns of increasing antibiotic resistance that may impact primary treatment. Orally administered fecal microbiota transplantation (FMT) is efficacious in the management of recurrent CDI, with specific bacterial species known to influence clinical outcomes. To date, little is known about the efficacy of FMT in primary CDI and the impact of the mycobiome on therapeutic outcomes. We performed matched bacterial and fungal sequencing on longitudinal samples from a cohort of patients treated with oral FMT for primary and recurrent CDI. We validated many bacterial signatures following oral therapy, confirmed engraftment of donor microbiome out to 6 months following therapy, and demonstrated coexclusion relationships between Candida albicans and two bacterial species in the gut microbiota, which has potential significance beyond CDI, including in the control of gut colonization by this fungal species.}, } @article {pmid33529409, year = {2021}, author = {Subba, R and Sandhir, R and Singh, SP and Mallick, BN and Mondal, AC}, title = {Pathophysiology linking Depression and Type 2 Diabetes: Psychotherapy, Physical Exercise and Fecal Microbiome Transplantation as damage control.}, journal = {The European journal of neuroscience}, volume = {}, number = {}, pages = {}, doi = {10.1111/ejn.15136}, pmid = {33529409}, issn = {1460-9568}, abstract = {Diabetes increases the likelihood of developing depression and vice versa. Research on this bidirectional association has somewhat managed to delineate the interplay among implicated physiological processes. Still, further exploration is required in this context. This review addresses the comorbidity by investigating suspected common pathophysiological mechanisms. One such factor is psychological stress which disturbs the hypothalamic-pituitary-adrenal axis causing hormonal imbalance. This includes elevated cortisol levels, a common biomarker of both depression and diabetes. Disrupted insulin signaling drives the hampered neurotransmission of serotonin, dopamine, and norepinephrine. Also, adipokine hormones such as adiponectin, leptin, and resistin, and the orexigenic hormone, ghrelin, are involved in both depression and T2DM. This disarray further interferes with physiological processes encompassing sleep, the gut-brain axis, metabolism, and mood stability. Behavioral coping mechanisms, such as unhealthy eating, mediate disturbed glucose homeostasis, and neuroinflammation. This is intricately linked to oxidative stress, redox imbalance, and mitochondrial dysfunction. However, interventions such as psychotherapy, physical exercise, fecal microbiota transplantation, and insulin-sensitizing agents can help to manage the distressing condition. The possibility of Glucagon-like peptide 1 possessing a therapeutic role has also been discussed. Nonetheless, there stands an urgent need for unraveling new correlating targets and biological markers for efficient treatment.}, } @article {pmid33523449, year = {2021}, author = {Liu, Y and Tran, DQ and Lindsey, JW and Rhoads, JM}, title = {The Association of Gut Microbiota and Treg Dysfunction in Autoimmune Diseases.}, journal = {Advances in experimental medicine and biology}, volume = {1278}, number = {}, pages = {191-203}, pmid = {33523449}, issn = {0065-2598}, abstract = {Autoimmune conditions affect 23 million Americans or 7% of the US population. There are more than 100 autoimmune disorders, affecting every major organ system in humans. This chapter aims to further explain Treg dysfunction autoimmune disorders, including monogenic primary immune deficiency such as immune dysregulation polyendocrinopathy, enteropathy, X-linked inheritance (IPEX) syndrome, and polygenic autoimmune diseases with Treg dysfunction such as multiple sclerosis (MS), inflammatory bowel disease (IBD), and food allergy. These conditions are associated with an abnormal small intestinal and colonic microbiome. Some disorders clearly improve with therapies aimed at microbial modification, including probiotics and fecal microbiota transplantation (FMT). Approaches to prevent and treat these disorders will need to focus on the acquisition and maintenance of a healthy colonic microbiota, in addition to more focused approaches at immune suppression during acute disease exacerbations.}, } @article {pmid33521100, year = {2021}, author = {Zheng, L and Wen, XL}, title = {Gut microbiota and inflammatory bowel disease: The current status and perspectives.}, journal = {World journal of clinical cases}, volume = {9}, number = {2}, pages = {321-333}, pmid = {33521100}, issn = {2307-8960}, abstract = {Inflammatory bowel disease (IBD) is a chronic immune-mediated disease that affects the gastrointestinal tract. It is argued that environment, microbiome, and immune-mediated factors interact in a genetically susceptible host to trigger IBD. Recently, there has been increased interest in the development, progression, and treatment of IBD because of our understanding of the microbiome. Researchers have proved that some factors can alter the microbiome and the pathogenesis of IBD. As a result, there has been increasing interest in the application of probiotics, prebiotics, antibiotics, fecal microbiota transplantation, and gene manipulation in treating IBD because of the possible curative effect of microbiome-modulating interventions. In this review, we summarize the findings from human and animal studies and discuss the effect of the gut microbiome in treating patients with IBD.}, } @article {pmid33517890, year = {2021}, author = {Hou, YF and Shan, C and Zhuang, SY and Zhuang, QQ and Ghosh, A and Zhu, KC and Kong, XK and Wang, SM and Gong, YL and Yang, YY and Tao, B and Sun, LH and Zhao, HY and Guo, XZ and Wang, WQ and Ning, G and Gu, YY and Li, ST and Liu, JM}, title = {Gut microbiota-derived propionate mediates the neuroprotective effect of osteocalcin in a mouse model of Parkinson's disease.}, journal = {Microbiome}, volume = {9}, number = {1}, pages = {34}, pmid = {33517890}, issn = {2049-2618}, abstract = {BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder with no absolute cure. The evidence of the involvement of gut microbiota in PD pathogenesis suggests the need to identify certain molecule(s) derived from the gut microbiota, which has the potential to manage PD. Osteocalcin (OCN), an osteoblast-secreted protein, has been shown to modulate brain function. Thus, it is of interest to investigate whether OCN could exert protective effect on PD and, if yes, whether the underlying mechanism lies in the subsequent changes in gut microbiota.

RESULTS: The intraperitoneal injection of OCN can effectively ameliorate the motor deficits and dopaminergic neuronal loss in a 6-hydroxydopamine-induced PD mouse model. The further antibiotics treatment and fecal microbiota transplantation experiments confirmed that the gut microbiota was required for OCN-induced protection in PD mice. OCN elevated Bacteroidetes and depleted Firmicutes phyla in the gut microbiota of PD mice with elevated potential of microbial propionate production and was confirmed by fecal propionate levels. Two months of orally administered propionate successfully rescued motor deficits and dopaminergic neuronal loss in PD mice. Furthermore, AR420626, the agonist of FFAR3, which is the receptor of propionate, mimicked the neuroprotective effects of propionate and the ablation of enteric neurons blocked the prevention of dopaminergic neuronal loss by propionate in PD mice.

CONCLUSIONS: Together, our results demonstrate that OCN ameliorates motor deficits and dopaminergic neuronal loss in PD mice, modulating gut microbiome and increasing propionate level might be an underlying mechanism responsible for the neuroprotective effects of OCN on PD, and the FFAR3, expressed in enteric nervous system, might be the main action site of propionate. Video abstract.}, } @article {pmid33512409, year = {2020}, author = {Khan, N and Lindner, S and Gomes, AL and Devlin, SM and Shah, G and Sung, AD and Sauter, CS and Landau, H and Dahi, PB and Perales, MA and Chung, D and Lesokhin, AM and Dai, A and Clurman, A and Slingerland, J and Slingerland, A and Brereton, DG and Giardina, PA and Maloy, M and Armijo, GK and Rondon-Clavo, C and Fontana, E and Bohannon, L and Ramalingam, S and Bush, AT and Lew, MV and Messina, JA and Littmann, E and Taur, Y and Jenq, RR and Chao, NJ and Giralt, S and Markey, KA and Pamer, E and van den Brink, MR and Peled, JU}, title = {Fecal microbiota diversity disruption and clinical outcomes after auto-HCT: a multicenter observational study.}, journal = {Blood}, volume = {}, number = {}, pages = {}, doi = {10.1182/blood.2020006923}, pmid = {33512409}, issn = {1528-0020}, support = {K08 HL143189/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, abstract = {We have previously described clinically relevant reductions in fecal microbiota diversity of patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). Recipients of high-dose chemotherapy and autologous hematopoietic cell transplantation (auto-HCT) incur similar antibiotic exposures and nutritional alterations. To characterize the fecal microbiota in the auto-HCT population, we analyzed 1,161 fecal samples collected from 534 adult recipients of auto-HCT for lymphoma, myeloma and amyloidosis in an observational study conducted at two transplant centers in the United States. Using 16S ribosomal gene sequencing, we assessed fecal microbiota diversity as measured by the inverse Simpson index, and composition. At both centers, early pre-transplant fecal microbiota diversity was lower than in healthy control subjects and decreased further during the course of transplantation. Loss of diversity and domination by specific bacterial taxa occurred during auto-HCT in patterns similar to allo-HCT. Above-median fecal intestinal diversity in the peri-engraftment period was associated with decreased risk of death or progression (PFS HR 0.46 [95% CI, 0.26-0.82], P=0.008), adjusting for disease and disease status. This suggests that further investigation into the health of the intestinal microbiota in auto-HCT patients and post-transplant outcomes should be undertaken.}, } @article {pmid33511356, year = {2021}, author = {Helve, O and Dikareva, E and Stefanovic, V and Kolho, KL and Salonen, A and de Vos, WM and Andersson, S}, title = {Protocol for oral transplantation of maternal fecal microbiota to newborn infants born by cesarean section.}, journal = {STAR protocols}, volume = {2}, number = {1}, pages = {100271}, pmid = {33511356}, issn = {2666-1667}, abstract = {Infants born by cesarean section have an intestinal microbiota that differs from that of infants delivered vaginally. Here, we report a protocol for performing oral transplantation of maternal fecal microbiota to newborn infants born by elective cesarean section. The crucial step of this protocol is the health screening process. This protocol can only be applied to healthy mothers and infants. For complete details on the use and execution of this protocol, please refer to Korpela et al. (2020).}, } @article {pmid33510784, year = {2021}, author = {Xu, HM and Huang, HL and Zhou, YL and Zhao, HL and Xu, J and Shou, DW and Liu, YD and Zhou, YJ and Nie, YQ}, title = {Fecal Microbiota Transplantation: A New Therapeutic Attempt from the Gut to the Brain.}, journal = {Gastroenterology research and practice}, volume = {2021}, number = {}, pages = {6699268}, pmid = {33510784}, issn = {1687-6121}, abstract = {Gut dysbacteriosis is closely related to various intestinal and extraintestinal diseases. Fecal microbiota transplantation (FMT) is a biological therapy that entails transferring the gut microbiota from healthy individuals to patients in order to reconstruct the intestinal microflora in the latter. It has been proved to be an effective treatment for recurrent Clostridium difficile infection. Studies show that the gut microbiota plays an important role in the pathophysiology of neurological and psychiatric disorders through the microbiota-gut-brain axis. Therefore, reconstruction of the healthy gut microbiota is a promising new strategy for treating cerebral diseases. We have reviewed the latest research on the role of gut microbiota in different nervous system diseases as well as FMT in the context of its application in neurological, psychiatric, and other nervous system-related diseases (Parkinson's disease, Alzheimer's disease, multiple sclerosis, epilepsy, autism spectrum disorder, bipolar disorder, hepatic encephalopathy, neuropathic pain, etc.).}, } @article {pmid33510783, year = {2021}, author = {Zhong, M and Buch, H and Wen, Q and Long, C and Cui, B and Zhang, F}, title = {Colonic Transendoscopic Enteral Tubing: Route for a Novel, Safe, and Convenient Delivery of Washed Microbiota Transplantation in Children.}, journal = {Gastroenterology research and practice}, volume = {2021}, number = {}, pages = {6676962}, pmid = {33510783}, issn = {1687-6121}, abstract = {Aim: Colonic transendoscopic enteral tubing (TET) has been used for delivering fecal microbiota transplantation by washed preparation since 2015, which was recently named as washed microbiota transplantation (WMT). However, there are few reports available regarding the feasibility and safety of these studies in low-age population. This study is aimed at evaluating the safety, feasibility, and value of colonic TET in 3-7 years old children.

Methods: All patients aged 3-7 years who underwent colonic TET in our center for WMT or medication were prospectively evaluated. The feasibility and safety of TET were evaluated. A questionnaire was completed by the children's parents to evaluate the children's response to the colonic TET as well as the parent's satisfaction.

Results: Forty-seven children were included (mean age 5 years). TET was implemented into the colon of all the patients, and the success rate of the procedure was 100%. The median retention time of TET tube within the colon was 6 (IQR 5-7) days in 45 patients with tube falling out spontaneously, and the maximum retention time was up to 21 days. Multivariate analysis demonstrated that endoscopic clip number (P = 0.009) was an independent contributing factor for the retaining time of tube. With increase in the number of large clips, the retention time of TET tube was prolonged. No discomfort was reported during injection of the microbiota or medication suspension through the TET tube. During the follow-up, no severe adverse events were observed. All children's parents were satisfied with TET. Interestingly, the proportion of children's parents choosing TET as the delivery way of WMT increased from 29.79% before to 70.21% after TET (P < 0.001).

Conclusions: This study, for the first time, demonstrates that colonic TET is a novel, safe, and convenient colonic delivery way for WMT and medication in children aged 3-7 years.}, } @article {pmid33508620, year = {2021}, author = {Li, X and Kang, Y and Huang, Y and Xiao, Y and Song, L and Lu, S and Ren, Z}, title = {A strain of Bacteroides thetaiotaomicron attenuates colonization of Clostridioides difficile and affects intestinal microbiota and bile acids profile in a mouse model.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {137}, number = {}, pages = {111290}, doi = {10.1016/j.biopha.2021.111290}, pmid = {33508620}, issn = {1950-6007}, abstract = {Clostridioides difficile infection (CDI) is a growing global public health threat. While fecal microbiota transplantation (FMT) is an effective therapy for CDI, a number of challenges limit its application. Studies suggest that probiotics may be a promising alternative therapy. In the current study, we evaluated whether Bacteroides thetaiotaomicron (B. thetaiotaomicron) would inhibit colonization of toxigenic BI/NAP1/027 C. difficile in a mouse model. We found that B. thetaiotaomicron administration decreased the copies of C. difficile and inhibited inflammation in the colon. 16S rRNA sequencing showed that B. thetaiotaomicron administration was associated with a significantly increased relative abundance of Bacteroidetes and decreased level of Proteobacteria, leading to the reversal of the effect of antibiotics treatment and C. difficile infection on microbiota. B. thetaiotaomicron administration was associated with increases in the concentrations of alpha-muricholic acid, beta-muricholic acid, 12 ketolithocholic acid, and deoxycholic acid which are known to inhibit the growth of C. difficile, as well as reductions in the level of taurocholic acid, which promotes germination of C. difficile. Altered profile of major high abundance bile acids by B. thetaiotaomicron administration was similar to that with FMT treatment. Based on these results, we proposed the concept of "the ratio of promotion/inhibition BAs" which would advance our understanding of the relation of C. difficile and BAs.}, } @article {pmid33508265, year = {2021}, author = {Yahia, SA and Audousset, C and Alvarez-Simon, D and Vorng, H and Togbe, D and Marquillies, P and Delacre, M and Rose, S and Bouscayrol, H and Rifflet, A and Quesniaux, V and Boneca, IG and Chamaillard, M and Tsicopoulos, A}, title = {NOD1 sensing of house dust mite-derived microbiota promotes allergic experimental asthma.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2020.12.649}, pmid = {33508265}, issn = {1097-6825}, abstract = {BACKGROUND: Asthma severity has been linked to exposure to Gram-negative bacteria from the environment, that are recognized by NOD1 receptor and are present in HDM extracts. NOD1 polymorphism has been associated with asthma.

OBJECTIVE: To evaluate if either host or HDM-derived microbiota may contribute to NOD1-dependent disease severity.

METHODS: A model of HDM-induced experimental asthma was used and the effect of NOD1 deficiency evaluated. Contribution of host microbiota was evaluated by fecal transplantation. Contribution of HDM-derived microbiota was assessed by 16S ribosomal RNA (rRNA) sequencing, mass spectrometry analysis, and peptidoglycan depletion of the extracts.

RESULTS: In this model, loss of the bacterial sensor NOD1 and its adaptor receptor-interacting protein kinase 2 improved asthma features. Such inhibitory effect was not related to dysbiosis caused by NOD1 deficiency, as shown by fecal transplantation of Nod1-deficient microbiota to wild-type germ-free mice. 16S rRNA gene sequencing and mass spectrometry analysis of HDM allergen, revealed the presence of some muropeptides from Gram-negative bacteria that belong to the Bartonellaceae family. While such HDM-associated muropeptides were found to activate NOD1 signaling in epithelial cells, peptidoglycan-depleted HDM had a decreased ability to instigate asthma in vivo.

CONCLUSION: These data show that NOD1-dependent sensing of HDM-associated Gram-negative bacteria aggravates the severity of experimental asthma, suggesting that inhibiting NOD1 signaling pathway may be a therapeutic approach to treating asthma.}, } @article {pmid33506928, year = {2021}, author = {Nakov, R and Lyutakov, I and Mitkova, A and Gerova, V and Petkova, V and Giragosyan, S and Vatcheva-Dobrevska, R and Kaneva, R and Nakov, V}, title = {Establishment of the first stool bank in an Eastern European country and the first series of successful fecal microbiota transplantations in Bulgaria.}, journal = {European review for medical and pharmacological sciences}, volume = {25}, number = {1}, pages = {390-396}, doi = {10.26355/eurrev_202101_24406}, pmid = {33506928}, issn = {2284-0729}, abstract = {OBJECTIVE: For safe implementation and broader application of fecal microbiota transplantation (FMT), quality controlled stool banking is a must. Establishing a stool bank is a complex, time-consuming, and expensive process, making it a real challenge in an Eastern European country. We aimed to establish the first stool bank in Eastern Europe - in Bulgaria.

SUBJECTS AND METHODS: A multidisciplinary team of gastroenterologists, microbiologists, infectionists, and geneticists was set up. We used a questionnaire based on the First European FMT Consensus in order to recruit possible stool donors. Laboratory blood and stool tests were performed on all potential donors.

RESULTS: Between October 2018 and April 2019, 112 donor volunteers completed a questionnaire; 70 (62.5%) were excluded, mainly because of age above 50, an unhealthy BMI, and risk behavior. Fourty-two (37.5%) donor candidates were invited for laboratory testing of blood and feces, of which 12 (28.6%) passed this screening. Of 12 donors, 4 (33%) failed at the following screening test, which is performed every 3-6 months. Finally, 8 (7.14%) active donors were enrolled. Ten successful FMTs were performed on patients with recurrent Clostridium difficile infection.

CONCLUSIONS: Even though we found many healthy volunteers, only a low percentage (7.14%) of them were suitable to become feces donors. Establishing a stool bank in an Eastern European country is essential for making FMT safe and more popular as a treatment method, finding further implementation and regulation of FMT and supporting physicians offering this treatment to their patients.}, } @article {pmid33505139, year = {2020}, author = {Qi, X and Yang, M and Stenberg, J and Dey, R and Fogwe, L and Alam, MS and Kimchi, ET and Staveley-O'Carroll, KF and Li, G}, title = {Gut microbiota mediated molecular events and therapy in liver diseases.}, journal = {World journal of gastroenterology}, volume = {26}, number = {48}, pages = {7603-7618}, pmid = {33505139}, issn = {2219-2840}, abstract = {Gut microbiota is a community of microorganisms that reside in the gastrointestinal tract. An increasing number of studies has demonstrated that the gut-liver axis plays a critical role in liver homeostasis. Dysbiosis of gut microbiota can cause liver diseases, including nonalcoholic fatty liver disease and alcoholic liver disease. Preclinical and clinical investigations have substantiated that the metabolites and other molecules derived from gut microbiota and diet interaction function as mediators to cause liver fibrosis, cirrhosis, and final cancer. This effect has been demonstrated to be associated with dysregulation of intrahepatic immunity and liver metabolism. Targeting these findings have led to the development of novel preventive and therapeutic strategies. Here, we review the cellular and molecular mechanisms underlying gut microbiota-mediated impact on liver disease. We also summarize the advancement of gut microbiota-based therapeutic strategies in the control of liver diseases.}, } @article {pmid33504365, year = {2021}, author = {Hao, X and Shang, X and Liu, J and Chi, R and Zhang, J and Xu, T}, title = {The gut microbiota in osteoarthritis: where do we stand and what can we do?.}, journal = {Arthritis research & therapy}, volume = {23}, number = {1}, pages = {42}, pmid = {33504365}, issn = {1478-6362}, abstract = {Osteoarthritis (OA) is one of the most frequent musculoskeletal diseases characterized by degeneration of articular cartilage, subchondral bone remodeling, and synovial membrane inflammation, which is a leading cause of global disability, morbidity, and decreased quality of life. Interpreting the potential mechanisms of OA pathogenesis is essential for developing novel prevention and disease-modifying therapeutic interventions. Gut microbiota is responsible for a series of metabolic, immunological, and structural and neurological functions, potentially elucidating the heterogeneity of OA phenotypes and individual features. In this narrative review, we summarized research evidence supporting the hypothesis of a "gut-joint axis" and the interaction between gut microbiota and the OA-relevant factors, including age, gender, genetics, metabolism, central nervous system, and joint injury, elucidating the underlying mechanisms of this intricate interaction. In the context, we also speculated the promising manipulation of gut microbiota in OA management, such as exercise and fecal microbiota transplantation (FMT), highlighting the clinical values of gut microbiota. Additionally, future research directions, such as more convincing studies by the interventions of gut microbiota, the gene regulation of host contributing to or attributed to the specific phenotypes of gut microbiota related to OA, and the relevance of distinct cell subgroups to gut microbiota, are expected. Moreover, gut microbiota is also the potential biomarker related to inflammation and gut dysbiosis that is able to predict OA progression and monitor the efficacy of therapeutic intervention.}, } @article {pmid33501942, year = {2021}, author = {Karjalainen, EK and Renkonen-Sinisalo, L and Satokari, R and Mustonen, H and Ristimäki, A and Arkkila, P and Lepistö, AH}, title = {Fecal Microbiota Transplantation in Chronic Pouchitis: A Randomized, Parallel, Double-Blinded Clinical Trial.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izab001}, pmid = {33501942}, issn = {1536-4844}, abstract = {BACKGROUND: In ulcerative colitis, a pouchitis is the most common long-term adverse effect after proctocolectomy and ileal pouch-anal anastomosis. Approximately 5% of patients develop chronic antibiotic-dependent or antibiotic-refractory pouchitis without any effective treatment. The aim of this trial was to investigate the efficacy and safety of fecal microbiota transplantation in the treatment of chronic pouchitis.

METHODS: This was a single-center, double-blinded, parallel group trial comparing donor fecal microbiota transplantation with placebo (autologous transplant) in chronic pouchitis. Twenty-six patients were recruited at the Helsinki University Hospital between December 2017 and August 2018 and were randomly allocated a 1:1 ratio to either donor fecal microbiota transplantation or placebo. The protocol included 2 transplantations into the pouch on weeks 0 and 4, and patients were followed up for 52 weeks.

RESULTS: Nine patients in the intervention group and 8 patients in the placebo group relapsed during the 52-week follow-up, and the relapse-free survival did not differ between the groups (P = 0.183, log-rank; hazard ratio, 1.90 [95% confidence interval, 0.73-4.98; P = 0.190]). In the subgroup analysis of patients using continuous antibiotics before the study, the relapse-free survival was shorter in the intervention group (P = 0.004, log-rank; hazard ratio, 13.08 [95% confidence interval, 1.47-116.60; P = 0.021]). No major adverse effects were reported.

CONCLUSIONS: The fecal microbiota transplantation treatment regime used in our study was not effective in the treatment of chronic pouchitis. The safety profile of fecal microbiota transplantation was good.

CLINICALTRIALS.GOV IDENTIFIER: NCT03378921.}, } @article {pmid33501941, year = {2021}, author = {Dalal, RS and Allegretti, JR}, title = {Fecal Microbiota Transplantation for Chronic Pouchitis: Promising Novel Therapeutic or Lost Cause?.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izab002}, pmid = {33501941}, issn = {1536-4844}, } @article {pmid33501940, year = {2021}, author = {Karjalainen, EK and Renkonen-Sinisalo, L and Satokari, R and Mustonen, H and Ristimäki, A and Arkkila, P and Lepistö, AH}, title = {Author's Reply: Fecal Microbiota Transplantation for Chronic Pouchitis: Promising Novel Therapeutic or Lost Cause?.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izab003}, pmid = {33501940}, issn = {1536-4844}, } @article {pmid33501400, year = {2020}, author = {Utay, NS and Monczor, AN and Somasunderam, A and Lupo, S and Jiang, ZD and Alexander, AS and Finkelman, M and Vigil, KJ and Lake, JE and Hanson, B and DuPont, HL and Arduino, RC}, title = {Evaluation of Six Weekly Oral Fecal Microbiota Transplants in People with HIV.}, journal = {Pathogens & immunity}, volume = {5}, number = {1}, pages = {364-381}, pmid = {33501400}, issn = {2469-2964}, abstract = {Background: Reduced microbiota diversity (dysbiosis) in people with HIV (PWH) likely contributes to inflammation, a driver of morbidity and mortality. We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis.

Methods: Six PWH on suppressive antiretroviral therapy (ART) received 6 weekly doses of lyophilized fecal microbiota product from healthy donors. Shotgun sequencing on stool before, after last FMT, and 20 weeks thereafter was performed. Inflammation and gut permeability biomarkers were measured.

Results: Median age at week 0 was 39 years, CD4+ T cell count 496 cells/mm3, HIV RNA levels <20 copies/mL. FMT was safe and well-tolerated. α diversity increased in 4 participants from weeks 0 to 6, including the 3 with the lowest α diversity at week 0. At week 26, α diversity more closely resembled week 0 than week 6 in these 4 participants. Metagenomic analysis showed no consistent changes across all participants. One participant had high gut permeability and inflammation biomarker levels and low α diversity that improved between weeks 0 and 6 with a shift in distribution.

Conclusions: Weekly FMT was safe and well-tolerated. α diversity increased in participants with the lowest baseline α diversity during the treatment period. Future randomized, controlled trials of FMT should consider evaluating PWH with greater inflammation, gut damage, or dysbiosis as this population may be most likely to show a significant response.ClinicalTrials.gov Identifier: NCT03329560.}, } @article {pmid33500411, year = {2021}, author = {Uzan-Yulzari, A and Turta, O and Belogolovski, A and Ziv, O and Kunz, C and Perschbacher, S and Neuman, H and Pasolli, E and Oz, A and Ben-Amram, H and Kumar, H and Ollila, H and Kaljonen, A and Isolauri, E and Salminen, S and Lagström, H and Segata, N and Sharon, I and Louzoun, Y and Ensenauer, R and Rautava, S and Koren, O}, title = {Neonatal antibiotic exposure impairs child growth during the first six years of life by perturbing intestinal microbial colonization.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {443}, pmid = {33500411}, issn = {2041-1723}, mesh = {Animals ; Anti-Bacterial Agents/*adverse effects ; Bacterial Infections/*drug therapy ; Body Height/drug effects/physiology ; Body Mass Index ; Body Weight/drug effects/physiology ; Child ; Child, Preschool ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome/*drug effects/physiology ; Germ-Free Life ; Growth Disorders/*chemically induced/microbiology/physiopathology ; Humans ; Infant, Newborn ; Intestinal Mucosa/microbiology ; Male ; Mice ; Pregnancy ; Risk Factors ; Sex Factors ; }, abstract = {Exposure to antibiotics in the first days of life is thought to affect various physiological aspects of neonatal development. Here, we investigate the long-term impact of antibiotic treatment in the neonatal period and early childhood on child growth in an unselected birth cohort of 12,422 children born at full term. We find significant attenuation of weight and height gain during the first 6 years of life after neonatal antibiotic exposure in boys, but not in girls, after adjusting for potential confounders. In contrast, antibiotic use after the neonatal period but during the first 6 years of life is associated with significantly higher body mass index throughout the study period in both boys and girls. Neonatal antibiotic exposure is associated with significant differences in the gut microbiome, particularly in decreased abundance and diversity of fecal Bifidobacteria until 2 years of age. Finally, we demonstrate that fecal microbiota transplant from antibiotic-exposed children to germ-free male, but not female, mice results in significant growth impairment. Thus, we conclude that neonatal antibiotic exposure is associated with a long-term gut microbiome perturbation and may result in reduced growth in boys during the first six years of life while antibiotic use later in childhood is associated with increased body mass index.}, } @article {pmid33499991, year = {2020}, author = {Sidiropoulos, DN and Al-Ghalith, GA and Shields-Cutler, RR and Ward, TL and Johnson, AJ and Vangay, P and Knights, D and Kashyap, PC and Xian, Y and Ramer-Tait, AE and Clayton, JB}, title = {Wild primate microbiomes prevent weight gain in germ-free mice.}, journal = {Animal microbiome}, volume = {2}, number = {1}, pages = {16}, pmid = {33499991}, issn = {2524-4671}, support = {T32 DA007097-32/DA/NIDA NIH HHS/United States ; DK114007//Foundation for the National Institutes of Health/ ; }, abstract = {BACKGROUND: The gut microbiome harbors trillions of bacteria that play a major role in dietary nutrient extraction and host metabolism. Metabolic diseases such as obesity and diabetes are associated with shifts in microbiome composition and have been on the rise in Westernized or highly industrialized countries. At the same time, Westernized diets low in dietary fiber have been shown to cause loss of gut microbial diversity. However, the link between microbiome composition, loss of dietary fiber, and obesity has not been well defined.

RESULTS: To study the interactions between gut microbiota, dietary fiber, and weight gain, we transplanted captive and wild douc gut microbiota into germ-free mice and then exposed them to either a high- or low-fiber diet. The group receiving captive douc microbiota gained significantly more weight, regardless of diet, while mice receiving a high-fiber diet and wild douc microbiota remained lean. In the presence of a low-fiber diet, the wild douc microbiota partially prevented weight gain. Using 16S rRNA gene amplicon sequencing we identified key bacterial taxa in each group, specifically a high relative abundance of Bacteroides and Akkermansia in captive douc FMT mice and a higher relative abundance of Lactobacillus and Clostridium in the wild douc FMT mice.

CONCLUSIONS: In the context of our germ-free mouse experiment, wild douc microbiota could serve as a reservoir for microbes for cross-species transplants. Our results suggest that wild douc microbiota are tailored to diverse fiber diets and can prevent weight gain when exposed to a native diet.}, } @article {pmid33498428, year = {2021}, author = {Kampouri, E and Croxatto, A and Prod'hom, G and Guery, B}, title = {Clostridioides difficile Infection, Still a Long Way to Go.}, journal = {Journal of clinical medicine}, volume = {10}, number = {3}, pages = {}, pmid = {33498428}, issn = {2077-0383}, abstract = {Clostridioides difficile is an increasingly common pathogen both within and outside the hospital and is responsible for a large clinical spectrum from asymptomatic carriage to complicated infection associated with a high mortality. While diagnostic methods have considerably progressed over the years, the optimal diagnostic algorithm is still debated and there is no single diagnostic test that can be used as a standalone test. More importantly, the heterogeneity in diagnostic practices between centers along with the lack of robust surveillance systems in all countries and an important degree of underdiagnosis due to lack of clinical suspicion in the community, hinder a more accurate evaluation of the burden of disease. Our improved understanding of the physiopathology of CDI has allowed some significant progress in the treatment of CDI, including a broader use of fidaxomicine, the use of fecal microbiota transplantation for multiples recurrences and newer approaches including antibodies, vaccines and new molecules, already developed or in the pipeline. However, the management of CDI recurrences and severe infections remain challenging and the main question remains: how to best target these often expensive treatments to the right population. In this review we discuss current diagnostic approaches, treatment and potential prevention strategies, with a special focus on recent advances in the field as well as areas of uncertainty and unmet needs and how to address them.}, } @article {pmid33497754, year = {2021}, author = {Settanni, CR and Ianiro, G and Bibbò, S and Cammarota, G and Gasbarrini, A}, title = {Gut microbiota alteration and modulation in psychiatric disorders: Current evidence on fecal microbiota transplantation.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {109}, number = {}, pages = {110258}, doi = {10.1016/j.pnpbp.2021.110258}, pmid = {33497754}, issn = {1878-4216}, abstract = {The micro-organisms residing within the gastrointestinal tract, namely gut microbiota, form a dynamic population proper of each individual, mostly composed by bacteria which co-evolved symbiotically with human species. The advances of culture-independent techniques allowed the understanding of the multiple functions of the gut microbiota in human physiology and disease, the latter often recognising a predisposing condition in an imbalanced intestinal microbial ecosystem (dysbiosis). A complex mutual interconnection between the central nervous system (CNS), the intestine and the gut microbiota, known as "microbiota-gut-brain axis", has been hypothesized to play a pivotal role in maintaining central and peripheral functions, as well as mental health. Thus, dysbiosis with specific microbiota imbalances seems to be strongly associated with the onset psychiatric disorders by altering neurodevelopment, enhancing neurodegeneration, affecting behaviour and mood. Fecal microbiota transplantation (FMT) consists of transferring the fecal matter from a donor into the gastrointestinal tract of a recipient, and it is used to quickly modulate the gut microbiota. This review focuses on the uses of FMT in psychiatric disorders. FMT has been used to induce dysbiosis and to study the disease development, or to heal dysbiosis-related mental disorders. Overall, FMT of impaired microbiota resulted effective in enhancing psychiatric-like disturbances (mainly depression and anxiety) in recipient animals, plausibly by impairing immune system, inflammatory and metabolic pathways, neurochemical processes and neuro-transmission. On the other side, preclinical and clinical data suggest that reversing or mitigating dysbiosis seems a promising strategy to restore behavioural impairments or to obtain psychiatric symptom relief. However, current evidence is limited by the lack of procedural standardization, the paucity of human studies in the vastity of psychiatric conditions and the need of a microbiota-targeted donor-recipient matching.}, } @article {pmid33496893, year = {2021}, author = {Tariq, R and Hayat, M and Pardi, D and Khanna, S}, title = {Predictors of failure after fecal microbiota transplantation for recurrent Clostridioides difficile infection: a systematic review and meta-analysis.}, journal = {European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology}, volume = {}, number = {}, pages = {}, pmid = {33496893}, issn = {1435-4373}, abstract = {Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridioides difficile infection (CDI), with ~15% 1-year recurrence rate. Small studies have identified variable risk factors associated with FMT failure. We, therefore, performed a systematic review and meta-analysis to evaluate the predictors of FMT failure. A systematic search of Medline, Embase, and Web of Science was performed from January 2013 up to June 2020. Meta-analyses were performed using random-effects models and pooled adjusted odds ratios for risk factors reported in ≥2 studies were calculated. Overall, 2671 patients with recurrent CDI who underwent FMT in 12 studies were included. FMT failure occurred in 454 patients (16.9%) with median follow-up of 3 months (range 2-7.7 months). A total of 9 risk factors were identified in ≥2 studies. Meta-analysis showed that use of non- CDI antibiotics, presence of inflammatory bowel disease, poor quality of bowel preparation, CDI-related hospitalization before FMT, inpatient FMT, and severe CDI were associated with statistically significant increased risk of failure after FMT. Increasing age, female gender, and immunocompromised status were not associated with increased risk for FMT failure. Several risk factors (both modifiable and non-modifiable) are associated with FMT failure. Lower use of antibiotics in the post-FMT period and good bowel preparation at the time of FMT are associated with lower risk of failure after FMT. Additionally, patients with non-modifiable risk factors should be counseled to be particularly alert about recurrent symptoms after FMT.}, } @article {pmid33483999, year = {2021}, author = {Marrs, T and Walter, J}, title = {Pros and Cons: Is Fecal Microbiota Transplantation a safe and efficient treatment option for gutdysbiosis?.}, journal = {Allergy}, volume = {}, number = {}, pages = {}, doi = {10.1111/all.14750}, pmid = {33483999}, issn = {1398-9995}, abstract = {Fecal Microbiota Transplantation (FMT) is wellestablished as an effective treatment for Clostridioides difficile infection (CDI), restoring gut microbiome diversity and function. The utility of FMTiscurrently being explored in relation to other immune-mediatedpathologies, such as Allergic Disease, Inflammatory Bowel Diseases and Autoimmune Diseases. Clinical trials in these areas are ongoing, and the altered gut microbiota (dysbiosis) that is often observed in these pathologies provides arationale forthe application ofFMT to restore the microbiome. However, there is controversy on the risk-benefit ratio as it relates to the use of FMTs in pathologies other than CDI. In this Pro and Con article, we present the arguments for and against the use of FMT in immune-mediated pathologies, such as Allergic Disease. We further identify research gaps and recommend how these may be addressed in future studies.}, } @article {pmid33483370, year = {2021}, author = {Di Modica, M and Gargari, G and Regondi, V and Bonizzi, A and Arioli, S and Belmonte, B and De Cecco, L and Fasano, E and Bianchi, F and Bertolotti, A and Tripodo, C and Villani, L and Corsi, F and Guglielmetti, S and Balsari, A and Triulzi, T and Tagliabue, E}, title = {Gut microbiota condition the therapeutic efficacy of trastuzumab in HER2-positive breast cancer.}, journal = {Cancer research}, volume = {}, number = {}, pages = {}, doi = {10.1158/0008-5472.CAN-20-1659}, pmid = {33483370}, issn = {1538-7445}, abstract = {Emerging evidence indicates that gut microbiota affect the response to anticancer therapies by modulating the host immune system. In this study, we investigated the impact of the gut microbiota on immune-mediated trastuzumab antitumor efficacy in preclinical models of HER2-positive breast cancer (BC) and in 24 patients with primary HER2-positive BC undergoing trastuzumab-containing neoadjuvant treatment. In mice, the antitumor activity of trastuzumab was impaired by antibiotic administration or fecal microbiota transplantation from antibiotic-treated donors. Modulation of the intestinal microbiota was reflected in tumors by impaired recruitment of CD4+ T cells and GZMB+ cells after trastuzumab treatment. Antibiotics caused reductions in dendritic cell (DC) activation and the release of IL12p70 upon trastuzumab treatment, a mechanism that was necessary for trastuzumab effectiveness in our model. In patients, lower α-diversity and lower abundance of Lachnospiraceae, Turicibacteriaceae, Bifidobacteriaceae and Prevotellaceae characterized nonresponsive patients (NR) compared to those who achieved pathological complete response (R), similar to antibiotic-treated mice. The transfer of fecal microbiota from R and NR into mice bearing HER2-positive BC recapitulated the response to trastuzumab observed in patients. Fecal microbiota β-diversity segregated patients according to response and positively correlated with immune signature related to interferon, IL12-NO, activated CD4+ T cells and activated DC in tumors. Overall, our data reveal the direct involvement of the gut microbiota in trastuzumab efficacy, suggesting that manipulation of the gut microbiota is an optimal future strategy to achieve a therapeutic effect or to exploit its potential as a biomarker for treatment response.}, } @article {pmid33483079, year = {2021}, author = {Sang, T and Guo, C and Guo, D and Wu, J and Wang, Y and Wang, Y and Chen, J and Chen, C and Wu, K and Na, K and Li, K and Fang, L and Guo, C and Wang, X}, title = {Suppression of obesity and inflammation by polysaccharide from sporoderm-broken spore of Ganoderma lucidum via gut microbiota regulation.}, journal = {Carbohydrate polymers}, volume = {256}, number = {}, pages = {117594}, doi = {10.1016/j.carbpol.2020.117594}, pmid = {33483079}, issn = {1879-1344}, abstract = {Ganoderma lucidum has been shown to have anti-obesity effects. However, polysaccharide extracted from the sporoderm-broken spores of Ganoderma lucidum (BSGLP) against obesity and its underlying mechanisms have never been reported. In the current study, we showed that BSGLP inhibited high-fat diet (HFD)-induced obesity, hyperlipidemia, inflammation, and fat accumulation in C57BL/6 J mice. BSGLP improved HFD-induced gut microbiota dysbiosis, maintained intestinal barrier function, increased short-chain fatty acids production and GPR43 expression, ameliorated endotoxemia, manifested by reduced serum lipopolysaccharide level, and increased ileum expression of tight junction proteins and antimicrobial peptides. Fecal microbiota transplantation study confirmed that BSGLP-induced microbiota change is responsible, at least in part, for obesity inhibition. Besides, BSGLP notably alleviated HFD-induced upregulation of TLR4/Myd88/NF-κB signaling pathway in adipose tissue. Collectively, our study showed for the first time that BSGLP might be used as a prebiotic agent to inhibit obesity and hyperlipidemia through modulating inflammation, gut microbiota, and gut barrier function.}, } @article {pmid33482620, year = {2020}, author = {Nejadghaderi, SA and Nazemalhosseini-Mojarad, E and Asadzadeh Aghdaei, H}, title = {Fecal microbiota transplantation for COVID-19; a potential emerging treatment strategy.}, journal = {Medical hypotheses}, volume = {147}, number = {}, pages = {110476}, pmid = {33482620}, issn = {1532-2777}, abstract = {At the end of 2019, an emerging outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that first reported from Wuhan, China. The first manifestations of patients infected with SARS-CoV-2 was flu-like symptoms, while other type of manifestations, especially gastrointestinal manifestations were discovered recently. As of June 2020, there is no specific drug or treatment strategy for COVID-19, a disease caused by SARS-CoV-2, so different combination of antiviral drugs is currently being used. Gut microbiota mostly consists of four phyla, including Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. The interaction between gut microbiota and immune system through releasing some cytokines such as IL-1β, IL-2, IL-10, TNF-α, and IFN-γ that play roles in the severity of COVID-19. In this article, a new potential treatment for COVID-19 by fecal microbiota transplantation (FMT) is described. FMT revealed promising results in different diseases, especially recurrent clostridium difficile infection, and it might reduce length of hospital admission and severity of the disease by modification of gut microbiota composition.}, } @article {pmid33477939, year = {2021}, author = {Burz, SD and Monnoye, M and Philippe, C and Farin, W and Ratziu, V and Strozzi, F and Paillarse, JM and Chêne, L and Blottière, HM and Gérard, P}, title = {Fecal Microbiota Transplant from Human to Mice Gives Insights into the Role of the Gut Microbiota in Non-Alcoholic Fatty Liver Disease (NAFLD).}, journal = {Microorganisms}, volume = {9}, number = {1}, pages = {}, pmid = {33477939}, issn = {2076-2607}, support = {ANR-15-CE14-0021-03//Agence Nationale de la Recherche/ ; }, abstract = {Non-alcoholic fatty liver diseases (NAFLD) are associated with changes in the composition and metabolic activities of the gut microbiota. However, the causal role played by the gut microbiota in individual susceptibility to NAFLD and particularly at its early stage is still unclear. In this context, we transplanted the microbiota from a patient with fatty liver (NAFL) and from a healthy individual to two groups of mice. We first showed that the microbiota composition in recipient mice resembled the microbiota composition of their respective human donor. Following administration of a high-fructose, high-fat diet, mice that received the human NAFL microbiota (NAFLR) gained more weight and had a higher liver triglycerides level and higher plasma LDL cholesterol than mice that received the human healthy microbiota (HR). Metabolomic analyses revealed that it was associated with lower and higher plasma levels of glycine and 3-Indolepropionic acid in NAFLR mice, respectively. Moreover, several bacterial genera and OTUs were identified as differently represented in the NAFLR and HR microbiota and therefore potentially responsible for the different phenotypes observed. Altogether, our results confirm that the gut bacteria play a role in obesity and steatosis development and that targeting the gut microbiota may be a preventive or therapeutic strategy in NAFLD management.}, } @article {pmid33477417, year = {2021}, author = {Hassouneh, R and Bajaj, JS}, title = {Gut Microbiota Modulation and Fecal Transplantation: An Overview on Innovative Strategies for Hepatic Encephalopathy Treatment.}, journal = {Journal of clinical medicine}, volume = {10}, number = {2}, pages = {}, pmid = {33477417}, issn = {2077-0383}, support = {2I0CX001076//Office of Research and Development/ ; R21TR002024/TR/NCATS NIH HHS/United States ; R21TR003095/TR/NCATS NIH HHS/United States ; }, abstract = {Hepatic encephalopathy (HE) is a major complication of cirrhosis, which is associated with gut microbial composition and functional alterations. Current treatments largely focus on gut microbiota using lactulose, rifaximin and other agents. However, despite these treatments, patients with HE have a high rate of readmission, morbidity and cognitive impairment. Fecal microbiota transplant (FMT) involves introduction of a donor microbiota into a recipient and is currently mainly used for recurrent C. difficile infection (rCDI). The role of FMT in cirrhosis and HE is evolving. There have been two randomized clinical trials (RCT) and several case reports/series in cirrhosis. Both RCTs were safety-focused phase 1 trials. One involved pre-FMT antibiotics and FMT enema versus standard of care, while the other involved 15 FMT capsules versus placebo without pre-FMT antibiotics. There was evidence of safety in both trials and the FMT group demonstrated reduction in hospitalizations compared to the non-FMT group. Changes in microbial function centered around short-chain fatty acids, bile acids and brain function showed improvement in the FMT groups. Long-term follow-up demonstrated continued safety and reduction in the antibiotic-resistance gene carriage. However, larger trials of FMT in HE are needed that can refine the dose, duration and route of FMT administration.}, } @article {pmid33476924, year = {2021}, author = {Wang, J and Ishfaq, M and Li, J}, title = {Lactobacillus salivarius ameliorated Mycoplasma gallisepticum-induced inflammatory injury and secondary Escherichia coli infection in chickens: Involvement of intestinal microbiota.}, journal = {Veterinary immunology and immunopathology}, volume = {233}, number = {}, pages = {110192}, doi = {10.1016/j.vetimm.2021.110192}, pmid = {33476924}, issn = {1873-2534}, abstract = {Mycoplasma gallisepticum (MG) infection alone or in combination with other pathogens have brought huge economic losses to the poultry industry. The intestinal microbiota plays a critical role in host defence against respiratory infection. To explore the role of intestinal microbiota in MG-induced inflammation-mediated lung injury and secondary Escherichia coli infection, MG infection model and fecal microbiota transplantation model were developed. The results showed that MG infection changed gut microbiota composition along with lung inflammation injury. Fecal microbiota transplantation from chickens infected with MG to antibiotics cocktail treated chickens decreased host defense against Escherichia coli due to impaired intestinal mucosal barrier, downregulated the mRNA expression levels of host defense enzymes and blocked autophagic flux. Lactobacillus salivarius intake alleviated lung inflammation injury caused by MG infection and increased host defense against Escherichia coli by improved gut microbiota composition. These results highlighted the role of gut microbiota in MG-infection induced lung inflammation injury and secondary infection that offered a new strategy for preventive intervention against MG infection.}, } @article {pmid33476379, year = {2021}, author = {Rupawala, AH and Gachette, D and Bakhit, M and Jimoh, L and Kelly, CR}, title = {Management of Severe and Severe/Complicated Clostridoides difficile Infection using Sequential Fecal Microbiota Transplant by Retention Enema.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciab041}, pmid = {33476379}, issn = {1537-6591}, abstract = {We evaluated serial FMT by retention enema in patients with severe or severe/complicated CDI unresponsive to at least 48 hours of standard antibiotic therapy. Of the 15 patients included, despite initial improvement in most patients, only 5 patients sustained cure at 30 days and serious adverse events occurred in 4 patients.}, } @article {pmid33471490, year = {2021}, author = {Du, C and Luo, Y and Walsh, S and Grinspan, A}, title = {Oral Fecal Microbiota Transplant Capsules Are Safe and Effective for Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001495}, pmid = {33471490}, issn = {1539-2031}, abstract = {GOALS: We performed a systematic review with meta-analysis to examine the efficacy and safety of oral fecal microbiota transplantation (FMT) capsules for recurrent Clostridioides difficile infection (rCDI).

BACKGROUND: FMT through colonoscopy is established as effective and safe in treating multiple recurrences of CDI, but consensus has not been established on delivery through oral capsules.

STUDY: A systematic literature search was performed with multiple databases including MEDLINE and EMBASE to identify original studies including at least 10 patients that investigated the role of oral FMT capsules to treat rCDI. Cure rates were pooled by a random effects model and publication bias was assessed with the Egger test. Secondary analyses assessed for differences between capsule preparation (frozen vs. lyophilized stool) and delivery modality (capsule vs. colonoscopy).

RESULTS: Fifteen studies (12 case series and 3 randomized controlled trials) encompassing 763 patients were identified for inclusion. Significant variability existed in baseline patient characteristics and protocols. Meta-analysis of proportions showed efficacy of oral FMT capsules to be 0.821 (95% confidence interval: 0.762-0.874). No evidence for publication bias was found (P=0.51). Secondary analyses did not find significant differences in efficacy. Fourteen adverse events leading to death or hospitalization were noted, none of which were attributed to FMT.

CONCLUSIONS: Oral FMT capsules for rCDI are promising because of ease of administration and noninvasive delivery. We found an overall efficacy of 82.1% with a low rate of serious adverse events. Further studies are needed to optimize protocols and outcomes.}, } @article {pmid33468164, year = {2021}, author = {Fang, H and Fu, L and Li, X and Lu, C and Su, Y and Xiong, K and Zhang, L}, title = {Long-term efficacy and safety of monotherapy with a single fresh fecal microbiota transplant for recurrent active ulcerative colitis: a prospective randomized pilot study.}, journal = {Microbial cell factories}, volume = {20}, number = {1}, pages = {18}, pmid = {33468164}, issn = {1475-2859}, support = {No. 1408085MH178//Natural Science Foundation of Anhui Province/ ; }, abstract = {BACKGROUND: To assess the long-term safety and efficacy of monotherapy with a single fresh fecal microbiota transplant (FMT) for recurrent ulcerative colitis (UC).

RESULTS: Twenty-six eligible patients were enrolled, and 6 patients were excluded. Ultimately, 20 patients were randomized to the FMT group (n = 10) and the control group (n = 10); 80% were females (F/M = 16/4), the mean age was 48 ± 14 years, and the mean duration was 6.4 ± 8.2 years. The mean length of post-FMT follow-up was 19.1 ± 10.1 months (6-38). No statistically significant differences in baseline demographic or clinical characteristics were found between the groups. Ninety percent of patients in the FMT group and 50% of patients in the control group met the primary endpoint at week 8. The Mayo score was significantly decreased compared with that of the control group (n = 10) when reassessed at week 4 (P = 0.001) and week 8 (P = 0.019) after FMT; there was no significant difference 6 months after treatment. The median remission time was 24 months (95% CI 68.26-131.7%) in both the FMT (range 6-38 months) and control groups (range 7-35 months), with no significant difference (P = 0.895). Participants tolerated FMT treatment, and no adverse events occurred during long-term follow-up, with one treatment-related significant adverse event (EBV infection) occurring within 2 weeks after FMT. Stool microbiota composition analysis indicated improved gut microbiota diversity after FMT, with expansion of stool-donor taxa. Bacteroidetes, Firmicutes and Proteobacteria were the dominant bacterial phyla of the gut microbiota in active UC patients. The relative abundance of Bacteroidetes decreased and that of Proteobacteria increased significantly in active UC patients compared with donors, while Firmicutes showed no significant changes. A single fresh FMT could effectively reconstruct the gut microbiota composition in patients with active UC and maintain stability, with increased Bacteroidetes and decreased Proteobacteria abundance. FMT significantly reduced the relative abundance of Escherichia and increased the relative abundance of Prevotella at the genus level. Pyruvate metabolism, glyoxylate and dicarboxylate metabolism, and pantothenate and CoA biosynthesis showed significant differences after transplantation.

CONCLUSIONS: Monotherapy with a single fresh FMT is an effective and safe strategy to induce long-term remission without drugs in patients with active UC and may be an alternative induction therapy for recurrent UC or even primary UC.}, } @article {pmid33462586, year = {2021}, author = {McGill, SK}, title = {Fecal Microbiota Transplant for Severe Clostridioides Difficile Infection: Let's Halt the Raging Fire.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciab047}, pmid = {33462586}, issn = {1537-6591}, } @article {pmid33459581, year = {2021}, author = {Lee, MW and Yeon, SH and Heo, BY and Kwon, J and Ryu, H and Lee, HJ and Yun, HJ and Jo, DY and Song, IC}, title = {Impact of pre-transplant use of antibiotics on the graft-versus-host disease in adult patients with hematological malignancies.}, journal = {Hematology (Amsterdam, Netherlands)}, volume = {26}, number = {1}, pages = {96-102}, doi = {10.1080/16078454.2021.1872957}, pmid = {33459581}, issn = {1607-8454}, abstract = {OBJECTIVES: Changes in fecal microbiota affect the incidence and extent of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Most patients with hematological malignancies receive antibiotics for the treatment of febrile neutropenia prior to allogeneic HSCT, and pre-transplant use of antibiotics may influence the fecal microbiota and GVHD.

METHODS: We retrospectively analysed consecutive adult patients with hematological malignancies who received allogeneic HSCT at Chungnam National University Hospital between 2007 and 2018. Pre-transplant use of antibiotics was defined as the use of antibiotics before conditioning chemotherapy.

RESULTS: This study included 131 patients with a median age of 46 (range, 18-71) years: 76 (58%) patients were AML, 28 (21.4%) with ALL, 23 (17.6%) with MDS, and 4 (3.1%) with CML. All patients received calcineurin inhibitors with short-course methotrexate for GVHD prophylaxis. A total of 31 (23.7%) patients received anti-thymocyte globulin. All patients received antibiotics prior to HSCT: 70 (53.4%) patients received glycopeptide, 114 (87.0%) received cefepime, 87 (66.4%) received piperacillin/tazobactam, and 51 (38.9%) received carbapenem. Patients who received glycopeptide had more frequently extensive chronic GVHD (cGVHD) than those who did not (51.1% vs. 28.1% at 5 years) and had more frequently cGVHD of the lung (34.8% vs. 15.8% at 5 years). Pre-transplant use of glycopeptide did not affect the overall survival (OS) or GVHD- and relapse-free survival (GRFS) (median OS; 49 months in glycopeptide group vs. not reached in non-glycopeptide group, p=0.475; median GRFS; 9 months in glycopeptide group vs. 16 months in non-glycopeptide group, p=0.092).

CONCLUSION: Pre-transplant use of glycopeptide tends to increase the incidence of extensive cGVHD.}, } @article {pmid33452411, year = {2021}, author = {Liu, Y and Fan, L and Cheng, Z and Yu, L and Cong, S and Hu, Y and Zhu, L and Zhang, B and Cheng, Y and Zhao, P and Zhao, X and Cheng, M}, title = {Fecal transplantation alleviates acute liver injury in mice through regulating Treg/Th17 cytokines balance.}, journal = {Scientific reports}, volume = {11}, number = {1}, pages = {1611}, pmid = {33452411}, issn = {2045-2322}, support = {81570543//National Nature Science Foundation of China/ ; }, abstract = {Changes in intestinal microecology during acute liver failure (ALF) directly affect the occurrence and development of the disease. The study aimed to investigate the relationship between the intestinal microbiota and the key immune cells. Fecal microbiota transplantation (FMT) was used to determine whether ALF can balance Th17/Treg cytokines. The relationship between gut microbiota and clinical indicators was analyzed. BALB/c mice were treated with D-galactosamine (D-GalN) to induce a murine ALF model. FMT to D-GalN mice was conducted to test for liver function indicators. Results showed that the proportions of Lachnospiraceae, Prevotella, S24-7, Odoribacter and Rikenellaceae in D-GalN mice with intestinal microbiota disorder were restored after FMT. Further, CIA analysis showed that bacteria had a covariant relationship with clinical indicators. Microbiota could account for changes in 49.9% of the overall clinical indicators. Adonis analysis showed that Ruminococcus, and Enterococcus have a greater impact on clinical indicators. FMT down-regulated the expression of IL-17A, TNF-α, and TGF-β, while up-regulated IL-10 and IL-22. Transplantation of feces from Saccharomyces boulardii donor mice improved GalN-induced liver damage. These findings indicate that FMT attenuates D-GalN-induced liver damage in mice, and a clinical trial is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with ALF.}, } @article {pmid33444574, year = {2021}, author = {Cook, L and Rees, WD and Wong, MQ and Peters, H and Levings, MK and Steiner, TS}, title = {Fecal microbiota transplant treatment for recurrent Clostridioides difficile infection enhances adaptive immunity to TcdB.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2021.01.009}, pmid = {33444574}, issn = {1528-0012}, } @article {pmid33444573, year = {2021}, author = {Saha, S and Mara, K and Pardi, DS and Khanna, S}, title = {Long-term Safety of Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2021.01.010}, pmid = {33444573}, issn = {1528-0012}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for treating recurrent Clostridioides difficile infection (CDI), with emerging data on intermediate and long-term safety.

METHODS: A prospective survey-based study was conducted (9/2012-6/2018) in patients undergoing FMT for recurrent CDI. Data on demographics and comorbidities were abstracted from medical records. Patients were contacted at 1 week, 1 month, 6 months, 1 year (short-term), ≥2 years post-FMT (long-term). Symptoms and new medical diagnoses were recorded at each time point. Data were weighted to account for survey non-response bias. Multivariate logistic regression models for adverse events were built using age (per 10-year increment), sex, time of survey and comorbidities. P<0.05 was considered statistically significant.

RESULTS: Overall, 609 patients underwent FMT; median age 56 years (range, 18-94), 64.8% were female, 22.8% had inflammatory bowel disease (IBD). At short-term follow up (n=609), >60% patients had diarrhea, <33% had constipation. At 1 year, 9.5% reported additional CDI episodes. On multivariable analysis, patients with IBD, dialysis dependent kidney disease and multiple FMTs had higher risk of diarrhea; risk of constipation was higher in females and lower in IBD (all p<0.05). For long-term follow up (n=447), median time of follow up was 3.7 years (range, 2.0-6.8). Overall, 73 new diagnoses were reported- 13% gastrointestinal, 10% weight gain, 11.8% new infections (all deemed unrelated to FMT). Median time to infections was 29 months (range, 0-73) post-FMT.

CONCLUSION: FMT appears safe with low risk of transmission of infections. Several new diagnoses were reported, which should be explored in future studies.}, } @article {pmid33444319, year = {2021}, author = {McKinney, CA and Bedenice, D and Pacheco, AP and Oliveira, BCM and Paradis, MR and Mazan, M and Widmer, G}, title = {Assessment of clinical and microbiota responses to fecal microbial transplantation in adult horses with diarrhea.}, journal = {PloS one}, volume = {16}, number = {1}, pages = {e0244381}, pmid = {33444319}, issn = {1932-6203}, support = {R21 AI125891/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND AND AIMS: Fecal microbial transplantation (FMT) is empirically implemented in horses with colitis to facilitate resolution of diarrhea. The purpose of this study was to assess FMT as a clinical treatment and modulator of fecal microbiota in hospitalized horses with colitis.

METHODS: A total of 22 horses with moderate to severe diarrhea, consistent with a diagnosis of colitis, were enrolled at two referral hospitals (L1: n = 12; L2: n = 10). FMT was performed in all 12 patients on 3 consecutive days at L1, while treatment at L2 consisted of standard care without FMT. Manure was collected once daily for 4 days from the rectum in all colitis horses, prior to FMT for horses at L1, and from each manure sample used for FMT. Fecal samples from 10 clinically healthy control horses housed at L2, and 30 healthy horses located at 5 barns in regional proximity to L1 were also obtained to characterize the regional healthy equine microbiome. All fecal microbiota were analyzed using 16S amplicon sequencing.

RESULTS AND CONCLUSIONS: As expected, healthy horses at both locations showed a greater α-diversity and lower β-diversity compared to horses with colitis. The fecal microbiome of healthy horses clustered by location, with L1 horses showing a higher prevalence of Kiritimatiellaeota. Improved manure consistency (lower diarrhea score) was associated with a greater α-diversity in horses with colitis at both locations (L1: r = -0.385, P = 0.006; L2: r = -0.479, P = 0.002). Fecal transplant recipients demonstrated a greater overall reduction in diarrhea score (median: 4±3 grades), compared to untreated horses (median: 1.5±3 grades, P = 0.021), with a higher incidence in day-over-day improvement in diarrhea (22/36 (61%) vs. 10/28 (36%) instances, P = 0.011). When comparing microbiota of diseased horses at study conclusion to that of healthy controls, FMT-treated horses showed a lower mean UniFrac distance (0.53±0.27) than untreated horses (0.62±0.26, P<0.001), indicating greater normalization of the microbiome in FMT-treated patients.}, } @article {pmid33443235, year = {2021}, author = {Cho, YS}, title = {Fecal Microbiota Transplantation Is Effective for the Treatment of Partially Treated Clostridioides difficile Infection.}, journal = {Gut and liver}, volume = {15}, number = {1}, pages = {1-2}, pmid = {33443235}, issn = {2005-1212}, } @article {pmid33442010, year = {2021}, author = {Stower, H}, title = {Microbiome transplant-induced response to immunotherapy.}, journal = {Nature medicine}, volume = {27}, number = {1}, pages = {21}, doi = {10.1038/s41591-020-01220-6}, pmid = {33442010}, issn = {1546-170X}, mesh = {Fecal Microbiota Transplantation ; Humans ; Immunotherapy ; *Melanoma ; *Microbiota ; }, } @article {pmid33441186, year = {2021}, author = {Yoshimatsu, Y and Mikami, Y and Kanai, T}, title = {Bacteriotherapy for inflammatory bowel disease.}, journal = {Inflammation and regeneration}, volume = {41}, number = {1}, pages = {3}, pmid = {33441186}, issn = {1880-9693}, support = {16gm1010003h0001//Japan Agency for Medical Research and Development/ ; 20gm1210001h0002//Japan Agency for Medical Research and Development/ ; NA//the Takeda Science Foundation/ ; NA//the Kanae Foundation for The Promotion of Medical Science/ ; 20H03666//Japan Society for the Promotion of Science/ ; 15H02534//Japan Society for the Promotion of Science/ ; 20H00536//Japan Society for the Promotion of Science/ ; NA//Mishima Kaiun Memorial Foundation/ ; NA//School of Medicine, Keio University/ ; }, abstract = {The number of patients with inflammatory bowel disease is rapidly increasing in developed countries. The main cause of this increase is thought not to be genetic, but secondary to rapidly modernized environmental change. Changes in the environment have been detrimental to enteric probiotics useful for fermentation, inducing an increase in pathobionts that survive by means other than fermentation. This dysregulated microbiota composition, the so-called dysbiosis, is believed to have increased the incidence of inflammatory bowel disease. Bacteriotherapy, a treatment that prophylactically and therapeutically corrects the composition of disturbed intestinal microbiota, is a promising recent development. In fact, fecal microbiome transplantation for recurrent Clostridioides difficile infection in 2013 was a significant contribution for bacteriotherapy. In this paper, we comprehensively review bacteriotherapy in an easy-to-understand format.}, } @article {pmid33439534, year = {2020}, author = {Zhao, HL and Chen, SZ and Xu, HM and Zhou, YL and He, J and Huang, HL and Xu, J and Nie, YQ}, title = {Efficacy and safety of fecal microbiota transplantation for treating patients with ulcerative colitis: A systematic review and meta-analysis.}, journal = {Journal of digestive diseases}, volume = {21}, number = {10}, pages = {534-548}, doi = {10.1111/1751-2980.12933}, pmid = {33439534}, issn = {1751-2980}, support = {//National Natural Science Foundation of China, Grant/Award Numbers: 81700487, 81871905; Guangdong Medical Science and Technology Research Fund, Grant/Award Number: A2019243; Fundamental Research Funds for the Central Universities, South China University of Technology, Grant/Award Number: 2018MS82; Guangzhou Planned Project of Science and Technology, Grant/Award Number: 202002030288; Innovative Clinical Technique of Guangzhou, Grant/Award Number: 2019GX05./ ; }, abstract = {OBJECTIVES: To assess the effect of donor selection, stool procedures and pretreatment with antibiotics on the efficacy and safety of fecal microbiota transplantation (FMT)-treated ulcerative colitis (UC).

METHODS: A systematic review and meta-analysis was conducted including studies on UC treated with FMT as the primary therapeutic agent published up to June 30, 2020. Primary end-point data included clinical remission (CR) or CR combined with endoscopic remission.

RESULTS: A total of 37 studies (seven random controlled trials [RCTs], five controlled and 25 uncontrolled cohort studies) and 959 patients with UC were enrolled. In controlled cohort studies and RCTs, FMT had a significantly greater benefit than placebo (pooled odds ratio [P-OR] 3.392, 95% CI 2.196-5.240, P < 0.001), with no heterogeneity (I2 = 0%). Furthermore, administration of FMT via the lower gastrointestinal (GI) tract was more effective in achieving CR than via the upper GI tract (44.3% vs 31.7%). The remission rate was also higher when the total stool dosage was over 275 g compared with less than 275 g (51.9% vs 29.5%). Overall, the incidence of serious adverse events of FMT was 5.9%. There was no significant difference between single and multiple donors, fresh and frozen stool sample used, and whether or not antibiotic pretreatment was administered before FMT.

CONCLUSION: FMT administration via the lower GI tract and using higher dosage appear to be effective and safe in inducing remission of active UC.}, } @article {pmid33439367, year = {2021}, author = {Hammeken, LH and Baunwall, SMD and Hvas, CL and Ehlers, LH}, title = {Health economic evaluations comparing faecal microbiota transplantation with antibiotics for treatment of recurrent Clostridioides difficile infection: a systematic review.}, journal = {Health economics review}, volume = {11}, number = {1}, pages = {3}, pmid = {33439367}, issn = {2191-1991}, support = {8056-00006B//Innovationsfonden/ ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is increasingly being used in the treatment of recurrent Clostridioides difficile infection (rCDI). Health economic evaluations may support decision-making regarding the implementation of FMT in clinical practice. Previous reviews have highlighted several methodological concerns in published health economic evaluations examining FMT. However, the impact of these concerns on the conclusions of the studies remains unclear.

AIMS: To present an overview and assess the methodological quality of health economic evaluations that compare FMT with antibiotics for treatment of rCDI. Furthermore, we aimed to evaluate the degree to which any methodological concerns would affect conclusions about the cost-effectiveness of FMT.

METHODS: We conducted a systematic literature review based on a search in seven medical databases up to 16 July 2020. We included research articles reporting on full health economic evaluations comparing FMT with antibiotic treatment for rCDI. General study characteristics and input estimates for costs, effectiveness and utilities were extracted from the articles. The quality of the studies was assessed by two authors using the Drummonds ten-point checklist.

RESULTS: We identified seven cost-utility analyses. All studies applied decision-analytic modelling and compared various FMT delivery methods with vancomycin, fidaxomicin, metronidazole or a combination of vancomycin and bezlotoxumab. The time horizons used in the analyses varied from 78 days to lifelong, and the perspectives differed between a societal, a healthcare system or a third-party payer perspective. The applied willingness-to-pay threshold ranged from 20,000 to 68,000 Great Britain pound sterling (GBP) per quality-adjusted life-year (QALY). FMT was considered the most cost-effective alternative in all studies. In five of the health economic evaluations, FMT was both more effective and cost saving than antibiotic treatment alternatives. The quality of the articles varied, and we identified several methodological concerns.

CONCLUSIONS: Economic evaluations consistently reported that FMT is a cost-effective and potentially cost-saving treatment for rCDI. Based on a comparison with recent evidence within the area, the multiple methodological concerns seem not to change this conclusion. Therefore, implementing FMT for rCDI in clinical practice should be strongly considered.}, } @article {pmid33437951, year = {2020}, author = {Baunwall, SMD and Lee, MM and Eriksen, MK and Mullish, BH and Marchesi, JR and Dahlerup, JF and Hvas, CL}, title = {Faecal microbiota transplantation for recurrent Clostridioides difficile infection: An updated systematic review and meta-analysis.}, journal = {EClinicalMedicine}, volume = {29-30}, number = {}, pages = {100642}, pmid = {33437951}, issn = {2589-5370}, abstract = {Background: Faecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (CDI), but inconsistent effect rates and uncertain evidence levels have warranted caution. To clarify, we aimed to establish the evidence of FMT for recurrent CDI, updated across different delivery methods, treatment regimens, and in comparison with standard antibiotics.

Methods: In this updated systematic review and meta-analysis, we searched PubMed, Scopus, Embase, Web of Science, Clinical Key, and Svemed+ for FMT literature published in English until November 11, 2019. We included observational and clinical trials with or without antibiotic comparators and excluded studies with below 8 weeks follow-up and fewer than 15 patients. The primary outcome was clinical outcome by week 8. We comprehensively extracted patient and procedural data. In a random-effects meta-analysis, we estimated the clinical effect for repeat or single FMT, different delivery methods, and versus antibiotics. We rated the evidence according to the Cochrane and GRADE methods. The PROSPERO preregistration number is CRD42020158112.

Findings: Of 1816 studies assessed, 45 studies were included. The overall clinical effect week 8 following repeat FMT (24 studies, 1855 patients) was 91% (95% CI: 89-94%, I2=53%) and 84% (80-88%, I2=86%) following single FMT (43 studies, 2937 patients). Delivery by lower gastrointestinal endoscopy was superior to all other delivery methods, and repeat FMT significantly increased the treatment effect week 8 (P<0·001). Compared with vancomycin, the number needed to treat (NNT) for repeat FMT was 1·5 (1·3-1·9, P<0·001) and 2.9 (1·5-37·1, P=0·03) for single FMT. Repeat FMT had high quality of evidence.

Interpretation: High-quality evidence supports FMT is effective for recurrent CDI, but its effect varies with the delivery method and the number of administrations. The superior NNT for FMT compared with antibiotics suggests that patients may benefit from advancing FMT to all instances of recurrent CDI.

Funding: Innovation Fund Denmark (j.no. 8056-00006B).}, } @article {pmid33436010, year = {2021}, author = {Liu, J and Liu, C and Yue, J}, title = {Radiotherapy and the gut microbiome: facts and fiction.}, journal = {Radiation oncology (London, England)}, volume = {16}, number = {1}, pages = {9}, pmid = {33436010}, issn = {1748-717X}, support = {81871895//National Natural Science Foundation of China/ ; 2019RC003//Young Taishan Scholars and Academic Promotion Program of Shandong First Medical University/ ; }, abstract = {An ever-growing body of evidence has linked the gut microbiome with both the effectiveness and the toxicity of cancer therapies. Radiotherapy is an effective way to treat tumors, although large variations exist among patients in tumor radio-responsiveness and in the incidence and severity of radiotherapy-induced side effects. Relatively little is known about whether and how the microbiome regulates the response to radiotherapy. Gut microbiota may be an important player in modulating "hot" versus "cold" tumor microenvironment, ultimately affecting treatment efficacy. The interaction of the gut microbiome and radiotherapy is a bidirectional function, in that radiotherapy can disrupt the microbiome and those disruptions can influence the effectiveness of the anticancer treatments. Limited data have shown that interactions between the radiation and the microbiome can have positive effects on oncotherapy. On the other hand, exposure to ionizing radiation leads to changes in the gut microbiome that contribute to radiation enteropathy. The gut microbiome can influence radiation-induced gastrointestinal mucositis through two mechanisms including translocation and dysbiosis. We propose that the gut microbiome can be modified to maximize the response to treatment and minimize adverse effects through the use of personalized probiotics, prebiotics, or fecal microbial transplantation. 16S rRNA sequencing is the most commonly used approach to investigate distribution and diversity of gut microbiome between individuals though it only identifies bacteria level other than strain level. The functional gut microbiome can be studied using methods involving metagenomics, metatranscriptomics, metaproteomics, as well as metabolomics. Multiple '-omic' approaches can be applied simultaneously to the same sample to obtain integrated results. That said, challenges and remaining unknowns in the future that persist at this time include the mechanisms by which the gut microbiome affects radiosensitivity, interactions between the gut microbiome and combination treatments, the role of the gut microbiome with regard to predictive and prognostic biomarkers, the need for multi "-omic" approach for in-depth exploration of functional changes and their effects on host-microbiome interactions, and interactions between gut microbiome, microbial metabolites and immune microenvironment.}, } @article {pmid33435800, year = {2021}, author = {Lau, HCH and Sung, JJ and Yu, J}, title = {Gut microbiota: impacts on gastrointestinal cancer immunotherapy.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-21}, pmid = {33435800}, issn = {1949-0984}, abstract = {The association of gut microbiota with gastrointestinal carcinogenesis has been heavily investigated since the recent advance in sequencing technology. Accumulating evidence has revealed the critical roles of commensal microbes in cancer progression. Given by its importance, emerging studies have focussed on targeting microbiota to ameliorate therapeutic effectiveness. It is now clear that the microbial community is closely related to the efficacy of chemotherapy, while the correlation of microbiota with immunotherapy is much less studied. Herein, we review the up-to-date findings on the influence of gut microbiota on three common immunotherapies including adoptive cell transfer, immune checkpoint blockade, and CpG-oligodeoxynucleotide therapy. We then explore three microbiota-targeted strategies that may improve treatment efficacy, involving dietary intervention, probiotics supplementation, and fecal microbiota transplantation.}, } @article {pmid33432923, year = {2021}, author = {Tyagi, AM and Darby, TM and Hsu, E and Yu, M and Pal, S and Dar, H and Li, JY and Adams, J and Jones, RM and Pacifici, R}, title = {The gut microbiota is a transmissible determinant of skeletal maturation.}, journal = {eLife}, volume = {10}, number = {}, pages = {}, pmid = {33432923}, issn = {2050-084X}, support = {DK112946/NH/NIH HHS/United States ; DK108842/NH/NIH HHS/United States ; RR028009/NH/NIH HHS/United States ; DK098391/NH/NIH HHS/United States ; }, abstract = {Genetic factors account for the majority of the variance of human bone mass, but the contribution of non-genetic factors remains largely unknown. By utilizing maternal/offspring transmission, cohabitation, or fecal material transplantation (FMT) studies, we investigated the influence of the gut microbiome on skeletal maturation. We show that the gut microbiome is a communicable regulator of bone structure and turnover in mice. In addition, we found that the acquisition of a specific bacterial strain, segmented filamentous bacteria (SFB), a gut microbe that induces intestinal Th17 cell expansion, was sufficient to negatively impact skeletal maturation. These findings have significant translational implications, as the identification of methods or timing of microbiome transfer may lead to the development of bacteriotherapeutic interventions to optimize skeletal maturation in humans. Moreover, the transfer of SFB-like microbes capable of triggering the expansion of human Th17 cells during therapeutic FMT procedures could lead to significant bone loss in fecal material recipients.}, } @article {pmid33428780, year = {2021}, author = {Citraro, R and Lembo, F and De Caro, C and Tallarico, M and Coretti, L and Iannone, LF and Leo, A and Palumbo, D and Cuomo, M and Buommino, E and Nesci, V and Marascio, N and Iannone, M and Quirino, A and Russo, R and Calignano, A and Constanti, A and Russo, E and De Sarro, G}, title = {First evidence of altered microbiota and intestinal damage and their link to absence epilepsy in a genetic animal model, the WAG/Rij rat.}, journal = {Epilepsia}, volume = {}, number = {}, pages = {}, doi = {10.1111/epi.16813}, pmid = {33428780}, issn = {1528-1167}, support = {2015XSZ9A2//Italian Ministry of University and Research (MIUR)/ ; 2017B9NCSX//Italian Ministry of University and Research (MIUR)/ ; 2017YZF7MA//Italian Ministry of University and Research (MIUR)/ ; GR-2013-02355028//Italian Ministry of Health/ ; }, abstract = {OBJECTIVE: A large number of studies have highlighted the important role of the gut microbiota in the pathophysiology of neurological disorders, suggesting that its manipulation might serve as a treatment strategy. We hypothesized that the gut microbiota participates in absence seizure development and maintenance in the WAG/Rij rat model and tested this hypothesis by evaluating potential gut microbiota and intestinal alterations in the model, as well as measuring the impact of microbiota manipulation using fecal microbiota transplantation (FMT).

METHODS: Initially, gut microbiota composition and intestinal histology of WAG/Rij rats (a well-recognized genetic model of absence epilepsy) were studied at 1, 4, and 8 months of age in comparison to nonepileptic Wistar rats. Subsequently, in a second set of experiments, at 6 months of age, untreated Wistar or WAG/Rij rats treated with ethosuximide (ETH) were used as gut microbiota donors for FMT in WAG/Rij rats, and electroencephalographic (EEG) recordings were obtained over 4 weeks. At the end of FMT, stool and gut samples were collected, absence seizures were measured on EEG recordings, and microbiota analysis and histopathological examinations were performed.

RESULTS: Gut microbiota analysis showed differences in beta diversity and specific phylotypes at all ages considered and significant variances in the Bacteroidetes/Firmicutes ratio between Wistar and WAG/Rij rats. FMT, from both Wistar and ETH-treated WAG/Rij donors to WAG/Rij rats, significantly decreased the number and duration of seizures. Histological results indicated that WAG/Rij rats were characterized by intestinal villi disruption and inflammatory infiltrates already at 1 month of age, before seizure occurrence; FMT partially restored intestinal morphology while also significantly modifying gut microbiota and concomitantly reducing absence seizures.

SIGNIFICANCE: Our results demonstrate for the first time that the gut microbiota is modified and contributes to seizure occurrence in a genetic animal model of absence epilepsy and that its manipulation may be a suitable therapeutic target for absence seizure management.}, } @article {pmid33427531, year = {2021}, author = {Khanna, S}, title = {Advances in Clostridioides difficile therapeutics.}, journal = {Expert review of anti-infective therapy}, volume = {}, number = {}, pages = {1-4}, doi = {10.1080/14787210.2021.1874919}, pmid = {33427531}, issn = {1744-8336}, } @article {pmid33424650, year = {2020}, author = {Zhao, HJ and Luo, X and Shi, YC and Li, JF and Pan, F and Ren, RR and Peng, LH and Shi, XY and Yang, G and Wang, J and Hu, LY and Zou, LP and Yang, YS}, title = {The Efficacy of Fecal Microbiota Transplantation for Children With Tourette Syndrome: A Preliminary Study.}, journal = {Frontiers in psychiatry}, volume = {11}, number = {}, pages = {554441}, pmid = {33424650}, issn = {1664-0640}, abstract = {Therapies for Tourette syndrome (TS) are insufficient, and novel therapies are needed. Fecal microbiota transplantation (FMT) has been a potential therapy for several neurological diseases. Here, we report a preliminary study to investigate the effects of FMT on patients with TS. Five patients with TS received a single administration of FMT via endoscopy. Tic symptoms were assessed by Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) and adverse effects were recorded at week 8 following FMT. Lipopolysaccharide (LPS) levels and 14 cytokines levels were measured. The microbiota profile in feces were analyzed by shotgun metagenomics. Four patients (4/5) responded positively to FMT (YGTSS-TTS reduction rate >25%) at week 8 with high safety. The levels of LPS and cytokines varied after FMT. FMT shifted the composition of the gut microbiota in patients close to that of the donor and continuously changed the abundance of Bacteroides coprocola, Dialister succinatiphilus and Bacteroides vulgatus. The restoration of B.coprocola was correlated with the improvement in tic symptoms (Spearman R = -0.900, P = 0.037). In conclusion, FMT was indicated a potential effective and safe alternative for patients with TS. However, larger clinical trials are needed to confirm the influence of microbiota in TS. Trial Registration: chictr.org.cn Identifier: ChiCTR-IIR-17011871, URL: http://www.chictr.org.cn/showproj.aspx?proj=19941.}, } @article {pmid33422641, year = {2021}, author = {Pu, Y and Tan, Y and Qu, Y and Chang, L and Wang, S and Wei, Y and Wang, X and Hashimoto, K}, title = {A role of the subdiaphragmatic vagus nerve in depression-like phenotypes in mice after fecal microbiota transplantation from Chrna7 knock-out mice with depression-like phenotypes.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2020.12.032}, pmid = {33422641}, issn = {1090-2139}, abstract = {The α7 subtype of the nicotinic acetylcholine receptor (α7 nAChR: coded by Chrna7) regulates the cholinergic ascending anti-inflammatory pathway involved in depression. We previously reported that Chrna7 knock-out (KO) mice show depression-like phenotypes through systemic inflammation. In this study, we investigated whether fecal microbiota transplantation (FMT) from Chrna7 KO mice causes depression-like phenotypes in mice treated with an antibiotic cocktail (ABX). Chrna7 KO mice with depression-like phenotypes show an abnormal gut microbiota composition, although the alpha diversity and beta diversity were not altered. FMT from Chrna7 KO mice caused depression-like phenotypes, systemic inflammation, and downregulation of synaptic proteins in the prefrontal cortex (PFC) in the ABX-treated mice compared to FMT from the control mice. The boxplots representing the FMT group from the KO mice were distanced from those representing the FMT group from the control mice in an unweighted UniFrac distance analysis. We found differences in abundance for several bacteria in the FMT group from the KO mice at the taxonomic level when compared with the other group. Interestingly, subdiaphragmatic vagotomy significantly blocked the development of depression-like phenotypes in the ABX-treated mice after FMT from Chrna7 KO mice. These data suggest that FMT from Chrna7 KO mice produce depression-like phenotypes in ABX-treated mice via the subdiaphragmatic vagus nerve. The brain-gut-microbiota axis association with the subdiaphragmatic vagus nerve plays an important role in the development of depression.}, } @article {pmid33420959, year = {2021}, author = {Allegretti, JR and Kassam, Z and Hurtado, J and Marchesi, JR and Mullish, BH and Chiang, A and Thompson, CC and Cummings, BP}, title = {Impact of fecal microbiota transplantation with capsules on the prevention of metabolic syndrome among patients with obesity.}, journal = {Hormones (Athens, Greece)}, volume = {}, number = {}, pages = {}, pmid = {33420959}, issn = {2520-8721}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; Junior Faculty Developement Award//Brigham and Women's Hospital/ ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) has been studied for the treatment of metabolic syndrome with varying success. However, the possibility of utilizing FMT to prevent metabolic syndrome is to date unknown.

METHODS: Secondary analysis of a previously published double-blind, randomized, placebo-controlled pilot trial of FMT in obese metabolically healthy patients was conducted. Post-prandial glucose and insulin levels were measured (NCT02741518).

RESULTS: A total of 22 patients were enrolled, 11 in each arm. There were no baseline differences in the area under the curve (AUC) of glucose or insulin in the FMT group compared to placebo. There was a significant change in glucose AUC at week 12 compared to baseline, and in the insulin AUC at week 6 compared to baseline in the FMT group vs. placebo (change in glucose AUC (mg/dl × 60 min): 579 vs 1978, p = 0.03) (change in insulin AUC (μU/ml × 60 min): 137 vs 2728, p = 0.01).

CONCLUSIONS: These data suggest that FMT may have a potential role in preventing the development of metabolic syndrome in patients with obesity.}, } @article {pmid33420064, year = {2021}, author = {Kim, HS and Whon, TW and Sung, H and Jeong, YS and Jung, ES and Shin, NR and Hyun, DW and Kim, PS and Lee, JY and Lee, CH and Bae, JW}, title = {Longitudinal evaluation of fecal microbiota transplantation for ameliorating calf diarrhea and improving growth performance.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {161}, pmid = {33420064}, issn = {2041-1723}, mesh = {Animals ; Bacteroidaceae/genetics/isolation & purification ; Cattle/*growth & development/microbiology ; Cattle Diseases/blood/metabolism/microbiology/*therapy ; DNA, Bacterial/isolation & purification ; Diarrhea/blood/metabolism/microbiology/*therapy ; Fecal Microbiota Transplantation/*veterinary ; Feces/microbiology ; Female ; Follow-Up Studies ; Gastrointestinal Microbiome/*genetics ; Genomics ; Male ; Metabolomics ; RNA, Ribosomal, 16S/genetics ; Treatment Outcome ; }, abstract = {Calf diarrhea is associated with enteric infections, and also provokes the overuse of antibiotics. Therefore, proper treatment of diarrhea represents a therapeutic challenge in livestock production and public health concerns. Here, we describe the ability of a fecal microbiota transplantation (FMT), to ameliorate diarrhea and restore gut microbial composition in 57 growing calves. We conduct multi-omics analysis of 450 longitudinally collected fecal samples and find that FMT-induced alterations in the gut microbiota (an increase in the family Porphyromonadaceae) and metabolomic profile (a reduction in fecal amino acid concentration) strongly correlate with the remission of diarrhea. During the continuous follow-up study over 24 months, we find that FMT improves the growth performance of the cattle. This first FMT trial in ruminants suggest that FMT is capable of ameliorating diarrhea in pre-weaning calves with alterations in their gut microbiota, and that FMT may have a potential role in the improvement of growth performance.}, } @article {pmid33418488, year = {2021}, author = {Iyama, S and Tatsumi, H and Shiraishi, T and Yoshida, M and Tatekoshi, A and Endo, A and Ishige, T and Shiwa, Y and Ibata, S and Goto, A and Nagashima, K and Horiguchi, H and Fujita, C and Ikeda, H and Takada, K and Nobuoka, T and Kamihara, Y and Kikuchi, S and Sato, T and Ohnishi, H and Yokota, SI and Kobune, M}, title = {Possible clinical outcomes using early enteral nutrition in individuals with allogeneic hematopoietic stem cell transplantation: A single-center retrospective study.}, journal = {Nutrition (Burbank, Los Angeles County, Calif.)}, volume = {83}, number = {}, pages = {111093}, doi = {10.1016/j.nut.2020.111093}, pmid = {33418488}, issn = {1873-1244}, abstract = {OBJECTIVES: Intensive nutritional support during allogeneic hematopoietic stem cell transplantation (allo-HSCT) yields improved clinical outcomes. However, the clinical implications of early enteral nutrition (EN) in allo-HSCT remain unclear. This retrospective study was conducted to determine the significance of early EN in individuals who underwent allo-HSCT, and the association between early nutritional intervention and clinical outcomes, including the status of the intestinal microbiome.

METHODS: Thirty-one participants received EN before conditioning. The intestinal microbiota was examined by meta 16S rRNA gene sequencing of fecal samples.

RESULTS: The median body mass variation was only -0.35 kg on day 60. The probability of 2-y overall survival was 61.1%. The cumulative incidence of treatment-related mortality was 17.4%, and those of acute graft-versus-host disease were 32.3% (grades II-IV) and 3.2% (grades III-IV). Chronic graft-versus-host disease was observed in four participants. Dysbiosis of the intestines and acute graft-versus-host disease occurred simultaneously, and Enterococcus species were abundant.

CONCLUSIONS: Our results suggest that early nutritional support can improve the outcomes for individuals who have undergone allo-HSCT and can maintain homeostasis of their intestinal microbiome. Future prospective clinical trials are required to elucidate the role of EN in allo-HSCT and the association between the intestinal microbiome and EN.}, } @article {pmid33416044, year = {2020}, author = {Carbone, EA and D'Amato, P and Vicchio, G and De Fazio, P and Segura-Garcia, C}, title = {A systematic review on the role of microbiota in the pathogenesis and treatment of eating disorders.}, journal = {European psychiatry : the journal of the Association of European Psychiatrists}, volume = {64}, number = {1}, pages = {e2}, doi = {10.1192/j.eurpsy.2020.109}, pmid = {33416044}, issn = {1778-3585}, abstract = {BACKGROUND: There is growing interest in new factors contributing to the genesis of eating disorders (EDs). Research recently focused on the study of microbiota. Dysbiosis, associated with a specific genetic susceptibility, may contribute to the development of anorexia nervosa (AN), bulimia nervosa, or binge eating disorder, and several putative mechanisms have already been identified. Diet seems to have an impact not only on modification of the gut microbiota, facilitating dysbiosis, but also on its recovery in patients with EDs.

METHODS: This systematic review based on the PICO strategy searching into PubMed, EMBASE, PsychINFO, and Cochrane Library examined the literature on the role of altered microbiota in the pathogenesis and treatment of EDs.

RESULTS: Sixteen studies were included, mostly regarding AN. Alpha diversity and short-chain fatty acid (SCFA) levels were lower in patients with AN, and affective symptoms and ED psychopathology seem related to changes in gut microbiota. Microbiota-derived proteins stimulated the autoimmune system, altering neuroendocrine control of mood and satiety in EDs. Microbial richness increased in AN after weight regain on fecal microbiota transplantation.

CONCLUSIONS: Microbiota homeostasis seems essential for a healthy communication network between gut and brain. Dysbiosis may promote intestinal inflammation, alter gut permeability, and trigger immune reactions in the hunger/satiety regulation center contributing to the pathophysiological development of EDs. A restored microbial balance may be a possible treatment target for EDs. A better and more in-depth characterization of gut microbiota and gut-brain crosstalk is required. Future studies may deepen the therapeutic and preventive role of microbiota in EDs.}, } @article {pmid33409398, year = {2021}, author = {Kwong, EK and Puri, P}, title = {Gut microbiome changes in Nonalcoholic fatty liver disease & alcoholic liver disease.}, journal = {Translational gastroenterology and hepatology}, volume = {6}, number = {}, pages = {3}, pmid = {33409398}, issn = {2415-1289}, support = {K23 AA021179/AA/NIAAA NIH HHS/United States ; }, abstract = {Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are some of the most common liver diseases worldwide. The human gut microbiome is dynamic and shifts in bacterial composition have been implicated in many diseases. Studies have shown that there is a shift in bacterial overgrowth favoring pro-inflammatory mediators in patients with advanced disease progression such as cirrhosis. Further investigation demonstrated that the transplantation of gut microbiota from advanced liver disease patients can reproduce severe liver inflammation and injury in mice. Various techniques in manipulating the gut microbiota have been attempted including fecal transplantation and probiotics. This review focuses on the changes in the gut microbiota as well as emerging lines of microbiome work with respect to NAFLD and ALD.}, } @article {pmid33405294, year = {2020}, author = {Donovan, C and Liu, G and Shen, S and Marshall, JE and Kim, RY and Alemao, CA and Budden, KF and Choi, JP and Kohonen-Corish, M and El-Omar, EM and Yang, IA and Hansbro, PM}, title = {The role of the microbiome and the NLRP3 inflammasome in the gut and lung.}, journal = {Journal of leukocyte biology}, volume = {108}, number = {3}, pages = {925-935}, doi = {10.1002/JLB.3MR0720-472RR}, pmid = {33405294}, issn = {1938-3673}, mesh = {Aging/immunology ; Air Pollutants/toxicity ; Animals ; Asthma/immunology ; Cigarette Smoking/immunology ; Colitis/immunology/microbiology/therapy ; Dysbiosis/immunology ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*immunology ; Heterocyclic Compounds, 4 or More Rings/pharmacology ; Humans ; Inflammasomes/*immunology ; Inflammation/*immunology ; Intestines/*immunology ; Lung/*immunology ; Mice ; Mice, Knockout ; NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors/deficiency/*physiology ; Pneumonia, Bacterial/immunology ; Pneumonia, Viral/immunology ; Pulmonary Disease, Chronic Obstructive/immunology ; Specific Pathogen-Free Organisms ; Sulfones/pharmacology ; Symbiosis ; }, abstract = {The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, is one of the most well-characterized inflammasomes, activated by pathogen-associated molecular patterns and damage-associated molecular patterns, including from commensal or pathogenic bacterial and viral infections. The NLRP3 inflammasome promotes inflammatory cell recruitment and regulates immune responses in tissues such as the gastrointestinal tract and the lung, and is involved in many diseases that affect the gut and lung. Recently, the microbiome in the gut and the lung, and the crosstalk between these organs (gut-lung axis), has been identified as a potential mechanism that may influence disease in a bidirectional manner. In this review, we focus on themes presented in this area at the 2019 World Congress on Inflammation. We discuss recent evidence on how the microbiome can affect NLRP3 inflammasome responses in the gut and lung, the role of this inflammasome in regulating gut and lung inflammation in disease, and its potential role in the gut-lung axis. We highlight the exponential increase in our understanding of the NLRP3 inflammasome due to the synthesis of the NLRP3 inflammasome inhibitor, MCC950, and propose future studies that may further elucidate the roles of the NLRP3 inflammasome in gut and lung diseases.}, } @article {pmid33399770, year = {2020}, author = {Quera, R and Sedano, R and Núñez, P}, title = {[Is fecal microbiota transplantation currently a therapeutic option in patients with irritable bowel syndrome?].}, journal = {Revista medica de Chile}, volume = {148}, number = {5}, pages = {713-714}, doi = {10.4067/S0034-98872020000500713}, pmid = {33399770}, issn = {0717-6163}, mesh = {*Fecal Microbiota Transplantation ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/microbiology/*therapy ; Treatment Outcome ; }, } @article {pmid33399007, year = {2021}, author = {Ramírez-Macías, I and Orenes-Piñero, E and Camelo-Castillo, A and Rivera-Caravaca, JM and López-García, C and Marín, F}, title = {Novel insights in the relationship of gut microbiota and coronary artery diseases.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-13}, doi = {10.1080/10408398.2020.1868397}, pmid = {33399007}, issn = {1549-7852}, abstract = {Atherosclerosis is a chronic, progressive, inflammatory disease in the vasculature and is common in both coronary and peripheral arteries. Human beings harbor a complex and dynamic population of microorganisms defined as the microbiota. Importantly, alterations in the bacterial composition (dysbiosis) and the metabolic compounds produced by these bacteria have been associated with the pathogenesis of many inflammatory diseases and infections. There is also a close relationship between intestinal microbiota and cardiovascular diseases. The aim of this review was to analyze how changes in the gut microbiota and their metabolites might affect coronary artery diseases. The most representative groups of bacteria that make up the intestinal microbiota are altered in coronary artery disease patients, resulting in a decrease in Bacteroidetes and an increase in Firmicutes. In relation to metabolites, trimethylamine-N-oxide plays an important role in atherosclerosis and may act as a cardiovascular risk predictor. In addition, the use of probiotics, prebiotics, diet modulation, and fecal transplantation, which may represent alternative treatments for these diseases, is thoroughly discussed. Finally, the role of lipid-lowering treatments is also analyzed as they may affect and alter the gut microbiota and, conversely, gut microbiota diversity could be associated with resistance or sensitivity to these treatments.}, } @article {pmid33397897, year = {2021}, author = {Zhang, F and Zuo, T and Yeoh, YK and Cheng, FWT and Liu, Q and Tang, W and Cheung, KCY and Yang, K and Cheung, CP and Mo, CC and Hui, M and Chan, FKL and Li, CK and Chan, PKS and Ng, SC}, title = {Longitudinal dynamics of gut bacteriome, mycobiome and virome after fecal microbiota transplantation in graft-versus-host disease.}, journal = {Nature communications}, volume = {12}, number = {1}, pages = {65}, pmid = {33397897}, issn = {2041-1723}, mesh = {Adolescent ; Biodiversity ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Graft vs Host Disease/*microbiology/*virology ; Humans ; Male ; Microbiota ; *Mycobiome ; *Virome ; }, abstract = {Fecal microbiota transplant (FMT) has emerged as a potential treatment for severe colitis associated with graft-versus-host disease (GvHD) following hematopoietic stem cell transplant. Bacterial engraftment from FMT donor to recipient has been reported, however the fate of fungi and viruses after FMT remains unclear. Here we report longitudinal dynamics of the gut bacteriome, mycobiome and virome in a teenager with GvHD after receiving four doses of FMT at weekly interval. After serial FMTs, the gut bacteriome, mycobiome and virome of the patient differ from compositions before FMT with variable temporal dynamics. Diversity of the gut bacterial community increases after each FMT. Gut fungal community initially shows expansion of several species followed by a decrease in diversity after multiple FMTs. In contrast, gut virome community varies substantially over time with a stable rise in diversity. The bacterium, Corynebacterium jeikeium, and Torque teno viruses, decrease after FMTs in parallel with an increase in the relative abundance of Caudovirales bacteriophages. Collectively, FMT may simultaneously impact on the various components of the gut microbiome with distinct effects.}, } @article {pmid33387515, year = {2020}, author = {Olesen, SW}, title = {Fecal microbiota transplantation "donor effects" are not clinically relevant for Clostridioides difficile infection.}, journal = {Gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1053/j.gastro.2020.12.057}, pmid = {33387515}, issn = {1528-0012}, } @article {pmid33387212, year = {2021}, author = {Zhou, G and Zeng, J and Peng, L and Wang, L and Zheng, W and Di Wu, and Yang, Y}, title = {Fecal microbiota transplantation for membranous nephropathy.}, journal = {CEN case reports}, volume = {}, number = {}, pages = {}, pmid = {33387212}, issn = {2192-4449}, abstract = {Membranous nephropathy is a pathological type of nephrotic syndrome. Current treatments including supportive therapy, corticosteroids, immunosuppressive agents are not effective for all patients. New therapies are needed to treat the disease safely and effectively. Gut microbiota may contribute to the pathogenesis of this disease. Fecal microbiota transplantation (FMT) has made achievements in many diseases. Here, we report a case in which FMT is used to treat a patient with membranous nephropathy and chronic diarrhea, whose symptoms ameliorated and renal function improved.}, } @article {pmid33382952, year = {2021}, author = {Brunse, A and Offersen, SM and Mosegaard, JJ and Deng, L and Damborg, P and Nielsen, DS and Sangild, PT and Thymann, T and Nguyen, DN}, title = {Enteral broad-spectrum antibiotics antagonize the effect of fecal microbiota transplantation in preterm pigs.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-16}, pmid = {33382952}, issn = {1949-0984}, abstract = {Preterm infants are at risk of multiple morbidities including necrotizing enterocolitis (NEC). Suspected NEC patients receive intravenous antibiotics (AB) to prevent sepsis, although enteral AB is arguably more effective at reducing NEC but is rarely used due to the risk of AB resistance. Fecal microbiota transplantation (FMT) has shown protective effects against NEC in animal experiments, but the interaction between AB and FMT has not been investigated in neonates. We hypothesized that administration of enteral AB followed by rectal FMT would effectively prevent NEC with negligible changes in AB resistance and systemic immunity. Using preterm piglets, we examined host and gut microbiota responses to AB, FMT, or a sequential combination thereof, with emphasis on NEC development. In a saline-controlled experiment, preterm piglets (n = 67) received oro-gastric neomycin (50 mg/kg/d) and amoxicillin-clavulanate (50/12.5 mg/kg/d) (hereafter AB) for four days after cesarean delivery, and were subsequently given rectal FMT from healthy suckling piglet donors. Whereas AB protected the stomach and small intestine, and FMT primarily protected the colon, the sequential combination treatment surprisingly provided no NEC protection. Furthermore, minor changes in the gut microbiota composition were observed in response to either treatment, although AB treatment decreased species diversity and increased AB resistance among coliform bacteria and Enterococci, which were both partly reversed by FMT. Besides, enteral AB treatment suppressed cellular and functional systemic immune development, which was not prevented by subsequent FMT. We discovered an antagonistic relationship between enteral AB and FMT in terms of NEC development. The outcome may depend on choice of AB compounds, FMT composition, doses, treatment duration, and administration routes, but these results challenge the applicability of enteral AB and FMT in preterm infants.}, } @article {pmid33382932, year = {2020}, author = {Chang, JT}, title = {Pathophysiology of Inflammatory Bowel Diseases.}, journal = {The New England journal of medicine}, volume = {383}, number = {27}, pages = {2652-2664}, doi = {10.1056/NEJMra2002697}, pmid = {33382932}, issn = {1533-4406}, mesh = {Fecal Microbiota Transplantation ; Host Microbial Interactions/physiology ; Humans ; Inflammatory Bowel Diseases/genetics/immunology/*physiopathology/therapy ; Interleukins/physiology ; Intestinal Mucosa/*immunology/physiopathology ; T-Lymphocytes/physiology ; }, } @article {pmid33382364, year = {2021}, author = {Xia, WJ and Xu, ML and Yu, XJ and Du, MM and Li, XH and Yang, T and Li, L and Li, Y and Kang, KB and Su, Q and Xu, JX and Shi, XL and Wang, XM and Li, HB and Kang, YM}, title = {Antihypertensive effects of exercise involve reshaping of gut microbiota and improvement of gut-brain axis in spontaneously hypertensive rat.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-24}, pmid = {33382364}, issn = {1949-0984}, abstract = {Exercise (Ex) has long been recognized to produce beneficial effects on hypertension (HTN). This coupled with evidence of gut dysbiosis and an impaired gut-brain axis led us to hypothesize that reshaping of gut microbiota and improvement in impaired gut-brain axis would, in part, be associated with beneficial influence of exercise. Male spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats were randomized into sedentary, trained, and detrained groups. Trained rats underwent moderate-intensity exercise for 12 weeks, whereas, detrained groups underwent 8 weeks of moderate-intensity exercise followed by 4 weeks of detraining. Fecal microbiota, gut pathology, intestinal inflammation, and permeability, brain microglia and neuroinflammation were analyzed. We observed that exercise training resulted in a persistent decrease in systolic blood pressure in the SHR. This was associated with increase in microbial α diversity, altered β diversity, and enrichment of beneficial bacterial genera. Furthermore, decrease in the number of activated microglia, neuroinflammation in the hypothalamic paraventricular nucleus, improved gut pathology, inflammation, and permeability were also observed in the SHR following exercise. Interestingly, short-term detraining did not abolish these exercise-mediated improvements. Finally, fecal microbiota transplantation from exercised SHR into sedentary SHR resulted in attenuated SBP and an improved gut-brain axis. These observations support our concept that an impaired gut-brain axis is linked to HTN and exercise ameliorates this impairment to induce antihypertensive effects.}, } @article {pmid33382360, year = {2021}, author = {Huus, KE and Frankowski, M and Pučić-Baković, M and Vučković, F and Lauc, G and Mullish, BH and Marchesi, JR and Monaghan, TM and Kao, D and Finlay, BB}, title = {Changes in IgA-targeted microbiota following fecal transplantation for recurrent Clostridioides difficile infection.}, journal = {Gut microbes}, volume = {13}, number = {1}, pages = {1-12}, pmid = {33382360}, issn = {1949-0984}, abstract = {Secretory immunoglobulin A (IgA) interacts with intestinal microbiota and promotes mucosal homeostasis. IgA-bacteria interactions are altered during inflammatory diseases, but how these interactions are shaped by bacterial, host, and environmental factors remains unclear. In this study, we utilized IgA-SEQ to profile IgA-bound fecal bacteria in 48 recurrent Clostridioides difficile patients before and after successful fecal microbiota transplantation (FMT) to gain further insight. Prior to FMT, Escherichia coli was the most highly IgA-targeted taxon; following restoration of the microbiota by FMT, highly IgA-targeted taxa included multiple Firmicutes species. Post-FMT IgA-targeting was unaffected by the route of FMT delivery (colonoscopy versus capsule), suggesting that both methods lead to the establishment of healthy immune-bacterial interactions in the gut. Interestingly, IgA-targeting in FMT recipients closely resembled the IgA-targeting patterns of the donors, and fecal donor identity was significantly associated with IgA-targeting of the recipient microbiota. These data support the concept that intrinsic bacterial properties drive IgA recognition across genetically distinct human hosts. Together, this study suggests that IgA-bacterial interactions are reestablished in human FMT recipients to resemble that of the healthy fecal donor.}, } @article {pmid33382357, year = {2020}, author = {Lu, XY and Han, B and Deng, X and Deng, SY and Zhang, YY and Shen, PX and Hui, T and Chen, RH and Li, X and Zhang, Y}, title = {Pomegranate peel extract ameliorates the severity of experimental autoimmune encephalomyelitis via modulation of gut microbiota.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1857515}, pmid = {33382357}, issn = {1949-0984}, abstract = {Multiple sclerosis (MS) is a CNS autoimmune disease characterized by demyelination and inflammatory infiltration with a high disability rate. Increasing evidence has demonstrated the importance of gut microbiota as an environmental risk factor in MS and its animal model experimental autoimmune encephalomyelitis (EAE). Diet is the main determinant of gut microbiota composition and function, which greatly affects the shaping of microbial structure. Pomegranate peel, a waste product in the production of juice, is rich in health-promoting compounds. However, its individual constituents, immunoregulatory activities, and action associated with bacterial diversity in the gut microbiota are largely unknown. Here, the main nutrient ingredients of pomegranate peel extract (PPE) were identified as phenols, flavonoids, amino acids, carbohydrates, fatty acids, lipids, nucleotides, organic acids, alcohols, and vitamins via metabolomics evaluation. We found, for the first time, oral PPE (100 mg/kg/day) not only effectively relieves EAE, inhibits CNS inflammatory factor infiltration and myelin loss, but also reshapes gut microbiota. Furthermore, recipient EAE mice with fecal transplantation from the PPE-treated donor delayed the disease development significantly. 16S rRNA gene sequencing revealed the increased gut microbiota richness in PPE-treated group. Among them, Lactobacillaceae enriched significantly, while Alcaligenaceae and Acidaminococcacea decreased remarkably. In conclusion, our data demonstrated that gut microbiota mediated the beneficial effects of oral PPE on EAE, and provided new ideas for developing the prebiotic value of pomegranate peel for the treatment of autoimmune diseases.}, } @article {pmid33381671, year = {2021}, author = {Rizk, MG and Thackray, VG}, title = {Intersection of Polycystic Ovary Syndrome and the Gut Microbiome.}, journal = {Journal of the Endocrine Society}, volume = {5}, number = {2}, pages = {bvaa177}, pmid = {33381671}, issn = {2472-1972}, support = {P50 HD012303/HD/NICHD NIH HHS/United States ; R01 HD095412/HD/NICHD NIH HHS/United States ; T32 HD007203/HD/NICHD NIH HHS/United States ; }, abstract = {The etiology of polycystic ovary syndrome (PCOS) remains unclear, although studies indicate that both genetic and environmental factors contribute to the syndrome. In 2012, Tremellen and Pearce proposed the idea that dysbiosis of the intestinal (gut) microbiome is a causative factor of metabolic and reproductive manifestations of PCOS. In the past 5 years, studies in both humans and rodent models have demonstrated that changes in the taxonomic composition of gut bacteria are associated with PCOS. Studies have also clearly shown that these changes in gut microbiota are associated with PCOS as opposed to obesity, since these changes are observed in women with PCOS that are both of a normal weight or obese, as well as in adolescent girls with PCOS and obesity compared with body mass index- and age-matched females without the disorder. Additionally, studies in both women with PCOS and rodent models of PCOS demonstrated that hyperandrogenism is associated with gut microbial dysbiosis, indicating that androgens may modulate the gut microbial community in females. One study reported that the fecal microbiome transplantation of stool from women with PCOS or exposure to certain bacteria resulted in a PCOS-like phenotype in mice, while other studies showed that exposure to a healthy gut microbiome, pre/probiotics, or specific gut metabolites resulted in protection from developing PCOS-like traits in mice. Altogether, these results suggest that dysbiosis of the gut microbiome may be sufficient to develop PCOS-like symptoms and that modulation of the gut microbiome may be a potential therapeutic target for PCOS.}, } @article {pmid33381475, year = {2020}, author = {Chi, X and Pan, CQ and Liu, S and Cheng, D and Cao, Z and Xing, H}, title = {Regulating Intestinal Microbiota in the Prevention and Treatment of Alcohol-Related Liver Disease.}, journal = {Canadian journal of gastroenterology & hepatology}, volume = {2020}, number = {}, pages = {6629196}, pmid = {33381475}, issn = {2291-2797}, abstract = {When alcohol-related liver disease occurs, the number and composition ratio of intestinal microorganisms will accordingly change. The alcohol-induced changes in the intestinal microbiota play a pivotal role in the process of developing the alcohol-related liver disease through the translocation of microbial products due to increased intestinal permeability. In recent years, therapeutic interventions with a concentration on regulating intestinal microbiota have been conducted for patients with alcohol-related liver disease. We aimed to provide a critical review and updates on the prevention and treatment of alcohol-related liver disease through regulating intestinal microbiota. A literature search was performed on the PubMed database for studies published in English about the therapeutic intervention with microbiota using animal models and patients with alcohol-related liver disease (1/2010-4/2020). The accumulating pieces of evidence suggest that the therapeutic use of probiotics, prebiotics, antibiotics, phages, or fecal microbial transplantation may have several influences on alcohol-related liver disease patients. Emergent data unveiled that these interventions can further regulate the composition of intestinal microbiota, minimize the negative impact of microbiota on the liver, and prevent disease progression from mild to severe alcoholic hepatitis, fibrosis, cirrhosis, or even liver cancer. The current review provides updates on the advances of therapeutic interventions with the effects of regulating intestinal microbiota on patients who have alcohol-related liver disease. In addition, the data gaps and research directions on further exploration of the role of intestinal microbiota for the management of the alcohol-related liver disease are also discussed.}, } @article {pmid33377391, year = {2020}, author = {Ling, Z and Liu, X and Cheng, Y and Yan, X and Wu, S}, title = {Gut microbiota and aging.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-56}, doi = {10.1080/10408398.2020.1867054}, pmid = {33377391}, issn = {1549-7852}, abstract = {Aging is characterized by the functional decline of tissues and organs and increased risk of aging-associated disorders, which pose major societal challenges and are a public health priority. Despite extensive human genetics studies, limited progress has been made linking genetics with aging. There is a growing realization that the altered assembly, structure and dynamics of the gut microbiota actively participate in the aging process. Age-related microbial dysbiosis is involved in reshaping immune responses during aging, which manifest as immunosenescence (insufficiency) and inflammaging (over-reaction) that accompany many age-associated enteric and extraenteric diseases. The gut microbiota can be regulated, suggesting a potential target for aging interventions. This review summarizes recent findings on the physiological succession of gut microbiota across the life-cycle, the roles and mechanisms of gut microbiota in healthy aging, alterations of gut microbiota and aging-associated diseases, and the gut microbiota-targeted anti-aging strategies.}, } @article {pmid33376261, year = {2020}, author = {Sharma, AP and Burton, J and Filler, G and Dave, S}, title = {Current update and future directions on gut microbiome and nephrolithiasis.}, journal = {Indian journal of urology : IJU : journal of the Urological Society of India}, volume = {36}, number = {4}, pages = {262-269}, pmid = {33376261}, issn = {0970-1591}, abstract = {The incidence of nephrolithiasis is increasing worldwide. Understanding how gut microbiome influences oxalate homeostasis has the potential to offer new strategies to prevent nephrolithiasis. The literature was reviewed to gather the evidence on the association between gut microbiome, hyperoxaluria and nephrolithiasis, and to identify the therapeutic interventions focused on the gut microbiome that could decrease hyperoxaluria and prevent nephrolithiasis. Gut microbiome is constituted by a plethora of microbiota including Oxalobacter formigenes (Oxf) and lactobacilli. Oxf can degrade dietary oxalate and induce enteral oxalate secretion. Animal studies suggested an association between oral Oxf supplementation and a decrease in hyperoxaluria. However, human studies have showed inconsistent results. Oral supplementation of lactobacilli did not show benefit in decreasing the hyperoxaluria. Antibiotic exposure, by affecting the gut microbiome, has been associated with an increase in nephrolithiasis. In vivo studies suggest fecal transplantation as a potential treatment option for reducing nephrolithiasis, but needs further evaluation in clinical studies. The current evidence suggests an association between gut microbiome and nephrolithiasis. However, the strategies focused on modulating gut microbiome for decreasing hyperoxaluria and preventing nephrolithiasis need further research. Judicious use of antibiotics in those predisposed to nephrolithiasis offers a preventative strategy for decreasing nephrolithiasis.}, } @article {pmid33363184, year = {2020}, author = {Yang, H and Cai, R and Kong, Z and Chen, Y and Cheng, C and Qi, S and Gu, B}, title = {Teasaponin Ameliorates Murine Colitis by Regulating Gut Microbiota and Suppressing the Immune System Response.}, journal = {Frontiers in medicine}, volume = {7}, number = {}, pages = {584369}, pmid = {33363184}, issn = {2296-858X}, abstract = {Background: Dietary intervention is an exciting topic in current research of inflammatory bowel disease (IBD). The effect of teasaponin (TS) on IBD has not been fully elucidated. Here, we aim to investigate the intestinal anti-inflammatory activity of TS in a dextran sodium sulfate (DSS)-induced colitis mouse model and identify potential mechanisms. Methods: We applied TS to mice with DSS-induced colitis and then monitored the body weight, disease activity index (DAI) daily. When sacrificed, the intestinal permeability was measured. The analysis of mucin and tight junction proteins was conducted. We detected the inflammatory cytokines, the immune cells and related inflammatory signaling pathways. In addition, the gut microbiota were analyzed by 16S rRNA sequencing and we also performed fecal microbiota transplantation (FMT). Results: It showed that TS ameliorated the colonic damage by lowering the DAI, prolonging the colon length, reducing inflammatory cytokines and improving the mucus barrier. Parallel to down-regulation of the inflammatory cytokines, the fecal lipocalin 2, p-P65, p-STAT3, and neutrophil accumulation were also decreased in TS-treated mice. Microbiota characterization showed that Campylobacteria, Proteobacteria, Helicobacter, and Enterobacteriaceae were the key bacteria associated with IBD. In addition, TS could reverse the Firmicutes/Bacteroidetes (F/B) ratio and increase the beneficial bacteria, including Akkermansia and Bacteroides. TS ameliorated DSS-induced colitis by regulating the gut microbiota, and the gut microbiota could regulate gut inflammation. Conclusions: These studies demonstrated that TS ameliorated murine colitis through the modulation of immune response, mucus barrier and gut microbiota, thus improving gut dysbiosis. In addition, the gut microbiota may play an important role in regulating the host's innate immune system, and the two coexist and are mutually beneficial. We provide a promising perspective on the clinical treatment of IBD.}, } @article {pmid33360370, year = {2021}, author = {Tang, J and Xu, L and Zeng, Y and Gong, F}, title = {Effect of gut microbiota on LPS-induced acute lung injury by regulating the TLR4/NF-kB signaling pathway.}, journal = {International immunopharmacology}, volume = {91}, number = {}, pages = {107272}, doi = {10.1016/j.intimp.2020.107272}, pmid = {33360370}, issn = {1878-1705}, abstract = {Acute lung injury (ALI) is a common acute respiratory disease treated in the clinic. Intestinal microflora disorder affect lung diseases through the gut-lung axis. In this study, we explored the regulatory mechanism of the gut flora in the host defense against lipopolysaccharide (LPS)-induced ALI through the TLR4/NF-kB pathway by constructing a gut microflora dysbiosis-model with antibiotic administration and reconstruction of the intestinal microecology. Then, high-throughput sequencing was performed, and the levels of secreted IgA (sIgA), β-defensins, and Muc2 were measured to assess the gut flora and mucosal barrier. The expression of TLR4, NF-kB, TNF-α, IL-1β, oxidative stress and the lung wet/dry (W/D) ratio were evaluated to assess lung damage. Hematoxylin and eosin (HE) staining was performed to evaluate the damage to the gut and lung tissues. Accordingly, gut microbiota imbalance may regulate the TLR4/NF-kB signaling pathway in the lung immune system, activating oxidative stress in the lung and mediating lung injury through the regulation of the gut barrier. However, fecal microbiota transplantation (FMT) impairs the activity of the TLR4/NF-kB signaling pathway in the lung and decreases oxidative stress in animals with ALI by restoring the gut microecology. CONCLUSIONS: Our results indicated the protective effect of gut flora in regulating immunity of LPS-induced ALI by modulating the TLR4/NF-kB signaling pathway which may induce inflammation and oxidative stress.}, } @article {pmid33358585, year = {2020}, author = {Wu, W and Shen, N and Luo, L and Deng, Z and Chen, J and Tao, Y and Mo, X and Cao, Q}, title = {Fecal microbiota transplantation before hematopoietic stem cell transplantation in a pediatric case of chronic diarrhea with a FOXP3 mutation.}, journal = {Pediatrics and neonatology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pedneo.2020.11.003}, pmid = {33358585}, issn = {2212-1692}, abstract = {BACKGROUND: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder caused by mutation of the forkhead box protein 3 (FOXP3) gene, often leading to intractable and life-threatening diarrhea. Fecal microbiota transplantation (FMT), has been regarded in recent years as an available approach to reconstruct disrupted gut microbiome and successfully used to attenuates diarrhea induced by different underlying diseases. Therefore, FMT may have curative potential on the symptoms of enteropathy in patients with IPEX syndrome.

METHODS: Physical and laboratory examinations were performed, and clinical data were collected. FMT was administered via frozen fecal microbial solution, and the fecal microbiota composition was analyzed using 16S rDNA sequencing before and after FMT.

RESULTS: The patient was diagnosed with IPEX syndrome with a mutation detected in the FOXP3 gene, which was identified as c.767T > C (p.M256T). He presented with recurrent watery diarrhea and respiratory infections after birth and developed a significant failure to thrive. Disturbances in the gut microbiota composition and marked decreased bacterial diversity were observed to be involved in the persistent and refractory diarrhea. After receiving FMT treatment, the patient responded with remission of the diarrhea without apparent side effects. His stool output significantly decreased, corresponding to increased microbial diversity and modification of his microbiota composition. The patient finally achieved full recovery after hematopoietic stem cell transplantation (HSCT).

CONCLUSION: Our data suggest an association between the gut microbiota and clinical symptoms of patient with IPEX syndrome and demonstrate FMT as an alternative therapy for severe diarrhea unresponsive to routine therapy in these patients.}, } @article {pmid33356668, year = {2021}, author = {Settanni, CR and Bibbò, S and Ianiro, G and Rinninella, E and Cintoni, M and Mele, MC and Cammarota, G and Gasbarrini, A}, title = {Gastrointestinal involvement of autism spectrum disorder: focus on gut microbiota.}, journal = {Expert review of gastroenterology & hepatology}, volume = {}, number = {}, pages = {1-24}, doi = {10.1080/17474124.2021.1869938}, pmid = {33356668}, issn = {1747-4132}, abstract = {INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder typical of early age, characterized by impaired communication, social interaction, and repetitive behaviors. ASD patients frequently suffer from gastrointestinal (GI) symptoms. Neuro-psychological functions, intestinal homeostasis, and functional GI disturbances are modulated by the gut microbiota through the so-called 'microbiota-gut-brain axis'.

AREAS COVERED: Literature regarding GI symptoms among the ASD community as well as the involvement and modulation of the gut microbiota in GI disturbances of ASD patients was searched. Constipation, diarrhea, reflux, abdominal bloating, pain, and discomfort are reported with variable prevalence. ASD is characterized by a reduction of Bacteroidetes/Firmicutes, of the abundance of Bacteroidetes and other imbalances. ASD patients with GI symptoms present microbial changes with plausible relation with deficiency of digestive enzymes, carbohydrate malabsorption, selective eating, bacterial toxins, serotonin metabolism, and inflammation. The strategies to mitigate the GI distress through the gut microbiota modulation comprise antimicrobials, probiotics, prebiotics, fecal microbiota transplantation, and dietary intervention.

EXPERT OPINION: The modulation of the gut microbiota in ASD individuals with GI disturbances seems a promising target for the future medicine. A standardization of the research strategies for large-scale studies together with a focus on poorly explored fields is necessary to strengthen this hypothesis.}, } @article {pmid33355168, year = {2021}, author = {}, title = {Gut Microbiome Manipulation May Facilitate Immunotherapy Response.}, journal = {Cancer discovery}, volume = {11}, number = {2}, pages = {221}, doi = {10.1158/2159-8290.CD-RW2020-181}, pmid = {33355168}, issn = {2159-8290}, abstract = {Some anti-PD-1-refractory patients responded to anti-PD-1 after fecal microbiota transplantation.}, } @article {pmid33350700, year = {2021}, author = {Rosenberg, K}, title = {Fecal Microbiota Transplantation is Safe and Effective for C. Difficile Infection.}, journal = {The American journal of nursing}, volume = {121}, number = {1}, pages = {56}, doi = {10.1097/01.NAJ.0000731676.97290.c0}, pmid = {33350700}, issn = {1538-7488}, abstract = {According to this study: In standard clinical practice, fecal microbiota transplantation has a high success rate in patients with refractory Clostridioides difficile infection. In most cases, cure can be achieved with only one treatment.}, } @article {pmid33347905, year = {2020}, author = {Rachid, R and Stephen-Victor, E and Chatila, TA}, title = {The microbial origins of food allergy.}, journal = {The Journal of allergy and clinical immunology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jaci.2020.12.624}, pmid = {33347905}, issn = {1097-6825}, abstract = {Food allergy (FA) is a significant public health issue, propelled by its rapidly increasing prevalence. Its sharp rise into prominence has focused attention on causative environmental factors and their interplay with the immune system in disease pathogenesis. In that regard, there is now substantial evidence that alterations in the gut microbiome early in life imprint the host gut mucosal immunity and may play a critical role in precipitating FA. These changes may impact key steps in the development of the infant gut microbiome, including its shaping by maternal factors and upon the introduction of solid food (the weaning reaction). These early-life changes may have long-range effects on host immunity that manifest later in time as disease pathology. Experimental studies have shown that resetting the host intestinal immune responses by treatment with either a healthy fecal microbiota transplantation or defined commensal bacterial taxa can prevent or treat FA. The mechanisms by which these interventions suppress FA include restoration of gut immune regulatory checkpoints, notably the retinoic orphan receptor gamma T+ regulatory T cells, the epithelial barrier, and healthy immunoglobulin A responses to the gut commensals. These findings inform human studies currently in progress that evaluate the role of microbial therapies in FA.}, } @article {pmid33346848, year = {2020}, author = {Leong, KSW and Jayasinghe, TN and Wilson, BC and Derraik, JGB and Albert, BB and Chiavaroli, V and Svirskis, DM and Beck, KL and Conlon, CA and Jiang, Y and Schierding, W and Vatanen, T and Holland, DJ and O'Sullivan, JM and Cutfield, WS}, title = {Effects of Fecal Microbiome Transfer in Adolescents With Obesity: The Gut Bugs Randomized Controlled Trial.}, journal = {JAMA network open}, volume = {3}, number = {12}, pages = {e2030415}, pmid = {33346848}, issn = {2574-3805}, mesh = {Adolescent ; Body Mass Index ; Double-Blind Method ; *Fecal Microbiota Transplantation/adverse effects/methods ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Monitoring, Physiologic/methods ; New Zealand ; *Pediatric Obesity/metabolism/physiopathology/psychology/therapy ; *Quality of Life ; Treatment Outcome ; }, abstract = {Importance: Treatment of pediatric obesity is challenging. Preclinical studies in mice indicated that weight and metabolism can be altered by gut microbiome manipulation.

Objective: To assess efficacy of fecal microbiome transfer (FMT) to treat adolescent obesity and improve metabolism.

This randomized, double-masked, placebo-controlled trial (October 2017-March 2019) with a 26-week follow-up was conducted among adolescents aged 14 to 18 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 30 or more in Auckland, New Zealand. A total of 87 individuals took part-565 individuals responded to advertisements, 328 were ineligible, and 150 declined participation. Clinical data were analyzed from September 2019 to May 2020.

Interventions: Single course of oral encapsulated fecal microbiome from 4 healthy lean donors of the same sex or saline placebo.

Main Outcomes and Measures: Primary outcome was BMI standard deviation score at 6 weeks using intention-to-treat analysis. Secondary outcomes included body composition, cardiometabolic parameters, well-being, and gut microbiome composition.

Results: Eighty-seven participants (59% female adolescents, mean [SD] age 17.2 [1.4] years) were randomized 1:1, in groups stratified by sex, to FMT (42 participants) or placebo (45 participants). There was no effect of FMT on BMI standard deviation score at 6 weeks (adjusted mean difference [aMD] -0.026; 95% CI -0.074, 0.022). Reductions in android-to-gynoid-fat ratio in the FMT vs placebo group were observed at 6, 12, and 26 weeks, with aMDs of -0.021 (95% CI, -0.041 to -0.001), -0.023 (95% CI, -0.043 to -0.003), and -0.029 (95% CI, -0.049 to -0.008), respectively. There were no observed effects on insulin sensitivity, liver function, lipid profile, inflammatory markers, blood pressure, total body fat percentage, gut health, and health-related quality of life. Gut microbiome profiling revealed a shift in community composition among the FMT group, maintained up to 12 weeks. In post-hoc exploratory analyses among participants with metabolic syndrome at baseline, FMT led to greater resolution of this condition (18 to 4) compared with placebo (13 to 10) by 26 weeks (adjusted odds ratio, 0.06; 95% CI, 0.01-0.45; P = .007). There were no serious adverse events recorded throughout the trial.

Conclusions and Relevance: In this randomized clinical trial of adolescents with obesite, there was no effect of FMT on weight loss in adolescents with obesity, although a reduction in abdominal adiposity was observed. Post-hoc analyses indicated a resolution of undiagnosed metabolic syndrome with FMT among those with this condition. Further trials are needed to confirm these results and identify organisms and mechanisms responsible for mediating the observed benefits.

Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12615001351505.}, } @article {pmid33346444, year = {2020}, author = {Goloshchapov, OV and Chukhlovin, AB and Bakin, EA and Stanevich, OV and Klementeva, RV and Shcherbakov, AA and Shvetsov, AN and Suvorova, MA and Bondarenko, SN and Kucher, MA and Kulagin, AD and Zubarovskaya, LS and Moiseev, IS}, title = {[Fecal microbiota transplantation for graft-versus-host disease in children and adults: methods, clinical effects, safety].}, journal = {Terapevticheskii arkhiv}, volume = {92}, number = {7}, pages = {43-54}, doi = {10.26442/00403660.2020.07.000773}, pmid = {33346444}, issn = {0040-3660}, mesh = {Adult ; Child ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; *Graft vs Host Disease/therapy ; *Hematopoietic Stem Cell Transplantation ; Humans ; Prospective Studies ; Treatment Outcome ; }, abstract = {AIM: Was to evaluate clinical efficacy, adverse events and changes in the gut microbiome after fecal microbiota transplantation (FMT) in patients with gastrointestinal (GI) form of graft-versus-host disease (GVHD).

MATERIALS AND METHODS: The prospective single-center study in R.M. Gorbacheva institute included 27 patients with GI GVHD after allogeneic stem cell transplantation. 19 patients received FMT, 8 patients received placebo. Clinical scales for GI autoimmune diseases were used to evaluate response. Microbiome alterations were assessed with multiplex PCR.

RESULTS: After FMT higher overall bacterial mass (р=0.00088), higher bacterial numbers ofBifidobacteriumspp. (р=0.021),Escherichia coli(р=0.049) andBacteroides fragilisgr. (р=0.000043) compared to placebo group. Also higher bacterial mass was observed in patients with clinical response (р=0.0057). The bacterial mass after procedure in non-responders was compared to the placebo group (р=0.31). Partial response of GVHD was achieved faster in the FMT group compared to placebo (median 4 days vs 48 days,p=0.014). Complete response was observed in 8 (42%), 14 (74%) and 16 (84%) at 30, 60 and 90 days respectively, while in the placebo group only 0%, 1 (13%) and 4 (50%) achieved complete response at the same time points. The incidence and severity of adverse events was comparable between FMT and the placebo group.

CONCLUSION: FMT in patients with refractory GI GVHD was associated with favorable clinical outcomes and recovery in certain marker bacterial populations. Multiplex PCR can be used to assess an engraftment of a donor microbiota. FMT in GI GVHD was not associated with life-threatening adverse events, but further studies are required to validate clinical efficacy.}, } @article {pmid33345703, year = {2020}, author = {Green, JE and Davis, JA and Berk, M and Hair, C and Loughman, A and Castle, D and Athan, E and Nierenberg, AA and Cryan, JF and Jacka, F and Marx, W}, title = {Efficacy and safety of fecal microbiota transplantation for the treatment of diseases other than Clostridium difficile infection: a systematic review and meta-analysis.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1-25}, pmid = {33345703}, issn = {1949-0984}, abstract = {The intestinal microbiome has been identified as a key modifier for a variety of health conditions. Fecal Microbiota Transplantation (FMT) has emerged as a fast, safe, and effective means by which to modify the intestinal microbiome and potentially treat a variety of health conditions. Despite extensive research of FMT for CDI, there is a lack of clarity informed by systematic synthesis of data regarding the safety and efficacy of FMT for other health conditions. This systematic review used PRISMA guidelines and was prospectively registered with PROSPERO (CRD42018104243). In March 2020, a search of MEDLINE, EMBASE, and PsycINFO was conducted. We identified 26 eligible studies. A meta-analysis of FMT for active Ulcerative Colitis (UC) showed that FMT significantly improved rates of clinical remission (OR = 3.634, 95% CI = 1.940 to 6.808, I2 = 0%, p < .001), clinical response (OR = 2.634, 95% CI = 1.441 to 4.815, I2 = 33%, p = .002) and endoscopic remission (OR = 4.431, 95% CI = 1.901 to 10.324, I2 = 0%, p = .001). With respect to Irritable Bowel Syndrome, a meta-analysis showed no significant change in symptoms following FMT (p = .739). Hepatic disorders, metabolic syndrome, and antibiotic-resistant organisms were conditions with emerging data on FMT. Serious adverse events (AE) were more often reported in control group participants (n = 43) compared with FMT group participants (n = 26). There were similar rates of mild to moderate AE in both groups. Preliminary data suggest that FMT is a potentially safe, well-tolerated and efficacious treatment for certain conditions other than CDI, with evidence for active UC being the most compelling.}, } @article {pmid33339331, year = {2020}, author = {Łusiak-Szelachowska, M and Weber-Dąbrowska, B and Żaczek, M and Borysowski, J and Górski, A}, title = {The Presence of Bacteriophages in the Human Body: Good, Bad or Neutral?.}, journal = {Microorganisms}, volume = {8}, number = {12}, pages = {}, pmid = {33339331}, issn = {2076-2607}, support = {.//This work was supported by the statutory funds from the Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences./ ; }, abstract = {The presence of bacteriophages (phages) in the human body may impact bacterial microbiota and modulate immunity. The role of phages in human microbiome studies and diseases is poorly understood. However, the correlation between a greater abundance of phages in the gut in ulcerative colitis and diabetes has been suggested. Furthermore, most phages found at different sites in the human body are temperate, so their therapeutic effects and their potential beneficial effects remain unclear. Hence, far, no correlation has been observed between the presence of widespread crAssphage in the human population and human health and diseases. Here, we emphasize the beneficial effects of phage transfer in fecal microbiota transplantation (FMT) in Clostridioides difficile infection. The safety of phage use in gastrointestinal disorders has been demonstrated in clinical studies. The significance of phages in the FMT as well as in gastrointestinal disorders remains to be established. An explanation of the multifaceted role of endogenous phages for the development of phage therapy is required.}, } @article {pmid33331486, year = {2020}, author = {Terra, DAA and Vilela, EG and Silva, ROS and LeÃo, LA and Lima, KS and Passos, RIFÂ and Diniz, AN and Coelho, LGV}, title = {STRUCTURING A FECAL MICROBIOTA TRANSPLANTATION CENTER IN A UNIVERSITY HOSPITAL IN BRAZIL.}, journal = {Arquivos de gastroenterologia}, volume = {57}, number = {4}, pages = {434-458}, doi = {10.1590/S0004-2803.202000000-79}, pmid = {33331486}, issn = {1678-4219}, mesh = {Brazil ; Clostridioides difficile ; Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Feces ; Humans ; Treatment Outcome ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an important therapeutic option for recurrent or refractory Clostridioides difficile infection, being a safe and effective method. Initial results suggest that FMT also plays an important role in other conditions whose pathogenesis involves alteration of the intestinal microbiota. However, its systematized use is not widespread, especially in Brazil. In the last decade, multiple reports and several cases emerged using different protocols for FMT, without standardization of methods and with variable response rates. In Brazil, few isolated cases of FMT have been reported without the implantation of a Fecal Microbiota Transplantation Center (FMTC).

OBJECTIVE: The main objective of this study is to describe the process of implanting a FMTC with a stool bank, in a Brazilian university hospital for treatment of recurrent and refractory C. difficile infection.

METHODS: The center was structured within the criteria required by international organizations such as the Food and Drug Administration, the European Fecal Microbiota Transplant Group and in line with national epidemiological and regulatory aspects.

RESULTS: A whole platform involved in structuring a transplant center with stool bank was established. The criteria for donor selection, processing and storage of samples, handling of recipients before and after the procedure, routes of administration, short and long-term follow-up of transplant patients were determined. Donor selection was conducted in three stages: pre-screening, clinical evaluation and laboratory screening. Most of the candidates were excluded in the first (75.4%) and second stage (72.7%). The main clinical exclusion criteria were: recent acute diarrhea, overweight (body mass index ≥25 kg/m2) and chronic gastrointestinal disorders. Four of the 134 candidates were selected after full screening, with a donor detection rate of 3%.

CONCLUSION: The implantation of a transplant center, unprecedented in our country, allows the access of patients with recurrent or refractory C. difficile infection to innovative, safe treatment, with a high success rate and little available in Brazil. Proper selection of qualified donors is vital in the process of implementing a FMTC. The rigorous clinical evaluation of donors allowed the rational use of resources. A transplant center enables treatment on demand, on a larger scale, less personalized, with more security and traceability. This protocol provides subsidies for conducting FMT in emerging countries.}, } @article {pmid33330910, year = {2020}, author = {Gerardin, Y and Timberlake, S and Allegretti, JR and Smith, MB and Kassam, Z}, title = {Beyond fecal microbiota transplantation: Developing drugs from the microbiome.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiaa700}, pmid = {33330910}, issn = {1537-6613}, abstract = {The transfer of live gut microbes may transform patient care across a range of autoimmune, metabolic, hepatic and infectious diseases. One early approach, fecal microbiota transplantation, has shown promise in Clostridiodes difficile infection and the potential for improving clinical and public health outcomes for other antibiotic-resistant bacteria. These clinical successes have motivated the development of microbiome drugs, which will need to address challenges in safety, uniformity, and delivery while seeking to preserve the benefits of using whole microbiome communities as novel therapeutics and an innovative platform for drug discovery.}, } @article {pmid33326127, year = {2020}, author = {Bilinski, J and Lis, K and Tomaszewska, A and Grzesiowski, P and Dzieciatkowski, T and Tyszka, M and Karakulska-Prystupiuk, E and Boguradzki, P and Tormanowska, M and Halaburda, K and Waszczuk-Gajda, A and Wiktor-Jedrzejczak, W and Basak, GW}, title = {Fecal microbiota transplantation in patients with acute and chronic graft-versus-host disease-spectrum of responses and safety profile. Results from a prospective, multicenter study.}, journal = {American journal of hematology}, volume = {}, number = {}, pages = {}, doi = {10.1002/ajh.26077}, pmid = {33326127}, issn = {1096-8652}, } @article {pmid33324357, year = {2020}, author = {Lee, KE and Kim, JK and Kim, DH}, title = {Orally Administered Antibiotics Vancomycin and Ampicillin Cause Cognitive Impairment With Gut Dysbiosis in Mice With Transient Global Forebrain Ischemia.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {564271}, pmid = {33324357}, issn = {1664-302X}, abstract = {Gut microbiota is closely associated with the occurrence of neuropsychiatric disorders. Antibiotics are frequently used to prevent pathogen infection in patients with brain ischemia. To understand the impact of prophylactic antibiotic treatment for patients with brain ischemia, we examined the effects of orally administered vancomycin and ampicillin on cognitive function and gut microbiota composition in mice with transient global forebrain ischemia (tIsc). tIsc operation and orally gavaged vancomycin mildly and moderately caused cognitive impairment, respectively. However, the exposure of mice with tIsc to vancomycin or ampicillin severely impaired cognitive function in the Y-maze, novel object recognition, and Banes maze tasks. Furthermore, their treatments induced NF-κB activation as well as active microglia (NF-κB+/Iba1+ and LPS+/Iba1+ cells) and apoptotic (caspase 3+/NeuN+) cell population in the hippocampus, whereas the brain-derived neurotrophic factor (BDNF)+/NeuN+ cell populations decreased. These treatments also caused colitis and gut dysbiosis. They increased the population of Proteobacteria including Enterobacter xiangfangenesis. Orally delivered fecal transplantation of vancomycin-treated mice with or without tIsc and oral gavage of Enterobacter xiangfangenesis also significantly deteriorated the cognitive impairment and colitis in transplanted mice with tIsc. These findings suggest that oral administration of antibiotics can deteriorate cognitive impairment with gut dysbiosis in patients with brain ischemia.}, } @article {pmid33321019, year = {2020}, author = {Leclercq, S and de Timary, P and Stärkel, P}, title = {Targeting the gut microbiota to treat alcoholic liver diseases: evidence and promises.}, journal = {Acta gastro-enterologica Belgica}, volume = {83}, number = {4}, pages = {616-621}, pmid = {33321019}, issn = {1784-3227}, mesh = {*Alcoholism ; Animals ; Dysbiosis ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Liver Diseases, Alcoholic/therapy ; *Probiotics/therapeutic use ; }, abstract = {The human intestine is colonized by a variety of microbes that influence the metabolic responses, the immune system and the nervous system. Dietary patterns are important factors that shape the composition of the gut microbiota. Many animal models of alcohol exposure have highlighted the key role of the alcohol-induced gut microbiota alterations, leaky gut and translocation of microbial products in the development of alcoholic liver disease (ALD). However, in humans, there is no clear picture defining an "alcoholic microbiome", and the link between intestinal dysbiosis and ALD development is far from being understood. Although we do not comprehend all the mechanistic insights, clinical studies aiming at modulating the gut microbiota of alcoholic patients have shown some beneficial effects. Here we review the potential therapeutic effects of probiotics in ALD and give some clinical perspectives on the role of prebiotics and the use of fecal microbiota transplantation.}, } @article {pmid33317795, year = {2020}, author = {Morkūnas, E and Skiecevičienė, J and Kupčinskas, J}, title = {The impact of modulating the gastrointestinal microbiota in cancer patients.}, journal = {Best practice & research. Clinical gastroenterology}, volume = {48-49}, number = {}, pages = {101700}, doi = {10.1016/j.bpg.2020.101700}, pmid = {33317795}, issn = {1532-1916}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*physiology ; Humans ; Immunotherapy/*methods ; Neoplasms/*microbiology/therapy ; }, abstract = {Gastrointestinal microbiota is vastly deregulated in cancer patients due to different factors, but the exact mechanisms of interaction between cancer and microbiome are still poorly understood. Current evidence suggests that alterations in the composition of the microbiota may affect efficacy and toxicity of anti-cancer therapies. Recent preclinical and clinical studies demonstrate different mechanisms and outcomes of deregulation of gut microbiome, and investigate effects of modulating gastrointestinal microbiota in cancer patients. This paper reviews effects of altered microbiome on anti-cancer management, including antibiotics, chemotherapy and immunotherapy, as well as possible outcomes of modulating altered microbiome by probiotics or faecal microbiome transplantation in cancer patients.}, } @article {pmid33311550, year = {2020}, author = {Aluthge, ND and Tom, WA and Bartenslager, AC and Burkey, TE and Miller, PS and Heath, KD and Kreikemeier-Bower, C and Kittana, H and Schmaltz, RJ and Ramer-Tait, AE and Fernando, SC}, title = {Differential longitudinal establishment of human fecal bacterial communities in germ-free porcine and murine models.}, journal = {Communications biology}, volume = {3}, number = {1}, pages = {760}, pmid = {33311550}, issn = {2399-3642}, support = {2018-67015-27496//United States Department of Agriculture | National Institute of Food and Agriculture (NIFA)/ ; 2018-68003-27545//United States Department of Agriculture | National Institute of Food and Agriculture (NIFA)/ ; }, abstract = {The majority of microbiome studies focused on understanding mechanistic relationships between the host and the microbiota have used mice and other rodents as the model of choice. However, the domestic pig is a relevant model that is currently underutilized for human microbiome investigations. In this study, we performed a direct comparison of the engraftment of fecal bacterial communities from human donors between human microbiota-associated (HMA) piglet and mouse models under identical dietary conditions. Analysis of 16S rRNA genes using amplicon sequence variants (ASVs) revealed that with the exception of early microbiota from infants, the more mature microbiotas tested established better in the HMA piglets compared to HMA mice. Of interest was the greater transplantation success of members belonging to phylum Firmicutes in the HMA piglets compared to the HMA mice. Together, these results provide evidence for the HMA piglet model potentially being more broadly applicable for donors with more mature microbiotas while the HMA mouse model might be more relevant for developing microbiotas such as those of infants. This study also emphasizes the necessity to exercise caution in extrapolating findings from HMA animals to humans, since up to 28% of taxa from some donors failed to colonize either model.}, } @article {pmid33311466, year = {2020}, author = {Chevalier, G and Siopi, E and Guenin-Macé, L and Pascal, M and Laval, T and Rifflet, A and Boneca, IG and Demangel, C and Colsch, B and Pruvost, A and Chu-Van, E and Messager, A and Leulier, F and Lepousez, G and Eberl, G and Lledo, PM}, title = {Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {6363}, pmid = {33311466}, issn = {2041-1723}, mesh = {Animals ; *Behavior, Animal ; Depression/*complications ; Disease Models, Animal ; Endocannabinoids/*pharmacology ; Fatty Acids/metabolism ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Lactobacillus/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Neurogenesis/drug effects ; Stress, Psychological/*complications ; }, abstract = {Depression is the leading cause of disability worldwide. Recent observations have revealed an association between mood disorders and alterations of the intestinal microbiota. Here, using unpredictable chronic mild stress (UCMS) as a mouse model of depression, we show that UCMS mice display phenotypic alterations, which could be transferred from UCMS donors to naïve recipient mice by fecal microbiota transplantation. The cellular and behavioral alterations observed in recipient mice were accompanied by a decrease in the endocannabinoid (eCB) signaling due to lower peripheral levels of fatty acid precursors of eCB ligands. The adverse effects of UCMS-transferred microbiota were alleviated by selectively enhancing the central eCB or by complementation with a strain of the Lactobacilli genus. Our findings provide a mechanistic scenario for how chronic stress, diet and gut microbiota generate a pathological feed-forward loop that contributes to despair behavior via the central eCB system.}, } @article {pmid33309073, year = {2021}, author = {Aràjol, C and Aira Gómez, A and González-Suárez, B and Casals-Pascual, C and Martí Martí, S and Domínguez Luzón, MÁ and Soriano, A and Guardiola Capón, J and , }, title = {Donor selection for faecal microbiota transplantation. Consensus document of the Catalan Society of Gastroenterology and the Catalan Society of Infectious Diseases and Clinical Microbiology.}, journal = {Gastroenterologia y hepatologia}, volume = {44}, number = {2}, pages = {175-180}, doi = {10.1016/j.gastrohep.2020.07.027}, pmid = {33309073}, issn = {0210-5705}, abstract = {Faecal microbiota transplantation (FMT) is an effective and safe treatment of recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and based on scientific knowledge. Selection of the faecal microbiota donor is a key part of the process to ensure recipient safety. Protocols of action must be implemented that allow clinicians to act with the maximum guarantees and to minimise the risks of the procedure. In this regard, a multidisciplinary working group has been set up with the aim of establishing recommendations for selecting the faecal microbiota donor.}, } @article {pmid33307184, year = {2020}, author = {Dawwas, G and Brensinger, CM and Vajravelu, RK and Wu, Q and Kelly, CR and Laine, L and Wu, GD and Lewis, JD}, title = {Long-Term Outcomes Following Multiply Recurrent Clostridioides difficile Infection and Fecal Microbiota Transplantation.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2020.12.004}, pmid = {33307184}, issn = {1542-7714}, abstract = {BACKGROUND AND AIMS: Fecal microbiota transplantation (FMT) is a commonly used therapy for multiply recurrent Clostridioides difficile (mrCDI). By altering the gut microbiota, there is the potential for FMT to impact the risk for cardiometabolic, intestinal or immune-mediated conditions. Likewise, the microbiota disturbance associated with mrCDI could potentially lead to these conditions. We aimed to assess the associations of mrCDI and FMT with cardiometabolic, immune-mediated diseases, and irritable bowel syndrome.

METHODS: This retrospective cohort study using a United States commercial claims database included persons diagnosed with CDI or undergoing FMT. We created 2 pairwise comparisons: mrCDI vs non-mrCDI, and non-mrCDI or mrCDI treated with FMT vs mrCDI without FMT.

RESULTS: We found no significant association between mrCDI (vs non-mrCDI) and inflammatory bowel disease (adjusted hazard ratio (aHR) = 1.65; 95% confidence interval, 0.67-4.04), rheumatoid arthritis (HR = 0.86; 0.47-1.56), psoriasis (HR = 0.72; 0.23-2.27), diabetes (aHR = 0.97; 0.67-1.40), hypertension (aHR = 1.05; 0.76-1.44), myocardial infarction (aHR = 0.82; 0.63-1.06), stroke (aHR = 0.83; 0.62-1.12), or irritable bowel syndrome (HR = 0.94; 0.61-1.45). Similarly, we found no association of CDI with FMT (vs mrCDI without FMT) and diabetes (aHR = 0.92; 0.27-3.11), hypertension (aHR = 1.41; 0.64-3.15), stroke (aHR = 1.27; 0.69-2.34) or inflammatory bowel syndrome (aHR = 0.80; 0.26-2.46). However, the incidence of myocardial infarction was increased following FMT (aHR = 1.68; 1.01-2.81).

CONCLUSION: Relative to those with CDI, persons with mrCDI do not appear to be intrinsically at higher risk of cardiometabolic, immune-mediated diseases, or irritable bowel syndrome. However, those who underwent FMT for CDI had a higher incidence of myocardial infarction. Future studies should assess this association to assess reproducibility.}, } @article {pmid33304339, year = {2020}, author = {Napolitano, M and Covasa, M}, title = {Microbiota Transplant in the Treatment of Obesity and Diabetes: Current and Future Perspectives.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {590370}, pmid = {33304339}, issn = {1664-302X}, abstract = {A wealth of evidence has revealed the critical role of the gut microbiota in health and disease. Many chronic diseases have been associated with gut microbiota imbalance in its composition, diversity and functional capacity. Several types of interventions have been shown to correct microbiota imbalance and restore the beneficial metabolic outcomes of a normal microbiota. Among them, fecal microbiota transplantation (FMT) is an emergent, promising technology employed to improve clinical outcomes of various pathological conditions through modifications in the gut microbiota composition. FMT has been used successfully as a treatment option in recurrent Clostridium difficile infection, a condition characterized by severe gut microbiota dysbiosis. However, the potential usage of FMT in other microbiota-associated conditions different from C. difficile such as metabolic syndrome or obesity that are also marked by gut dysbiosis is still under investigation. Furthermore, the contribution of the gut microbiota as a cause or consequence in metabolic disease is still largely debated. This review provides critical information on the methodological approaches of FMT and its technological innovation in clinical applications. This review sheds light on the current findings and gaps in our understanding of how FMT can be used as a future biotherapeutic to restore microbial homeostasis in amelioration of obesity and diabetes.}, } @article {pmid33303685, year = {2021}, author = {Baruch, EN and Youngster, I and Ben-Betzalel, G and Ortenberg, R and Lahat, A and Katz, L and Adler, K and Dick-Necula, D and Raskin, S and Bloch, N and Rotin, D and Anafi, L and Avivi, C and Melnichenko, J and Steinberg-Silman, Y and Mamtani, R and Harati, H and Asher, N and Shapira-Frommer, R and Brosh-Nissimov, T and Eshet, Y and Ben-Simon, S and Ziv, O and Khan, MAW and Amit, M and Ajami, NJ and Barshack, I and Schachter, J and Wargo, JA and Koren, O and Markel, G and Boursi, B}, title = {Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients.}, journal = {Science (New York, N.Y.)}, volume = {371}, number = {6529}, pages = {602-609}, doi = {10.1126/science.abb5920}, pmid = {33303685}, issn = {1095-9203}, abstract = {The gut microbiome has been shown to influence the response of tumors to anti-PD-1 (programmed cell death-1) immunotherapy in preclinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. In this study, we performed a phase 1 clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and reinduction of anti-PD-1 immunotherapy in 10 patients with anti-PD-1-refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. These early findings have implications for modulating the gut microbiota in cancer treatment.}, } @article {pmid33301807, year = {2021}, author = {Jing, Y and Bai, F and Yu, Y}, title = {Spinal cord injury and gut microbiota: A review.}, journal = {Life sciences}, volume = {266}, number = {}, pages = {118865}, doi = {10.1016/j.lfs.2020.118865}, pmid = {33301807}, issn = {1879-0631}, mesh = {Animals ; *Gastrointestinal Microbiome ; Humans ; *Neuroprotection ; Spinal Cord Injuries/microbiology/*prevention & control ; }, abstract = {After spinal cord injury (SCI), intestinal dysfunction has a serious impact on physical and mental health, quality of life, and social participation. Recent data from rodent and human studies indicated that SCI causes gut dysbiosis. Remodeling gut microbiota could be beneficial for the recovery of intestinal function and motor function after SCI. However, few studies have explored SCI with focus on the gut microbiota and "microbiota-gut-brain" axis. In this review, the complications following SCI, including intestinal dysfunction, anxiety and depression, metabolic disorders, and neuropathic pain, are directly or indirectly related to gut dysbiosis, which may be mediated by "gut-brain" interactions. Furthermore, we discuss the research strategies that can be beneficial in this regard, including germ-free animals, fecal microbiota transplantation, probiotics, phages, and brain imaging techniques. The current microbial research has shifted from descriptive to mechanismal perspective, and future research using new technologies may further demonstrate the pathophysiological mechanism of association of SCI with gut microbiota, elucidate the mode of interaction of gut microbiota and hosts, and help develop personalized microbiota-targeted therapies and drugs based on microbiota or corresponding metabolites.}, } @article {pmid33301497, year = {2020}, author = {Hyde, MK and Masser, BM}, title = {Determinants of community members' willingness to donate stool for faecal microbiota transplantation.}, journal = {PloS one}, volume = {15}, number = {12}, pages = {e0243751}, pmid = {33301497}, issn = {1932-6203}, mesh = {Adult ; Australia ; Cross-Sectional Studies ; *Donor Selection/methods ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Motivation ; Surveys and Questionnaires ; *Tissue Donors ; Young Adult ; }, abstract = {Universal stool banks rely on, but face difficulties recruiting, community volunteers to donate stool for faecal microbiota transplantation (FMT) to effectively treat recurrent Clostridioides difficile. This study sought to identify determinants of community members' willingness to donate stool to guide donor recruitment. 397 Australian residents (52% male, 47% 21-30 years, 63% university educated) completed a survey to gauge willingness to donate stool, bowel habits, information needs, attitudes, barriers, and motives for donation. Most reported regular bowel movements (BMs; 90%), morning BMs (63%), BMs ≤5 minutes duration (67%), and some discomfort doing BMs in public restrooms (69%). Less than half were willing to donate stool in-centre (45% willing) or at home (48%). Important information needs identified by >80% were convenience and travel requirements associated with donation. Main barriers were logistics, capabilities to donate, disgust (e.g., donation process), and discomfort (e.g., privacy). The main motivator was altruism, with compensation secondary. Linear regression models identified less discomfort doing BMs in public restrooms (β = -0.15), understanding benefits to patients (β = 0.15), placing less importance on understanding the donation process (β = -0.13), and positive attitudes (β = 0.56) as determinants of willingness to donate in-centre. Understanding benefits to self (β = 0.11) and patients (β = 0.24), placing less importance on understanding the donation purpose (β = -0.19), and positive attitudes (β = 0.50) determined willingness to donate at home. Stool banks should consider donor's bowel habits, comfort donating in-centre, and information needs early in recruitment; and implement flexible logistics for potential donors who face time constraints and limited access to stool banks.}, } @article {pmid33293406, year = {2020}, author = {Liu, Z and Coales, I and Penney, N and McDonald, JAK and Phetcharaburanin, J and Seyfried, F and Li, JV}, title = {A Subset of Roux-en-Y Gastric Bypass Bacterial Consortium Colonizes the Gut of Nonsurgical Rats without Inducing Host-Microbe Metabolic Changes.}, journal = {mSystems}, volume = {5}, number = {6}, pages = {}, pmid = {33293406}, issn = {2379-5077}, abstract = {Roux-en-Y gastric bypass (RYGB) is an effective weight loss surgery, resulting in a characteristic increase of fecal Gammaproteobacteria The contribution of this compositional change to metabolic benefits of RYGB is currently debatable. Therefore, this study employed 16S rRNA gene sequencing and metabolic profiling to monitor the dynamic colonization of the RYGB microbial consortium and their metabolic impact on the host. Eleven Wistar rats received vancomycin and enrofloxacin, followed by fecal microbiota transplantation (FMT) of cecal slurry obtained from either RYGB- or sham-operated rats. Urine and feces from the microbiota recipients (RYGB microbiota recipients [RYGBr], n = 6; sham microbiota recipients [SHAMr], n = 5) were collected pre- and post-antibiotics and 1, 3, 6, 9, and 16 days post-FMT. No significant differences in body weight and food intake were observed between RYGBr and SHAMr. While neither group reached the community richness of that of their donors, by day 6, both groups reached the richness and diversity of that prior to antibiotic treatment. However, the typical signature of RYGB microbiome-increased Enterobacteriaceae-was not replicated in these recipients after two consecutive FMT, suggesting that the environmental changes induced by the anatomical rearrangements of RYGB could be key for sustaining such a consortium. The transplanted bacteria did not induce the same metabolic signature of urine and feces as those previously reported in RYGB-operated rats. Future work is required to explore environmental factors that shape the RYGB microbiota in order to further investigate the metabolic functions of the RYGB microbiota, thereby teasing out the mechanisms of the RYGB surgery.IMPORTANCE Roux-en-Y gastric bypass (RYGB) surgery results in a long-term gut bacterial shift toward Gammaproteobacteria in both patients and rodents. The contribution of this compositional shift, or the RYGB bacterial consortium, to the metabolic benefit of the surgery remains debatable. It is unclear how well these bacteria colonize in an anatomically normal gut. This is a fundamental question in both defining the function of the RYGB microbiota and evaluating its potential as a nonsurgical treatment for obesity. We monitored the dynamic colonization of the RYGB bacterial consortium and observed that while approximately one-third of the bacterial taxa from the RYGB donor colonized in the gut of the nonoperated recipients, Gammaproteobacteria were unable to colonize for longer than 3 days. The study highlighted that a successful long-term colonization of Gammaproteobacteria-rich RYGB microbiota in nonsurgical animals requires key environmental factors that may be dictated by the intestinal anatomical modification by the surgery itself.}, } @article {pmid33292670, year = {2020}, author = {Yu, J and Sun, H and Cao, W and Han, L and Song, Y and Wan, D and Jiang, Z}, title = {Applications of gut microbiota in patients with hematopoietic stem-cell transplantation.}, journal = {Experimental hematology & oncology}, volume = {9}, number = {1}, pages = {35}, pmid = {33292670}, issn = {2162-3619}, support = {20A320062//Foundation of Henan Educational Committee/ ; LHGJ20190039//Science and Technology Department of Henan Province/ ; }, abstract = {Studies of the gut microbiota (GM) have demonstrated the close link between human wellness and intestinal commensal bacteria, which mediate development of the host immune system. The dysbiosis, a disruption of the microbiome natural balance, can cause serious health problems. Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) may cause significant changes in GM due to their underlying malignancies and exposure to extensive chemotherapy and systemic antibiotics, which may lead to different disorders. There are complex and multi-directional interactions among intestinal inflammation, GM and immune reactivity after HSCT. There is considerable effect of the human intestinal microbiome on clinical course following HSCT. Some bacteria in the intestinal ecosystem may be potential biomarkers or therapeutic targets for preventing relapse and improving survival rate after HSCT. Microbiota can be used as predictor of mortality in allo-HSCT. Two different strategies with targeted modulation of GM, preemptive and therapeutic, have been used for preventing or treating GM dysbiosis in patients with HSCT. Preemptive strategies include enteral nutrition (EN), prebiotic, probiotic, fecal microbiota transplantation (FMT) and antibiotic strategies, while therapeutic strategies include FMT, probiotic and lactoferrine usages. In this review, we summarize the advance of therapies targeting GM in patients with HSCT.}, } @article {pmid33282868, year = {2020}, author = {Liu, TH and Tao, WC and Liang, QE and Tu, WQ and Xiao, Y and Chen, LG}, title = {Gut Microbiota-Related Evidence Provides New Insights Into the Association Between Activating Transcription Factor 4 and Development of Salt-Induced Hypertension in Mice.}, journal = {Frontiers in cell and developmental biology}, volume = {8}, number = {}, pages = {585995}, pmid = {33282868}, issn = {2296-634X}, abstract = {Activating transcription factor 4 (ATF4), which regulates genes associated with endoplasmic reticulum stress, apoptosis, autophagy, the gut microbiome, and metabolism, has been implicated in many diseases. However, its mechanistic role in hypertension remains unclear. In the present study, we investigated its role in salt-sensitive hypertensive mice. Wild-type (WT) C57BL/6J mice were used to establish Atf4 knockout (KO) and overexpression mice using CRISPR-Cas9 and lentiviral overexpression vectors. Then, fecal microbiota transplantation (FMT) from Atf4± mice and vitamin K2 (VK2) supplementation were separately carried out in high-salt-diet (8% NaCl)-induced mice for 4 weeks. We found that Atf4 KO inhibited and Atf4 overexpression enhanced the increase in blood pressure and endothelial dysfunction induced by high salt intake in mice, while regulating the gut microbiota composition and VK2 expression. It was further verified that ATF4 is involved in the regulation of salt-sensitive hypertension and vascular endothelial function, which is achieved through association with gut microbiota and may be related to VK2 and different bacteria such as Dubosiella. In addition, we found that VK2 supplementation prevents the development of salt-sensitive hypertension and maintains vascular endothelial function; moreover, VK2 supplementation increases the abundance of intestinal Dubosiella and downregulates the relative expression of Atf4 in the thoracic aorta of mice. We conclude that ATF4 plays an important role in regulating gut microbiota and VK2 production, providing new insights into the association between ATF4 and development of salt-induced hypertension in mice, meanwhile contributing to the development for a new preventive strategy of hypertension.}, } @article {pmid33279615, year = {2020}, author = {Zhang, P and Zhang, X and Huang, Y and Chen, J and Shang, W and Shi, G and Zhang, L and Zhang, C and Chen, R}, title = {Atorvastatin alleviates microglia-mediated neuroinflammation via modulating the microbial composition and the intestinal barrier function in ischemic stroke mice.}, journal = {Free radical biology & medicine}, volume = {162}, number = {}, pages = {104-117}, doi = {10.1016/j.freeradbiomed.2020.11.032}, pmid = {33279615}, issn = {1873-4596}, abstract = {Our previous work has shown that atorvastatin exerts anti-inflammatory properties in ischemic stroke, and recent studies have revealed that intestinal microbiota plays a vital role in the pathogenesis of stroke. However, it is not clear whether the anti-inflammatory effects of atorvastatin against ischemic stroke is related to gut function and microbiota. We report herein that atorvastatin significantly ameliorated the defects in sensorimotor behaviors and reduced microglia-mediated neuroinflammation by inhibiting proinflammatory polarization of microglia in the peri-infarct cortex of the mice with permanent middle cerebral artery occlusion (pMCAO). Moreover, atorvastatin reversed microbial composition (characterized by increased abundance of Firmicutes and Lactobacillus and decreased Bacteroidetes abundance), increased fecal butyrate level, promoted intestinal barrier function (elevated protein levels of claudin-1, occludin and mucoprotein 2), as well as regulated intestinal immune function (decreased MCP-1, TNF-α and increased IL-10). Atorvastatin also significantly reduced the level of circulating endotoxin (lipopolysaccharide-binding protein), which is a biomarker of leaky gut. Transplantation of fecal microbiota collected from atorvastatin treated mice potently attenuated neuroinflammation in pMCAO mice, and the anti-inflammatory effects of fecal microbiota transplantation were similar to those of oral atorvastatin administration. These results suggested that the atorvastatin-mediated restoration of gut microbiota, improvement of intestinal barrier function and regulation of intestinal immunity were involved in the anti-inflammatory function in stroke mice.}, } @article {pmid33279588, year = {2021}, author = {Huang, L and Duan, C and Xia, X and Wang, H and Wang, Y and Zhong, Z and Wang, B and Ding, W and Yang, Y}, title = {Commensal microbe-derived propionic acid mediates juvenile social isolation-induced social deficits and anxiety-like behaviors.}, journal = {Brain research bulletin}, volume = {166}, number = {}, pages = {161-171}, doi = {10.1016/j.brainresbull.2020.12.001}, pmid = {33279588}, issn = {1873-2747}, abstract = {Social experiences during early life are thought to be critical for proper social and emotional development. Conversely, social insults during development causes long-lasting behavioral abnormalities later in life. However, how juvenile social deprivation influences social and emotional behaviors remains poorly understood. Here, we show that juvenile social isolation induces a shift in microbial ecology that negatively impacts social and emotional behaviors in adulthood. These behavioral changes, which occur during this critical period are transferable to antibiotic pre-treated mice by fecal microbiota transplant. In addition, juvenile social isolation decreases the expression of oxytocin receptor (OXTR) in the medial prefrontal cortex (mPFC), and increases the amounts of fecal propionic acid (PA), a short-chain fatty acid derived from gut micobiota. Accordingly, infusion with an OXTR antagonist (OXTR-A, l-368,899) specifically in the mPFC or supplementation of PA both can cause social deficits and anxiety-like behaviors in group housed mice. Collectively, our findings reveal that juvenile social experience regulates prefrontal cortical OXTR expression through gut microbiota-produced PA and that is essential for normal social and emotional behaviors, thus providing a cellular and molecular context to understand the consequences of juvenile social deprivation.}, } @article {pmid33278650, year = {2020}, author = {Mehta, SR and Yen, EF}, title = {Microbiota-based Therapies Clostridioides difficile infection that is refractory to antibiotic therapy.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.trsl.2020.11.013}, pmid = {33278650}, issn = {1878-1810}, abstract = {Clostridioides difficile infection (CDI) has had a devastating impact worldwide with significant rates of mortality, especially among the elderly. Despite effective antibiotics, the incidence of recurrent CDI (rCDI) is increasing and more difficult to treat with antibiotics alone. Fecal Microbiota Transplantation (FMT) has emerged as a consistently effective treatment for rCDI. Mechanisms for FMT are not entirely understood, but remain an area of active investigation. There have been recent safety reports with the use of FMT regarding transmission of pathogens in a few patients that have led to serious illness. With appropriate screening, FMT can be safely administered and continue to have a significant impact on eradication of rCDI and improve the lives of patients suffering from this disease. In this review, we summarize current treatments for CDI with a focus on microbiota-based therapies used for antibiotic refractory disease.}, } @article {pmid33277504, year = {2020}, author = {Tian, L and Wang, XW and Wu, AK and Fan, Y and Friedman, J and Dahlin, A and Waldor, MK and Weinstock, GM and Weiss, ST and Liu, YY}, title = {Deciphering functional redundancy in the human microbiome.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {6217}, pmid = {33277504}, issn = {2041-1723}, support = {UH3 OD023268/OD/NIH HHS/United States ; U19 AI095219/AI/NIAID NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Algorithms ; Bacteria/classification/genetics ; Feces/*microbiology ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; Gene Regulatory Networks ; Gene Transfer, Horizontal ; Humans ; Metagenome/*genetics ; Metagenomics/*methods ; Microbiota/*genetics ; Models, Genetic ; }, abstract = {Although the taxonomic composition of the human microbiome varies tremendously across individuals, its gene composition or functional capacity is highly conserved - implying an ecological property known as functional redundancy. Such functional redundancy has been hypothesized to underlie the stability and resilience of the human microbiome, but this hypothesis has never been quantitatively tested. The origin of functional redundancy is still elusive. Here, we investigate the basis for functional redundancy in the human microbiome by analyzing its genomic content network - a bipartite graph that links microbes to the genes in their genomes. We find that this network exhibits several topological features that favor high functional redundancy. Furthermore, we develop a simple genome evolution model to generate genomic content network, finding that moderate selection pressure and high horizontal gene transfer rate are necessary to generate genomic content networks with key topological features that favor high functional redundancy. Finally, we analyze data from two published studies of fecal microbiota transplantation (FMT), finding that high functional redundancy of the recipient's pre-FMT microbiota raises barriers to donor microbiota engraftment. This work elucidates the potential ecological and evolutionary processes that create and maintain functional redundancy in the human microbiome and contribute to its resilience.}, } @article {pmid33276482, year = {2020}, author = {Tanase, DM and Gosav, EM and Neculae, E and Costea, CF and Ciocoiu, M and Hurjui, LL and Tarniceriu, CC and Maranduca, MA and Lacatusu, CM and Floria, M and Serban, IL}, title = {Role of Gut Microbiota on Onset and Progression of Microvascular Complications of Type 2 Diabetes (T2DM).}, journal = {Nutrients}, volume = {12}, number = {12}, pages = {}, pmid = {33276482}, issn = {2072-6643}, abstract = {Type 2 diabetes mellitus (T2DM) remains one of the most problematic and economic consumer disorders worldwide, with growing prevalence and incidence. Over the last years, substantial research has highlighted the intricate relationship among gut microbiota, dysbiosis and metabolic syndromes development. Changes in the gut microbiome composition lead to an imbalanced gastrointestinal habitat which promotes abnormal production of metabolites, inflammatory status, glucose metabolism alteration and even insulin resistance (IR). Short-chain fatty acids (SCFAs), trimethylamine N-oxide (TMAO), lipopolysaccharide, aromatic amino acids and their affiliated metabolites, contribute to T2DM via different metabolic and immunologic pathways. In this narrative review, we discuss the immunopathogenic mechanism behind gut dysbiosis, T2DM development and the major known diabetic microvascular complications (retinopathy, neuropathy and nephropathy), the beneficial use of pre- and pro-biotics and fecal microbiota transplantation in T2DM management and new findings and future perspectives in this field.}, } @article {pmid33274207, year = {2020}, author = {Zhan, K and Zheng, H and Li, J and Wu, H and Qin, S and Luo, L and Huang, S}, title = {Gut Microbiota-Bile Acid Crosstalk in Diarrhea-Irritable Bowel Syndrome.}, journal = {BioMed research international}, volume = {2020}, number = {}, pages = {3828249}, pmid = {33274207}, issn = {2314-6141}, abstract = {The occurrence of diarrhea-predominant irritable bowel syndrome (IBS-D) is the result of multiple factors, and its pathogenesis has not yet been clarified. Emerging evidence indicates abnormal changes in gut microbiota and bile acid (BA) metabolism have a close relationship with IBS-D. Gut microbiota is involved in the secondary BA production via deconjugation, 7α-dehydroxylation, oxidation, epimerization, desulfation, and esterification reactions respectively. Changes in the composition and quantity of gut microbiota have an important impact on the metabolism of BAs, which can lead to the occurrence of gastrointestinal diseases. BAs, synthesized in the hepatocytes, play an important role in maintaining the homeostasis of gut microbiota and the balance of glucose and lipid metabolism. In consideration of the complex biological functional connections among gut microbiota, BAs, and IBS-D, it is urgent to review the latest research progress in this field. In this review, we summarized the alterations of gut microbiota in IBS-D and discussed the mechanistic connections between gut microbiota and BA metabolism in IBS-D, which may be involved in activating two important bile acid receptors, G-protein coupled bile acid receptor 1 (TGR5) and farnesoid X receptor (FXR). We also highlight the strategies of prevention and treatment of IBS-D via regulating gut microbiota-bile acid axis, including probiotics, fecal microbiota transplantation (FMT), cholestyramine, and the cutting-edge technology about bacteria genetic engineering.}, } @article {pmid33273738, year = {2020}, author = {Ratner, M}, title = {Microbial cocktails raise bar for C. diff. treatments.}, journal = {Nature biotechnology}, volume = {38}, number = {12}, pages = {1366-1367}, doi = {10.1038/s41587-020-00765-8}, pmid = {33273738}, issn = {1546-1696}, mesh = {Clinical Trials, Phase III as Topic ; Clostridioides difficile/*physiology ; Clostridium Infections/*microbiology/therapy ; Drug Approval ; Fecal Microbiota Transplantation ; Humans ; Spores, Bacterial/physiology ; }, } @article {pmid33273413, year = {2020}, author = {Sabus, A and Merrow, M and Heiden, A and Boster, J and Koo, J and Franklin, ARK}, title = {Fecal Microbiota Transplantation for Treatment of Severe Clostridioides difficile Colitis in a Pediatric Patient With Non-Hodgkin Lymphoma.}, journal = {Journal of pediatric hematology/oncology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MPH.0000000000002023}, pmid = {33273413}, issn = {1536-3678}, abstract = {BACKGROUND: Patients with malignant diseases are at high risk for refractory Clostridioides difficile infections (CDI). Fecal microbiota transplantation (FMT) restores the gastrointestinal microbiome and may be an effective treatment for patients who fail pharmacotherapy. However, FMT is not commonly used in the oncology population because of risk for donor-derived infection.

OBSERVATIONS: The authors report successful use of FMT in a pediatric patient with refractory CDI actively receiving chemotherapy. The patient's symptoms improved 1 day following FMT. He did not experience infectious complications or other adverse effects.

CONCLUSIONS: FMT may be a feasible option for treatment of refractory CDI in pediatric oncology patients.}, } @article {pmid33271427, year = {2020}, author = {Rosel-Pech, C and Chávez-Torres, M and Bekker-Méndez, VC and Pinto-Cardoso, S}, title = {Therapeutic avenues for restoring the gut microbiome in HIV infection.}, journal = {Current opinion in pharmacology}, volume = {54}, number = {}, pages = {188-201}, doi = {10.1016/j.coph.2020.09.010}, pmid = {33271427}, issn = {1471-4973}, abstract = {The interplay between the gut microbiota, the intestinal barrier and the mucosal immune system is profoundly altered in Human Immunodeficiency Virus (HIV) infection. An HIV-associated microbial dysbiotic signature has been difficult to define due to the strong impact of confounders that are intimately linked with HIV infection, namely HIV risk behaviors. When controlling for sexual preference and gender, HIV-associated microbial dysbiotic signatures are characterized by an increase in deleterious taxa and a decrease in beneficial bacteria and their respective metabolic end-products. First attempts to restore the gut microbiota of HIV subjects on Antiretroviral Therapy using Fecal Microbiota Transplantation proved to be safe and reported mild transient engraftment of donor microbiota and no effect on markers of HIV disease progression. This review focuses on the current evidence supporting a role for microbial dysbiosis in HIV pathogenesis, and reviews current microbiome-based therapeutics for restoring the gut microbiota in HIV infection.}, } @article {pmid33263886, year = {2020}, author = {Federici, S and Suez, J and Elinav, E}, title = {Our Microbiome: On the Challenges, Promises, and Hype.}, journal = {Results and problems in cell differentiation}, volume = {69}, number = {}, pages = {539-557}, doi = {10.1007/978-3-030-51849-3_20}, pmid = {33263886}, issn = {0080-1844}, mesh = {Fecal Microbiota Transplantation ; Humans ; *Microbiota ; Prebiotics ; Probiotics ; }, abstract = {The microbiome field is increasingly raising interest among scientists, clinicians, biopharmaceutical entities, and the general public. Technological advances from the past two decades have enabled the rapid expansion of our ability to characterize the human microbiome in depth, highlighting its previously underappreciated role in contributing to multifactorial diseases including those with unknown etiology. Consequently, there is growing evidence that the microbiome could be utilized in medical diagnosis and patient stratification. Moreover, multiple gut microbes and their metabolic products may be bioactive, thereby serving as future potential microbiome-targeting or -associated therapeutics. Such therapies could include new generation probiotics, prebiotics, fecal microbiota transplantations, postbiotics, and dietary modulators. However, microbiome research has also been associated with significant limitations, technical and conceptual challenges, and, at times, "over-hyped" expectations that microbiome research will produce quick solutions to chronic and mechanistically complex human disorders. Herein, we summarize these challenges and also discuss some of the realistic promises associated with microbiome research and its applicability into clinical application.}, } @article {pmid33260902, year = {2020}, author = {Grammatikopoulou, MG and Goulis, DG and Gkiouras, K and Nigdelis, MP and Papageorgiou, ST and Papamitsou, T and Forbes, A and Bogdanos, DP}, title = {Low FODMAP Diet for Functional Gastrointestinal Symptoms in Quiescent Inflammatory Bowel Disease: A Systematic Review of Randomized Controlled Trials.}, journal = {Nutrients}, volume = {12}, number = {12}, pages = {}, pmid = {33260902}, issn = {2072-6643}, support = {97509//MSc in Health and Environmental Factors, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece/ ; }, abstract = {A low FODMAP diet (LFD) has been hypothesized to relieve symptoms of functional gastrointestinal disorders (FGD) in patients with inflammatory bowel disease (IBD). The aim of the study was to systematically review the literature for randomized controlled trials (RCTs) assessing the effectiveness of the LFD in patients with IBD and FGD. Four databases were searched, but a meta-analysis was not performed due to methodological and outcomes heterogeneity. Four RCTs fulfilled the criteria, with three having some concerns in their risk of bias assessment. All interventions compared the LFDs against a "typical" or sham diet, spanning in duration from 21 days to 6 weeks. Quality of life was improved in two RCTs, while revealing inconsistent findings in the third trial, based on different assessment tools. The fecal assays revealed non-significant findings for most variables (fecal weight, pH, water content, gene count, and gut transit time) and inconsistent findings concerning stool frequency and short-chain fatty acids concentration. Levels of fecal calprotectin, CRP, or T-cell phenotype did not differ between intervention and comparator arms. Two RCTs reported a reduction in abdominal pain, while results concerning pain duration and bloating were inconsistent. In one trial, energy intake was considerably reduced among LFD participants. Regarding gut microbiota, no differences were noted. A considerable degree of methodological and outcome heterogeneity was observed, paired with results inconsistency. The available data are not sufficient to justify the claim that an LFD induces relief of FGD symptoms, although it may pave the way to a placebo response.}, } @article {pmid33259159, year = {2020}, author = {Mamoon, L and Olesen, SW}, title = {Fecal Microbiota Transplants Annually and Their Positive Clinical Impact.}, journal = {Clinical and translational gastroenterology}, volume = {11}, number = {11}, pages = {e00247}, pmid = {33259159}, issn = {2155-384X}, abstract = {INTRODUCTION: Although fecal microbiota transplantation (FMT) is a recommended, clinically efficacious, and cost-effective treatment for recurrent Clostridioides difficile infection (CDI), the scale of FMT use in the United States is unknown.

METHODS: We developed a population-level CDI model.

RESULTS: We estimated that 48,000 FMTs could be performed annually, preventing 32,000 CDI recurrences.

DISCUSSION: Improving access to FMT could lead to tens of thousands fewer C. difficile episodes per year.}, } @article {pmid33256346, year = {2020}, author = {He, Z and Ye, F and Zhang, GX}, title = {[Advances of fecal microbiota transplantation in improving the prognosis of cancer patients].}, journal = {Zhonghua nei ke za zhi}, volume = {59}, number = {12}, pages = {1003-1008}, doi = {10.3760/cma.j.cn112138-20200305-00189}, pmid = {33256346}, issn = {0578-1426}, mesh = {*Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Neoplasms/therapy ; Prognosis ; Treatment Outcome ; }, } @article {pmid33255588, year = {2020}, author = {Ballini, A and Scacco, S and Boccellino, M and Santacroce, L and Arrigoni, R}, title = {Microbiota and Obesity: Where Are We Now?.}, journal = {Biology}, volume = {9}, number = {12}, pages = {}, pmid = {33255588}, issn = {2079-7737}, abstract = {Genetic and environmental factors are underlying causes of obesity and other metabolic diseases, so it is therefore difficult to find suitable and effective medical treatments. However, without a doubt, the gut microbiota-and also the bacteria present in the oral cavity-act as key factors in the development of these pathologies, yet the mechanisms have not been fully described. Certainly, a more detailed knowledge of the structure of the microbiota-composition, intra- and inter-species relationships, metabolic functions-could be of great help in counteracting the onset of obesity. Identifying key bacterial species will allow us to create a database of "healthy" bacteria, making it possible to manipulate the bacterial community according to metabolic and clinical needs. Targeting gut microbiota in clinical care as treatment for obesity and health-related complications-even just for weight loss has become a real possibility. In this topical review we provide an overview of the role of the microbiota on host energy homeostasis and obesity-related metabolic diseases, therefore addressing the therapeutic potential of novel and existing strategies (impact of nutrition/dietary modulation, and fecal microbiota transplantation) in the treatment of metabolic disease.}, } @article {pmid33255454, year = {2020}, author = {Barba, C and Soulage, CO and Caggiano, G and Glorieux, G and Fouque, D and Koppe, L}, title = {Effects of Fecal Microbiota Transplantation on Composition in Mice with CKD.}, journal = {Toxins}, volume = {12}, number = {12}, pages = {}, pmid = {33255454}, issn = {2072-6651}, abstract = {BACKGROUND: Chronic kidney disease (CKD) is a renal disorder characterized by the accumulation of uremic toxins with limited strategies to reduce their concentrations. A large amount of data supports the pivotal role of intestinal microbiota in CKD complications and as a major source of uremic toxins production. Here, we explored whether fecal microbiota transplantation (FMT) could be attenuated in metabolic complication and uremic toxin accumulation in mice with CKD.

METHODS: Kidney failure was chemically induced by a diet containing 0.25% (w/w) of adenine for four weeks. Mice were randomized into three groups: control, CKD and CKD + FMT groups. After four weeks, CKD mice underwent fecal microbiota transplantation (FMT) from healthy mice or phosphate buffered saline as control. The gut microbiota structure, uremic toxins plasmatic concentrations, and metabolic profiles were explored three weeks after transplantation.

RESULTS: Associated with the increase of alpha diversity, we observed a noticeable improvement of gut microbiota disturbance, after FMT treatment. FMT further decreased p-cresyl sulfate accumulation and improved glucose tolerance. There was no change in kidney function.

CONCLUSIONS: These data indicate that FMT limited the accumulation of uremic toxins issued from intestinal cresol pathway by a beneficial effect on gut microbiota diversity. Further studies are needed to investigate the FMT efficiency, the timing and feces amount for the transplantation before, to become a therapeutic option in CKD patients.}, } @article {pmid33254107, year = {2020}, author = {Waldbaum, C and López, F and Antelo, P and Sorda, J}, title = {[Faecal microbiota transplantation for Clostridioides difficile infection].}, journal = {Medicina}, volume = {80}, number = {6}, pages = {633-639}, pmid = {33254107}, issn = {1669-9106}, mesh = {Adult ; Aged ; Aged, 80 and over ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/therapy ; Fecal Microbiota Transplantation ; Humans ; Male ; Middle Aged ; Recurrence ; Treatment Outcome ; }, abstract = {Clostridiodes difficile infection (CDi) is the most common cause of nosocomial diarrhea. Vancomycin, associated or not to metronidazol, is the treatment of choice. However, the rate of treatment failure has increased over the last years and fecal microbiota transplantation (FMT) has emerged as a therapeutic option. To evaluate safety and efficacy of FMT were enrolled 21 hospitalized patients with refractory or recurrent CDi between 2016 and 2019. Fourteen (66%) patients were men and the average age was 76.5 years (range 33-92). Ten had recurrent and 11 refractory CDi, and 18 presented severe and 3 fulminant clinical forms. In 20 cases the FMT was delivered through a nasojejunal tube and in one patient with ileo via enema infusion. Frozen fecal from a stool bank were administered in 20 and in the remaining was used fresh fecal matter. The rate of resolution was observed in 20 patients (95.2%) and none presented recurrence. The response rate was similar in recurrent or refractory forms (9/10 vs 11/11 respectively). One patient with osteomyelitis and multiple organ failure received 2 FMT without response and died. Seven patients (31%) presented mild and self-limited adverse effects. FMT has shown a high efficacy as rescue treatment in cases with refractory or recurrent CDi regardless of severity, with mild side effects. Availability of a stool banks provide reliable, timely and equitable access to FMT for CDi.}, } @article {pmid33253686, year = {2021}, author = {Acharya, C and Bajaj, JS}, title = {Chronic Liver Diseases and the Microbiome-Translating Our Knowledge of Gut Microbiota to Management of Chronic Liver Disease.}, journal = {Gastroenterology}, volume = {160}, number = {2}, pages = {556-572}, doi = {10.1053/j.gastro.2020.10.056}, pmid = {33253686}, issn = {1528-0012}, support = {R21 TR003095/TR/NCATS NIH HHS/United States ; }, abstract = {Chronic liver disease is reaching epidemic proportions with the increasing prevalence of obesity, nonalcoholic liver disease, and alcohol overuse worldwide. Most patients are not candidates for liver transplantation even if they have end-stage liver disease. There is growing evidence of a gut microbial basis for many liver diseases, therefore, better diagnostic, prognostic, and therapeutic approaches based on knowledge of gut microbiota are needed. We review the questions that need to be answered to successfully translate our knowledge of the intestinal microbiome and the changes associated with liver disease into practice.}, } @article {pmid33249800, year = {2020}, author = {Sehgal, K and Khanna, S}, title = {Gut microbiome and checkpoint inhibitor colitis.}, journal = {Intestinal research}, volume = {}, number = {}, pages = {}, doi = {10.5217/ir.2020.00116}, pmid = {33249800}, issn = {1598-9100}, abstract = {Immune checkpoint inhibitor therapies such as ipilimumab, are increasingly being used as a treatment option for a variety of cancers, including metastatic melanoma and have demonstrated effectively a prolonged survival. These agents have an immunological mode of action that predisposes patients to a number of immune-related adverse events, colitis being one of the most commonly encountered complications. The pathogenesis for the development of colitis is unclear, and there is a growing consensus that the ecosystem of the gastrointestinal microbiota plays a significant role. Based on this suspected connection, studies are being carried out to explore the changes in the microbiota in patients on these medications who develop colitis. Conceivably, the modulation of the gut microbiota could offer a therapeutic benefit. Fecal microbiota transplantation is one therapeutic option that is currently being investigated, though there are still more data needed to evaluate its efficacy. In this review, we recapitulate the mechanisms of action of immune checkpoint inhibitors, their adverse events, with a focus on colitis and the role gut microbiota are suspected to play, and finally discuss the microbiota modulation therapies being investigated.}, } @article {pmid33246175, year = {2021}, author = {Doifode, T and Giridharan, VV and Generoso, JS and Bhatti, G and Collodel, A and Schulz, PE and Forlenza, OV and Barichello, T}, title = {The impact of the microbiota-gut-brain axis on Alzheimer's disease pathophysiology.}, journal = {Pharmacological research}, volume = {164}, number = {}, pages = {105314}, doi = {10.1016/j.phrs.2020.105314}, pmid = {33246175}, issn = {1096-1186}, abstract = {The gut microbiota is a complex ecosystem that comprises of more than 100 trillion symbiotic microbial cells. The microbiota, the gut, and the brain form an association, 'the microbiota-gut-brain axis,' and synchronize the gut with the central nervous system and modify the behavior and brain immune homeostasis. The bidirectional communication between gut and brain occurs via the immune system, the vagus nerve, the enteric nervous system, and microbial metabolites, including short-chain fatty acids (SCFAs), proteins, and tryptophan metabolites. Recent studies have implicated the gut microbiota in many neurodegenerative diseases, including Alzheimer's disease (AD). In this review, we present an overview of gut microbiota, including Firmicutes, Bacteroidetes, SCFA, tryptophan, bacterial composition, besides age-related changes in gut microbiota composition, the microbiota-gut-brain axis pathways, the role of gut metabolites in amyloid-beta clearance, and gut microbiota modulation from experimental and clinical AD models. Understanding the role of the microbiota may provide new targets for treatment to delay the onset, progression, or reverse AD, and may help in reducing the prevalence of AD.}, } @article {pmid33243141, year = {2020}, author = {Dang, XF and Qing-Xi Wang, and Yin, Z and Sun, L and Yang, WH}, title = {Recurrence of moderate to severe ulcerative colitis after fecal microbiota transplantation treatment and the efficacy of re-FMT: a case series.}, journal = {BMC gastroenterology}, volume = {20}, number = {1}, pages = {401}, pmid = {33243141}, issn = {1471-230X}, abstract = {BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), the pathogenesis of which is complicated, and it is difficult to treat. In recent years, the emerging fecal microbiota transplantation (FMT) has shown good effects in UC treatment and is therefore accepted by increasing numbers of patients. Our hospital has carried out FMT since 2017, and has achieved good results in UC treatment. We have found in our clinical work that the efficacy of re-FMT after recurrence decreased. This is difference from reported literatures. In order to attract clinical attention, here we selected typical cases for analysis.

METHODS: Among all UC patients who received FMT in our hospital, 12 patients with moderate to severe UC were selected. They all received multiple FMT and were followed up for 52 weeks. Besides, none of them had other underlying diseases. Colonoscopy images of patients were presentated, SCCAI and UCDAI were used assess the effect of FMT.

RESULTS: On the whole, FMT has a significant effect on moderate to severe UC. Of the 12 patients, 11 (91.7%) achieved a clinical response, 9 (75.0%) achieved clinical remission, and only one patient did not respond to FMT treatment. However, 6 patients relapsed within 52 weeks after remission, with a recurrence rate of 54.5%. Four of the six relapsed patients received FMT again, but the efficacy of FMT after relapse was significantly lower than that of the initial FMT. Fortunately, compared to before the initial FMT treatment, the severity of the disease after relapse was significantly reduced.

CONCLUSION: FMT has a good effect on the relief of moderate to severe UC. However, the effect of FMT treatment after relapse is reduced. For patients who relapse after remission, the efficacy of FMT reapplication requires more experiments to verify.}, } @article {pmid33242652, year = {2020}, author = {Sun, N and Hu, H and Wang, F and Li, L and Zhu, W and Shen, Y and Xiu, J and Xu, Q}, title = {Antibiotic-induced microbiome depletion in adult mice disrupts blood-brain barrier and facilitates brain infiltration of monocytes after bone-marrow transplantation.}, journal = {Brain, behavior, and immunity}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.bbi.2020.11.032}, pmid = {33242652}, issn = {1090-2139}, abstract = {The crosstalk between intestinal bacteria and the central nervous system, so called "the gut-brain axis", is critically important for maintaining brain homeostasis and function. This study aimed to investigate the integrity of the blood-brain barrier (BBB) and migration of bone marrow (BM)-derived cells to the brain parenchyma after intestinal microbiota depletion in adult mice. Gut microbiota dysbiosis was induced with 5 non-absorbable antibiotics in drinking water in mice that had received bone marrow transplantation (BMT) from green fluorescent protein (GFP) transgenic mice. Antibiotic-induced microbiome depletion reduced expression of tight-junction proteins of the brain blood vessels and increased BBB permeability. Fecal microbiota transplantation of antibiotics treated mice with pathogen-free gut microbiota decreased BBB permeability and up-regulated the expression of tight junction proteins. The BM-derived GFP+ cells were observed to infiltrate specific brain regions, including the nucleus accumbens (NAc), the septal nucleus (SPT) and the hippocampus (CA3). The infiltrated cells acquired a ramified microglia-like morphology and Iba1, a microglia marker, was expressed in all GFP+ cells, whereas they were negative for the astrocyte marker GFAP. Furthermore, treatment with CCR2 antagonist (RS102895) suppressed the recruitment of BM-derived monocytes to the brain. We report for the first time the migration of BM-derived monocytes to the brain regions involved in regulating emotional behaviors after depletion of intestinal microbiota in BMT background mice. However, mechanisms responsible for the migration and functions of the microglia-like infiltrated cells in the brain need further investigation. These findings indicate that monocyte recruitment to the brain in response to gut microbiota dysbiosis may represent a novel cellular mechanism that contributes to the development of brain disorders.}, } @article {pmid33241674, year = {2020}, author = {Henig, I and Yehudai-Ofir, D and Zuckerman, T}, title = {The clinical role of the gut microbiome and fecal microbiota transplantation in allogeneic stem cell transplantation.}, journal = {Haematologica}, volume = {Online ahead of print}, number = {}, pages = {}, doi = {10.3324/haematol.2020.247395}, pmid = {33241674}, issn = {1592-8721}, abstract = {Outcomes of allogeneic hematopoietic stem cell transplantation (allo- HSCT) have improved in the recent decade; however, infections and graft-versus-host disease remain two leading complications significantly contributing to early transplant-related mortality. In past years, the human intestinal microbial composition (microbiota) has been found to be associated with various disease states, including cancer, response to cancer immunotherapy and to modulate the gut innate and adaptive immune response. In the setting of allo-HSCT, the intestinal microbiota diversity and composition appear to have an impact on infection risk, mortality and overall survival. Microbial metabolites have been shown to contribute to the health and integrity of intestinal epithelial cells during inflammation, thus mitigating graft-versus-host disease in animal models. While the cause-andeffect relationship between the intestinal microbiota and transplant-associated complications has not yet been fully elucidated, the above findings have already resulted in the implementation of various interventions aiming to restore the intestinal microbiota diversity and composition. Among others, these interventions include the administration of fecal microbiota transplantation. The present review, based on published data, is intended to define the role of the latter approach in the setting of allo-HSCT.}, } @article {pmid33241161, year = {2020}, author = {Olesen, SW}, title = {Power calculations for detecting differences in efficacy of fecal microbiota donors.}, journal = {Contemporary clinical trials communications}, volume = {20}, number = {}, pages = {100674}, pmid = {33241161}, issn = {2451-8654}, abstract = {Fecal microbiota transplantation (FMT) is a recommended therapy for recurrent Clostridioides difficile infection and is being investigated as a potential therapy for dozens of other indications, notably inflammatory bowel disease. The immense variability in human stool, combined with anecdotal reports from FMT studies, have suggested the existence of "donor effects", in which stool from some FMT donors is more efficacious than stool from other donors. In this study, simulated clinical trials were used to estimate the number of patients that would be required to detect donor effects under a variety of study designs. In most cases, reliable detection of donor effects required more than 100 patients treated with FMT. These results suggest that previous reports of donor effects need to be verified with results from large clinical trials and that patient biomarkers may be the most promising route to robustly identifying donor effects.}, } @article {pmid33235890, year = {2020}, author = {Olesen, SW and Zaman, A and Osman, M and Ramakrishna, B}, title = {Modeling Donor Screening Strategies to Reduce the Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Transmission via Fecal Microbiota Transplantation.}, journal = {Open forum infectious diseases}, volume = {7}, number = {11}, pages = {ofaa499}, doi = {10.1093/ofid/ofaa499}, pmid = {33235890}, issn = {2328-8957}, abstract = {The potential for transmission of severe acute respiratory syndrome coronavirus 2 shed in stool via fecal microbiota transplantation is not yet known, and the effectiveness of various testing strategies to prevent fecal microbiota transplantation-based transmission has also not yet been quantified. In this study, we use a mathematical model to simulate the utility of different testing strategies.}, } @article {pmid33233042, year = {2020}, author = {Xi, M and Li, J and Hao, G and An, X and Song, Y and Wei, H and Ge, W}, title = {Stachyose increases intestinal barrier through Akkermansia muciniphila and reduces gut inflammation in germ-free mice after human fecal transplantation.}, journal = {Food research international (Ottawa, Ont.)}, volume = {137}, number = {}, pages = {109288}, doi = {10.1016/j.foodres.2020.109288}, pmid = {33233042}, issn = {1873-7145}, abstract = {Early life is a crucial period for the development of the intestinal microbiota and is related to the body's immunity. Yet research is lacking regarding the effect of stachyose on infants gut microbiomes at this stage and the mechanism is not clear. Therefore, in this experiment, feces samples collected from infants were transplanted into germ-free mice, to explore the effect of stachyose on the intestinal microbiota and host gut barrier. We found that stachyose promoted the relative abundance of A. muciniphila in human feces; enhanced the symbiotic relationships of A. muciniphila; increased the short-chain fatty acid level, and secretory immunoglobulin A level; reduced the levels of lipopolysaccharide, IL-1, IL-17 and TNF-α through downregulated the expression of NF-κB; increased expression of tight junction proteins (occludin and ZO-1) and goblet cell through A. muciniphila. The intake of stachyose is conducive to promoting the proliferation of beneficial bacteria and enhancing the intestinal barrier in germ-free mice. This research provides a theoretical basis for the use of prebiotics to improve intestinal microbiota and barrier in humans.}, } @article {pmid33232785, year = {2020}, author = {Ait Chait, Y and Mottawea, W and Tompkins, TA and Hammami, R}, title = {Nutritional and therapeutic approaches for protecting human gut microbiota from psychotropic treatments.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {}, number = {}, pages = {110182}, doi = {10.1016/j.pnpbp.2020.110182}, pmid = {33232785}, issn = {1878-4216}, abstract = {Emerging evidence highlighted the essential role played by the microbiota-gut-brain axis in maintaining human homeostasis, including nutrition, immunity, and metabolism. Much recent work has linked the gut microbiota to many psychiatric and neurodegenerative disorders such as depression, schizophrenia, and Alzheimer's disease. Shared gut microbiota alterations or dysbiotic microbiota have been identified in these separate disorders relative to controls. Much attention has focused on the bidirectional interplay between the gut microbiota and the brain, establishing gut dysbiotic status as a critical factor in psychiatric disorders. Still, the antibiotic-like effect of psychotropic drugs, medications used for the treatment of these disorders, on gut microbiota is largely neglected. In this review, we summarize the current findings on the impact of psychotropics on gut microbiota and how their antimicrobial potency can trigger dysbiosis. We also discuss the potential therapeutic strategies, including probiotics, prebiotics, and fecal transplantation, to attenuate the dysbiosis related to psychotropics intake.}, } @article {pmid33230077, year = {2020}, author = {Popov, J and Hartung, E and Hill, L and Chauhan, U and Pai, N}, title = {Pediatric Patient and Parent Perceptions of Fecal Microbiota Transplantation for the Treatment of Ulcerative Colitis.}, journal = {Journal of pediatric gastroenterology and nutrition}, volume = {}, number = {}, pages = {}, doi = {10.1097/MPG.0000000000002995}, pmid = {33230077}, issn = {1536-4801}, abstract = {BACKGROUND: Fecal microbiota transplant (FMT) has gained attention for its role in the treatment of ulcerative colitis (UC). Acceptance of this treatment, particularly among children and their parents, is an important aspect of assessing its feasibility for pediatric inflammatory bowel disease care. To date, no studies have assessed FMT acceptance among pediatric patients who underwent FMT treatment. Here, we explored the perceptions and experiences of FMT in a population of pediatric UC patients who participated in a recent FMT pilot randomized controlled trial.

METHODS: Children who received bi-weekly FMT treatments for six-weeks through a clinical trial (NCT02606032) and their parents participated in face-to-face, semi-structured interviews led by study investigators. Interviews were audiotaped, transcribed, and analyzed using validated qualitative research methods.

RESULTS: Eight patients and eight parents were interviewed, with qualitative data summarized across four themes and 11 subthemes. The majority of participants perceived FMT as a "natural treatment" and cited lack of response to conventional medications and fear of medication side-effects as motivators for pursuing FMT. Pre-treatment, patients and parents expressed concerns regarding physical discomfort with FMT administration; post-treatment, most patients reported feeling "completely normal". Both patients and parents uniformly expressed interest in pursuing FMT again in the future if available. Convenience of medication therapies, and perceived naturality and efficacy of FMT were all endorsed.

CONCLUSIONS: This is the first study to describe pediatric and parent experiences receiving FMT. This information is valuable to develop and encourage future FMT trials involving children. Pre-treatment, concerns about FMT were common. Post-treatment, patients reported tolerance to FMT and a desire to continue receiving this therapy if available. Further trials of FMT in UC are needed. Investigators should include pediatric patients without concern of acceptance.}, } @article {pmid33227623, year = {2021}, author = {Araujo, DV and Watson, GA and Oliva, M and Heirali, A and Coburn, B and Spreafico, A and Siu, LL}, title = {Bugs as drugs: The role of microbiome in cancer focusing on immunotherapeutics.}, journal = {Cancer treatment reviews}, volume = {92}, number = {}, pages = {102125}, doi = {10.1016/j.ctrv.2020.102125}, pmid = {33227623}, issn = {1532-1967}, mesh = {Animals ; Gastrointestinal Microbiome/*physiology ; Humans ; Immunotherapy/*methods ; Mice ; Microbiota/*physiology ; Neoplasms/*drug therapy ; Prebiotics/*standards ; Probiotics/pharmacology/*therapeutic use ; }, abstract = {The human microbiome comprising microorganisms, their collective genomes and metabolic products has gained tremendous research interest in oncology, as multiple cohorts and case studies have demonstrated discernible interpatient differences in this ecosystem based on clinical variables including disease type, stage, diet, antibiotic usage, cancer treatments, therapeutic responses and toxicities. The modulation of the gut microbiome is the subject of many ongoing preclinical and clinical investigations, through the manipulation of diet, as well as the use of prebiotics, probiotics, specific antibiotics, fecal microbial transplantation, microbial consortia and stool substitutes. Standardization and quality control are needed to maximize the information being generated in this growing field, ranging from technical assays to measure microbiome composition, to methodological aspects in the analysis and reporting of results. Proof-of-mechanism and proof-of-concept clinical trials with appropriate controls are needed to confirm or refute the feasibility, safety and ultimately the clinical utility of human microbiome modulation in cancer patients.}, } @article {pmid33225985, year = {2020}, author = {Huang, H and Ren, Z and Gao, X and Hu, X and Zhou, Y and Jiang, J and Lu, H and Yin, S and Ji, J and Zhou, L and Zheng, S}, title = {Integrated analysis of microbiome and host transcriptome reveals correlations between gut microbiota and clinical outcomes in HBV-related hepatocellular carcinoma.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {102}, pmid = {33225985}, issn = {1756-994X}, support = {81721091//Innovative Research Groups of National Natural Science Foundation of China/ ; 2019-I2M-5-030/2019RU019//Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Sciences/ ; 2017ZX100203205//National S&T Major Project of China/ ; 2018ZX10301201-008//National S&T Major Project of China/ ; LGF18C100001//Zhejiang Provincial Public Welfare Technology Research Program/ ; 2016C04003//Zhejiang International Science and Technology Cooperation Project/ ; 2018YFC2000501//National Key Research and Development Program of China/ ; }, abstract = {BACKGROUND: The gut-liver axis plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC). However, the correlations between the gut microbiome and the liver tumor transcriptome in patients with HCC and the impact of the gut microbiota on clinical outcome are less well-understood.

METHODS: Fecal samples collected from HBV-related HCC patients (n = 113) and healthy volunteers (n = 100) were subjected to 16S rRNA sequencing of the microbiome. After a rigorous selection process, 32 paired tumor and adjacent non-tumor liver tissues from the HCC group were subjected to next-generation sequencing (NGS) RNA-seq. The datasets were analyzed individually and integrated with clinical characteristics for combined analysis using bioinformatics approaches. We further verified the potential of the gut microbiota to predict clinical outcome by a random forest model and a support vector machine model.

RESULTS: We found that Bacteroides, Lachnospiracea incertae sedis, and Clostridium XIVa were enriched in HCC patients with a high tumor burden. By integrating the microbiome and transcriptome, we identified 31 robust associations between the above three genera and well-characterized genes, indicating possible mechanistic relationships in tumor immune microenvironment. Clinical characteristics and database analysis suggested that serum bile acids may be important communication mediators between these three genera and the host transcriptome. Finally, among these three genera, six important microbial markers associated with tumor immune microenvironment or bile acid metabolism showed the potential to predict clinical outcome (AUC = 81%).

CONCLUSIONS: This study revealed that changes in tumor immune microenvironment caused by the gut microbiota via serum bile acids may be important factors associated with tumor burden and adverse clinical outcome. Gut microbes can be used as biomarkers of clinical features and outcomes, and the microbe-associated transcripts of host tumors can partly explain how gut microbiota promotes HCC pathogenesis.}, } @article {pmid33225575, year = {2020}, author = {Whon, TW and Kim, HS and Shin, NR and Jung, ES and Tak, EJ and Sung, H and Jung, MJ and Jeong, YS and Hyun, DW and Kim, PS and Jang, YK and Lee, CH and Bae, JW}, title = {Male castration increases adiposity via small intestinal microbial alterations.}, journal = {EMBO reports}, volume = {}, number = {}, pages = {e50663}, pmid = {33225575}, issn = {1469-3178}, support = {918011-04-1-SB010//Ministry of Agriculture, Food and Rural Affairs (MAFRA)/ ; NRF-2018R1A5A1025077//National Research Foundation of Korea (NRF)/ ; NRF-2020R1A2C3012797//National Research Foundation of Korea (NRF)/ ; NRF-2017M3A9F3046549//National Research Foundation of Korea (NRF)/ ; }, abstract = {Castration of young males is widely used in the cattle industry to improve meat quality, but the mechanism linking hypogonadism and host metabolism is not clear. Here, we use metataxonomic and metabolomic approaches to evaluate the intestinal microbiota and host metabolism in male, castrated male (CtM), and female cattle. After pubescence, the CtM cattle harbor distinct ileal microbiota dominated by the family Peptostreptococcaceae and exhibit distinct serum and muscle amino acid profiles (i.e., highly abundant branched-chain amino acids), with increased extra- and intramuscular fat storage. We also evaluate the causative factor(s) that underpin the alteration of the intestinal microbiota and host metabolic phenotype in response to hypogonadism. Castration of male mice phenocopies both the intestinal microbial alterations and obese-prone metabolism observed in cattle. Antibiotic treatment and fecal microbiota transplantation experiments in a mouse model confirm that the intestinal microbial alterations associated with hypogonadism are a key contributor to the obese phenotype in the CtM animals. Collectively, targeting the gut microbiota is a potential therapeutic strategy for the treatment of both hypogonadism and obesity.}, } @article {pmid33222603, year = {2020}, author = {Zhang, XY and Chen, J and Yi, K and Peng, L and Xie, J and Gou, X and Peng, T and Tang, L}, title = {Phlorizin ameliorates obesity-associated endotoxemia and insulin resistance in high-fat diet-fed mice by targeting the gut microbiota and intestinal barrier integrity.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1-18}, pmid = {33222603}, issn = {1949-0984}, abstract = {Phlorizin (PHZ) is one of phytonutrients in apples that contributes to the health-promoting effect implicated by the saying, 'an apple a day keeps the doctor away'. PHZ was firstly identified as a competitive inhibitor of sodium-glucose co-transporters-2 (SGLT2); however, its low bioavailability makes it hard to fully explain its pharmacological mechanisms. This study aimed to investigate the ameliorating effect of PHZ on high-fat diet (HFD)-induced obesity via modulating the "gut microbiota-barrier axis". Firstly, C57BL/6 J mice were fed a normal chow diet (NCD) or HFD coadministered with or without PHZ for 12 weeks. Our results showed that PHZ supplementation significantly reduced HFD-induced body weight gain (P < .001), alleviated metabolic disorders (MDs) like insulin resistance (P < .001) and elevation of serum lipopolysaccharides (LPS) (P < .001), attenuated HFD-induced gut microbiota alterations, enhanced short-chain fatty acids (SCFAs) production (P < .001), and inhibited fecal LPS production (P < .001). To investigate the role of the fecal microbiota in the observed beneficial effects, a fecal microbiota transplantation (FMT) experiment was performed by transplanting the feces of the four groups of mice (as donor mice) daily collected from the fourth week to a new batch of acclimatized HFD-fed mice. Our results confirmed that feeding the gut contents of the PHZ-modulated mice could attenuate HFD-induced MDs, accompanied by enhanced glucagon-like peptide 2 (GLP-2) secretion (P < .001) and restoration of HFD-induced damage in the gut epithelial barrier. This study has provided evidence that the "gut microbiota-barrier axis" was an alternative target for the anti-obesity effect of PHZ. This work has also provided an explanation for the high efficacy of PHZ despite the low bioavailability, and PHZ holds great potential to be developed as a functional food ingredient.}, } @article {pmid33208178, year = {2020}, author = {Li, N and Zuo, B and Huang, S and Zeng, B and Han, D and Li, T and Liu, T and Wu, Z and Wei, H and Zhao, J and Wang, J}, title = {Spatial heterogeneity of bacterial colonization across different gut segments following inter-species microbiota transplantation.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {161}, pmid = {33208178}, issn = {2049-2618}, abstract = {BACKGROUND: The microbiota presents a compartmentalized distribution across different gut segments. Hence, the exogenous microbiota from a particular gut segment might only invade its homologous gut location during microbiota transplantation. Feces as the excreted residue contain most of the large-intestinal microbes but lack small-intestinal microbes. We speculated that whole-intestinal microbiota transplantation (WIMT), comprising jejunal, ileal, cecal, and colonic microbiota, would be more effective for reshaping the entire intestinal microbiota than conventional fecal microbiota transplantation fecal microbiota transplantation (FMT).

RESULTS: We modeled the compartmentalized colonization of the gut microbiota via transplanting the microbiota from jejunum, ileum, cecum, and colon, respectively, into the germ-free mice. Transplanting jejunal or ileal microbiota induced more exogenous microbes' colonization in the small intestine (SI) of germ-free mice rather than the large intestine (LI), primarily containing Proteobacteria, Lactobacillaceae, and Cyanobacteria. Conversely, more saccharolytic anaerobes from exogenous cecal or colonic microbiota, such as Bacteroidetes, Prevotellaceae, Lachnospiraceae, and Ruminococcaceae, established in the LI of germ-free mice that received corresponding intestinal segmented microbiota transplantation. Consistent compartmentalized colonization patterns of microbial functions in the intestine of germ-free mice were also observed. Genes related to nucleotide metabolism, genetic information processing, and replication and repair were primarily enriched in small-intestinal communities, whereas genes associated with the metabolism of essential nutrients such as carbohydrates, amino acids, cofactors, and vitamins were mainly enriched in large-intestinal communities of germ-free mice. Subsequently, we compared the difference in reshaping the community structure of germ-free mice between FMT and WIMT. FMT mainly transferred LI-derived microorganisms and gene functions into the recipient intestine with sparse SI-derived microbes successfully transplanted. However, WIMT introduced more SI-derived microbes and associated microbial functions to the recipient intestine than FMT. Besides, WIMT also improved intestinal morphological development as well as reduced systematic inflammation responses of recipients compared with FMT.

CONCLUSIONS: Segmented exogenous microbiota transplantation proved the spatial heterogeneity of bacterial colonization along the gastrointestinal tract, i.e., the microbiota from one specific location selectively colonizes its homologous gut region. Given the lack of exogenous small-intestinal microbes during FMT, WIMT may be a promising alternative for conventional FMT to reconstitute the microbiota across the entire intestinal tract. Video Abstract.}, } @article {pmid33205871, year = {2020}, author = {Perttu, L and Jonna, J and Anna, H and Eero, M and Markku, H and Jari, P and Jari, K and Veli-Jukka, A and Jyrki, T and Reetta, S and Perttu, A}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome-which improvements are required? Authors' reply.}, journal = {Alimentary pharmacology & therapeutics}, volume = {52}, number = {11-12}, pages = {1754-1755}, doi = {10.1111/apt.16122}, pmid = {33205871}, issn = {1365-2036}, mesh = {*Fecal Microbiota Transplantation ; Feces ; Humans ; *Irritable Bowel Syndrome/therapy ; }, } @article {pmid33205867, year = {2020}, author = {El-Salhy, M and Hausken, T and Gunnar Hatlebakk, J}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome-which improvements are required?.}, journal = {Alimentary pharmacology & therapeutics}, volume = {52}, number = {11-12}, pages = {1752-1753}, doi = {10.1111/apt.16112}, pmid = {33205867}, issn = {1365-2036}, mesh = {Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; }, } @article {pmid33204401, year = {2020}, author = {Li, J and Han, J and Lv, J and Wang, S and Qu, L and Jiang, Y}, title = {Saikosaponin A-Induced Gut Microbiota Changes Attenuate Severe Acute Pancreatitis through the Activation of Keap1/Nrf2-ARE Antioxidant Signaling.}, journal = {Oxidative medicine and cellular longevity}, volume = {2020}, number = {}, pages = {9217219}, pmid = {33204401}, issn = {1942-0994}, abstract = {Objective: Severe acute pancreatitis (SAP) is a serious and life-threatening disease associated with multiple organ failure and a high mortality rate and is accompanied by distinct oxidative stress and inflammatory responses. Saikosaponin A has strong antioxidant properties and can affect the composition of gut microbiota. We sought to determine the effects of Saikosaponin A interventions on SAP by investigating the changes of gut microbiota and related antioxidant signaling.

Methods: A SAP model was established in Sprague-Dawley (SD) rats through the injection of sodium taurocholate into the biliopancreatic duct and confirmed by elevated levels of serum lipase and amylase. The model was fed a standard diet either with saline solution or with Saikosaponin A. Fecal microbiota transplantation (FMT) from Saikosaponin A-induced rats into the rat model was performed to test the effects of gut microbiota. The composition of gut microbiota was analyzed by using 16S rRNA gene sequencing. We measured apoptotic status, inflammatory biomarkers, and Keap1-Nrf2-ARE ((Kelch-like ECH-associated protein 1) nuclear factor erythroid 2-related factor 2-antioxidant response element) antioxidant signaling.

Results: Saikosaponin A intervention attenuated SAP lesions and reduced the levels of serum amylase and lipase, oxidative stress, and inflammatory responses by reducing pathological scores and affecting the serum level of oxidative and inflammatory factors. Meanwhile, the expression of Keap1-Nrf2-ARE was increased. Saikosaponin A intervention improved microbiota composition by increasing the relative abundance of Lactobacillus and Prevotella species. FMT resulted in similar results as those caused by the Saikosaponin A intervention, suggesting Saikosaponin A may exert its function via the improvement of gut microbiota composition.

Conclusions: Saikosaponin A-induced gut microbiota changes attenuate SAP progression in the rat model and may be a potential natural drug for adjuvant treatment of SAP. Further work is needed to clear up the points.}, } @article {pmid33203880, year = {2020}, author = {Song, L and Liu, Z and Hu, HH and Yang, Y and Li, TY and Lin, ZZ and Ye, J and Chen, J and Huang, X and Liu, DT and Zhou, J and Shi, Y and Zhao, H and Xie, C and Chen, L and Song, E and Lin, SY and Lin, SC}, title = {Proto-oncogene Src links lipogenesis via lipin-1 to breast cancer malignancy.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {5842}, pmid = {33203880}, issn = {2041-1723}, mesh = {Animals ; Breast Neoplasms/genetics/metabolism/mortality/*pathology ; CSK Tyrosine-Protein Kinase/*genetics/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Female ; Humans ; Lipogenesis/physiology ; Male ; Mammary Neoplasms, Animal/genetics/pathology ; Mice, Mutant Strains ; Mice, Transgenic ; Phosphatidate Phosphatase/genetics/*metabolism ; Phosphorylation ; Tyrosine/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Increased lipogenesis has been linked to an increased cancer risk and poor prognosis; however, the underlying mechanisms remain obscure. Here we show that phosphatidic acid phosphatase (PAP) lipin-1, which generates diglyceride precursors necessary for the synthesis of glycerolipids, interacts with and is a direct substrate of the Src proto-oncogenic tyrosine kinase. Obesity-associated microenvironmental factors and other Src-activating growth factors, including the epidermal growth factor, activate Src and promote Src-mediated lipin-1 phosphorylation on Tyr398, Tyr413 and Tyr795 residues. The tyrosine phosphorylation of lipin-1 markedly increases its PAP activity, accelerating the synthesis of glycerophospholipids and triglyceride. Alteration of the three tyrosine residues to phenylalanine (3YF-lipin-1) disables lipin-1 from mediating Src-enhanced glycerolipid synthesis, cell proliferation and xenograft growth. Re-expression of 3YF-lipin-1 in PyVT;Lpin1-/- mice fails to promote progression and metastasis of mammary tumours. Human breast tumours exhibit increased p-Tyr-lipin-1 levels compared to the adjacent tissues. Importantly, statistical analyses show that levels of p-Tyr-lipin-1 correlate with tumour sizes, lymph node metastasis, time to recurrence and survival of the patients. These results illustrate a direct lipogenesis-promoting role of the pro-oncogenic Src, providing a mechanistic link between obesity-associated mitogenic signaling and breast cancer malignancy.}, } @article {pmid33198506, year = {2020}, author = {Duan, H and Yu, L and Tian, F and Zhai, Q and Fan, L and Chen, W}, title = {Antibiotic-induced gut dysbiosis and barrier disruption and the potential protective strategies.}, journal = {Critical reviews in food science and nutrition}, volume = {}, number = {}, pages = {1-26}, doi = {10.1080/10408398.2020.1843396}, pmid = {33198506}, issn = {1549-7852}, abstract = {The oral antibiotic therapies administered widely to people and animals can cause gut dysbiosis and barrier disruption inevitably. Increasing attention has been directed toward antibiotic-induced gut dysbiosis, which involves a loss of diversity, changes in the abundances of certain taxa and consequent effects on their metabolic capacity, and the spread of antibiotic-resistant bacterial strains. Treatment with beta-lactam, glycopeptide, and macrolide antibiotics is associated with the depletion of beneficial commensal bacteria in the genera Bifidobacterium and Lactobacillus. The gut microbiota is a reservoir for antibiotic resistance genes, the prevalence of which increases sharply after antibiotic ingestion. The intestinal barrier, which comprises secretory, physical, and immunological barriers, is also a target of antibiotics. Antibiotic induced changes in the gut microbiota composition could induce weakening of the gut barrier through changes in mucin, cytokine, and antimicrobial peptide production by intestinal epithelial cells. Reports have indicated that dietary interventions involving prebiotics, probiotics, omega-3 fatty acids, and butyrate supplementation, as well as fecal microbiota transplantation, can alleviate antibiotic-induced gut dysbiosis and barrier injuries. This review summarizes the characteristics of antibiotic-associated gut dysbiosis and barrier disruption, as well as the strategies for alleviating this condition. This information is intended to provide a foundation for the exploration of safer, more efficient, and affordable strategies to prevent or relieve antibiotic-induced gut injuries.}, } @article {pmid33198059, year = {2020}, author = {Krishnamoorthy, M and Lenehan, JG and Burton, JP and Maleki Vareki, S}, title = {Immunomodulation in Pancreatic Cancer.}, journal = {Cancers}, volume = {12}, number = {11}, pages = {}, pmid = {33198059}, issn = {2072-6694}, support = {N/A//London Regional Cancer Program's Catalyst Grant Program, Keith Smitt Translational Research Grants./ ; }, abstract = {Pancreatic cancer has a high mortality rate, and its incidence is increasing worldwide. The almost universal poor prognosis of pancreatic cancer is partly due to symptoms presenting only at late stages and limited effective treatments. Recently, immune checkpoint blockade inhibitors have drastically improved patient survival in metastatic and advanced settings in certain cancers. Unfortunately, these therapies are ineffective in pancreatic cancer. However, tumor biopsies from long-term survivors of pancreatic cancer are more likely to be infiltrated by cytotoxic T-cells and certain species of bacteria that activate T-cells. These observations suggest that T-cell activation is essential for anti-tumor immunity in pancreatic cancers. This review discusses the immunological mechanisms responsible for effective anti-tumor immunity and how immune-based strategies can be exploited to develop new pancreatic cancer treatments.}, } @article {pmid33198044, year = {2020}, author = {Yang, J and Fu, X and Liao, X and Li, Y}, title = {Effects of gut microbial-based treatments on gut microbiota, behavioral symptoms, and gastrointestinal symptoms in children with autism spectrum disorder: A systematic review.}, journal = {Psychiatry research}, volume = {293}, number = {}, pages = {113471}, doi = {10.1016/j.psychres.2020.113471}, pmid = {33198044}, issn = {1872-7123}, abstract = {Many studies have identified some abnormalities in gastrointestinal (GI) physiology (e.g., increased intestinal permeability, overall microbiota alterations, and gut infection) in children with autism spectrum disorder (ASD). Furthermore, changes in the intestinal flora may be related to GI and ASD symptom severity. Thus, we decided to systematically review the effects of gut microbial-based interventions on gut microbiota, behavioral symptoms, and GI symptoms in children with ASD. We reviewed current evidence from the Cochrane Library, EBSCO PsycARTICLES, PubMed, Web of Science, and Scope databases up to July 12, 2020. Experimental studies that used gut microbial-based treatments among children with ASD were included. Independent data extraction and quality assessment of studies were conducted according to the PRISMA statement. Finally, we identified 16 articles and found that some interventions (i.e., prebiotic, probiotic, vitamin A supplementation, antibiotics, and fecal microbiota transplantation) could alter the gut microbiota and improve behavioral symptoms and GI symptoms among ASD patients. Our findings highlight that the gut microbiota could be a novel target for ASD patients in the future. However, we only provided suggestive but not conclusive evidence regarding the efficacy of interventions on GI and behavioral symptoms among ASD patients. Additional rigorous trials are needed to evaluate the effects of gut microbial-based treatments and explore potential mechanisms.}, } @article {pmid33194651, year = {2020}, author = {Chen, YC and Miao, ZF and Yip, KL and Cheng, YA and Liu, CJ and Li, LH and Lin, CY and Wang, JW and Wu, DC and Cheng, TL and Wang, JY}, title = {Gut Fecal Microbiota Transplant in a Mouse Model of Orthotopic Rectal Cancer.}, journal = {Frontiers in oncology}, volume = {10}, number = {}, pages = {568012}, pmid = {33194651}, issn = {2234-943X}, abstract = {The gut microbiota is reported to play an important role in carcinogenesis and the treatment of CRC. SW480 and SW620 colon cancer cells integrated with infrared fluorescent proteins were injected into the rectal submucosa of nude mice. In the subsequent 30 days, we observed tumor growth weekly using an in vivo imaging system. The bacterial solution was infused anally into the mice to perform bacterial transplant. Phosphate-buffered saline, Acinetobacter lwoffii, and Bifidobacterium longum solutions were infused individually. The 16S ribosomal DNA (rDNA) and polymerase chain reaction of murine feces were investigated to confirm the colonization of target bacteria. In the SW620 orthotopic xenograft rectal cancer model, 4 of 5 mice developed rectal cancer by 30 days after submucosal injection. In the SW480 orthotopic xenograft rectal cancer model, 2 of 6 mice developed rectal cancer by 30 days after submucosal injection. For the 16S rDNA analysis, the mice receiving the bacterial solution infusion demonstrated positive findings for A. lwoffii and B. longum. With the successful establishment of a mouse model of orthotopic rectal cancer and transplant of target bacteria, we can further explore the relationship between gut microbiota and CRC. The role of fecal microbiota transplant in the treatment and alleviation of adverse events of chemotherapy in CRC could be clarified in subsequent studies.}, } @article {pmid33193813, year = {2020}, author = {Tian, Y and Zuo, L and Guo, Q and Li, J and Hu, Z and Zhao, K and Li, C and Li, X and Zhou, J and Zhou, Y and Li, XA}, title = {Potential role of fecal microbiota in patients with constipation.}, journal = {Therapeutic advances in gastroenterology}, volume = {13}, number = {}, pages = {1756284820968423}, pmid = {33193813}, issn = {1756-283X}, abstract = {Background: We evaluated the safety and efficacy of fecal microbiota transplantation (FMT) for chronic functional constipation (CFC) ineffectively treated by conventional constipation medication.

Methods: Thirty-four patients with CFC underwent FMT treatment (three rounds, via gastroscopy). Clinical scales, including the Wexner constipation score as the main index of efficiency, were completed at baseline; after each treatment, and at 2 and 3 months of follow up. Secondary evaluation indices included the self-assessment of constipation symptoms, patient assessment constipation quality-of-life questionnaire, Bristol stool form scale, and Zung's self-rating depression and anxiety scales. Gastrointestinal motility, motilin, gastrin, nitric oxide (NO), and 5-hydroxytryptamine (5-HT) were assessed before and after treatment. Intestinal flora changes were assessed by 16S ribosomal ribonucleic acid (rRNA) sequencing.

Results: There were no serious adverse reactions. The clinical cure rate was 73.5% (25/34), clinical remission rate was 14.7% (5/34), and the inefficiency rate was 11.8% (4/34). Clinical scale data indicated that the FMT treatment was effective. Furthermore, FMT treatment promoted intestinal peristalsis, increased gastrointestinal motility, and increased serum NO and 5-HT levels. The 16S rRNA sequencing data indicated that high abundances of Bacteroides, Klebsiella, Megamonas, Erysipelotrichaceae and Epulopiscium may be the cause of constipation, and high abundances of Prevotella, Acidaminococcus and Butyricimonas may be the main factors in curing constipation.

Conclusion: Treatment with FMT regulates the intestinal microflora and changes the abundance of CFC-associated bacterial flora to improve constipation.}, } @article {pmid33193352, year = {2020}, author = {Schmidt, CJ and Wenndorf, K and Ebbers, M and Volzke, J and Müller, M and Strübing, J and Kriebel, K and Kneitz, S and Kreikemeyer, B and Müller-Hilke, B}, title = {Infection With Clostridioides difficile Attenuated Collagen-Induced Arthritis in Mice and Involved Mesenteric Treg and Th2 Polarization.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {571049}, pmid = {33193352}, issn = {1664-3224}, abstract = {Objectives: Rheumatoid arthritis is an autoimmune disease with multifactorial etiopathogenesis. Among the environmental factors, mucosal infections and the inducing pathobionts are gaining increasing attention. We here set out to explore the gut-joint-axis and the impact of Clostridioides difficile infection on subsequent arthritis.

Methods: We combined C. difficile infection in DBA/1J × B10.Q F1 mice with collagen induced arthritis (CIA). Mice were infected via oral gavage and infection was monitored by weight loss, colonic histology, and antibodies against bacteria. Scoring of arthritis was performed macroscopically. Intestinal microbiomes were analyzed and immune responses were monitored via quantification of transcription factor-specific mRNA isolated from the inguinal and mesenteric lymph nodes.

Results: Infection with C. difficile VPI 10463 resulted in significant weight loss and severe colitis yet accelerated the reversal towards the original microbiome after antibiotic treatment. Spontaneous clearance of VPI 10463 infection reduced the incidence of subsequent CIA and led to mesenteric Treg and Th2 polarization. However, this attenuating effect was abrogated if VPI 10463 was eradicated via vancomycin followed by fecal microbiota transplantation. Moreover, VPI 10463 infection following the onset of CIA lacked therapeutic potential.

Conclusion: Our results demonstrate that infection with C. difficile VPI10463 induced an inflammation of the gut that protected from subsequent arthritis development in mice. Both, microbial changes to the gut and immune cell mobilization and/or polarization may have contributed to arthritis protection. The prospect of potential therapeutic benefits resulting from C. difficile infections or some byproduct thereof call for further experiments that help elucidate exact mechanisms.}, } @article {pmid33193273, year = {2020}, author = {Geng, ST and Zhang, ZY and Wang, YX and Lu, D and Yu, J and Zhang, JB and Kuang, YQ and Wang, KH}, title = {Regulation of Gut Microbiota on Immune Reconstitution in Patients With Acquired Immunodeficiency Syndrome.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {594820}, pmid = {33193273}, issn = {1664-302X}, abstract = {Human immunodeficiency virus type 1 (HIV-1) infection of CD4+ T cells in the gut plays an insidious role in acquired immunodeficiency syndrome (AIDS) pathogenesis. Host immune function is closely related to gut microbiota. Changes in the gut microbiota cause a different immune response. Previous studies revealed that HIV-1 infection caused changes in gut microbiota, which induced immune deficiency. HIV-1 infection results in an abnormal composition and function of the gut microbiota, which may disrupt the intestinal epithelial barrier and microbial translocation, leading to long-term immune activation, including inflammation and metabolic disorders. At the same time, an abnormal gut microbiota also hinders the effect of antiviral therapy and affects the immune reconstruction of patients. However, studies on the impact of the gut microbiota on immune reconstitution in patients with HIV/AIDS are still limited. In this review, we focus on changes in the gut microbiota caused by HIV infection, as well as the impact and regulation of the gut microbiota on immune function and immune reconstitution, while we also discuss the potential impact of probiotics/prebiotics and fecal microbiota transplantation (FMT) on immune reconstitution.}, } @article {pmid33190214, year = {2020}, author = {Zhou, Y and Ni, X and Duan, L and Niu, L and Liu, Q and Zeng, Y and Wang, Q and Wang, J and Khalique, A and Pan, K and Jing, B and Zeng, D}, title = {Lactobacillus plantarum BSGP201683 Improves the Intestinal Barrier of Giant Panda Microbiota-Associated Mouse Infected by Enterotoxigenic Escherichia coli K88.}, journal = {Probiotics and antimicrobial proteins}, volume = {}, number = {}, pages = {}, doi = {10.1007/s12602-020-09722-y}, pmid = {33190214}, issn = {1867-1314}, support = {31970503//National Natural Science Foundation of China/ ; CPF2014-15//Chengdu Giant Panda Breeding Research Foundation/ ; 201906910016//China Scholarship Council/ ; }, abstract = {Giant pandas often suffered from gastrointestinal disease, especially the captive sub-adult one. Our study aims to investigate whether L. plantarum G83, a good panda-derived probiotic, can improve the intestinal barrier against the enterotoxigenic Escherichia coli K88 (E. coli K88) infection in giant panda microbiota-associated mice (GPAM). We treated SPF mice with antibiotics cocktail and transplanted the giant panda intestinal microbiota to set up a GPAM. Our results demonstrated that the microbiota of GPAM changed over time and was relatively stable in the short-term experiment (2-4 weeks). Whereafter, the GPAM pretreated with L. plantarum G83 for 15 days and infected with enterotoxigenic E. coli K88. The result indicated that the number of Bifidobacteria spp. increased in GPAM-G and GPAM-GE groups; the Lactobacillus spp. only increased in the GPAM-G group. Although the abundance of Enterobacteriaceae spp. only decreased in the GPAM-G group, the copy number of Escherichia coli in the GPAM-E group was significantly lower than that in the other groups. Meanwhile, the L. plantarum G83-induced alteration of microbiota could increase the mRNA expression of Claudin-1, Zo-1, and Occludin-1 in the GPAM-G group in the ileum; only Occludin-1 was increased in the GPAM-GE group. The sIgA in the ileum showed a positive response, also the result of body weight and histology in both the GPAM-G and GPAM-GE group. These results indicated that the L. plantarum G83 could improve the intestinal barrier to defense the enterotoxigenic E. coli K88 invasion.}, } @article {pmid33187097, year = {2020}, author = {Nourrisson, C and Brunet, J and Flori, P and Moniot, M and Bonnin, V and Delbac, F and Poirier, P}, title = {Comparison of DNA Extraction Methods and Real-Time PCR Assays for the Detection of Blastocystis sp. in Stool Specimens.}, journal = {Microorganisms}, volume = {8}, number = {11}, pages = {}, pmid = {33187097}, issn = {2076-2607}, abstract = {Diagnosis of Blastocystis in stool may be challenging, as microscopic examination and culture-based methods have demonstrated low sensitivity. Molecular detection assays are now available for this enteric parasite, based on "in-house" or commercial-developed techniques. The aim of this study was to assess and compare the performance of (i) two DNA extraction methods (manual versus automated), and (ii) four qPCR assays (three "in-house" and one commercialized), for detection of Blastocystis sp. in human stools. One hundred and forty stools were included, among which 76 were confirmed to be positive for Blastocystis. The manual DNA extraction method allowed for the identification of significantly more positive specimens than the automated method (p < 0.05). In particular, specimens with a low parasite load were negative when DNA was extracted with the automated process. The four qPCR assays also had variable performances, with the commercialized assay being the most sensitive (84%) but the least specific (82%). Overall, for all qPCR assays, the specificity decreased when the sensitivity increased. Blastocystis' subtype, notably the subtype 4, influenced these performances. Our results indicate that the positivity rate for the detection of Blastocystis in stools could be variable according to the DNA extraction method and the qPCR assay used. These pitfalls need to be considered for the selection of method and interpretation of results, particularly considering the search of this intestinal parasite in a donor before fecal microbiota transplantation.}, } @article {pmid33186366, year = {2020}, author = {Ramírez, GA and Richardson, E and Clark, J and Keshri, J and Drechsler, Y and Berrang, ME and Meinersmann, RJ and Cox, NA and Oakley, BB}, title = {Broiler chickens and early life programming: Microbiome transplant-induced cecal community dynamics and phenotypic effects.}, journal = {PloS one}, volume = {15}, number = {11}, pages = {e0242108}, pmid = {33186366}, issn = {1932-6203}, mesh = {Animals ; Cecum/microbiology ; Chickens/growth & development/*microbiology ; Fecal Microbiota Transplantation/methods/*veterinary ; *Gastrointestinal Microbiome ; *Phenotype ; }, abstract = {The concept of successional trajectories describes how small differences in initial community composition can magnify through time and lead to significant differences in mature communities. For many animals, the types and sources of early-life exposures to microbes have been shown to have significant and long-lasting effects on the community structure and/or function of the microbiome. In modern commercial poultry production, chicks are reared as a single age cohort and do not directly encounter adult birds. This scenario is likely to initiate a trajectory of microbial community development that is significantly different than non-industrial settings where chicks are exposed to a much broader range of environmental and fecal inocula; however, the comparative effects of these two scenarios on microbiome development and function remain largely unknown. In this work, we performed serial transfers of cecal material through multiple generations of birds to first determine if serial transfers exploiting the ceca in vivo, rather than the external environment or artificial incubations, can produce a stable microbial community. Subsequently, we compared microbiome development between chicks receiving this passaged, i.e. host-selected, cecal material orally, versus an environmental inoculum, to test the hypothesis that the first exposure of newly hatched chicks to microbes determines early GI microbiome structure and may have longer-lasting effects on bird health and development. Cecal microbiome dynamics and bird weights were tracked for a two-week period, with half of the birds in each treatment group exposed to a pathogen challenge at 7 days of age. We report that: i) a relatively stable community was derived after a single passage of transplanted cecal material, ii) this cecal inoculum significantly but ephemerally altered community structure relative to the environmental inoculum and PBS controls, and iii) either microbiome transplant administered at day-of-hatch appeared to have some protective effects against pathogen challenge relative to uninoculated controls. Differentially abundant taxa identified across treatment types may inform future studies aimed at identifying strains associated with beneficial phenotypes.}, } @article {pmid33176177, year = {2021}, author = {Zhang, Y and Xie, B and Chen, X and Zhang, J and Yuan, S}, title = {A key role of gut microbiota-vagus nerve/spleen axis in sleep deprivation-mediated aggravation of systemic inflammation after LPS administration.}, journal = {Life sciences}, volume = {265}, number = {}, pages = {118736}, doi = {10.1016/j.lfs.2020.118736}, pmid = {33176177}, issn = {1879-0631}, mesh = {Animals ; Cytokines ; Gastrointestinal Microbiome/drug effects/*physiology ; Inflammation ; Interleukin-10 ; Interleukin-6 ; Lipopolysaccharides/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Sepsis ; Sleep Deprivation/metabolism/*physiopathology ; Spleen/drug effects/*metabolism/physiology ; Tumor Necrosis Factor-alpha ; Vagus Nerve/drug effects/metabolism/*physiology ; }, abstract = {AIMS: Sleep deprivation (SD) correlates with exacerbated systemic inflammation after sepsis. However, the underlying mechanisms remain unclear. This study aimed to evaluate the roles and mechanisms of SD in inflammatory organ injury after lipopolysaccharide (LPS) administration.

MAIN METHODS: Mice were intraperitoneally injected with LPS followed by 3 consecutive days of SD. The pseudo germ-free (PGF) mice received fecal microbiota transplant by being gavaged with supernatant from fecal suspension of septic mice with or without SD. The subdiaphragmatic vagotomy (SDV) or splenectomy was performed 14 days prior to LPS injection or antibiotics administration.

KEY FINDINGS: Post-septic SD increased the plasma levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α), reduced IL-10 plasma level, increased spleen weight, and promoted inflammatory injury of the lung, liver and kidney. The relative abundance of Proteobacteria and its subgroups were increased after post-septic SD. PGF mice transplanted with fecal bacteria from septic mice subjected to SD developed splenomegaly, systemic inflammation, organ inflammation and damage as their donors did. Intriguingly, SDV abolished the aggravated effects of SD on splenomegaly and inflammatory organ injury in septic mice received SD or in PGF mice transplanted with fecal bacteria from septic mice subjected to SD. Furthermore, splenectomy also abrogated the increase in IL-6 and TNF-α plasma levels and the decrease in IL-10 plasma level in PGF mice transplanted with fecal bacteria from septic mice subjected to SD.

SIGNIFICANCE: Gut microbiota-vagus nerve axis and gut microbiota-spleen axis play key roles in modulating systemic inflammation induced by SD after LPS administration.}, } @article {pmid33175698, year = {2020}, author = {Ademe, M}, title = {Benefits of fecal microbiota transplantation: A comprehensive review.}, journal = {Journal of infection in developing countries}, volume = {14}, number = {10}, pages = {1074-1080}, doi = {10.3855/jidc.12780}, pmid = {33175698}, issn = {1972-2680}, abstract = {A growing body of literatures showed the interaction of dysbiotic gut with a wide range of disorders, and the clinical use of fecal microbiota transplantation (FMT) shifted from infectious disease to non-communicable disorders. Despite the promising therapeutic benefits of FMT, the exact mechanisms through which fecal recipients benefit from the fecal intervention are not well understood. However, owing to the advantages of having a healthy gut microbiome, possible mechanisms of actions of FMT has been described. On the one hand, through direct ecological competition, FMT may potentially stimulate decolonization of pathogenic microorganisms and increase host resistance to pathogens. Moreover, following dysbiosis, abnormal microbial colonization of the gastrointestinal tract may also cause excessive or dysregulated immune response, resulting in chronic inflam-mation and the development of mucosal lesions. In this regard, repopulating gut microbiome through FMT helps to restore immune function and reduce host damage. On the other hand, FMT helps to restore essential metabolites used for host metabolism, including short-chain fatty acids (SCFA), antimicrobial peptides (AMP), bacteriocins and bile acids. Therefore, in this review, the existing evidences regarding the mechanisms of action, current opportunities and challenges of FMT will be described.}, } @article {pmid33172329, year = {2020}, author = {Kim, S and Lee, JY and Shin, SG and Kim, JK and Silwal, P and Kim, YJ and Shin, NR and Kim, PS and Won, M and Lee, SH and Kim, SY and Sasai, M and Yamamoto, M and Kim, JM and Bae, JW and Jo, EK}, title = {ESRRA (estrogen related receptor alpha) is a critical regulator of intestinal homeostasis through activation of autophagic flux via gut microbiota.}, journal = {Autophagy}, volume = {}, number = {}, pages = {1-20}, doi = {10.1080/15548627.2020.1847460}, pmid = {33172329}, issn = {1554-8635}, abstract = {The orphan nuclear receptor ESRRA (estrogen related receptor alpha) is critical in mitochondrial biogenesis and macroautophagy/autophagy function; however, the roles of ESRRA in intestinal function remain uncharacterized. Herein we identified that ESRRA acts as a key regulator of intestinal homeostasis by amelioration of colonic inflammation through activation of autophagic flux and control of host gut microbiota. Esrra-deficient mice presented with increased susceptibility to dextran sodium sulfate (DSS)-induced colitis with upregulation of intestinal inflammation. In addition, esrra-null mice had depressed AMP-activated protein kinase phosphorylation (AMPK), lower levels of TFEB (transcription factor EB), and accumulation of SQSTM1/p62 (sequestosome 1) with defective mitochondria in intestinal tissues. Esrra-deficient mice showed distinct gut microbiota composition and significantly higher microbial diversity than wild-type (WT) mice. Cohousing or fecal microbiota transplantation from WT mice to Esrra-deficient mice ameliorated DSS-induced colitis severity. Importantly, patients with ulcerative colitis (UC) had significantly decreased ESRRA expression in intestinal mucosal tissues that correlated with disease activity, suggesting clinical relevance of ESRRA in UC. Taken together, our results show that ESRRA contributes to intestinal homeostasis through autophagy activation and gut microbiota control to protect the host from detrimental inflammation and dysfunctional mitochondria.}, } @article {pmid33166939, year = {2021}, author = {Singh, R and Zogg, H and Wei, L and Bartlett, A and Ghoshal, UC and Rajender, S and Ro, S}, title = {Gut Microbial Dysbiosis in the Pathogenesis of Gastrointestinal Dysmotility and Metabolic Disorders.}, journal = {Journal of neurogastroenterology and motility}, volume = {27}, number = {1}, pages = {19-34}, pmid = {33166939}, issn = {2093-0879}, abstract = {Of all microorganisms in the human body, the largest and most complex population resides in the gastrointestinal (GI) tract. The gut microbiota continuously adapts to the host environment and serves multiple critical functions for their hosts, including regulating host immunity, procuring energy from food, and preventing the colonization of pathogens. Mounting evidence has suggested gut microbial imbalance (dysbiosis) as a core pathophysiology in the development of GI motility and metabolic disorders, such as irritable bowel syndrome and diabetes. Current research has focused on discovering associations between these disorders and gut microbial dysbiosis; however, whether these associations are a consequence or cause is still mostly unexplored. State-of-the-art studies have investigated how gut microbes communicate with our body systems through microbiota-derived metabolites and how they are able to modulate host physiology. There is now mounting evidence that alterations in the composition of small intestinal microbes have an association with GI dysmotility and metabolic disorders. Although treatment options for gut microbial dysbiosis are currently limited, antibiotics, fecal microbiota transplantation, probiotics, and dietary interventions are currently the best options. However, treatment with broad-spectrum antibiotics has been viewed with skepticism due to the risk of developing antibiotic resistant bacteria. Studies are warranted to elucidate the cellular and molecular pathways underlying gut microbiota-host crosstalk and for the development of a powerful platform for future therapeutic approaches. Here, we review recent literature on gut microbial alterations and/or interactions involved in the pathophysiology of GI dysmotility and metabolic disorders.}, } @article {pmid33166735, year = {2021}, author = {Koszewicz, M and Jaroch, J and Brzecka, A and Ejma, M and Budrewicz, S and Mikhaleva, LM and Muresanu, C and Schield, P and Somasundaram, SG and Kirkland, CE and Avila-Rodriguez, M and Aliev, G}, title = {Dysbiosis is one of the risk factor for stroke and cognitive impairment and potential target for treatment.}, journal = {Pharmacological research}, volume = {164}, number = {}, pages = {105277}, doi = {10.1016/j.phrs.2020.105277}, pmid = {33166735}, issn = {1096-1186}, abstract = {More than 50 million people have various forms of cognitive impairment basically caused by neurodegenerative diseases, such as Alzheimer's, Parkinson's, and cerebrovascular diseases as well as stroke. Often these conditions coexist and exacerbate one another. The damaged area in post-stroke dementia may lead to neurodegenerative lesions. Gut microbiome functions like an endocrine organ by generating bioactive metabolites that can directly or indirectly impact human physiology. An alteration in the composition and function of intestinal flora, i.e. gut dysbiosis, is implicated in neurodegenerative and cerebrovascular diseases. Additionally, gut dysbiosis may accelerate the progression of cognitive impairment. Dysbiosis may result from obesity; metabolic disorders, cardiovascular disease, and sleep disorders, Lack of physical activity is associated with dysbiosis as well. These may coexist in various patterns in older people, enhancing the risk, incidence, and progression of cerebrovascular lesions, neurodegenerative disorders, and cognitive impairment, creating a vicious circle. Recently, it has been reported that several metabolites produced by gut microbiota (e.g., trimethylamine/trimethylamine N-oxide, short-chain fatty acids, secondary bile acids) may be linked to neurodegenerative and cerebrovascular diseases. New treatment modalities, including prebiotic and probiotics, may normalize the gut microbiota composition, change the brain-gut barrier, and decrease the risk of the pathology development. Fecal microbiota transplantation, sometimes in combination with other methods, is used for remodeling and replenishing the symbiotic gut microbiome. This promising field of research is associated with basic findings of bidirectional communication between body organs and gut microbiota that creates new possibilities of pharmacological treatments of many clinical conditions. The authors present the role of gut microbiota in physiology, and the novel therapeutic targets in modulation of intestinal microbiota Personalized therapies based on their personal genome make up could offer benefits by modulating microbiota cross-talk with brain and cardiovascular system. A healthy lifestyle, including pre and probiotic nutrition is generally recommended. Prevention may also be enhanced by correcting gut dysbiosis resulting a reduced risk of post-stroke cognitive impairment including dementia.}, } @article {pmid33163830, year = {2020}, author = {Witjes, JJ and Smits, LP and Pekmez, CT and Prodan, A and Meijnikman, AS and Troelstra, MA and Bouter, KEC and Herrema, H and Levin, E and Holleboom, AG and Winkelmeijer, M and Beuers, UH and van Lienden, K and Aron-Wisnewky, J and Mannisto, V and Bergman, JJ and Runge, JH and Nederveen, AJ and Dragsted, LO and Konstanti, P and Zoetendal, EG and de Vos, W and Verheij, J and Groen, AK and Nieuwdorp, M}, title = {Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis.}, journal = {Hepatology communications}, volume = {4}, number = {11}, pages = {1578-1590}, pmid = {33163830}, issn = {2471-254X}, abstract = {The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant-based, low-animal-protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. We therefore performed a double-blind randomized controlled proof-of-principle study in which individuals with hepatic steatosis on ultrasound were randomized to two study arms: lean vegan donor (allogenic n = 10) or own (autologous n = 11) FMT. Both were performed three times at 8-week intervals. A liver biopsy was performed at baseline and after 24 weeks in every subject to determine histopathology (Nonalcoholic Steatohepatitis Clinical Research Network) classification and changes in hepatic gene expression based on RNA sequencing. Secondary outcome parameters were changes in intestinal microbiota composition and fasting plasma metabolomics. We observed a trend toward improved necro-inflammatory histology, and found significant changes in expression of hepatic genes involved in inflammation and lipid metabolism following allogenic FMT. Intestinal microbial community structure changed following allogenic FMT, which was associated with changes in plasma metabolites as well as markers of . Conclusion: Allogenic FMT using lean vegan donors in individuals with hepatic steatosis shows an effect on intestinal microbiota composition, which is associated with beneficial changes in plasma metabolites and markers of steatohepatitis.}, } @article {pmid33163828, year = {2020}, author = {Acharya, C and Bajaj, JS}, title = {Transmitting Diet-Related Microbial Benefit through Fecal Microbiota Transplant in NASH: Can Microbiota Cut Through the Fat?.}, journal = {Hepatology communications}, volume = {4}, number = {11}, pages = {1559-1561}, pmid = {33163828}, issn = {2471-254X}, } @article {pmid33162889, year = {2020}, author = {Xue, A and Qian, X and Gao, X and Wang, P and Wang, L and Zheng, C and Huang, Z and Hu, W and Shi, J and Huang, Y}, title = {Fecal Microbial Signatures Are Associated With Engraftment Failure Following Umbilical Cord Blood Transplantation in Pediatric Crohn's Disease Patients With IL10RA Deficiency.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {580817}, pmid = {33162889}, issn = {1663-9812}, abstract = {Objectives: Umbilical cord blood transplantation (UCBT) is associated with a relatively high rate of engraftment failure. This study aimed at exploring whether any fecal microbiota could be associated with engraftment failure following UCBT in Crohn's disease patients with IL10RA deficiency.

Methods: Thirteen patients were recruited and their 230 fecal samples were collected longitudinally from immediately before conditioning chemotherapy to 8 weeks post the UCBT. The V3-V4 regions of the bacterial 16S rRNA gene were amplified by PCR and sequenced, followed by bioinformatics analyses.

Results: Following the UCBT, 7 out of 13 patients achieved neutrophil and platelet engraftment with a median of 21 and 28 days, respectively (S group), while 6 patients failed to achieve engraftment (F group). In comparison with that in the S group, significantly lower Shannon diversity values on the UCBT day (P = 0.0176) and less abundance of Bifidobacterium longum, Bifidobacterium pseudolongum, Enterobacteriaceae_538000, and one taxon of Lachnospiraceae family was detected in the F group, accompanied by significantly higher abundances of four taxa including Lautropia, Pseudomonas, and species Microvirgula aerodenitrificans during the chemotherapy period as well as UCBT. The abundances of thirty OTUs were correlated significantly with clinical indices.

Conclusions: Microbial indicators of reduced diversity of microbiota and signatures of specific bacterial abundances, such as a lower abundance of Bifidobacterium longum, for engraftment failure would require validation. These indicators may help for the risk stratification in patients with IL10RA deficiency undergoing UCBT.}, } @article {pmid33160712, year = {2020}, author = {Aira, A and Arajol, C and Casals-Pascual, C and González-Suárez, B and Martí, S and Domínguez, MÁ and Guardiola, J and Soriano, Á and , }, title = {Recommendations for stool donor selection for fecal microbiota transplant. Consensus document endorsed by the Catalan Society of Digestology, Catalan Society of Infectious diseases and Clinical microbiology and the GEMBIOTA group from Spanish Society of Infectious Diseases and Clinical Microbiology.}, journal = {Enfermedades infecciosas y microbiologia clinica}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.eimc.2020.09.002}, pmid = {33160712}, issn = {1578-1852}, abstract = {Fecal microbiota transplantation (FMT) is an effective and safe treatment to treat recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and based on scientific knowledge. Selection of the fecal microbiota donor is a key point of the process to ensure recipient safety. It is necessary to have protocols of action that allow clinicians to act with the maximum guarantees and to minimize the risks of the procedure. For this reason, a multidisciplinary working group has been set up in Cataluña with the aim of establishing recommendations for the selection of the fecal microbiota donor.}, } @article {pmid33159210, year = {2020}, author = {Zellmer, C and Sater, MRA and Huntley, MH and Osman, M and Olesen, SW and Ramakrishna, B}, title = {Shiga Toxin-Producing Escherichia coli Transmission via Fecal Microbiota Transplant.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa1486}, pmid = {33159210}, issn = {1537-6591}, abstract = {Fecal microbiota transplantation (FMT) is recommended therapy for multiply recurrent Clostridioides difficile infection. We report adverse events in 7 patients who received FMT from a stool donor who was colonized with Shiga toxin-producing Escherichia coli (STEC). No patients died of FMT-transmitted STEC. Improved screening can likely avoid future transmission.}, } @article {pmid33158078, year = {2020}, author = {Souai, N and Zidi, O and Mosbah, A and Kosai, I and Manaa, JE and Mokhtar, NB and Asimakis, E and Stathopoulou, P and Cherif, A and Tsiamis, G and Kouidhi, S}, title = {Impact of the Post-Transplant Period and Lifestyle Diseases on Human Gut Microbiota in Kidney Graft Recipients.}, journal = {Microorganisms}, volume = {8}, number = {11}, pages = {}, pmid = {33158078}, issn = {2076-2607}, support = {KA107//Erasmus+/ ; }, abstract = {Gaining long-term graft function and patient life quality remain critical challenges following kidney transplantation. Advances in immunology, gnotobiotics, and culture-independent molecular techniques have provided growing insights into the complex relationship of the microbiome and the host. However, little is known about the over time-shift of the gut microbiota in the context of kidney transplantation and its impact on both graft and health stability. Here we aimed to characterize the structure of gut microbiota within stable kidney graft recipients. We enrolled forty kidney transplant patients after at least three months of transplantation and compared them to eighteen healthy controls. The overall microbial community structure of the kidney transplanted group was clearly different from control subjects. We found lower relative abundances of Actinobacteria, Bacteroidetes, and Verrucomicrobia within the patient group and a higher abundance of Proteobacteria compared to the control group. Both richness and Shannon diversity indexes were significantly lower in the kidney graft recipients than in healthy controls. Post-graft period was positively correlated with the relative abundance of the Proteobacteria phylum, especially Escherichia.Shigella genus. Interestingly, only Parabacteroides was found to significantly differentiate patients that were not suffering from lifestyle diseases and those who suffer from post-graft complications. Furthermore, network analysis showed that the occurrence of lifestyle diseases was significantly linked with a higher number of negative interactions of Sutterella and Succinivibrio genera within patients. This study characterizes gut microbiome fluctuation in stable kidney transplant patients after a long post-allograft period. Analysis of fecal microbiota could be useful for nephrologists as a new clinical tool that can improve kidney allograft monitoring and outcomes.}, } @article {pmid33156122, year = {2021}, author = {Adelman, MW and Woodworth, MH and Shaffer, VO and Martin, GS and Kraft, CS}, title = {Critical Care Management of the Patient with Clostridioides difficile.}, journal = {Critical care medicine}, volume = {49}, number = {1}, pages = {127-139}, doi = {10.1097/CCM.0000000000004739}, pmid = {33156122}, issn = {1530-0293}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; }, abstract = {OBJECTIVES: To review published clinical evidence on management of Clostridioides difficile infection in critically ill patients.

DATA SOURCES: We obtained relevant studies from a PubMed literature review and bibliographies of reviewed articles.

STUDY SELECTION: We selected English-language studies addressing aspects of C. difficile infection relevant to critical care clinicians including epidemiology, risk factors, diagnosis, treatment, and prevention, with a focus on high-quality clinical evidence.

DATA EXTRACTION: We reviewed potentially relevant studies and abstracted information on study design, methods, patient selection, and results of relevant studies. This is a synthetic (i.e., not systematic) review.

DATA SYNTHESIS: C. difficile infection is the most common healthcare-associated infection in the United States. Antibiotics are the most significant C. difficile infection risk factor, and among antibiotics, cephalosporins, clindamycin, carbapenems, fluoroquinolones, and piperacillin-tazobactam confer the highest risk. Age, diabetes mellitus, inflammatory bowel disease, and end-stage renal disease are risk factors for C. difficile infection development and mortality. C. difficile infection diagnosis is based on testing appropriately selected patients with diarrhea or on clinical suspicion for patients with ileus. Patients with fulminant disease (C. difficile infection with hypotension, shock, ileus, or megacolon) should be treated with oral vancomycin and IV metronidazole, as well as rectal vancomycin in case of ileus. Patients who do not respond to initial therapy should be considered for fecal microbiota transplant or surgery. Proper infection prevention practices decrease C. difficile infection risk.

CONCLUSIONS: Strong clinical evidence supports limiting antibiotics when possible to decrease C. difficile infection risk. For patients with fulminant C. difficile infection, oral vancomycin reduces mortality, and adjunctive therapies (including IV metronidazole) and interventions (including fecal microbiota transplant) may benefit select patients. Several important questions remain regarding fulminant C. difficile infection management, including which patients benefit from fecal microbiota transplant or surgery.}, } @article {pmid33155639, year = {2020}, author = {Allegretti, JR and Kelly, CR and Grinspan, A and Mullish, BH and Hurtado, J and Carrellas, M and Marcus, J and Marchesi, JR and McDonald, JAK and Gerardin, Y and Silverstein, M and Pechlivanis, A and Barker, GF and Miguens Blanco, J and Alexander, JL and Gallagher, KI and Pettee, W and Phelps, E and Nemes, S and Sagi, SV and Bohm, M and Kassam, Z and Fischer, M}, title = {Inflammatory Bowel Disease Outcomes Following Fecal Microbiota Transplantation for Recurrent C. difficile Infection.}, journal = {Inflammatory bowel diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/ibd/izaa283}, pmid = {33155639}, issn = {1536-4844}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: Recurrent Clostridioides difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is a clinical challenge. Fecal microbiota transplantation (FMT) has emerged as a recurrent CDI therapy. Anecdotal concerns exist regarding worsening of IBD activity; however, prospective data among IBD patients are limited.

METHODS: Secondary analysis from an open-label, prospective, multicenter cohort study among IBD patients with 2 or more CDI episodes was performed. Participants underwent a single FMT by colonoscopy (250 mL, healthy universal donor). Secondary IBD-related outcomes included rate of de novo IBD flares, worsening IBD, and IBD improvement-all based on Mayo or Harvey-Bradshaw index (HBI) scores. Stool samples were collected for microbiome and targeted metabolomic profiling.

RESULTS: Fifty patients enrolled in the study, among which 15 had Crohn's disease (mean HBI, 5.8 ± 3.4) and 35 had ulcerative colitis (mean partial Mayo score, 4.2 ± 2.1). Overall, 49 patients received treatment. Among the Crohn's disease cohort, 73.3% (11 of 15) had IBD improvement, and 4 (26.6%) had no disease activity change. Among the ulcerative colitis cohort, 62% (22 of 34) had IBD improvement, 29.4% (11 of 34) had no change, and 4% (1 of 34) experienced a de novo flare. Alpha diversity significantly increased post-FMT, and ulcerative colitis patients became more similar to the donor than Crohn's disease patients (P = 0.04).

CONCLUSION: This prospective trial assessing FMT in IBD-CDI patients suggests IBD outcomes are better than reported in retrospective studies.}, } @article {pmid33155247, year = {2020}, author = {Kaźmierczak-Siedlecka, K and Vitale, E and Makarewicz, W}, title = {COVID-19 - gastrointestinal and gut microbiota-related aspects.}, journal = {European review for medical and pharmacological sciences}, volume = {24}, number = {20}, pages = {10853-10859}, doi = {10.26355/eurrev_202010_23448}, pmid = {33155247}, issn = {2284-0729}, mesh = {COVID-19 ; Coronavirus Infections/*microbiology ; Diarrhea/virology ; Feces/virology ; Gastrointestinal Diseases/*microbiology/virology ; Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology/virology ; Humans ; Pandemics ; Pneumonia, Viral/*microbiology ; Severity of Illness Index ; Vomiting/virology ; }, abstract = {OBJECTIVE: The aim of this review paper was to discuss the gut microbiota-related aspects of COVID-19 patients. We presented the faecal-oral transmission of SARS-CoV-2, gut microbiota imbalance, and fecal microbiota transplantation as a hidden source of this virus.

MATERIALS AND METHODS: We analyzed the available literature (PubMed, Embase, Google Scholar databases) regarding COVID-19 and gut microbiota related aspects.

RESULTS: The gastrointestinal symptoms, such as nausea, vomiting, diarrhea, abdominal discomfort/pain, may occur in these patients. Notably, these symptoms may contribute to the severity of COVID-19. Recent several studies have revealed a new SARS-CoV-2 transmission possibility, opening a fresh view on COVID-19. It is observed the possibility of SARS-CoV-2 transmission via faecal-oral route. Fecal microbiota transplantation may be a hidden source of SARS-CoV-2. Additionally, the pharmacological treatment of COVID-19 and other factors may significantly alter the composition of gut microbiota. Among others, loss of bacterial diversity, the decrease of commensal microbes as well as the increase of opportunistic pathogens are observed.

CONCLUSIONS: The alterations of gut microbiota in COVID-19 patients consequently may lead to the development of gut dysbiosis-related diseases even after recovery from COVID-19. Therefore, it is recommended to screen stool samples taken from recovered patients at least 35 days after clearance of virus from respiratory tract. Before 35 days period, SARS-CoV-2 may still be detected in feces. It is also recommended to screen the composition as well as the activity of gut microbiota to assess its balance. In the case of gut dysbiosis, there should be introduced an appropriate method of its modulation. Additionally, all the fecal samples which are prepared for fecal microbiota transplantation should be tested for SARS-CoV-2 to provide protection for its recipients.}, } @article {pmid33153085, year = {2020}, author = {Borsom, EM and Lee, K and Cope, EK}, title = {Do the Bugs in Your Gut Eat Your Memories? Relationship between Gut Microbiota and Alzheimer's Disease.}, journal = {Brain sciences}, volume = {10}, number = {11}, pages = {}, pmid = {33153085}, issn = {2076-3425}, support = {CTR040636//Arizona Alzheimer's Consortium DHS/ ; }, abstract = {The human microbiota is composed of trillions of microbial cells inhabiting the oral cavity, skin, gastrointestinal (GI) tract, airways, and reproductive organs. The gut microbiota is composed of dynamic communities of microorganisms that communicate bidirectionally with the brain via cytokines, neurotransmitters, hormones, and secondary metabolites, known as the gut microbiota-brain axis. The gut microbiota-brain axis is suspected to be involved in the development of neurological diseases, including Alzheimer's disease (AD), Parkinson's disease, and Autism Spectrum Disorder. AD is an irreversible, neurodegenerative disease of the central nervous system (CNS), characterized by amyloid-β plaques, neurofibrillary tangles, and neuroinflammation. Microglia and astrocytes, the resident immune cells of the CNS, play an integral role in AD development, as neuroinflammation is a driving factor of disease severity. The gut microbiota-brain axis is a novel target for Alzheimer's disease therapeutics to modulate critical neuroimmune and metabolic pathways. Potential therapeutics include probiotics, prebiotics, fecal microbiota transplantation, and dietary intervention. This review summarizes our current understanding of the role of the gut microbiota-brain axis and neuroinflammation in the onset and development of Alzheimer's disease, limitations of current research, and potential for gut microbiota-brain axis targeted therapies.}, } @article {pmid33151664, year = {2020}, author = {Shi, L and Zheng, J and Yan, S and Li, Y and Wang, Y and Liu, X and Xiao, C}, title = {Exposure to Perfluorooctanoic Acid Induces Cognitive Deficits via Altering Gut Microbiota Composition, Impairing Intestinal Barrier Integrity, and Causing Inflammation in Gut and Brain.}, journal = {Journal of agricultural and food chemistry}, volume = {68}, number = {47}, pages = {13916-13928}, doi = {10.1021/acs.jafc.0c05834}, pmid = {33151664}, issn = {1520-5118}, abstract = {Perfluorooctanoic acid (PFOA) is an eight-carbon perfluoroalkyl chemical and has been detected widely in many media. Although the toxic effect of PFOA has been confirmed, the influence on gut and brain has not been cleared. Male C57BL/6J mice were exposed to different concentrations (0, 0.5, 1, and 3 mg/Kg (bw)/day of PFOA for 35 days in this work. The results indicate that exposure to PFOA could damage intestinal barrier integrity and impair the synaptic structure. PFOA exposure also caused inflammation in gut and brain by increasing lipopolysaccharide, tumor necrosis factor-α, interleukin-1 beta, and cyclooxygenase-2 and decreasing interleukin-10. Interestingly, fecal microbiota transplantation treatment could attenuate a series of PFOA-induced changes to a certain extent. The results suggest that exposure to PFOA has potential deleterious effects on gut and brain, and inflammation may play an essential role in evaluating the influence induced by PFOA exposure.}, } @article {pmid33151137, year = {2020}, author = {Keller, JJ and Ooijevaar, RE and Hvas, CL and Terveer, EM and Lieberknecht, SC and Högenauer, C and Arkkila, P and Sokol, H and Gridnyev, O and Mégraud, F and Kump, PK and Nakov, R and Goldenberg, SD and Satokari, R and Tkatch, S and Sanguinetti, M and Cammarota, G and Dorofeev, A and Gubska, O and Ianiro, G and Mattila, E and Arasaradnam, RP and Sarin, SK and Sood, A and Putignani, L and Alric, L and Baunwall, SM and Kupcinskas, J and Link, A and Goorhuis, AG and Verspaget, HW and Ponsioen, C and Hold, GL and Tilg, H and Kassam, Z and Kuijper, EJ and Gasbarrini, A and Mulder, CJ and Williams, HR and Vehreschild, MJ}, title = {A standardised model for stool banking for faecal microbiota transplantation: a consensus report from a multidisciplinary UEG working group.}, journal = {United European gastroenterology journal}, volume = {}, number = {}, pages = {2050640620967898}, doi = {10.1177/2050640620967898}, pmid = {33151137}, issn = {2050-6414}, abstract = {BACKGROUND: Fecal microbiota transplantation is an emerging therapeutic option, particularly for the treatment of recurrent Clostridioides difficile infection. Stool banks that organise recruitment and screening of feces donors are being embedded within the regulatory frameworks described in the European Union Tissue and Cells Directive and the technical guide to the quality and safety of tissue and cells for human application, published by the European Council.

OBJECTIVE: Several European and international consensus statements concerning fecal microbiota transplantation have been issued. While these documents provide overall guidance, we aim to provide a detailed description of all processes that relate to the collection, handling and clinical application of human donor stool in this document.

METHODS: Collaborative subgroups of experts on stool banking drafted concepts for all domains pertaining to stool banking. During a working group meeting in the United European Gastroenterology Week 2019 in Barcelona, these concepts were discussed and finalised to be included in our overall guidance document about fecal microbiota transplantation.

RESULTS: A guidance document for all domains pertaining to stool banking was created. This document includes standard operating manuals for several processes involved with stool banking, such as handling of donor material, storage and donor screening.

CONCLUSION: The implementation of fecal microbiota transplantation by stool banks in concordance with our guidance document will enable quality assurance and guarantee the availability of donor feces preparations for patients.}, } @article {pmid33145316, year = {2020}, author = {Wang, D and Hao, H and Li, X and Wang, Z}, title = {The effect of intestinal flora on immune checkpoint inhibitors in tumor treatment: a narrative review.}, journal = {Annals of translational medicine}, volume = {8}, number = {17}, pages = {1097}, pmid = {33145316}, issn = {2305-5839}, abstract = {Tremendous progress has been achieved in understanding of the interaction between tumor microenvironment and intestinal flora in the past decades. Immune checkpoint inhibitors (ICIs) are a promising treatment strategy for advanced tumors, most prominently cytotoxic T-lymphocyte-associated protein (CTLA-4) and programmed cell death protein-1 (PD-1), its major ligand PD-L1, its beneficial to part of the population and obtaining excellent clinical results. However, the majority of patients do not respond or develop early progressive disease. Reached consensus by experts currently believe that the intestinal flora plays an important role in the explanation of the limited therapeutic effect of ICIs, there are differences in the composition of intestinal flora between patients with good response and patients with poor response, cloned mice by fecal microbiota transplantation (FMT) proved that the mice with transplanted feces from patients with good response can reduce tumor volume and obtain a better progress free survival (PFS). Therefore, "beneficial bacteria" seem to be enriched in the intestinal flora of patients who are well-responsive to ICIs and can be potentially used as a marker and cancer immunotherapeutic adjuvant of ICIs. In this review, we aim to summarize some of the studies demonstrating intestinal flora on tumor immunotherapy through anti-PD1, anti-PD-L1, anti-CTLA-4 and discuss possible mechanisms of this effect.}, } @article {pmid33139601, year = {2020}, author = {Gesualdo, M and Rizzi, F and Bonetto, S and Rizza, S and Cravero, F and Saracco, GM and De Angelis, CG}, title = {Pancreatic Diseases and Microbiota: A Literature Review and Future Perspectives.}, journal = {Journal of clinical medicine}, volume = {9}, number = {11}, pages = {}, pmid = {33139601}, issn = {2077-0383}, abstract = {Gut microbiota represent an interesting worldwide research area. Several studies confirm that microbiota has a key role in human diseases, both intestinal (such as inflammatory bowel disease, celiac disease, intestinal infectious diseases, irritable bowel syndrome) and extra intestinal disorders (such as autism, multiple sclerosis, rheumatologic diseases). Nowadays, it is possible to manipulate microbiota by administering prebiotics, probiotics or synbiotics, through fecal microbiota transplantation in selected cases. In this scenario, pancreatic disorders might be influenced by gut microbiota and this relationship could be an innovative and inspiring field of research. However, data are still scarce and controversial. Microbiota manipulation could represent an important therapeutic strategy in the pancreatic diseases, in addition to standard therapies. In this review, we analyze current knowledge about correlation between gut microbiota and pancreatic diseases, by discussing on the one hand existing data and on the other hand future possible perspectives.}, } @article {pmid33136284, year = {2020}, author = {Gomaa, EZ}, title = {Human gut microbiota/microbiome in health and diseases: a review.}, journal = {Antonie van Leeuwenhoek}, volume = {113}, number = {12}, pages = {2019-2040}, doi = {10.1007/s10482-020-01474-7}, pmid = {33136284}, issn = {1572-9699}, abstract = {The human gut microbiota has received considerable interest in the recent years and our knowledge of the inhabitant species and their potential applications is increased particularly after the development of metagenomic studies. Gut microbiota is highly diverse and harboring trillions of microorganisms in human digestive system. The shaping and multiplication of gut microbiome starts at birth, while the modification of their composition depends mainly on various genetic, nutritional and environmental factors. The modification in the composition and function of the gut microbiota can change intestinal permeability, digestion and metabolism as well as immune responses. The pro inflammatory state caused by alternation of gut microbiota balance lead to the onset of many diseases ranging from gastrointestinal and metabolic conditions to immunological and neuropsychiatric diseases. In this context, the present review clarifies the role of gut microbiota in maintaining host health and investigates how nutritional and environmental factors affect the gut microbial structure and function. In addition, many therapeutic strategies of gut microbiota aimed at modulating and restoring of the intestinal ecosystem balance have been surveyed.}, } @article {pmid33136261, year = {2020}, author = {Aira, A and Rubio, E and Vergara Gómez, A and Fehér, C and Casals-Pascual, C and González, B and Morata, L and Rico, V and Soriano, A}, title = {rUTI Resolution After FMT for Clostridioides difficile Infection: A Case Report.}, journal = {Infectious diseases and therapy}, volume = {}, number = {}, pages = {}, doi = {10.1007/s40121-020-00365-8}, pmid = {33136261}, issn = {2193-8229}, abstract = {Clostridioides difficile infection (CDI) is the leading cause of nosocomial infectious diarrhea. Fecal microbiota transplantation (FMT) is a successful treatment for recurrent CDI (rCDI), and in some patients FMT has been associated with the resolution of recurrent urinary tract infections (rUTI). Recent evidence suggests that the origin of most bacterial infections in the urinary tract is the gut. Thus, the possibility of using FMT to displace pathogens commonly involved in rUTIs has major therapeutic implications. We report the case of a 93-year-old female patient with a rCDI and rUTI that underwent FMT and reported a complete clinical resolution of CDI; unexpectedly, no new symptomatic UTI episodes were diagnosed post-FMT. We characterized the gut microbiota of the stool donor and of the patient before and after the procedure. Our patient presented a dysbiosis with clear predominance of Enterobacteriaceae (74%) before FMT, which was significantly reduced to 0.07% after FMT. These findings were maintained for almost a year. We also observed an increase in microbial diversity indices compared with the pre-FMT sample reaching diversity values comparable to the donor stool samples. We reasoned that the disappearance of UTIs in our patient resulted from the reduction of Enterobacteriaceae in the gut microbiota. Our findings support previous evidence suggesting the potential of FMT for rUTI, particularly in cases due to multi-drug resistant pathogens where conventional antibiotic treatment is not an option.}, } @article {pmid33134739, year = {2020}, author = {Dong, LT and Espinoza, HV and Espinoza, JL}, title = {Emerging superbugs: The threat of Carbapenem Resistant Enterobacteriaceae.}, journal = {AIMS microbiology}, volume = {6}, number = {3}, pages = {176-182}, pmid = {33134739}, issn = {2471-1888}, abstract = {Carbapenem-resistant Enterobacteriaceae (CRE) are gram-negative bacteria that are resistant to carbapenems, a group of antibiotics considered as the last-resource for the treatment of infections caused by multidrug-resistant bacteria. CRE constitutes a major threat to health care systems because infections caused by these pathogens are difficult to treat and are commonly associated with high mortality due to the limited availability of effective antibiotics. While infection prevention and timely detection are of vital importance to control CRE infections, developing new and effective anti-CRE therapies is also crucial. Accumulating evidence indicates that gut microbiota alteration (dysbiosis) is associated with an increased intestinal colonization with CRE and consequently with higher risk of developing CRE infections. Importantly, therapeutic interventions aimed to modify the gut microbiota composition via fecal microbiota transplantation (FMT) have been explored in various clinical settings with some of them showing promising results, although larger clinical trials are needed to confirm the efficacy of this strategy. Here, we highlight the challenges associated with the emergence of CRE infections.}, } @article {pmid33133183, year = {2020}, author = {Ye, ZN and Xia, HH and Zhang, R and Li, L and Wu, LH and Liu, XJ and Xie, WR and He, XX}, title = {The Efficacy of Washed Microbiota Transplantation on Helicobacter pylori Eradication: A Pilot Study.}, journal = {Gastroenterology research and practice}, volume = {2020}, number = {}, pages = {8825189}, pmid = {33133183}, issn = {1687-6121}, abstract = {Aim: The fecal microbiota transplantation by washed preparation was recently coined as washed microbiota transplantation (WMT). This pilot study is aimed at exploring the feasibility and efficacy of WMT on Helicobacter pylori eradication.

Methods: Consecutive patients who had been treated with WMT for various indications and who were positive for H. pylori infection before WMT treatment but had never received eradication therapy for H. pylori infection were invited to take a follow-up 13C-urea breath test. The associations of demographic, clinical factors, and laboratory indicators for gastric function and intestinal barrier function with the therapeutic effect were determined.

Results: A total of 32 eligible patients were included, and the overall H. pylori eradication rate was 40.6% (13/32). Patients with H. pylori eradication had a higher pepsinogen ratio (PGR) than those without (13.00 ± 6.97vs.8.31 ± 3.733; P = 0.02). Female patients had a higher, albeit not statistically significant, eradication rate than male patients (53.85% vs. 31.58%; P = 0.208). Compared with lower gastrointestinal tract delivery route, middle gastrointestinal tract delivery route seems to be a more suitable way for the treatment of H. pylori infection (58.33% vs 16.67%; P = 0.152). There was no significant difference in other demographic and clinical factors between patients with and without H. pylori eradication.

Conclusion: H. pylori infection is eradicated in a proportion of patients who have received WMT. An increased pre-WMT PGR appears to be associated with the therapeutic effect. Further studies are required to confirm the efficacy of WMT, especially in combination with currently recommended regimens in randomized controlled trials.}, } @article {pmid33132658, year = {2020}, author = {Wen, Q and Liu, KJ and Cui, BT and Li, P and Wu, X and Zhong, M and Wei, L and Tu, H and Yuan, Y and Lin, D and Hsu, WH and Wu, DC and Yin, H and Zhang, FM}, title = {Impact of cap-assisted colonoscopy during transendoscopic enteral tubing: A randomized controlled trial.}, journal = {World journal of gastroenterology}, volume = {26}, number = {39}, pages = {6098-6110}, pmid = {33132658}, issn = {2219-2840}, abstract = {BACKGROUND: Colonic transendoscopic enteral tubing (TET) requires double cecal intubation, raising a common concern of how to save cecal intubation time and make the tube stable. We hypothesized that cap-assisted colonoscopy (CC) might reduce the second cecal intubation time and bring potential benefits during the TET procedure.

AIM: To investigate if CC can decrease the second cecal intubation time compared with regular colonoscopy (RC).

METHODS: This prospective multicenter, randomized controlled trial was performed at four centers. Subjects ≥ 7 years needing colonic TET were recruited from August 2018 to January 2020. All subjects were randomly assigned to two groups. The primary outcome was the second cecal intubation time. Secondary outcomes included success rate, insertion pain score, single clip fixation time, purpose and retention time of TET tube, length of TET tube inserted into the colon, and all procedure-related (serious) adverse events.

RESULTS: A total of 331 subjects were randomized to the RC (n = 165) or CC (n = 166) group. The median time of the second cecal intubation was significantly shorter for CC than RC (2.2 min vs 2.8 min, P < 0.001). In patients with constipation, the median time of second cecal intubation in the CC group (n = 50) was shorter than that in the RC group (n = 43) (2.6 min vs 3.8 min, P = 0.004). However, no difference was observed in the CC (n = 42) and RC (n = 46) groups of ulcerative colitis patients (2.0 min vs 2.5 min, P = 0.152). The insertion pain score during the procedure in CC (n = 14) was lower than that in RC (n = 19) in unsedated colonoscopy (3.8 ± 1.7 vs 5.4 ± 1.9; P = 0.015). Multivariate analysis revealed that only CC (odds ratio [OR]: 2.250, 95% confidence interval [CI]: 1.161-4.360; P = 0.016) was an independent factor affecting the second cecal intubation time in difficult colonoscopy. CC did not affect the colonic TET tube's retention time and length of the tube inserted into the colon. Moreover, multivariate analysis found that only endoscopic clip number (OR: 2.201, 95%CI: 1.541-3.143; P < 0.001) was an independent factor affecting the retention time. Multiple regression analysis showed that height (OR: 1.144, 95%CI: 1.027-1.275; P = 0.014) was the only independent factor influencing the length of TET tube inserted into the colon in adults.

CONCLUSION: CC for colonic TET procedure is a safe and less painful technique, which can reduce cecal intubation time.}, } @article {pmid33131919, year = {2021}, author = {Chaitman, J and Gaschen, F}, title = {Fecal Microbiota Transplantation in Dogs.}, journal = {The Veterinary clinics of North America. Small animal practice}, volume = {51}, number = {1}, pages = {219-233}, doi = {10.1016/j.cvsm.2020.09.012}, pmid = {33131919}, issn = {1878-1306}, abstract = {In people, fecal microbiota transplantation is recognized as the best treatment modality for recurrent Clostridioides difficile infection in people, and its value is currently investigated in the treatment of other diseases associated with an abnormal gut microbiome. In dogs, intestinal dysbiosis has been documented in many acute and chronic digestive diseases as well as in diseases of other organ systems. There are only few published studies evaluating the benefits of fecal microbiota transplantation (FMT) in canine gastrointestinal disorders. They provide evidence that FMT may be beneficial in the treatment of acute intestinal diseases and hope that the technique might also be useful for the management of chronic enteropathies.}, } @article {pmid33131263, year = {2020}, author = {Merli, P and Putignani, L and Ruggeri, A and Del Chierico, F and Gargiullo, L and Galaverna, F and Gaspari, S and Pagliara, D and Russo, A and Pane, S and Strocchio, L and Algeri, M and Rea, F and Francesca Romeo, E and Bernaschi, P and Onetti Muda, A and Dallapiccola, B and Locatelli, F}, title = {Decolonization of multi-drug resistant bacteria by fecal microbiota transplantation in five pediatric patients before allogeneic hematopoietic stem cell transplantation: gut microbiota profiling, infectious and clinical outcomes.}, journal = {Haematologica}, volume = {105}, number = {11}, pages = {2686-2690}, doi = {10.3324/haematol.2019.244210}, pmid = {33131263}, issn = {1592-8721}, } @article {pmid33130602, year = {2020}, author = {Nagy, GG and Tudlik, Z and Gergely, L and Kónya, J and Orosi, P and Rákóczi, É and Szabó, J and Várvölgyi, C and Vitális, E and Paragh, G}, title = {Reconsidering the technical aspects and quality management background of faecal microbiota transplantation due to the novel coronavirus pandemic.}, journal = {Orvosi hetilap}, volume = {161}, number = {44}, pages = {1858-1871}, doi = {10.1556/650.2020.32023}, pmid = {33130602}, issn = {1788-6120}, mesh = {Betacoronavirus ; COVID-19 ; Clostridioides difficile ; Clostridium Infections/*therapy ; *Coronavirus ; Coronavirus Infections/epidemiology/*prevention & control ; Fecal Microbiota Transplantation/methods/*standards ; Humans ; Hungary ; Pandemics ; Pneumonia, Viral/epidemiology/*prevention & control ; Quality Improvement ; SARS-CoV-2 ; Treatment Outcome ; }, abstract = {Összefoglaló. A székletmikrobiota-transzplantáció (faecalismikrobiota-transzplantáció - FMT) a Clostridioides difficile fertőzés (CDI) kezelésében nemzetközileg széles körben elfogadott, megfelelő szakmai háttér mellett végezve biztonságos, potenciálisan életmentő, költséghatékony, valamint a hospitalizációs idő és az orvos-beteg találkozások jelentős redukálására képes eljárás. Az FMT elvégzésére egyes országokban magas szintű minőségirányítási háttérrel működő, célfeladatra szerveződött donor- és székletbankok rendezkedtek be. Máshol, így például hazánkban, az eljáráshoz az egyértelmű jogi szabályozási környezet, a standardizált technológiai háttér és a finanszírozás hiánya miatt nem egységes a hozzáférés. Régóta időszerű továbbá, hogy a heterogén, nemegyszer háztartási eszközökkel előkészített beavatkozások helyett a nemzetközi és legújabban már a hazai ajánlásokban is megfogalmazott, a betegbiztonságot legjobban garantáló elvárások mellett történjen a széklettranszplantáció. Az új koronavírus (SARS-CoV-2) okozta pandémia megjelenése erőteljes szakmai érv országos szinten az FMT minőségirányítási környezetének és technológiai hátterének újragondolására, mert a SARS-CoV-2 egyszerre jelent kockázatot a CDI miatt kórházban kezelt sérülékeny betegpopulációnak, és egyben veszélyezteti az FMT biztonságosságát mind a recipiens, mind pedig az eljárást végző egészségügyi személyzet tekintetében. Ezekre a szakmai és társadalmi kihívásokra reagálva, a széles körű beteghozzáférés és a legmagasabb szintű betegbiztonság garantálására, a Debreceni Egyetemen új eljárásrendet dolgoztunk ki az FMT végzésére. Ezen eljárásrendnek a COVID-19-pandémia miatt módosított, a fagyasztottgraftbank üzemeltetése és a rendszerszemlélet tekintetében releváns elemeit ismertetjük. Javasolt, hogy országos szinten hasonló, megfelelő minőségirányítási és technológiai környezettel, a SARS-CoV-2-fertőzés kizárását is integráló donorszűrési rendszerrel, továbbá fagyasztottgraft-banki háttérrel működő laboratóriumok vegyenek részt a széklettranszplantációk végzésében. Felmerül továbbá, hogy az eljárást a számos analógia és a donor-recipiens koncepció alapján a sejt- és szövettranszplantációkra vonatkozó szabályozórendszer keretei közé ajánlott beágyazni. Orv Hetil. 2020; 161(44): 1858-1871. Summary. Stool transplantation (faecal microbiota transplantation - FMT) is a widely accepted, potentially life-saving, cost-effective medical intervention for the treatment of Clostridioides difficile infection (CDI), which has an acceptable safety profile if performed with an appropriate professional background. FMT can significantly reduce hospitalization time and the number of patient visits. National donor and stool banks with high-standard quality management systems were established in certain countries for supporting the procedures. In other regions, including Hungary, patient access is not uniform due to the lack of clear legal regulations, standardized technology or financial reimbursement. It has been expected for a long time to replace the heterogenous techniques, occasionally utilizing household equipment with a technology providing improved patient safety and fulfilling international and recently published local FMT guidelines. The emergence of the novel coronavirus (SARS-CoV-2) pandemic is a very powerful argument in favour of urgently reconsidering the quality management and technological background of FMT procedures. SARS-CoV-2 is a major threat to the vulnerable patients suffering from CDI and also impose risks for the recipient and healthcare personnel involved in carrying out the transplantation. New FMT guidelines were implemented at the University of Debrecen to address these professional and public challenges, to provide wide patient access and to guarantee the highest achievable patient safety. Relevant elements of this new protocol are presented, focusing on a systemic quality management approach, on the operation of a frozen stool bank and on a modified donor screening algorithm taking the risks of COVID-19 into consideration. We suggest that laboratories with proper quality assurance and technological conditions, implementing SARS-CoV-2 donor screening and operating a frozen graft bank should participate in faecal microbiota transplantations. It is also recommended that, based on the analogies and the similar donor-recipient concept, FMT should be embedded under the organ tissue and cell transplantation polices in Hungary. Orv Hetil. 2020; 161(44): 1858-1871.}, } @article {pmid33123253, year = {2020}, author = {Wang, J and Yang, HR and Wang, DJ and Wang, XX}, title = {Association between the gut microbiota and patient responses to cancer immune checkpoint inhibitors.}, journal = {Oncology letters}, volume = {20}, number = {6}, pages = {342}, pmid = {33123253}, issn = {1792-1074}, abstract = {Studies are increasingly investigating the association between the gut microbiota and the outcomes of immunotherapy in patients with cancer. Notably, certain studies have demonstrated that the gut microbiota serves a key role in regulating a patient's response to immunotherapy. In the present review, the potential associations between the gut microbiota, and cancer, host immunity and cancer immunotherapy are reviewed. Furthermore, the effects of fecal microbiota transplantation, antibiotics, probiotics, prebiotics, synbiotics, components of traditional Chinese medicine and various lifestyle factors on the gut microbiota and cancer immunotherapy outcomes are discussed. Certain dominant bacterial groups in the context of cancer immunotherapy and certain effective methods for optimizing immunotherapy by regulating the gut microbiota have been identified. Further investigation may enable the rapid conversion of these discoveries into practical products and clinically applicable methods.}, } @article {pmid33122357, year = {2020}, author = {Guo, H and Chou, WC and Lai, Y and Liang, K and Tam, JW and Brickey, WJ and Chen, L and Montgomery, ND and Li, X and Bohannon, LM and Sung, AD and Chao, NJ and Peled, JU and Gomes, ALC and van den Brink, MRM and French, MJ and Macintyre, AN and Sempowski, GD and Tan, X and Sartor, RB and Lu, K and Ting, JPY}, title = {Multi-omics analyses of radiation survivors identify radioprotective microbes and metabolites.}, journal = {Science (New York, N.Y.)}, volume = {370}, number = {6516}, pages = {}, doi = {10.1126/science.aay9097}, pmid = {33122357}, issn = {1095-9203}, support = {P40 OD010995/OD/NIH HHS/United States ; R01 CA228308/CA/NCI NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; R21 AG066388/AG/NIA NIH HHS/United States ; U01 AI124275/AI/NIAID NIH HHS/United States ; P01 CA023766/CA/NCI NIH HHS/United States ; R01 HL147584/HL/NHLBI NIH HHS/United States ; R01 ES024950/ES/NIEHS NIH HHS/United States ; P01 AG052359/AG/NIA NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R35 CA232109/CA/NCI NIH HHS/United States ; T32 CA009156/CA/NCI NIH HHS/United States ; P30 AG028716/AG/NIA NIH HHS/United States ; P30 DK056350/DK/NIDDK NIH HHS/United States ; P01 DK094779/DK/NIDDK NIH HHS/United States ; P30 ES010126/ES/NIEHS NIH HHS/United States ; R01 CA228358/CA/NCI NIH HHS/United States ; U19 AI067798/AI/NIAID NIH HHS/United States ; }, mesh = {Acute Radiation Syndrome/*microbiology/prevention & control/therapy ; Animals ; Clostridiales/*metabolism ; Enterococcaceae/*metabolism ; Fatty Acids, Volatile/*metabolism/therapeutic use ; *Gastrointestinal Microbiome ; Humans ; Metabolomics ; Mice ; Mice, Inbred C57BL ; *Radiation Protection ; Survivors ; Tryptophan/*metabolism ; }, abstract = {Ionizing radiation causes acute radiation syndrome, which leads to hematopoietic, gastrointestinal, and cerebrovascular injuries. We investigated a population of mice that recovered from high-dose radiation to live normal life spans. These "elite-survivors" harbored distinct gut microbiota that developed after radiation and protected against radiation-induced damage and death in both germ-free and conventionally housed recipients. Elevated abundances of members of the bacterial taxa Lachnospiraceae and Enterococcaceae were associated with postradiation restoration of hematopoiesis and gastrointestinal repair. These bacteria were also found to be more abundant in leukemia patients undergoing radiotherapy, who also displayed milder gastrointestinal dysfunction. In our study in mice, metabolomics revealed increased fecal concentrations of microbially derived propionate and tryptophan metabolites in elite-survivors. The administration of these metabolites caused long-term radioprotection, mitigation of hematopoietic and gastrointestinal syndromes, and a reduction in proinflammatory responses.}, } @article {pmid33121693, year = {2020}, author = {Cheng, YW and Fischer, M}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis. Are We Ready for Primetime?.}, journal = {Gastroenterology clinics of North America}, volume = {49}, number = {4}, pages = {739-752}, doi = {10.1016/j.gtc.2020.08.006}, pmid = {33121693}, issn = {1558-1942}, abstract = {"Patients with inflammatory bowel disease, including ulcerative colitis (UC) and Crohn disease, have altered gut microbiomes. The success of fecal microbiota transplantation (FMT) in the treatment of Clostridioides difficile infection, a disease that is also marked by dysbiosis, has spurred research in applying FMT to UC. So far, 3 randomized controlled trials have demonstrated benefit in mild to moderate UC disease course after FMT. However, important questions regarding optimal stool preparation, route, and frequency of administration, as well as characteristics of the stool donor and recipient still remain."}, } @article {pmid33118360, year = {2020}, author = {Silva, JC and Ponte, A and Mota, M and Pinho, R and Vieira, N and Oliveira, R and Mota-Carvalho, N and Gomes, AC and Afecto, E and Carvalho, J}, title = {Fecal microbiota transplantation in the intestinal decolonization of carbapenamase-producing enterobacteriaceae.}, journal = {Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva}, volume = {112}, number = {12}, pages = {925-928}, doi = {10.17235/reed.2020.7150/2020}, pmid = {33118360}, issn = {1130-0108}, abstract = {BACKGROUND AND AIMS: fecal microbiota transplantation (FMT) is effective for recurrent Clostridium difficile infection (CDI). Intestinal decolonization of carbapenamase-producing enterobacteriaceae (CPE) can prevent transmission and infection by these agents. The aim of this study was to assess CPE decolonization after FMT.

METHODS: this was a case-series study that consecutively included all CPE-carriers that underwent FMT between 2014 and 2019. The indications included refractory/recurrent CDI and CPE-decolonization.

RESULTS: out of 21 CPE-carriers, eight were excluded due to incomplete post-FMT testing. CPE decolonization was confirmed in 76.9 % (n = 10). The median decolonization time was 16-weeks (IQR-23) and ranged from two to 53 weeks.

CONCLUSION: FMT may be used in the clinical practice for CPE-decolonization as an alternative to combined antibiotic regimens.}, } @article {pmid33117731, year = {2020}, author = {Li, Q and Jin, M and Liu, Y and Jin, L}, title = {Gut Microbiota: Its Potential Roles in Pancreatic Cancer.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {572492}, pmid = {33117731}, issn = {2235-2988}, abstract = {Pancreatic cancer is considered a lethal disease with a low survival rate due to its late-stage diagnosis, few opportunities for resection and lack of effective therapeutic strategies. Multiple, highly complex effects of gut microbiota on pancreatic cancer have been recognized as potential strategies for targeting tumorigenesis, development and treatment in recent decades; some of the treatments include antibiotics, probiotics, and fecal microbiota transplantation. Several bacterial species are associated with carcinogenesis of the pancreas, while some bacterial metabolites contribute to tumor-associated low-grade inflammation and immune responses via several proinflammatory factors and signaling pathways. Given the limited evidence on the interplay between gut microbiota and pancreatic cancer, risk factors associated with pancreatic cancer, such as diabetes, chronic pancreatitis and obesity, should also be taken into consideration. In terms of treatment of pancreatic cancer, gut microbiota has exhibited multiple effects on both traditional chemotherapy and the recently successful immunotherapy. Therefore, in this review, we summarize the latest developments and advancements in gut microbiota in relation to pancreatic cancer to elucidate its potential value.}, } @article {pmid33117316, year = {2020}, author = {Dai, X and Hou, H and Zhang, W and Liu, T and Li, Y and Wang, S and Wang, B and Cao, H}, title = {Microbial Metabolites: Critical Regulators in NAFLD.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {567654}, pmid = {33117316}, issn = {1664-302X}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease throughout the world. The relationship between gut microbiota and NAFLD has been extensively investigated. The gut microbiota is involved in the regulation of NAFLD by participating in the fermentation of indigestible food, interacting with the intestinal mucosal immune system, and influencing the intestinal barrier function, leading to signaling alteration. Meanwhile, the microbial metabolites not only affect the signal transduction pathway in the gut but also reach the liver far away from gut. In this review, we focus on the effects of certain key microbial metabolites such as short-chain fatty acids, trimethylamine-N-oxide, bile acids, and endogenous ethanol and indole in NAFLD, and also summarize several potential therapies targeting the gut-liver axis and modulation of gut microbiota metabolites including antibiotics, prebiotics, probiotics, bile acid regulation, and fecal microbiota transplantation. Understanding the complex interactions between microbial metabolites and NAFLD may provide crucial insight into the pathogenesis and treatment of NAFLD.}, } @article {pmid33116952, year = {2020}, author = {Kullar, R and Tran, MN and Goldstein, EJC}, title = {Investigational Treatment Agents for Recurrent Clostridioides difficile Infection (rCDI).}, journal = {Journal of experimental pharmacology}, volume = {12}, number = {}, pages = {371-384}, pmid = {33116952}, issn = {1179-1454}, abstract = {Clostridioides difficile infection (CDI) is a major cause of nosocomial diarrhea that is deemed a global health threat. C. difficile strain BI/NAP1/027 has contributed to the increase in the mortality, severity of CDI outbreaks and recurrence rates (rCDI). Updated CDI treatment guidelines suggest vancomycin and fidaxomicin as initial first-line therapies that have initial clinical cure rates of over 80%. Unacceptably high recurrence rates of 15-30% in patients for the first episode and 40% for the second recurrent episode are reported. Alternative treatments for rCDI include fecal microbiota transplant and a human monoclonal antibody, bezlotoxumab, that can be used in patients with high risk of rCDI. Various emerging potential therapies with narrow spectrum of activity and little systemic absorption that are in development include 1) Ibezapolstat (formerly ACX-362E), MGB-BP-3, and DS-2969b-targeting bacterial DNA replication, 2) CRS3213 (REP3123)-inhibiting toxin production and spore formation, 3) ramizol and ramoplanin-affecting bacterial cell wall, 4) LFF-571-blocking protein synthesis, 5) Alanyl-L-Glutamine (alanylglutamine)-inhibiting damage caused by C. difficile by protecting intestinal mucosa, and 6) DNV3837 (MCB3681)-prodrug consisting of an oxazolidinone-quinolone combination that converts to the active form DNV3681 that has activity in vitro against C. difficile. This review article provides an overview of these developing drugs that can have potential role in the treatment of rCDI and in lowering recurrence rates.}, } @article {pmid33116044, year = {2020}, author = {Han, Y and Wu, L and Ling, Q and Wu, P and Zhang, C and Jia, L and Weng, H and Wang, B}, title = {Intestinal Dysbiosis Correlates With Sirolimus-Induced Metabolic Disorders in Mice.}, journal = {Transplantation}, volume = {}, number = {}, pages = {}, doi = {10.1097/TP.0000000000003494}, pmid = {33116044}, issn = {1534-6080}, abstract = {BACKGROUND: Long-time use of pharmacological immunosuppressive agents frequently leads to metabolic disorders. Most studies have focused on islet toxicity leading to post-transplantation diabetes mellitus. In contrast, the link between intestinal dysbiosis and immunosuppressive drug-induced metabolic disorders remains unclear.

METHODS: We established a mouse model of metabolic abnormality via sirolimus treatment. Fecal microbiota was examined using 16S rRNA gene MiSeq sequencing. Intestinal barrier function was assessed using fluorescein isothiocyanate-dextran assay and mucus immunostaining. Systemic inflammation was determined using a multiplexed fluorescent bead-based immunoassay.

RESULTS: Sirolimus induced dyslipidemia and glucose intolerance in mice in a dose-dependent manner. Interestingly, the clinical-mimicking dose of sirolimus altered the intestinal microbiota community, which was characterized by the enrichment of Proteobacteria, depletion of Akkermansia, and potential function shifts to those involved in lipid metabolism and the immune system. In addition, the clinical-mimicking dose of sirolimus reduced the thickness of the intestinal mucosal layer, increased the intestinal permeability, and enriched the circulating pro-inflammatory factors, including IL-12, IL-6, MCP-1, GM-CSF, and IL-1β. Our results showed a close association between intestinal dysbiosis, intestinal barrier failure, systemic inflammation, and metabolic disorders. Furthermore, we demonstrated that oral intervention in the gut microbiota by Lactobacillus rhamnosus HN001 protected against intestinal dysbiosis, especially by depleting the LPS-producing Proteobacteria, and attenuated the sirolimus-induced systemic inflammation, dyslipidemia, and insulin resistance.

CONCLUSION: Our study demonstrated a potentially causative role of intestinal dysbiosis in sirolimus-induced metabolic disorders, which will provide a novel therapeutic target for transplant recipients.}, } @article {pmid33111793, year = {2020}, author = {Luz, MRMPD and Waizbort, RF}, title = {[Fecal microbiota transplants in the treatment of pseudomembranous colitis (1958-2013): priority of discovery and thought styles in the academic literature].}, journal = {Historia, ciencias, saude--Manguinhos}, volume = {27}, number = {3}, pages = {859-878}, doi = {10.1590/S0104-59702020000400009}, pmid = {33111793}, issn = {1678-4758}, abstract = {In 1958, Eiseman and contributors published the first scientific paper reporting the use of fecal microbiota transplant for treating pseudomembranous colitis. The relevance of this innovative paper was only acknowledged in 1990. The academic literature on the theme is characterized by a narrative that has undergone successive revisions. We suggest that such revisions were based on claims of priority of scientific discoveries, as described by Merton. The revival of fecal microbiota transplants is interpreted as a process of genesis of a scientific fact, as defined by Fleck: there is a switch from a thought style based on the use of antibiotics to treat infectious diseases to another that accepts the ecological relations between hosts, vectors and parasites.}, } @article {pmid33110112, year = {2020}, author = {Kazemian, N and Ramezankhani, M and Sehgal, A and Khalid, FM and Kalkhoran, AHZ and Narayan, A and Wong, GK and Kao, D and Pakpour, S}, title = {The trans-kingdom battle between donor and recipient gut microbiome influences fecal microbiota transplantation outcome.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {18349}, pmid = {33110112}, issn = {2045-2322}, abstract = {Fundamental restoration ecology and community ecology theories can help us better understand the underlying mechanisms of fecal microbiota transplantation (FMT) and to better design future microbial therapeutics for recurrent Clostridioides difficile infections (rCDI) and other dysbiosis-related conditions. In this study, stool samples were collected from donors and rCDI patients one week prior to FMT (pre-FMT), as well as from patients one week following FMT (post-FMT). Using metagenomic sequencing and machine learning, our results suggested that FMT outcome is not only dependent on the ecological structure of the recipients, but also the interactions between the donor and recipient microbiomes at the taxonomical and functional levels. We observed that the presence of specific bacteria in donors (Clostridioides spp., Desulfovibrio spp., Odoribacter spp. and Oscillibacter spp.) and the absence of fungi (Yarrowia spp.) and bacteria (Wigglesworthia spp.) in recipients prior to FMT could predict FMT success. Our results also suggested a series of interlocked mechanisms for FMT success, including the repair of the disturbed gut ecosystem by transient colonization of nexus species followed by secondary succession of bile acid metabolizers, sporulators, and short chain fatty acid producers.}, } @article {pmid33106983, year = {2020}, author = {Dembrovszky, F and Gede, N and Szakács, Z and Hegyi, P and Kiss, S and Farkas, N and Molnár, Z and Imrei, M and Dohos, D and Péterfi, Z}, title = {Fecal Microbiota Transplantation May Be the Best Option in Treating Multiple Clostridioides difficile Infection: A Network Meta-Analysis.}, journal = {Infectious diseases and therapy}, volume = {}, number = {}, pages = {}, doi = {10.1007/s40121-020-00356-9}, pmid = {33106983}, issn = {2193-8229}, support = {GINOP-2.3.2-15-2016-00048//European Regional Development Fund/ ; EFOP-3.6.2-16-2017-00006//European Regional Development Fund/ ; }, abstract = {INTRODUCTION: Clostridioides difficile (formerly Clostridium) infection (CDI) is the most common cause of healthcare-associated diarrhea with high mortality and recurrence rate; furthermore, the treatment of recurrent cases is a challenge. In this network meta-analysis, we aimed to compare all available therapies against multiple recurrent CDI (mrCDI) and rank them by efficacy.

METHODS: After a systematic search, randomized controlled trials (RCT) with any interventions against mrCDI were included. Data were extracted to the study database using Excel. Risk of bias assessment was performed with the Cochrane RoB 2 tool. The primary outcome was the clinical cure of CDI and the secondary outcome was the recurrence of CDI. A Bayesian method was performed to investigate the efficacy rank order of therapies. We registered our protocol with the Prospero Center for Reviews and Dissemination (registration no. CRD42020160365).

RESULTS: Six RCTs with seven interventions were included in the quantitative synthesis. According to the surface under the cumulative ranking curve values, fecal microbiota transplantation (FMT) after a short course of vancomycin therapy (83%) shows the highest efficacy for clinical cure. Tolevamer and vancomycin + FMT seemed to be the most effective in preventing recurrence (87% and 75%, respectively).

CONCLUSION: Vancomycin + FMT is perhaps the most effective option for the treatment and prevention of mrCDI, while tolevamer is also effective in preventing recurrence.}, } @article {pmid33102769, year = {2020}, author = {Gill, M and Blacketer, C and Chitti, F and Telfer, K and Papanicolas, L and Dann, LM and Tucker, EC and Bryant, RV and Costello, SP}, title = {Physician and patient perceptions of fecal microbiota transplant for recurrent or refractory Clostridioides difficile in the first 6 years of a central stool bank.}, journal = {JGH open : an open access journal of gastroenterology and hepatology}, volume = {4}, number = {5}, pages = {950-957}, pmid = {33102769}, issn = {2397-9070}, abstract = {Background and Aim: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent or refractory Clostridioides difficile infection (rCDI). Despite inclusion in society guidelines, the uptake of FMT therapy has been variable. Physician and patient attitudes may be a barrier to evidence-based uptake of therapies; however, data assessing attitudes regarding FMT for rCDI are limited.

Methods: The South Australian FMT for CDI database prospectively recorded patient outcomes of FMT for CDI from August 2013 to January 2019. A total of 93 consecutive patients who underwent FMT for rCDI in South Australia were invited to participate in a 20-question survey regarding the patient experience of FMT. All gastroenterologists and infectious disease physicians practicing in South Australia were invited to participate in an online survey comprised of 22 questions that addressed referral experience, indications for referral, perceived risks, and regulation and funding.

Results: Fifty-four patients (54/93, 58%) returned the survey, of whom 52 (96%) would recommend FMT to others, and 51 (94%) were satisfied with treatment outcome. Fifty physicians returned the online survey (50/100, 50%), of whom 23 (46%) were concerned about disease transmission risk, and 15 (30%) believed that the risk of FMT would outweigh the benefit. Infectious diseases physicians and advanced trainees had significantly greater concern regarding the potential alteration of the microbiome than gastroenterology physicians and advanced trainees (8/17 (47%) vs 6/33 (18%); P = 0.047).

Conclusion: Despite high levels of patient-reported satisfaction following FMT, physician-reported reservations exist and may present a barrier to uptake of this therapy.}, } @article {pmid33102555, year = {2020}, author = {Rossi, G and Pengo, G and Galosi, L and Berardi, S and Tambella, AM and Attili, AR and Gavazza, A and Cerquetella, M and Jergens, AE and Guard, BC and Lidbury, JA and Stainer, JM and Crovace, AM and Suchodolski, JS}, title = {Effects of the Probiotic Mixture Slab51® (SivoMixx®) as Food Supplement in Healthy Dogs: Evaluation of Fecal Microbiota, Clinical Parameters and Immune Function.}, journal = {Frontiers in veterinary science}, volume = {7}, number = {}, pages = {613}, pmid = {33102555}, issn = {2297-1769}, abstract = {The gut microbiota plays a crucial role in several physiologic functions of the host. In humans and animals, manipulation of the intestinal microbiota by oral administration of probiotic lactic acid bacteria plays a significant role in modulating the immune system. The aim of this study was to evaluate the safety of the probiotic mixture Slab51® and the capacity of this mixture to stimulate immune function in healthy dogs. Twenty dogs were divided in two groups and received a control diet or the same diet supplemented with a dose of 400 billion cfu of lyophilized bacteria for a period of 60 days. Body weight, food intake, body condition score (BCS), fecal score (FSS), fecal immunoglobulin IgA concentration, plasma IgG concentration, and fecal microbiota composition were monitored. Weight, food intake, BCS, FSS, and biochemical parameters remained unchanged during the treatment in both groups of animals. The fecal microbiota showed a significant decrease in the abundance of Clostridium perfringens and a significant increase in the abundance of beneficial Bifidobacterium and Lactobacillus organisms (p < 0.05). Fecal IgA and plasma IgG levels were significantly higher in the group receiving the probiotic compared to healthy controls. These data show that dietary supplementation with the probiotic mixture Slab51® is safe and well-tolerated, modulating the composition of the intestinal microbiota, and enhancing specific immune functions in healthy dogs.}, } @article {pmid33102406, year = {2020}, author = {Koo, H and Crossman, DK and Morrow, CD}, title = {Strain Tracking to Identify Individualized Patterns of Microbial Strain Stability in the Developing Infant Gut Ecosystem.}, journal = {Frontiers in pediatrics}, volume = {8}, number = {}, pages = {549844}, pmid = {33102406}, issn = {2296-2360}, abstract = {Stable microbe and host interactions are established during the development of the infant gut microbial community that provide essential functions for the efficient digestion of food, immune development, and resistance to colonization with pathogens. To further delineate the stability of the gut microbial community during this time, we have used microbial strain tracking analysis with published longitudinal metagenomic data sets to identify strains that persist in the developing infant gut ecosystem. In the first study, 17 infants were evaluated that had not received antibiotics for 3 years after birth. An infant specific pattern was seen for stable and unstable microbial strains during this time, with only one infant having no stable strains identified out of available strains during the first 3 years. Strain tracking was also applied to follow microbes in a separate set of 14 infants that had multiple doses of antibiotics over the 3 years. In 10 out of 14 infants given multiple antibiotics during the first 3 years, we identified a unique pattern of transient strains that appeared after multiple antibiotic treatments for a short time compared to that in infants not on antibiotics. In a second, independent study, we selected a subset of 9 infants from a previously published study consisting of high-density longitudinal fecal sampling to analyze the gut microbial strain stability of Bacteroides vulgatus and Bifidobacterium adolescentis for up to 6 years following birth. Individual specific patterns were found consisting of varying dominant microbial strains that were independent of antibiotic exposure and birth mode. Our analysis demonstrates an individual specific inherent variability of extinction and persistence of microbial strains in the infant gut community during a time of development that is critical for interactions necessary for establishing normal metabolism and the development of the host immune response.}, } @article {pmid33098239, year = {2020}, author = {Li, W and Chen, C and Chen, M and Zhang, X and Ji, Q and Wang, Y and Zheng, Q and Tan, S and Gao, X and Lu, Y}, title = {Salted and Unsalted Zhàcài (Brassica juncea var. tumida) Alleviated High-Fat Diet-Induced Dyslipidemia by Regulating Gut Microbiota: A Multiomics Study.}, journal = {Molecular nutrition & food research}, volume = {}, number = {}, pages = {e2000798}, doi = {10.1002/mnfr.202000798}, pmid = {33098239}, issn = {1613-4133}, abstract = {SCOPE: Zhàcài (ZC), a salting-processed Brassica juncea var. tumida vegetable, is widely consumed as a pickle, but little is known about the health benefits of both salted and unsalted ZC as a whole food.

METHODS AND RESULTS: The preventive effects of salted and unsalted ZC against dyslipidemia are assessed in high-fat (HF) diet-fed mice. HF intake for 12 continuous weeks cause dyslipidemia in mice, as evidenced by the elevations in serum total triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels by 30%, 66%, and 117%, respectively. Metabolomics analysis and the 16S rRNA genes sequencing suggest that dietary administration of salted and unsalted ZC (2.5% w/w) alleviates HF-induced dyslipidemia, metabolic disorders of short-chain fatty acids, and disturbance of intestinal flora in mice. These positive effects of unsalted ZC are stronger than those of salted ZC. Moreover, fecal bacteria transplantation confirms the antidyslipidemia of ZC.

CONCLUSION: These results suggest that consumption of ZC may prevent HF-induced dyslipidemia by regulating gut microbiota.}, } @article {pmid33094595, year = {2020}, author = {Poortmans, P and Kindt, S}, title = {Diagnostic approach to chronic diarrhoea and recent insights in treatment of functional diarrhoea including irritable bowel syndrome.}, journal = {Acta gastro-enterologica Belgica}, volume = {83}, number = {3}, pages = {461-474}, pmid = {33094595}, issn = {1784-3227}, mesh = {Bile Acids and Salts ; *Diarrhea/diagnosis/etiology/therapy ; Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome/diagnosis/therapy ; Parasympatholytics ; }, abstract = {Chronic diarrhoea is a common clinical problem with a plethora of possible causes and underlying pathophysiological mechanisms. The value of diagnostic assessment by laboratory testing, stool analysis, evaluation of bile acid malabsorption, endoscopy, breath testing and radiological imaging techniques is discussed. The decision to focus investigations on excluding certain pathologies remains a matter of clinical judgement. Functional diarrhoea and irritable bowel syndrome (IBS) being the most frequent causes of chronic diarrhoea, recent insights in the role of dietary management, management of dysbiosis by pre-, pro- and antibiotics and faecal microbiota transplantation, as well as targeted treatment by spasmolytics, 5-HT3 receptor antagonists and eluxadoline will be reviewed.}, } @article {pmid33087514, year = {2020}, author = {Kang, DW and Adams, JB and Vargason, T and Santiago, M and Hahn, J and Krajmalnik-Brown, R}, title = {Distinct Fecal and Plasma Metabolites in Children with Autism Spectrum Disorders and Their Modulation after Microbiota Transfer Therapy.}, journal = {mSphere}, volume = {5}, number = {5}, pages = {}, pmid = {33087514}, issn = {2379-5042}, abstract = {Accumulating evidence has strengthened a link between dysbiotic gut microbiota and autism. Fecal microbiota transplant (FMT) is a promising therapy to repair dysbiotic gut microbiota. We previously performed intensive FMT called microbiota transfer therapy (MTT) for children with autism spectrum disorders (ASD) and observed a substantial improvement of gastrointestinal and behavioral symptoms. We also reported modulation of the gut microbiome toward a healthy one. In this study, we report comprehensive metabolite profiles from plasma and fecal samples of the children who participated in the MTT trial. With 619 plasma metabolites detected, we found that the autism group had distinctive metabolic profiles at baseline. Eight metabolites (nicotinamide riboside, IMP, iminodiacetate, methylsuccinate, galactonate, valylglycine, sarcosine, and leucylglycine) were significantly lower in the ASD group at baseline, while caprylate and heptanoate were significantly higher in the ASD group. MTT drove global shifts in plasma profiles across various metabolic features, including nicotinate/nicotinamide and purine metabolism. In contrast, for 669 fecal metabolites detected, when correcting for multiple hypotheses, no metabolite was significantly different at baseline. Although not statistically significant, p-cresol sulfate was relatively higher in the ASD group at baseline, and after MTT, the levels decreased and were similar to levels in typically developing (TD) controls. p-Cresol sulfate levels were inversely correlated with Desulfovibrio, suggesting a potential role of Desulfovibrio on p-cresol sulfate modulation. Further studies of metabolites in a larger ASD cohort, before and after MTT, are warranted, as well as clinical trials of other therapies to address the metabolic changes which MTT was not able to correct.IMPORTANCE Despite the prevalence of autism and its extensive impact on our society, no U.S. Food and Drug Administration-approved treatment is available for this complex neurobiological disorder. Based on mounting evidences that support a link between autism and the gut microbiome, we previously performed a pioneering open-label clinical trial using intensive fecal microbiota transplant. The therapy significantly improved gastrointestinal and behavioral symptoms. Comprehensive metabolomic measurements in this study showed that children with autism spectrum disorder (ASD) had different levels of many plasma metabolites at baseline compared to those in typically developing children. Microbiota transfer therapy (MTT) had a systemic effect, resulting in substantial changes in plasma metabolites, driving a number of metabolites to be more similar to those from typically developing children. Our results provide evidence that changes in metabolites are one mechanism of the gut-brain connection mediated by the gut microbiota and offer plausible clinical evidence for a promising autism treatment and biomarkers.}, } @article {pmid33085984, year = {2020}, author = {Craven, LJ and McIlroy, JR and Mullish, BH and Marchesi, JR}, title = {Letter: intestinal microbiota transfer-updating the nomenclature to increase acceptability.}, journal = {Alimentary pharmacology & therapeutics}, volume = {52}, number = {10}, pages = {1622-1623}, doi = {10.1111/apt.16109}, pmid = {33085984}, issn = {1365-2036}, mesh = {*Fecal Microbiota Transplantation ; Humans ; *Microbiota ; }, } @article {pmid33081767, year = {2020}, author = {Uzan-Yulzari, A and Morr, M and Tareef-Nabwani, H and Ziv, O and Magid-Neriya, D and Armoni, R and Muller, E and Leibovici, A and Borenstein, E and Louzoun, Y and Shai, A and Koren, O}, title = {The intestinal microbiome, weight, and metabolic changes in women treated by adjuvant chemotherapy for breast and gynecological malignancies.}, journal = {BMC medicine}, volume = {18}, number = {1}, pages = {281}, pmid = {33081767}, issn = {1741-7015}, mesh = {Adolescent ; Adult ; Aged ; Animals ; Breast Neoplasms/*complications/drug therapy ; Chemotherapy, Adjuvant/*adverse effects ; Cohort Studies ; Female ; Gastrointestinal Microbiome/*genetics ; Genital Neoplasms, Female/*complications/drug therapy ; Humans ; Mice ; Middle Aged ; Weight Gain/*drug effects ; Young Adult ; }, abstract = {BACKGROUND: Adjuvant chemotherapy induces weight gain, glucose intolerance, and hypertension in about a third of women. The mechanisms underlying these events have not been defined. This study assessed the association between the microbiome and weight gain in patients treated with adjuvant chemotherapy for breast and gynecological cancers.

METHODS: Patients were recruited before starting adjuvant therapy. Weight and height were measured before treatment and 4-6 weeks after treatment completion. Weight gain was defined as an increase of 3% or more in body weight. A stool sample was collected before treatment, and 16S rRNA gene sequencing was performed. Data regarding oncological therapy, menopausal status, and antibiotic use was prospectively collected. Patients were excluded if they were treated by antibiotics during the study. Fecal transplant experiments from patients were conducted using Swiss Webster germ-free mice.

RESULTS: Thirty-three patients were recruited; of them, 9 gained 3.5-10.6% of baseline weight. The pretreatment microbiome of women who gained weight following treatment was significantly different in diversity and taxonomy from that of control women. Fecal microbiota transplantation from pretreatment samples of patients that gained weight induced metabolic changes in germ-free mice compared to mice transplanted with pretreatment fecal samples from the control women.

CONCLUSION: The microbiome composition is predictive of weight gain following adjuvant chemotherapy and induces adverse metabolic changes in germ-free mice, suggesting it contributes to adverse metabolic changes seen in patients. Confirmation of these results in a larger patient cohort is warranted.}, } @article {pmid33077775, year = {2020}, author = {Zhang, J and Rodríguez, F and Navas, MJ and Costa-Hurtado, M and Almagro, V and Bosch-Camós, L and López, E and Cuadrado, R and Accensi, F and Pina-Pedrero, S and Martínez, J and Correa-Fiz, F}, title = {Fecal microbiota transplantation from warthog to pig confirms the influence of the gut microbiota on African swine fever susceptibility.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {17605}, pmid = {33077775}, issn = {2045-2322}, mesh = {African Swine Fever/*immunology/virology ; Animals ; Disease Susceptibility ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Sus scrofa ; Swine ; }, abstract = {African swine fever virus (ASFV) is the causative agent of a devastating hemorrhagic disease (ASF) that affects both domestic pigs and wild boars. Conversely, ASFV circulates in a subclinical manner in African wild pigs, including warthogs, the natural reservoir for ASFV. Together with genetic differences, other factors might be involved in the differential susceptibility to ASF observed among Eurasian suids (Sus scrofa) and African warthogs (Phacochoerus africanus). Preliminary evidence obtained in our laboratory and others, seems to confirm the effect that environmental factors might have on ASF infection. Thus, domestic pigs raised in specific pathogen-free (SPF) facilities were extremely susceptible to highly attenuated ASFV strains that were innocuous to genetically identical domestic pigs grown on conventional farms. Since gut microbiota plays important roles in maintaining intestinal homeostasis, regulating immune system maturation and the functionality of the innate/adaptive immune responses, we decided to examine whether warthog fecal microbiota transplantation (FMT) to domestic pigs affects host susceptibility to ASFV. The present work demonstrates that warthog FMT is not harmful for domestic weaned piglets, while it modifies their gut microbiota; and that FMT from warthogs to pigs confers partial protection against attenuated ASFV strains. Future work is needed to elucidate the protective mechanisms exerted by warthog FMT.}, } @article {pmid33076980, year = {2020}, author = {Hamamoto, Y and Ouhara, K and Munenaga, S and Shoji, M and Ozawa, T and Hisatsune, J and Kado, I and Kajiya, M and Matsuda, S and Kawai, T and Mizuno, N and Fujita, T and Hirata, S and Tanimoto, K and Nakayama, K and Kishi, H and Sugiyama, E and Kurihara, H}, title = {Effect of Porphyromonas gingivalis infection on gut dysbiosis and resultant arthritis exacerbation in mouse model.}, journal = {Arthritis research & therapy}, volume = {22}, number = {1}, pages = {249}, pmid = {33076980}, issn = {1478-6362}, support = {DE027851/DE/NIDCR NIH HHS/United States ; DE029709/DE/NIDCR NIH HHS/United States ; }, abstract = {BACKGROUND: Porphyromonas gingivalis (Pg) infection causes periodontal disease and exacerbates rheumatoid arthritis (RA). It is reported that inoculation of periodontopathogenic bacteria (i.e., Pg) can alter gut microbiota composition in the animal models. Gut microbiota dysbiosis in human has shown strong associations with systemic diseases, including RA, diabetes mellitus, and inflammatory bowel disease. Therefore, this study investigated dysbiosis-mediated arthritis by Pg oral inoculation in an experimental arthritis model mouse.

METHODS: Pg inoculation in the oral cavity twice a week for 6 weeks was performed to induce periodontitis in SKG mice. Concomitantly, a single intraperitoneal (i.p.) injection of laminarin (LA) was administered to induce experimental arthritis (Pg-LA mouse). Citrullinated protein (CP) and IL-6 levels in serum as well as periodontal, intestinal, and joint tissues were measured by ELISA. Gut microbiota composition was determined by pyrosequencing the 16 s ribosomal RNA genes after DNA purification of mouse feces. Fecal microbiota transplantation (FMT) was performed by transferring Pg-LA-derived feces to normal SKG mice. The effects of Pg peptidylarginine deiminase (PgPAD) on the level of citrullinated proteins and arthritis progression were determined using a PgPAD knockout mutant.

RESULTS: Periodontal alveolar bone loss and IL-6 in gingival tissue were induced by Pg oral infection, as well as severe joint destruction, increased arthritis scores (AS), and both IL-6 and CP productions in serum, joint, and intestinal tissues. Distribution of Deferribacteres and S24-7 was decreased, while CP was significantly increased in gingiva, joint, and intestinal tissues of Pg-inoculated experimental arthritis mice compared to experimental arthritis mice without Pg inoculation. Further, FMT from Pg-inoculated experimental arthritis mice reproduced donor gut microbiota and resulted in severe joint destruction with increased IL-6 and CP production in joint and intestinal tissues. The average AS of FMT from Pg-inoculated experimental arthritis was much higher than that of donor mouse. However, inoculation of the PgPAD knockout mutant inhibited the elevation of arthritis scores and ACPA level in serum and reduced CP amount in gingival, joint, and intestinal tissues compared to Pg wild-type inoculation.

CONCLUSION: Pg oral infection affected gut microbiota dysbiosis and joint destruction via increased CP generation.}, } @article {pmid33075447, year = {2021}, author = {Evrensel, A and Tarhan, KN}, title = {Emerging role of Gut-microbiota-brain axis in depression and therapeutic implication.}, journal = {Progress in neuro-psychopharmacology & biological psychiatry}, volume = {106}, number = {}, pages = {110138}, doi = {10.1016/j.pnpbp.2020.110138}, pmid = {33075447}, issn = {1878-4216}, abstract = {The human body can be considered a superorganism in which it's eukaryotic cells and prokaryotic microorganisms coexist. Almost every organ system of the body lives a symbiotic life with these commensal bacteria. Intestinal microbiota has an important role in shaping, organizing and maintaining mental functions from as early as the intrauterine period. Microbiota-based approaches are becoming more prominent in understanding and treating the etiopathogenesis of neuropsychiatric disorders, especially depression. Antidepressant drugs, which are the first-line option in the treatment of depression today, also contain antimicrobial and immunomodulatory mechanisms of action. Treatment options for directly modifying the microbiota composition include prebiotics, probiotics (psychobiotics) and fecal microbiota transplantation. There are few preclinical and clinical studies on the efficacy and reliability of these treatment options in depression. This article will review pertinent studies on the role of intestinal microbiota in depression and discuss the treatment potential of altering ones gut microbiome.}, } @article {pmid33073887, year = {2020}, author = {Mossad, O and Erny, D}, title = {The microbiota-microglia axis in central nervous system disorders.}, journal = {Brain pathology (Zurich, Switzerland)}, volume = {30}, number = {6}, pages = {1159-1177}, doi = {10.1111/bpa.12908}, pmid = {33073887}, issn = {1750-3639}, support = {SFB/TRR167//Deutsche Forschungsgemeinschaft/ ; }, abstract = {The innate immune system in the central nervous system (CNS) is mainly represented by specialized tissue-resident macrophages, called microglia. In the past years, various species-, host- and tissue-specific as well as environmental factors were recognized that essentially affect microglial properties and functions in the healthy and diseased brain. Host microbiota are mostly residing in the gut and contribute to microglial activation states, for example, via short-chain fatty acids (SCFAs) or aryl hydrocarbon receptor (AhR) ligands. Thereby, the gut microorganisms are deemed to influence numerous CNS diseases mediated by microglia. In this review, we summarize recent findings of the interaction between the host microbiota and the CNS in health and disease, where we specifically highlight the resident gut microbiota as a crucial environmental factor for microglial function as what we coin "the microbiota-microglia axis."}, } @article {pmid33066233, year = {2020}, author = {Schierová, D and Březina, J and Mrázek, J and Fliegerová, KO and Kvasnová, S and Bajer, L and Drastich, P}, title = {Gut Microbiome Changes in Patients with Active Left-Sided Ulcerative Colitis after Fecal Microbiome Transplantation and Topical 5-aminosalicylic Acid Therapy.}, journal = {Cells}, volume = {9}, number = {10}, pages = {}, pmid = {33066233}, issn = {2073-4409}, abstract = {Ulcerative colitis (UC) is an inflammatory bowel disease, and intestinal bacteria are implicated in the pathogenesis of this disorder. The administration of aminosalicylates (5-ASA) is a conventional treatment that targets the mucosa, while fecal microbial transplantation (FMT) is a novel treatment that directly targets the gut microbiota. The aim of this study was to identify changes in fecal bacterial composition after both types of treatments and evaluate clinical responses. Sixteen patients with active left-sided UC underwent enema treatment using 5-ASA (n = 8) or FMT (n = 8) with a stool from a single donor. Fecal microbiota were analyzed by 16S rDNA high-throughput sequencing, and clinical indices were used to assess the efficacy of treatments. 5-ASA therapy resulted in clinical remission in 50% (4/8) of patients, but no correlation with changes in fecal bacteria was observed. In FMT, remission was achieved in 37.5% (3/8) of patients and was associated with a significantly increased relative abundance of the families Lachnospiraceae, Ruminococcaceae, and Clostridiaceae of the phylum Firmicutes, and Bifidobacteriaceae and Coriobacteriaceae of the phylum Actinobacteria. At the genus level, Faecalibacterium, Blautia, Coriobacteria, Collinsela, Slackia, and Bifidobacterium were significantly more frequent in patients who reached clinical remission. However, the increased abundance of beneficial taxa was not a sufficient factor to achieve clinical improvement in all UC patients. Nevertheless, our preliminary results indicate that FMT as non-drug-using method is thought to be a promising treatment for UC patients.}, } @article {pmid33066156, year = {2020}, author = {Suganya, K and Koo, BS}, title = {Gut-Brain Axis: Role of Gut Microbiota on Neurological Disorders and How Probiotics/Prebiotics Beneficially Modulate Microbial and Immune Pathways to Improve Brain Functions.}, journal = {International journal of molecular sciences}, volume = {21}, number = {20}, pages = {}, pmid = {33066156}, issn = {1422-0067}, support = {2019R1F1A1060821//National Research Foundation/ ; }, abstract = {The gut microbiome acts as an integral part of the gastrointestinal tract (GIT) that has the largest and vulnerable surface with desirable features to observe foods, nutrients, and environmental factors, as well as to differentiate commensals, invading pathogens, and others. It is well-known that the gut has a strong connection with the central nervous system (CNS) in the context of health and disease. A healthy gut with diverse microbes is vital for normal brain functions and emotional behaviors. In addition, the CNS controls most aspects of the GI physiology. The molecular interaction between the gut/microbiome and CNS is complex and bidirectional, ensuring the maintenance of gut homeostasis and proper digestion. Besides this, several mechanisms have been proposed, including endocrine, neuronal, toll-like receptor, and metabolites-dependent pathways. Changes in the bidirectional relationship between the GIT and CNS are linked with the pathogenesis of gastrointestinal and neurological disorders; therefore, the microbiota/gut-and-brain axis is an emerging and widely accepted concept. In this review, we summarize the recent findings supporting the role of the gut microbiota and immune system on the maintenance of brain functions and the development of neurological disorders. In addition, we highlight the recent advances in improving of neurological diseases by probiotics/prebiotics/synbiotics and fecal microbiota transplantation via the concept of the gut-brain axis.}, } @article {pmid33064448, year = {2020}, author = {Arulsamy, A and Tan, QY and Balasubramaniam, V and O'Brien, TJ and Shaikh, MF}, title = {Gut Microbiota and Epilepsy: A Systematic Review on Their Relationship and Possible Therapeutics.}, journal = {ACS chemical neuroscience}, volume = {11}, number = {21}, pages = {3488-3498}, doi = {10.1021/acschemneuro.0c00431}, pmid = {33064448}, issn = {1948-7193}, abstract = {Dysbiosis of gut microbiota may lead to a range of diseases including neurological disorders. Thus, it is hypothesized that regulation of the intestinal microbiota may prevent or treat epilepsy. The purpose of this systematic review is to evaluate the evidence investigating the relationship between gut microbiota and epilepsy and possible interventions. A systematic review of the literature was done on four databases (PubMed, Scopus, EMBASE, and Web of Science). Study selection was restricted to original research articles while following the PRISMA guidelines. Six studies were selected. These studies cohesively support the interaction between gut microbiota and epileptic seizures. Gut microbiota analysis identified increases in Firmicutes, Proteobacteria, Verrucomicrobia, and Fusobacteria with decreases in Bacteroidetes and Actinobacteria in epileptic patients. Ketogenic diet, probiotics, and fecal microbiota transplantation (FMT) improved the dysbiosis of the gut microbiota and seizure activity. However, the studies either had a small sample size, lack of subject variability, or short study or follow-up period, which may question their reliability. Nevertheless, these limited studies conclusively suggest that gut microbiota diversity and dysbiosis may be involved in the pathology of epilepsy. Future studies providing more reliable and in depth insight into the gut microbial community will spark promising alternative therapies to current epilepsy treatment.}, } @article {pmid33055258, year = {2020}, author = {Steed, DB and Wang, T and Raheja, D and Waldman, AD and Babiker, A and Dhere, T and Kraft, CS and Woodworth, MH}, title = {Gram-Negative Taxa and Antimicrobial Susceptibility after Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {mSphere}, volume = {5}, number = {5}, pages = {}, pmid = {33055258}, issn = {2379-5042}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; UM1 AI104681/AI/NIAID NIH HHS/United States ; }, abstract = {Fecal microbiota transplantation (FMT) has promising applications in reducing multidrug-resistant organism (MDRO) colonization and antibiotic resistance (AR) gene abundance. However, data on clinical microbiology results after FMT are limited. We examined the changes in antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after treatment with FMT for recurrent Clostridioides difficile infection (RCDI). We also examined whether a history of FMT changed health care provider behavior with respect to culture ordering and antibiotic prescription. Medical records for RCDI patients who underwent FMT at Emory University between July 2012 and March 2017 were reviewed retrospectively. FMT-treated patients with Gram-negative culture data in the 1-year period preceding and the 1-year period following FMT were included. Demographic and clinical data were abstracted, including CDI history, frequency of Gram-negative cultures, microbiological results, and antibiotic prescription in response to positive cultures in the period following FMT. Twelve patients were included in this case series. We pooled data from infections at all body sites and found a decrease in the number of total and Gram-negative cultures post-FMT. We compared susceptibility profiles across taxa given the potential for horizontal transmission of AR elements and observed increased susceptibility to nitrofurantoin, trimethoprim-sulfamethoxazole, and the aminoglycosides. FMT did not drastically influence health care provider ordering of bacterial cultures or antibiotic prescribing practices. We observed a reduction in Gram-negative cultures and a trend toward increased antimicrobial susceptibility. This study supports further investigation of FMT as a means of improving antimicrobial susceptibility.IMPORTANCE Fecal microbiota transplantation (FMT), which is highly efficacious in treating recurrent C. difficile infection (RCDI), has a promising application in decolonization of multidrug-resistant organisms, reduction of antibiotic resistance gene abundance, and restoration of healthy intestinal microbiota. However, data representing clinical microbiology results after FMT are limited. We sought to characterize the differences in culture positivity and antimicrobial susceptibility profiles in patients with Gram-negative infections in the year before and the year after FMT for RCDI. Drawing on prior studies that had demonstrated the success of FMT in eradicating extraintestinal infections and the occurrence of patient-level interspecies transfer of resistance elements, we employed an agnostic analytic approach of reviewing the data irrespective of body site or species. In a small RCDI population, we observed an improvement in the antimicrobial susceptibility profile of Gram-negative bacteria following FMT, which supports further study of FMT as a strategy to combat antibiotic resistance.}, } @article {pmid33053936, year = {2020}, author = {Sarin, SK and Sharma, S}, title = {Predictors of steroid non-response and new approaches in severe alcoholic hepatitis.}, journal = {Clinical and molecular hepatology}, volume = {26}, number = {4}, pages = {639-651}, pmid = {33053936}, issn = {2287-285X}, abstract = {Severe alcoholic hepatitis (SAH) remains a disease with high mortality. Steroid is the main stay and has been shown to give modest 28-day survival benefit in carefully selected patients, but no 90-day survival benefit. Since non-responders have high incidence of infections and increased mortality, it would be worthwhile to identify them before starting steroid therapy. A high and rising bilirubin, urinary acetyl carnitine >2,500 ng/mL, high asiloglycoprotein positive microparticles, and specific features in liver biopsy could predict steroid non-response at baseline. There is an ever-growing need to find new and effective therapies for SAH patients. Besides aggressive nutrition, granulocyte colony stimulating factor, fecal microbiota transplantation, and plasma exchange appear promising therapies and provide a hope for steroid ineligible or steroid non-responsive patients. Suppression of hepatic inflammation, preventing new bacterial or fungal infections, and enhancing liver regeneration will remain the key targets for next generation therapies.}, } @article {pmid33051451, year = {2020}, author = {Wang, H and Liu, L and Rao, X and Zeng, B and Yu, Y and Zhou, C and Zeng, L and Zheng, P and Pu, J and Xu, S and Cheng, K and Zhang, H and Ji, P and Wei, H and Xie, P}, title = {Integrated phosphoproteomic and metabolomic profiling reveals perturbed pathways in the hippocampus of gut microbiota dysbiosis mice.}, journal = {Translational psychiatry}, volume = {10}, number = {1}, pages = {346}, pmid = {33051451}, issn = {2158-3188}, abstract = {The dysbiosis of gut microbiota is an important environmental factor that can induce mental disorders, such as depression, through the microbiota-gut-brain axis. However, the underlying pathogenic mechanisms are complex and not completely understood. Here we utilized mass spectrometry to identify the global phosphorylation dynamics in hippocampus tissue in germ-free mice and specific pathogen-free mice (GF vs SPF), fecal microbiota transplantation (FMT) model ("depression microbiota" and the "healthy microbiota" recipient mice). As a result, 327 phosphosites of 237 proteins in GF vs SPF, and 478 phosphosites of 334 proteins in "depression microbiota" vs "healthy microbiota" recipient mice were identified as significant. These phosphorylation dysregulations were consistently associated with glutamatergic neurotransmitter system disturbances. The FMT mice exhibited disturbances in lipid metabolism and amino acid metabolism in both the periphery and brain through integrating phosphoproteomic and metabolomic analysis. Moreover, CAMKII-CREB signaling pathway, in response to these disturbances, was the primary common perturbed cellular process. In addition, we demonstrated that the spliceosome, never directly implicated in mental disorders previously, was a substantially neuronal function disrupted by gut microbiota dysbiosis, and the NCBP1 phosphorylation was identified as a novel pathogenic target. These results present a new perspective to study the pathologic mechanisms of gut microbiota dysbiosis related depression and highlight potential gut-mediated therapies for depression.}, } @article {pmid33046129, year = {2020}, author = {Binyamin, D and Werbner, N and Nuriel-Ohayon, M and Uzan, A and Mor, H and Abbas, A and Ziv, O and Teperino, R and Gutman, R and Koren, O}, title = {The aging mouse microbiome has obesogenic characteristics.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {87}, pmid = {33046129}, issn = {1756-994X}, abstract = {BACKGROUND: During aging, there is a physiological decline, an increase of morbidity and mortality, and a natural change in the gut microbiome. In this study, we investigated the influence of the gut microbiome on different metabolic parameters in adult and aged mice.

METHODS: Fecal and blood samples from adult (n = 42, 100-300 days) and aging (n = 32, 550-750 days) mice were collected. Microbiome analysis was done using QIIME2. Mouse weight and body composition were measured using NMR, and insulin and leptin levels in the blood were measured with Mouse Adipokine Magnetic Bead Panel kit. Fecal microbiota transplantation experiments from adult and aged mice into young germ-free mice were carried out in order to examine the effect of the gut microbiome of adult and aging mice on weight, body composition, insulin, and leptin.

RESULTS: We demonstrate that the microbiomes from adult and aged mice are distinguishable. We also report changes in metabolic parameters as we observed significantly higher weight and fat mass and low lean mass in aged compared to adult mice along with high insulin and leptin levels in the blood. The transplanted gut microbiome from aged mice transferred part of the phenotypes seen in aged mice. Fat body mass and insulin levels were higher in the mice who received feces from aged mice than mice receiving feces from adult mice. In addition, they consumed more food and had a higher respiratory quotient compared to mice receiving adult feces.

CONCLUSIONS: We conclude that aged mice have a gut microbiota with obesogenic characteristics. In addition, the gut bacterial population itself is sufficient to induce some of the manifestations of obesity.}, } @article {pmid33044577, year = {2020}, author = {Gerdes, LA and Yoon, H and Peters, A}, title = {[Microbiota and multiple sclerosis].}, journal = {Der Nervenarzt}, volume = {91}, number = {12}, pages = {1096-1107}, doi = {10.1007/s00115-020-01012-w}, pmid = {33044577}, issn = {1433-0407}, mesh = {Animals ; Central Nervous System ; *Encephalomyelitis, Autoimmune, Experimental ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; *Multiple Sclerosis ; }, abstract = {Multiple sclerosis (MS) is an inflammatory disease of the central nervous system driven by autoreactive lymphocytes. Due to its close contact with the gut-associated lymphoid tissue, the intestinal microbiota and/or their metabolites may be one of the factors that influence the activation of autoreactive lymphocytes. This article summarizes and discusses the current research efforts to characterize the microbiome of MS patients using human material. In addition, we present research studies that utilized classical or humanized animal models to determine the influence of certain microbiota species or compositions of microbiota on the immune system and disease progression and to define possible causal associations.}, } @article {pmid33042284, year = {2020}, author = {Xu, Y and Wang, N and Tan, HY and Li, S and Zhang, C and Zhang, Z and Feng, Y}, title = {Panax notoginseng saponins modulate the gut microbiota to promote thermogenesis and beige adipocyte reconstruction via leptin-mediated AMPKα/STAT3 signaling in diet-induced obesity.}, journal = {Theranostics}, volume = {10}, number = {24}, pages = {11302-11323}, pmid = {33042284}, issn = {1838-7640}, abstract = {Background: Activation of the thermogenic program in white and brown adipocytes presents a promising avenue for increasing energy expenditure during the treatment of obesity. The endogenous mechanism for promoting thermogenesis in brown adipocytes or browning in white adipocytes has indicated that the gut microbiota is a crucial regulator of the host energy balance. However, whether the effects of the therapeutic intervention-induced modulation of the gut microbiota on adipocyte browning involved the regulation of leptin remains unclear. Method: The adipose features were analyzed by body composition analysis, infrared camera observations, transmission electron microscopy and H&E staining. The gene and protein expression in adipose tissue were detected by qRT-PCR, immunoblotting, immunohistochemistry and immunofluorescence staining. The gut microbiome signature was identified by 16S rRNA gene amplicon sequencing, and both mice with high-fat diet-induced obesity (DIO) and mice with antibiotics-induced microbiome depletion were subjected to fecal microbiota transplantation. Results: Treatment with Panax notoginseng saponins (PNS) shaped the murine gut microbiome by increasing the abundances of Akkermansia muciniphila and Parabacteroides distasonis, and as a result, DIO mice harbored a distal gut microbiota with a significantly increased capacity to reduce host adiposity. The PNS-induced modulation of the gut microbiota in DIO mice could increase brown adipose tissue (BAT) thermogenesis and beige adipocyte reconstruction by activating the leptin-AMPK/STAT3 signaling pathway, which results in the promotion of energy expenditure. Leptin has an essential influence on the anti-obesity effects of PNS. In cases of leptin deficiency, the PNS-induced modulation of the gut microbiota exerts negative effects on thermogenesis and browning in white adipose tissue (WAT), which indicates that PNS fail to reduce obesity in leptin gene-deficient mice. The PNS-induced modulation of the gut microbiota exerted a minimal effect on DIO mice with antibiotic-induced microbiome depletion, which confirmed the correlation between altered gut microbiota and the remodeling of adipose tissues in DIO mice. The direct influence of leptin on browning via the AMPKα/STAT3 signaling pathway in C3H101/2 cells supported our in vivo results that signalling through the leptin-AMPK/STAT3 pathway induced by the PNS-modulated gut microbiota was involved in beige adipocyte reconstruction. Conclusion: Our results revealed that leptin signaling is critical for alterations in microbiota-fat crosstalk and provide promising avenues for therapeutic intervention in the treatment of obesity.}, } @article {pmid33042155, year = {2020}, author = {Macpherson, ME and Hov, JR and Ueland, T and Dahl, TB and Kummen, M and Otterdal, K and Holm, K and Berge, RK and Mollnes, TE and Trøseid, M and Halvorsen, B and Aukrust, P and Fevang, B and Jørgensen, SF}, title = {Gut Microbiota-Dependent Trimethylamine N-Oxide Associates With Inflammation in Common Variable Immunodeficiency.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {574500}, pmid = {33042155}, issn = {1664-3224}, abstract = {A substantial proportion of patients with common variable immunodeficiency (CVID) have inflammatory and autoimmune complications of unknown etiology. We have previously shown that systemic inflammation in CVID correlates with their gut microbial dysbiosis. The gut microbiota dependent metabolite trimethylamine N-oxide (TMAO) has been linked to several metabolic and inflammatory disorders, but has hitherto not been investigated in relation to CVID. We hypothesized that TMAO is involved in systemic inflammation in CVID. To explore this, we measured plasma concentrations of TMAO, inflammatory markers, and lipopolysaccharide (LPS) in 104 CVID patients and 30 controls. Gut microbiota profiles and the bacterial genes CutC and CntA, which encode enzymes that can convert dietary metabolites to trimethylamine in the colon, were examined in fecal samples from 40 CVID patients and 86 controls. Furthermore, a food frequency questionnaire and the effect of oral antibiotic rifaximin on plasma TMAO concentrations were explored in these 40 patients. We found CVID patients to have higher plasma concentrations of TMAO than controls (TMAO 5.0 [2.9-8.6] vs. 3.2 [2.2-6.3], p = 0.022, median with IQR). The TMAO concentration correlated positively with tumor necrosis factor (p = 0.008, rho = 0.26), interleukin-12 (p = 0.012, rho = 0.25) and LPS (p = 0.034, rho = 0.21). Dietary intake of meat (p = 0.678), fish (p = 0.715), egg (p = 0.138), dairy products (p = 0.284), and fiber (p = 0.767) did not significantly impact on the TMAO concentrations in plasma, nor did a 2-week course of the oral antibiotic rifaximin (p = 0.975). However, plasma TMAO concentrations correlated positively with gut microbial abundance of Gammaproteobacteria (p = 0.021, rho = 0.36). Bacterial gene CntA was present in significantly more CVID samples (75%) than controls (53%), p = 0.020, potentially related to the increased abundance of Gammaproteobacteria in these samples. The current study demonstrates that elevated TMAO concentrations are associated with systemic inflammation and increased gut microbial abundance of Gammaproteobacteria in CVID patients, suggesting that TMAO could be a link between gut microbial dysbiosis and systemic inflammation. Gut microbiota composition could thus be a potential therapeutic target to reduce systemic inflammation in CVID.}, } @article {pmid33041818, year = {2020}, author = {Tan, P and Li, X and Shen, J and Feng, Q}, title = {Fecal Microbiota Transplantation for the Treatment of Inflammatory Bowel Disease: An Update.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {574533}, pmid = {33041818}, issn = {1663-9812}, abstract = {Fecal microbiota transplantation (FMT) has successfully been applied for the treatment of recurrent Clostridioides difficile infection (CDI), which has led to studies on its application to other gastrointestinal diseases and extraintestinal diseases associated with gut microbiota dysbiosis. Recently, the results of FMT for patients with inflammatory bowel disease (IBD) have been encouraging. However, studies have not fully clarified the clinical application of this emerging therapy. Here, we aimed to review the current knowledge in this fast-growing field and characterize the effectiveness, safety and mechanisms of FMT for the treatment of IBD patients.}, } @article {pmid33039712, year = {2020}, author = {Li, X and Lin, Y and Li, X and Xu, X and Zhao, Y and Xu, L and Gao, Y and Li, Y and Tan, Y and Qian, P and Huang, H}, title = {Tyrosine supplement ameliorates murine aGVHD by modulation of gut microbiome and metabolome.}, journal = {EBioMedicine}, volume = {61}, number = {}, pages = {103048}, pmid = {33039712}, issn = {2352-3964}, abstract = {BACKGROUND: Microbial communities and their metabolic components in the gut are of vital importance for immune homeostasis and have an influence on the susceptibility of the host to a number of immune-mediated diseases like acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, little is known about the functional connections between microbiome and metabolome in aGVHD due to the complexity of the gastrointestinal environment.

METHOD: Initially, gut microbiota and fecal metabolic phenotype in aGVHD murine models were unleashed by performing 16S ribosomal DNA gene sequencing and ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS)-based metabolomics.

FINDINGS: The group with aGVHD experienced a significant drop in Lachnospiraceae_unclassified but an increase in the relative abundance of Clostridium XI, Clostridium XIVa and Enterococcus. Meanwhile, a lower content of tyrosine was observed in the gut of aGVHD mice. The correlation analysis revealed that tyrosine-related metabolites were inversely correlated with Clostridium XIVa, besides, Blautia and Enterococcus also displayed the negative tendency in aGVHD condition. Apart from exploring the importance and function of tyrosine, different tyrosine diets were offered to mice during transplantation. Additional tyrosine supplements can improve overall survival, ameliorate symptoms at the early stage of aGVHD and change the structure and composition of gut microbiota and fecal metabolic phenotype. In addition, aGVHD mice deprived from tyrosine displayed worse manifestations than the vehicle diet group.

INTERPRETATION: The results demonstrated the roles and mechanisms of gut microbiota, indispensable metabolites and tyrosine in the progression of aGVHD, which can be an underlying biomarker for aGVHD diagnosis and treatment.

FUNDING: This research was funded by the International Cooperation and Exchange Program (81520108002), the National Key R&D Program of China, Stem Cell and Translation Research (2018YFA0109300), National Natural Science Foundation of China (81670169, 81670148, 81870080 and 91949115) and Natural Science Foundation of Zhejiang Province (LQ19H080006).}, } @article {pmid33034846, year = {2020}, author = {Brown, EG and Goldman, SM}, title = {Modulation of the Microbiome in Parkinson's Disease: Diet, Drug, Stool Transplant, and Beyond.}, journal = {Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics}, volume = {17}, number = {4}, pages = {1406-1417}, pmid = {33034846}, issn = {1878-7479}, abstract = {The gastrointestinal microbiome is altered in Parkinson's disease and likely plays a key role in its pathophysiology, affecting symptoms and response to therapy and perhaps modifying progression or even disease initiation. Gut dysbiosis therefore has a significant potential as a therapeutic target in Parkinson's disease, a condition elusive to disease-modifying therapy thus far. The gastrointestinal environment hosts a complex ecology, and efforts to modulate the relative abundance or function of established microorganisms are still in their infancy. Still, these techniques are being rapidly developed and have important implications for our understanding of Parkinson's disease. Currently, modulation of the microbiome can be achieved through non-pharmacologic means such as diet, pharmacologically through probiotic, prebiotic, or antibiotic use and procedurally through fecal transplant. Novel techniques being explored include the use of small molecules or genetically engineered organisms, with vast potential. Here, we review how some of these approaches have been used to date, important areas of ongoing research, and how microbiome modulation may play a role in the clinical management of Parkinson's disease in the future.}, } @article {pmid33033580, year = {2020}, author = {Nie, X and Chen, J and Ma, X and Ni, Y and Shen, Y and Yu, H and Panagiotou, G and Bao, Y}, title = {A metagenome-wide association study of gut microbiome and visceral fat accumulation.}, journal = {Computational and structural biotechnology journal}, volume = {18}, number = {}, pages = {2596-2609}, pmid = {33033580}, issn = {2001-0370}, abstract = {Purpose: Visceral fat is an independent risk factor for metabolic and cardiovascular disease. The study aimed to investigate the associations between gut microbiome and visceral fat.

Methods: We recruited 32 obese adults and 30 healthy controls at baseline. Among the obese subjects, 14 subjects underwent laparoscopic sleeve gastrectomy (LSG) and were followed 6 months after surgery. Abdominal visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by magnetic resonance imaging. Waist, hipline, waist-to-hip ratio (WHR) and body mass index (BMI) were included as simple obese parameters. Gut microbiome was analyzed by metagenomic sequencing.

Results: Among the obese parameters, VFA had the largest number of correlations with the species that were differentially enriched between obese and healthy subjects, following by waist, WHR, BMI, hipline, and SFA. Within the species negatively correlated with VFA, Eubacterium eligens had the strongest correlation, following by Clostridium citroniae, C. symbiosum, Bacteroides uniformis, E. ventriosum, Ruminococcaceae bacterium D16, C. hathewayi, etc. C. hathewayi and C. citroniae were increased after LSG. Functional analyses showed that among all the obese parameters, VFA had strongest correlation coefficients with the obesity-related microbial pathways. Microbial pathways involved in carbohydrate fermentation and biosynthesis of L-glutamate and L-glutamine might contribute to visceral fat accumulation.

Conclusions: Visceral fat was more closely correlated with gut microbiome compared with subcutaneous fat, suggesting an intrinsic connection between gut microbiome and metabolic cardiovascular diseases. Specific microbial species and pathways which were closely associated with visceral fat accumulation might contribute to new targeted therapies for metabolic disorders.}, } @article {pmid33027674, year = {2020}, author = {Arnoriaga-Rodríguez, M and Mayneris-Perxachs, J and Burokas, A and Contreras-Rodríguez, O and Blasco, G and Coll, C and Biarnés, C and Miranda-Olivos, R and Latorre, J and Moreno-Navarrete, JM and Castells-Nobau, A and Sabater, M and Palomo-Buitrago, ME and Puig, J and Pedraza, S and Gich, J and Pérez-Brocal, V and Ricart, W and Moya, A and Fernández-Real, X and Ramió-Torrentà, L and Pamplona, R and Sol, J and Jové, M and Portero-Otin, M and Maldonado, R and Fernández-Real, JM}, title = {Obesity Impairs Short-Term and Working Memory through Gut Microbial Metabolism of Aromatic Amino Acids.}, journal = {Cell metabolism}, volume = {32}, number = {4}, pages = {548-560.e7}, doi = {10.1016/j.cmet.2020.09.002}, pmid = {33027674}, issn = {1932-7420}, abstract = {The gut microbiome has been linked to fear extinction learning in animal models. Here, we aimed to explore the gut microbiome and memory domains according to obesity status. A specific microbiome profile associated with short-term memory, working memory, and the volume of the hippocampus and frontal regions of the brain differentially in human subjects with and without obesity. Plasma and fecal levels of aromatic amino acids, their catabolites, and vegetable-derived compounds were longitudinally associated with short-term and working memory. Functionally, microbiota transplantation from human subjects with obesity led to decreased memory scores in mice, aligning this trait from humans with that of recipient mice. RNA sequencing of the medial prefrontal cortex of mice revealed that short-term memory associated with aromatic amino acid pathways, inflammatory genes, and clusters of bacterial species. These results highlight the potential therapeutic value of targeting the gut microbiota for memory impairment, specifically in subjects with obesity.}, } @article {pmid33024394, year = {2020}, author = {Wu, YN and Zhang, L and Chen, T and Li, X and He, LH and Liu, GX}, title = {Granulocyte-macrophage colony-stimulating factor protects mice against hepatocellular carcinoma by ameliorating intestinal dysbiosis and attenuating inflammation.}, journal = {World journal of gastroenterology}, volume = {26}, number = {36}, pages = {5420-5436}, pmid = {33024394}, issn = {2219-2840}, abstract = {BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. The gut microbiota can help maintain healthy metabolism and immunity. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a critical factor in promoting health and homeostasis; it promotes intestinal immunity, stimulates bone marrow precursors to generate macrophage colonies, and enhances the antibacterial and antitumor activity of circulating monocytes. As such, GM-CSF may protect against HCC development by regulating immunity as well as intestinal microecology.

AIM: To investigate the impact of GM-CSF on the gut microbiome and metabolic characteristics of HCC.

METHODS: Thirty-six male BALB/c nude mice were divided into three groups: Control (n = 10), HCC (n = 13), and HCC + GM-CSF (GM-CSF overexpression, n = 13). We utilized HCC cells to establish orthotopic transplantation tumor models of HCC with normal and over-expressing GM-CSF. Liver injury, immune inflammatory function and intestinal barrier function were evaluated. The fecal microbiome and metabolome were studied using 16S rRNA absolute quantification sequencing and gas chromatography-mass spectrometry.

RESULTS: GM-CSF overexpression significantly affected the gut microbiome of mice with HCC and resulted in a high abundance of organisms of the genera Roseburia, Blautia and Butyricimonass, along with a significant reduction in Prevotella, Parabacteroides, Anaerotruncus, Streptococcus, Clostridium, and Mucispirillum. Likewise, GM-CSF overexpression resulted in a substantial increase in fecal biotin and oleic acid levels, along with a prominent decrease in the fecal succinic acid, adenosine, fumaric acid, lipoic acid, and maleic acid levels. Correlation analysis revealed that the intestinal microbiota and fecal metabolites induced by GM-CSF were primarily involved in pathways related to reducing the inflammatory response, biotin metabolism, and intestinal barrier dysfunction.

CONCLUSION: GM-CSF can protect against HCC development by regulating immunity and modulating the abundance of specific intestinal microorganisms and their metabolites. This study provides new insights into the therapeutic approaches for HCC.}, } @article {pmid33023268, year = {2020}, author = {Qureshi, F and Adams, J and Hanagan, K and Kang, DW and Krajmalnik-Brown, R and Hahn, J}, title = {Multivariate Analysis of Fecal Metabolites from Children with Autism Spectrum Disorder and Gastrointestinal Symptoms before and after Microbiota Transfer Therapy.}, journal = {Journal of personalized medicine}, volume = {10}, number = {4}, pages = {}, pmid = {33023268}, issn = {2075-4426}, support = {1R01AI110642/NH/NIH HHS/United States ; }, abstract = {Fecal microbiota transplant (FMT) holds significant promise for patients with Autism Spectrum Disorder (ASD) and gastrointestinal (GI) symptoms. Prior work has demonstrated that plasma metabolite profiles of children with ASD become more similar to those of their typically developing (TD) peers following this treatment. This work measures the concentration of 669 biochemical compounds in feces of a cohort of 18 ASD and 20 TD children using ultrahigh performance liquid chromatography-tandem mass spectroscopy. Subsequent measurements were taken from the ASD cohort over the course of 10-week Microbiota Transfer Therapy (MTT) and 8 weeks after completion of this treatment. Univariate and multivariate statistical analysis techniques were used to characterize differences in metabolites before, during, and after treatment. Using Fisher Discriminant Analysis (FDA), it was possible to attain multivariate metabolite models capable of achieving a sensitivity of 94% and a specificity of 95% after cross-validation. Observations made following MTT indicate that the fecal metabolite profiles become more like those of the TD cohort. There was an 82-88% decrease in the median difference of the ASD and TD group for the panel metabolites, and among the top fifty most discriminating individual metabolites, 96% report more comparable values following treatment. Thus, these findings are similar, although less pronounced, as those determined using plasma metabolites.}, } @article {pmid33022904, year = {2021}, author = {Jung, CY and Bae, JM}, title = {Pathophysiology and protective approaches of gut injury in critical illness.}, journal = {Yeungnam University journal of medicine}, volume = {38}, number = {1}, pages = {27-33}, pmid = {33022904}, issn = {2384-0293}, abstract = {The gut is a complex organ that has played an important role in digestion, absorption, endocrine functions, and immunity. The gut mucosal barriers consist of the immunologic barrier and nonimmunologic barrier. During critical illnesses, the gut is susceptible to injury due to the induction of intestinal hyperpermeability. Gut hyperpermeability and barrier dysfunction may lead to systemic inflammatory response syndrome. Additionally, gut microbiota are altered during critical illnesses. The etiology of such microbiome alterations in critical illnesses is multifactorial. The interaction or systemic host defense modulation between distant organs and the gut microbiome is increasingly studied in disease research. No treatment modality exists to significantly enhance the gut epithelial integrity, permeability, or mucus layer in critically ill patients. However, multiple helpful approaches including clinical and preclinical strategies exist. Enteral nutrition is associated with an increased mucosal barrier in animal and human studies. The trophic effects of enteral nutrition might help to maintain the intestinal physiology, prevent atrophy of gut villi, reduce intestinal permeability, and protect against ischemia-reperfusion injury. The microbiome approach such as the use of probiotics, fecal microbial transplantation, and selective decontamination of the digestive tract has been suggested. However, its evidence does not have a high quality. To promote rapid hypertrophy of the small bowel, various factors have been reported, including the epidermal growth factor, membrane permeant inhibitor of myosin light chain kinase, mucus surrogate, pharmacologic vagus nerve agonist, immune-enhancing diet, and glucagon-like peptide-2 as preclinical strategies. However, the evidence remains unclear.}, } @article {pmid33022571, year = {2021}, author = {Yu, X and Lv, K and Guan, S and Zhang, X and Sun, L}, title = {Long-term exposure to phenanthrene at environmental-level induces intestinal dysbiosis and disrupted hepatic lipid metabolism in mice.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {268}, number = {Pt B}, pages = {115738}, doi = {10.1016/j.envpol.2020.115738}, pmid = {33022571}, issn = {1873-6424}, mesh = {Animals ; Dysbiosis/chemically induced ; *Gastrointestinal Microbiome ; Lipid Metabolism ; Liver/metabolism ; Male ; Mice ; *Phenanthrenes/metabolism/toxicity ; }, abstract = {Phenanthrene (Phe), among the most ubiquitous polycyclic aromatic hydrocarbons (PAHs) existing in nature and foodstuffs, has severe effects on hepatic lipids metabolism. However, the detailed mechanism involved is still unknown. For environmental chemicals can disturb intestinal microbiota, which plays a vital role in lipids metabolism, we hypothesized that oral exposure to Phe may disrupt the intestinal microbiota, leading to the induction of an abnormal inflammatory response and lipid metabolism dysfunction. Herein, male mice were orally exposed to Phe (0.05, 0.5 and 5 mg/kg/2d) for ten weeks and the results showed that long term exposure to Phe induced significant alteration in relative Bacteroidetes, Firmicutes and Proteobacteria abundance in male mice. Histopathological anomalies, and significantly increased hepatic levels of free fatty acid, cholesterol and triglyceride were observed as well. The expression of hepatic proteins linked to lipid metabolism including peroxisome proliferator-activated receptors (PPARs), liver X receptor β (LXRβ) and retinoid X receptors (RXRs) were upregulated. The importance of the gut microbiota in Phe-altered lipid metabolism disorder was further confirmed by fecal microbiota transplantation (FMT). FMT intervention boosted microbial diversity and attenuated Phe-induced elevation in liver somatic index and hepatic total lipids levels. These results demonstrated that environmental-level Phe altered the composition of gastrointestinal bacteria and subsequently induced hepatic lipid metabolism disorder. These results would be helpful for understanding the health risk posed by Phe.}, } @article {pmid33020290, year = {2020}, author = {Bonomo, RR and Cook, TM and Gavini, CK and White, CR and Jones, JR and Bovo, E and Zima, AV and Brown, IA and Dugas, LR and Zakharian, E and Aubert, G and Alonzo, F and Calcutt, NA and Mansuy-Aubert, V}, title = {Fecal transplantation and butyrate improve neuropathic pain, modify immune cell profile, and gene expression in the PNS of obese mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {42}, pages = {26482-26493}, pmid = {33020290}, issn = {1091-6490}, support = {R01 DK111848/DK/NIDDK NIH HHS/United States ; R01 DK117404/DK/NIDDK NIH HHS/United States ; R01 HL130231/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Butyrates/metabolism ; Diet, High-Fat ; Diet, Western ; Fatty Acids, Volatile/metabolism ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/drug effects ; Gene Expression ; Insulin Resistance ; Lipid Metabolism/drug effects ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Microbiota ; Neuralgia/metabolism ; Obesity/*microbiology/physiopathology ; Peripheral Nervous System/metabolism/physiology ; Peripheral Nervous System Diseases/*therapy ; }, abstract = {Obesity affects over 2 billion people worldwide and is accompanied by peripheral neuropathy (PN) and an associated poorer quality of life. Despite high prevalence, the molecular mechanisms underlying the painful manifestations of PN are poorly understood, and therapies are restricted to use of painkillers or other drugs that do not address the underlying disease. Studies have demonstrated that the gut microbiome is linked to metabolic health and its alteration is associated with many diseases, including obesity. Pathologic changes to the gut microbiome have recently been linked to somatosensory pain, but any relationships between gut microbiome and PN in obesity have yet to be explored. Our data show that mice fed a Western diet developed indices of PN that were attenuated by concurrent fecal microbiome transplantation (FMT). In addition, we observed changes in expression of genes involved in lipid metabolism and calcium handling in cells of the peripheral nerve system (PNS). FMT also induced changes in the immune cell populations of the PNS. There was a correlation between an increase in the circulating short-chain fatty acid butyrate and pain improvement following FMT. Additionally, butyrate modulated gene expression and immune cells in the PNS. Circulating butyrate was also negatively correlated with distal pain in 29 participants with varied body mass index. Our data suggest that the metabolite butyrate, secreted by the gut microbiome, underlies some of the effects of FMT. Targeting the gut microbiome, butyrate, and its consequences may represent novel viable approaches to prevent or relieve obesity-associated neuropathies.}, } @article {pmid33013647, year = {2020}, author = {Engen, PA and Zaferiou, A and Rasmussen, H and Naqib, A and Green, SJ and Fogg, LF and Forsyth, CB and Raeisi, S and Hamaker, B and Keshavarzian, A}, title = {Single-Arm, Non-randomized, Time Series, Single-Subject Study of Fecal Microbiota Transplantation in Multiple Sclerosis.}, journal = {Frontiers in neurology}, volume = {11}, number = {}, pages = {978}, pmid = {33013647}, issn = {1664-2295}, abstract = {Emerging evidence suggests intestinal microbiota as a central contributing factor to the pathogenesis of Relapsing-Remitting-Multiple-Sclerosis (RRMS). This novel RRMS study evaluated the impact of fecal-microbiota-transplantation (FMT) on a broad array of physiological/clinical outcomes using deep metagenome sequencing of fecal microbiome. FMT interventions were associated with increased abundances of putative beneficial stool bacteria and short-chain-fatty-acid metabolites, which were associated with increased/improved serum brain-derived-neurotrophic-factor levels and gait/walking metrics. This proof-of-concept single-subject longitudinal study provides evidence of potential importance of intestinal microbiota in the pathogenesis of MS, and scientific rationale to help design future randomized controlled trials assessing FMT in RRMS patients.}, } @article {pmid33011173, year = {2021}, author = {Kelly, CR and Yen, EF and Grinspan, AM and Kahn, SA and Atreja, A and Lewis, JD and Moore, TA and Rubin, DT and Kim, AM and Serra, S and Nersesova, Y and Fredell, L and Hunsicker, D and McDonald, D and Knight, R and Allegretti, JR and Pekow, J and Absah, I and Hsu, R and Vincent, J and Khanna, S and Tangen, L and Crawford, CV and Mattar, MC and Chen, LA and Fischer, M and Arsenescu, RI and Feuerstadt, P and Goldstein, J and Kerman, D and Ehrlich, AC and Wu, GD and Laine, L}, title = {Fecal Microbiota Transplantation Is Highly Effective in Real-World Practice: Initial Results From the FMT National Registry.}, journal = {Gastroenterology}, volume = {160}, number = {1}, pages = {183-192.e3}, doi = {10.1053/j.gastro.2020.09.038}, pmid = {33011173}, issn = {1528-0012}, support = {R24 AI118629/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is used commonly for treatment of Clostridioides difficile infections (CDIs), although prospective safety data are limited and real-world FMT practice and outcomes are not well described. The FMT National Registry was designed to assess FMT methods and both safety and effectiveness outcomes from North American FMT providers.

METHODS: Patients undergoing FMT in clinical practices across North America were eligible. Participating investigators enter de-identified data into an online platform, including FMT protocol, baseline patient characteristics, CDI cure and recurrence, and short and long-term safety outcomes.

RESULTS: Of the first 259 participants enrolled at 20 sites, 222 had completed short-term follow-up at 1 month and 123 had follow-up to 6 months; 171 (66%) were female. All FMTs were done for CDI and 249 (96%) used an unknown donor (eg, stool bank). One-month cure occurred in 200 patients (90%); of these, 197 (98%) received only 1 FMT. Among 112 patients with initial cure who were followed to 6 months, 4 (4%) had CDI recurrence. Severe symptoms reported within 1-month of FMT included diarrhea (n = 5 [2%]) and abdominal pain (n = 4 [2%]); 3 patients (1%) had hospitalizations possibly related to FMT. At 6 months, new diagnoses of irritable bowel syndrome were made in 2 patients (1%) and inflammatory bowel disease in 2 patients (1%).

CONCLUSIONS: This prospective real-world study demonstrated high effectiveness of FMT for CDI with a good safety profile. Assessment of new conditions at long-term follow-up is planned as this registry grows and will be important for determining the full safety profile of FMT.}, } @article {pmid33010597, year = {2020}, author = {Zhao, Y and Tang, Y and Chen, L and Lv, S and Liu, S and Nie, P and Aguilar, ZP and Xu, H}, title = {Restraining the TiO2 nanoparticles-induced intestinal inflammation mediated by gut microbiota in juvenile rats via ingestion of Lactobacillus rhamnosus GG.}, journal = {Ecotoxicology and environmental safety}, volume = {206}, number = {}, pages = {111393}, doi = {10.1016/j.ecoenv.2020.111393}, pmid = {33010597}, issn = {1090-2414}, mesh = {Adult ; Animals ; Child ; Feces/chemistry/microbiology ; Female ; Gastrointestinal Microbiome/*drug effects ; Homeostasis ; Humans ; Inflammation ; Intestinal Mucosa/*drug effects/immunology/metabolism/microbiology ; Lactobacillus rhamnosus/*growth & development ; Liver/drug effects/metabolism ; Male ; Nanoparticles/metabolism/*toxicity ; Probiotics/*therapeutic use ; Rats ; Titanium/metabolism/*toxicity ; }, abstract = {Human were given a lot of opportunities to ingest TiO2 NPs in the environment. Children have low, sensitive intestinal tolerance, and they could be exposed to higher levels of TiO2 NPs than adults. Few studies have been conducted on the interaction between TiO2 NPs and juvenile intestine phase models. Thus, in this work, weaning rats were orally exposed to TiO2 NPs for 7 and 14 days. Results indicate that Ti accumulated in the intestine, liver, and feces. Inflammatory infiltration damage was observed in the colonic epithelial tissue, and gut microbiota fluctuated with a decreased abundance of Lactobacilli in feces. Oral supplementation with Lactobacillus rhamnosus GG (LGG) lessened TiO2 NPs-induced colonic inflammatory injury, which might due to downregulation of nuclear factor kappa-B (NF-κB). Meanwhile, LGG maintained normal intestinal microbiome homeostasis, thereby improving TiO2 NPs-induced colon injury in juvenile rats. Moreover, fecal microbiota transplant (FMT) experiment indicated possible TiO2 NPs-induced intestinal microbiota disorder led to colonic inflammation. Our works suggested the urgent need for additional studies on the risk safety assessment, mechanism, and prevention of juvenile health damage from exposure to TiO2 NPs.}, } @article {pmid33007265, year = {2020}, author = {Korpela, K and Helve, O and Kolho, KL and Saisto, T and Skogberg, K and Dikareva, E and Stefanovic, V and Salonen, A and Andersson, S and de Vos, WM}, title = {Maternal Fecal Microbiota Transplantation in Cesarean-Born Infants Rapidly Restores Normal Gut Microbial Development: A Proof-of-Concept Study.}, journal = {Cell}, volume = {183}, number = {2}, pages = {324-334.e5}, doi = {10.1016/j.cell.2020.08.047}, pmid = {33007265}, issn = {1097-4172}, abstract = {Infants born by vaginal delivery are colonized with maternal fecal microbes. Cesarean section (CS) birth disturbs mother-to-neonate transmission. In this study (NCT03568734), we evaluated whether disturbed intestinal microbiota development could be restored in term CS-born infants by postnatal, orally delivered fecal microbiota transplantation (FMT). We recruited 17 mothers, of whom seven were selected after careful screening. Their infants received a diluted fecal sample from their own mothers, taken 3 weeks prior to delivery. All seven infants had an uneventful clinical course during the 3-month follow-up and showed no adverse effects. The temporal development of the fecal microbiota composition of FMT-treated CS-born infants no longer resembled that of untreated CS-born infants but showed significant similarity to that of vaginally born infants. This proof-of-concept study demonstrates that the intestinal microbiota of CS-born infants can be restored postnatally by maternal FMT. However, this should only be done after careful clinical and microbiological screening.}, } @article {pmid33006187, year = {2020}, author = {Hyde, MK and Masser, BM}, title = {Eligible blood donors' decisions about donating stool for fecal microbiota transplantation: Does ambivalence play a role?.}, journal = {Transfusion}, volume = {}, number = {}, pages = {}, doi = {10.1111/trf.16109}, pmid = {33006187}, issn = {1537-2995}, support = {//This work was supported by an award made from The University of Queensland (UQ) Vice-Chancellor's Strategic Funds (B.M.M.) and internal funds granted by the UQ School of Psychology (M.K.H.). Australian governments fund Australian Red Cross Lifeblood for the provision of blood, blood products, and services to the Australian community/ ; }, abstract = {Blood collection agencies (BCAs) are expanding core business by inviting blood donors to donate stool for fecal microbiota transplantation (FMT). However, whether blood donors also want to donate stool is unclear since, despite its benefits, stool donation is viewed by many as unpleasant. This study examined the prevalence, contributors to, and role of these mixed feelings (ambivalence) in stool donation intentions.

STUDY DESIGN AND METHODS: This cross-sectional study surveyed Australian residents aged 18 years or more who believed themselves eligible to donate blood and met broad criteria for prescreening as a stool donor (eg, healthy, not taking medication). Survey questions assessed attitude, norms, self-efficacy, motives, disgust, ambivalence, and intentions to donate stool.

RESULTS: A total of 382 eligible blood donors aged not more than 50 years (mean, 28.71 years; 48% female, 62% "healthy" body mass index) participated. Six percent indicated no ambivalence about donating stool. In regression, significant determinants of ambivalence were less awareness of FMT, lower self-efficacy, motivated by ensuring that stool is available for loved ones, and more disgust about stool donation. Higher ambivalence contributed to decreased donation intention. Self-efficacy and disgust differentiated participants with moderate ambivalence, a group likely responsive to intervention, from those with low or high ambivalence.

CONCLUSION: Ambivalence about donating stool was common among eligible blood donors. BCAs should raise awareness about stool donation and FMT before requesting donation. BCAs may increase cost savings and donor retention by giving clear guidance about donation requirements and implementing processes that build confidence. Early screening of potential donors for ambivalence and disgust will enable BCAs to provide decision support.}, } @article {pmid33006061, year = {2020}, author = {Patel, SD and Hung, YC and Hashmi, ZG and Feinman, M and D'Adamo, CR and Svoboda, S and Wolf, JH}, title = {Surgical Management of Diverticulitis-Associated Clostridioides Difficile Infection.}, journal = {Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11605-020-04812-2}, pmid = {33006061}, issn = {1873-4626}, } @article {pmid33004295, year = {2020}, author = {Ianiro, G and Bibbò, S and Masucci, L and Quaranta, G and Porcari, S and Settanni, CR and Lopetuso, LR and Fantoni, M and Sanguinetti, M and Gasbarrini, A and Cammarota, G}, title = {Maintaining standard volumes, efficacy and safety, of fecal microbiota transplantation for C. difficile infection during the COVID-19 pandemic: A prospective cohort study.}, journal = {Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver}, volume = {52}, number = {12}, pages = {1390-1395}, pmid = {33004295}, issn = {1878-3562}, mesh = {Adult ; Aged ; Aged, 80 and over ; COVID-19/diagnosis/*prevention & control/transmission ; COVID-19 Nucleic Acid Testing ; COVID-19 Serological Testing ; *Clostridioides difficile ; Clostridium Infections/*therapy ; Cohort Studies ; Delivery of Health Care/*methods ; Donor Selection ; Fecal Microbiota Transplantation/*methods ; Feces/virology ; Female ; *Gastroenterology ; Humans ; Infection Control/methods ; Italy ; Male ; Middle Aged ; Patient Selection ; Prospective Studies ; Quarantine ; Recurrence ; Specimen Handling/methods ; Workflow ; Young Adult ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) can be a life-saving treatment against recurrent Clostridioides difficile infection (CDI). It is therefore necessary to maintain this procedure available for these patients during the COVID-19 pandemic while keeping high efficacy and safety standards.

AIMS: To report outcomes of a FMT service that has adapted its operational workflow during COVID-19 pandemic to continue offering FMT to patients with CDI.

METHODS: All patients with CDI referred to our center for FMT during pandemic were prospectively included. Each step of the FMT working protocol was adapted with specific security measures to prevent the transmission of SARS-CoV-2.

RESULTS: Of 26 patients evaluated for FMT, 21 were treated for recurrent or refractory CDI. Eighteen patients completed the 8-week follow-up, and no one recurred after FMT. Follow-up is ongoing in 3 patients, although in all of them diarrhea disappeared after the first procedure. No serious adverse events were reported. Two patients had also COVID-19-related pneumonia, and were cured both from CDI and COVID-19.

CONCLUSION: This is the first report to show that it is possible to maintain standard volumes, efficacy and safety of FMT for recurrent CDI during the COVID-19 pandemic, by adopting specific changes in the operational workflow.}, } @article {pmid33003421, year = {2020}, author = {Heimesaat, MM and Genger, C and Klove, S and Weschka, D and Mousavi, S and Bereswill, S}, title = {The Host-Specific Intestinal Microbiota Composition Impacts Campylobacter coli Infection in a Clinical Mouse Model of Campylobacteriosis.}, journal = {Pathogens (Basel, Switzerland)}, volume = {9}, number = {10}, pages = {}, pmid = {33003421}, issn = {2076-0817}, support = {Zoonoses research consortium PAC-Campylobacter (IP7/ 01KI1725D)//Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie/ ; ZIM: ZF4117904 AJ8//Bundesministerium für Wirtschaft und Energie/ ; }, abstract = {Human Campylobacter-infections are progressively rising globally. However, the molecular mechanisms underlying C. coli-host interactions are incompletely understood. In this study, we surveyed the impact of the host-specific intestinal microbiota composition during peroral C. coli infection applying an established murine campylobacteriosis model. Therefore, microbiota-depleted IL-10-/- mice were subjected to peroral fecal microbiota transplantation from murine versus human donors and infected with C. coli one week later by gavage. Irrespective of the microbiota, C. coli stably colonized the murine gastrointestinal tract until day 21 post-infection. Throughout the survey, C. coli-infected mice with a human intestinal microbiota displayed more frequently fecal blood as their murine counterparts. Intestinal inflammatory sequelae of C. coli-infection could exclusively be observed in mice with a human intestinal microbiota, as indicated by increased colonic numbers of apoptotic epithelial cells and innate as well as adaptive immune cell subsets, which were accompanied by more pronounced pro-inflammatory cytokine secretion in the colon and mesenteric lymph nodes versus mock controls. However, in extra-intestinal, including systemic compartments, pro-inflammatory responses upon pathogen challenge could be assessed in mice with either microbiota. In conclusion, the host-specific intestinal microbiota composition has a profound effect on intestinal and systemic pro-inflammatory immune responses during C. coli infection.}, } @article {pmid33002829, year = {2020}, author = {Fan, Q and Guan, X and Hou, Y and Liu, Y and Wei, W and Cai, X and Zhang, Y and Wang, G and Zheng, X and Hao, H}, title = {Paeoniflorin modulates gut microbial production of indole-3-lactate and epithelial autophagy to alleviate colitis in mice.}, journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology}, volume = {79}, number = {}, pages = {153345}, doi = {10.1016/j.phymed.2020.153345}, pmid = {33002829}, issn = {1618-095X}, mesh = {Animals ; Autophagy/drug effects ; Bridged-Ring Compounds/pharmacology ; Colitis/chemically induced/*drug therapy/*microbiology ; Drugs, Chinese Herbal/pharmacology ; Dysbiosis/drug therapy/microbiology ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects/physiology ; Glucosides/immunology/*pharmacology ; HCT116 Cells ; Humans ; Immunologic Factors/pharmacology ; Indoles/*metabolism ; Male ; Mice, Inbred BALB C ; Monoterpenes/*pharmacology ; Paeonia/chemistry ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Total glucosides of peony (TGP), extracted from the root and rhizome of Paeonia lactiflora Pall, has well-confirmed immunomodulatory efficacy in the clinic. However, the mechanism and active ingredients remain largely unclear.

HYPOTHESIS/PURPOSE: Our previous study revealed a low systemic exposure but predominant gut distribution of TGP components. The aim of this study was to investigate involvement of the gut microbiota in the immunoregulatory effects and identify the active component.

METHODS: Mice received 3% DSS to establish a model of colitis. The treatment group received TGP or single paeoniflorin (PF) or albiflorin (AF). Body weight, colon length, inflammatory and histological changes were assessed. Gut microbiota structure was profiled by 16s rRNA sequencing. Antibiotic treatment and fecal transplantation were used to explore the involvement of gut microbiota. Metabolomic assay of host and microbial metabolites in colon was performed.

RESULTS: TGP improved colonic injury and gut microbial dysbiosis in colitis mice, and PF was responsible for the protective effects. Fecal microbiota transfer from TGP-treated mice conferred resilience to colitis, while antibiotic treatment abrogated the protective effects. Both TGP and PF decreased colonic indole-3-lactate (ILA), a microbial tryptophan metabolite. ILA was further identified as an inhibitor of epithelial autophagy and ILA supplementation compromised the benefits of TGP.

CONCLUSION: Our findings suggest that TGP acts in part through a gut microbiota-ILA-epithelial autophagy axis to alleviate colitis.}, } @article {pmid32999906, year = {2020}, author = {Ortigão, R and Pimentel-Nunes, P and Dinis-Ribeiro, M and Libânio, D}, title = {Gastrointestinal Microbiome - What We Need to Know in Clinical Practice.}, journal = {GE Portuguese journal of gastroenterology}, volume = {27}, number = {5}, pages = {336-351}, pmid = {32999906}, issn = {2341-4545}, abstract = {Human gut microbiota plays an important role in individual health. When the balance between host and gut microbiota is disrupted, changes in microbiota composition and function occur, which is referred as dysbiosis. Environmental factors as diet, proton pump inhibitors, and antibiotics can lead to a permanent dysbiotic disruption. Clarification of these imbalances was made possible by recent advances in genome sequencing methods that supported acknowledgment of the interplay between microbiome and intestinal and extraintestinal disorders. This review focuses on the microbiota impact in inflammatory bowel disease, gastric cancer, colorectal cancer, nonalcoholic fatty liver disease (NAFLD), irritable bowel syndrome (IBS), and Clostridium difficile infection (CDI). Furthermore, novel therapies are summarized. Fecal microbiota transplant (FMT) is a successful and established therapy in recurrent CDI, and its application in other dysbiosis-related diseases is attracting enormous interest. Pre- and probiotics target microbial rebalance and have positive effects mainly in NAFLD, ulcerative colitis, IBS, and CDI patients. Promising anticarcinogenic effects have also been demonstrated in animal models. The literature increasingly describes microbial changes in many dysbiotic disorders and shows what needs to be treated. However, probiotics and FMT application in clinical practice suffers from a shortage of randomized controlled trials with standardized therapy regimens to support their recommendation.}, } @article {pmid32993381, year = {2020}, author = {Li, Q and Guo, L and Wang, L and Miao, J and Cui, H and Li, L and Geng, K and Zhao, L and Sun, X and Jia, J and Bian, Y}, title = {Composition of "gold juice" using an ancient method based on intestinal microecology.}, journal = {The Journal of international medical research}, volume = {48}, number = {9}, pages = {300060520931288}, pmid = {32993381}, issn = {1473-2300}, abstract = {OBJECTIVE: To identify potentially effective bacterial components of gold juice, a traditional Chinese medicine treatment used for fecal microbiota transplantation.

METHODS: Fecal samples were collected from five healthy children (two boys and three girls; mean age, 7.52 ± 2.31 years). The children had no history of antibiotic use or intestinal microecological preparation in the preceding 3 months. Fresh fecal samples were collected from children to prepare gold juice in mid-to-late November, in accordance with traditional Chinese medicine methods, then used within 7 days. Finally, 16S rDNA sequence analysis was used to identify potentially effective bacterial components of gold juice. QIIME software was used for comparisons of microbial species among gold juice, diluent, filtrate, and loess samples.

RESULTS: Microflora of gold juice exhibited considerable changes following "ancient method" processing. Microbial components significantly differed between gold juice and filtrate samples. The gold juice analyzed in our study consisted of microbes that synthesize carbohydrates and amino acids by degrading substances, whereas the filtrate contained probiotic flora, Bacteroides, and Prevotella 9.

CONCLUSIONS: This study of microbial components in gold juice and filtrate provided evidence regarding effective bacterial components in gold juice, which may aid in clinical decisions concerning fecal microbiota transplantation.}, } @article {pmid32992653, year = {2020}, author = {Quagliariello, A and Del Chierico, F and Reddel, S and Russo, A and Onetti Muda, A and D'Argenio, P and Angelino, G and Romeo, EF and Dall'Oglio, L and De Angelis, P and Putignani, L and All The Other Fmt Opbg Committee Collaborators, }, title = {Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations.}, journal = {Microorganisms}, volume = {8}, number = {10}, pages = {}, pmid = {32992653}, issn = {2076-2607}, support = {201702P003961//Ministero della Salute/ ; 201802G004314//MINISTERO DELLA SALUTE/ ; }, abstract = {Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts' time-point profiles, donors and control cohorts' baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient's condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.}, } @article {pmid32991818, year = {2020}, author = {Goll, R and Johnsen, PH and Hjerde, E and Diab, J and Valle, PC and Hilpusch, F and Cavanagh, JP}, title = {Effects of fecal microbiota transplantation in subjects with irritable bowel syndrome are mirrored by changes in gut microbiome.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1794263}, pmid = {32991818}, issn = {1949-0984}, abstract = {Irritable bowel syndrome (IBS) is a common disorder of the lower gastrointestinal tract. The pathophysiology is far from settled, but a gut microbial dysbiosis is hypothesized to be a contributing factor. We earlier published a randomized double-blind placebo-controlled clinical trial on fecal microbiota transplantation (FMT) for IBS - the REFIT trial. The present data set describes the engraftment and includes participants from the study who received active FMT; 14 participants with effect of FMT (Effect) and 8 without (No effect). Samples were collected at baseline, after 6 and 12 months. Samples from the transplants (Donor) served as a comparator. In total 66 recipient samples and 17 donor samples were subjected to deep metagenomic sequencing, and taxonomic and functional analyses were performed. Alpha diversity measures showed a significantly increased diversity and evenness in the IBS groups compared to the donors. Taxonomic profiles showed higher relative abundance of phylum Firmicutes, and lower relative abundance of phylum Bacteroidetes, compared to donors at baseline. This profile was shifted toward the donor profile following FMT. Imputed growth rates showed that the resulting growth pattern was a conglomerate of donor and recipient activity. Thirty-four functional subclasses showed distinct differences between baseline samples and donors, most of which were shifted toward a donor-like profile after FMT. All of these changes were less pronounced in the No effect group. We conclude that FMT induces long-term changes in gut microbiota, and these changes mirror the clinical effect of the treatment. The study was registered in ClinicalTrials.gov (NCT02154867).}, } @article {pmid32991720, year = {2020}, author = {Yoshifuji, K and Inamoto, K and Kiridoshi, Y and Takeshita, K and Sasajima, S and Shiraishi, Y and Yamashita, Y and Nisaka, Y and Ogura, Y and Takeuchi, R and Toya, T and Igarashi, A and Najima, Y and Doki, N and Kobayashi, T and Ohashi, K and Suda, W and Atarashi, K and Shiota, A and Hattori, M and Honda, K and Kakihana, K}, title = {Prebiotics protect against acute graft-versus-host disease and preserve the gut microbiota in stem cell transplantation.}, journal = {Blood advances}, volume = {4}, number = {19}, pages = {4607-4617}, pmid = {32991720}, issn = {2473-9537}, abstract = {Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Therefore, management of aGVHD is important for successful transplantation. Mucosal damage and alteration of the gut microbiota after allo-HSCT are key factors in the development of aGVHD. We conducted a prospective study to evaluate the ability of prebiotics, which can alleviate mucosal damage and manipulate the gut microbiota, to mitigate posttransplantation complications, including aGVHD. Resistant starch (RS) and a commercially available prebiotics mixture, GFO, were administered to allo-HSCT recipients from pretransplantation conditioning to day 28 after allo-HSCT. Prebiotic intake mitigated mucosal injury and reduced the incidence of all aGVHD grades combined and of aGVHD grades 2 to 4. The cumulative incidence of skin aGVHD was markedly decreased by prebiotics intake. Furthermore, the gut microbial diversity was well maintained and butyrate-producing bacterial population were preserved by prebiotics intake. In addition, the posttransplantation fecal butyrate concentration was maintained or increased more frequently in the prebiotics group. These observations indicate that prebiotic intake may be an effective strategy for preventing aGVHD in allo-HSCT, thereby improving treatment outcomes and the clinical utility of stem cell transplantation approaches. This study was registered on the University Hospital Medical Information Network (UMIN) clinical trials registry (https://www.umin.ac.jp/ctr/index.htm) as #UMIN000027563.}, } @article {pmid32991697, year = {2020}, author = {Khanna, S and Kraft, CS}, title = {Fecal Microbiota Transplantation: Tales of Caution.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa1492}, pmid = {32991697}, issn = {1537-6591}, } @article {pmid32991434, year = {2020}, author = {Zheng, YM and He, XX and Xia, HH and Yuan, Y and Xie, WR and Cai, JY and Xu, JT and Wu, LH}, title = {Multi-donor multi-course faecal microbiota transplantation relieves the symptoms of chronic hemorrhagic radiation proctitis: A case report.}, journal = {Medicine}, volume = {99}, number = {39}, pages = {e22298}, doi = {10.1097/MD.0000000000022298}, pmid = {32991434}, issn = {1536-5964}, mesh = {Aftercare ; Chronic Disease ; Colonoscopy/methods ; Diarrhea/etiology ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Hemorrhage/*therapy ; Humans ; Magnetic Resonance Imaging/methods ; Middle Aged ; Proctitis/diagnosis/*etiology/pathology ; RNA, Ribosomal, 16S/genetics ; Radiation Injuries/*complications/diagnostic imaging/pathology ; Tissue Donors ; Treatment Outcome ; }, abstract = {RATIONALE: There are many treatments for chronic hemorrhagic radiation colorectal inflammation, but only a few treatments are supported by high-quality research evidence. Studies have shown that the occurrence and development of radiation proctitis are closely associated with the intestinal flora. Animal studies have indicated that faecal microbiota transplantation (FMT) can improve radiation enteropathy in a mouse model.

PATIENT CONCERNS: A 45-year-old female patient suffered from recurrent hematochezia and diarrhea for half a year after radiotherapy and underwent recurrent transfusion treatments. Colonoscopy showed obvious congestion of the sigmoid colon and rectal mucosa, a smooth surface, and bleeding that was easily induced by touch, which are consistent with radiation proctitis. The pathological findings revealed chronic mucosal inflammation. The magnetic resonance imaging examination of the pelvic cavity with a plain scan and enhancement showed changes after radiotherapy and chemotherapy, and no obvious tumor recurrence or metastasis was found. The laboratory examinations excluded pathogen infection.

DIAGNOSES: Based on the history and examinations, the final diagnosis of this patient was chronic hemorrhagic radiation proctitis.

INTERVENTIONS: The patient was treated with a total of 4 individual courses of FMT.

OUTCOMES: After the six-month follow-up, her hematochezia, abdominal pain and diarrhea were relieved. Furthermore, 16S rRNA sequencing of the feces showed that the intestinal bacterial composition of the patient obviously changed after FMT and became similar to that of the donors.

LESSONS: This case report shows that FMT can relieve the symptoms of hematochezia and diarrhea by changing the bacterial community structure in patients with chronic hemorrhagic radiation proctitis.}, } @article {pmid32988391, year = {2020}, author = {Schwartz, DJ and Langdon, AE and Dantas, G}, title = {Understanding the impact of antibiotic perturbation on the human microbiome.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {82}, pmid = {32988391}, issn = {1756-994X}, support = {TL1 TR002344/TR/NCATS NIH HHS/United States ; 1U1CI000033 301/CC/CDC HHS/United States ; R01 HD092414/HD/NICHD NIH HHS/United States ; AT009741/AT/NCCIH NIH HHS/United States ; TL1 TR000449/NH/NIH HHS/United States ; R01 AI123394/AI/NIAID NIH HHS/United States ; }, abstract = {The human gut microbiome is a dynamic collection of bacteria, archaea, fungi, and viruses that performs essential functions for immune development, pathogen colonization resistance, and food metabolism. Perturbation of the gut microbiome's ecological balance, commonly by antibiotics, can cause and exacerbate diseases. To predict and successfully rescue such perturbations, first, we must understand the underlying taxonomic and functional dynamics of the microbiome as it changes throughout infancy, childhood, and adulthood. We offer an overview of the healthy gut bacterial architecture over these life stages and comment on vulnerability to short and long courses of antibiotics. Second, the resilience of the microbiome after antibiotic perturbation depends on key characteristics, such as the nature, timing, duration, and spectrum of a course of antibiotics, as well as microbiome modulatory factors such as age, travel, underlying illness, antibiotic resistance pattern, and diet. In this review, we discuss acute and chronic antibiotic perturbations to the microbiome and resistome in the context of microbiome stability and dynamics. We specifically discuss key taxonomic and resistance gene changes that accompany antibiotic treatment of neonates, children, and adults. Restoration of a healthy gut microbial ecosystem after routine antibiotics will require rationally managed exposure to specific antibiotics and microbes. To that end, we review the use of fecal microbiota transplantation and probiotics to direct recolonization of the gut ecosystem. We conclude with our perspectives on how best to assess, predict, and aid recovery of the microbiome after antibiotic perturbation.}, } @article {pmid32987284, year = {2020}, author = {Proença, IM and Allegretti, JR and Bernardo, WM and de Moura, DTH and Ponte Neto, AM and Matsubayashi, CO and Flor, MM and Kotinda, APST and de Moura, EGH}, title = {Fecal microbiota transplantation improves metabolic syndrome parameters: systematic review with meta-analysis based on randomized clinical trials.}, journal = {Nutrition research (New York, N.Y.)}, volume = {83}, number = {}, pages = {1-14}, doi = {10.1016/j.nutres.2020.06.018}, pmid = {32987284}, issn = {1879-0739}, abstract = {Obesity and metabolic syndrome are important health problems that can lead to significant morbidity/mortality as well as subsequent health concerns. Alterations in the gut microbiota have been implicated in both obesity and metabolic syndrome. Fecal Microbiota Transplantation (FMT) has emerged as a new promising therapeutic approach aimed at manipulating the gut microbiota in various chronic diseases. Randomized clinical trials assessing the use of FMT in obese and metabolic syndrome patients have been reported. The purpose of this systematic review with meta-analysis using randomized clinical trials (RCT) is to evaluate the role of FMT for the treatment of obesity and metabolic syndrome and its impact on clinically relevant parameters. We searched the main databases, as well as the gray literature, to identify RCTs comparing FMT from lean donor(s) vs placebo for obese/metabolic syndrome patients. We included all studies that utilized any form of placebo (sham, saline, autologous FMT, or placebo capsules). Six studies met the inclusion criteria and were included for final analysis with a total of 154 patients. We looked for clinically significant parameters related to obesity and metabolic syndrome and organized the findings into early (2-6 weeks after intervention) and late (12 weeks after intervention) outcomes. Two to 6 weeks after intervention, mean HbA1c was lower in the FMT group (MD = -1.69 mmol/L, CI [-2.88, -0.56], P = .003) and mean HDL cholesterol was higher in the FMT group (MD = 0.09 mmol/L, CI [0.02, 0.15], P = .008). There was no difference in obesity parameters 6 to 12 weeks after intervention. No serious adverse events were reported. The findings for this meta-analysis show that FMT may have a role for the treatment of metabolic syndrome, but there is currently not enough evidence to support its use in clinical practice. High-quality well-powered RCTS with longer follow-up are necessary to clarify the role of FMT in this patient cohort.}, } @article {pmid32987062, year = {2020}, author = {Goo, N and Bae, HJ and Park, K and Kim, J and Jeong, Y and Cai, M and Cho, K and Jung, SY and Kim, DH and Ryu, JH}, title = {The effect of fecal microbiota transplantation on autistic-like behaviors in Fmr1 KO mice.}, journal = {Life sciences}, volume = {262}, number = {}, pages = {118497}, doi = {10.1016/j.lfs.2020.118497}, pmid = {32987062}, issn = {1879-0631}, mesh = {Animals ; Autistic Disorder/microbiology/*therapy ; Behavior, Animal/physiology ; Brain/metabolism ; Cognitive Dysfunction/etiology/microbiology/therapy ; Disease Models, Animal ; Fecal Microbiota Transplantation/*methods ; Female ; Fragile X Mental Retardation Protein/*genetics ; Fragile X Syndrome/microbiology/psychology/*therapy ; *Gastrointestinal Microbiome ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; }, abstract = {The importance of alterations in bidirectional communication between gut and brain has become obvious in neuropsychiatric disorders. Gastrointestinal (GI) disturbances are very common in autism spectrum disorders (ASD), and the GI microbiota profiles in children with ASD are significantly different from those in the general population. Fragile X syndrome (FXS) is an inheritable developmental disability in humans, and patients with FXS exhibit autistic behaviors such as mental retardation and impaired social communication or interaction. We hypothesized that an increase in specific gut microbiota by fecal microbiota transplantation (FMT) would mitigate autistic-like behaviors. To test this hypothesis, we measured the effects of FMT from normal mice to Fmr1 KO mice on autistic-like behaviors using several behavioral tests. Because the amounts of A. muciniphila in Fmr1 KO mice was very low, we assessed A. muciniphila population, tested the expression of MUC2, and analyzed goblet cells in the gut after the FMT. We found that FMT ameliorated autistic-like behaviors, especially memory deficits and social withdrawal, and we observed that the levels of A. muciniphila were normalized to wild-type levels. In addition, FMT attenuated the increased levels of TNFα and Iba1 in the brains of Fmr1 KO mice. These results suggest that FMT could be a useful tool for the treatments of cognitive deficits and social withdrawal symptoms observed in FXS or ASD because it increases the population of A. muciniphila and decreases TNFα and Iba1 levels.}, } @article {pmid32982371, year = {2020}, author = {Azimirad, M and Yadegar, A and Gholami, F and Shahrokh, S and Asadzadeh Aghdaei, H and Ianiro, G and Suzuki, H and Cammarota, G and Zali, MR}, title = {Treatment of Recurrent Clostridioides difficile Infection Using Fecal Microbiota Transplantation in Iranian Patients with Underlying Inflammatory Bowel Disease.}, journal = {Journal of inflammation research}, volume = {13}, number = {}, pages = {563-570}, pmid = {32982371}, issn = {1178-7031}, abstract = {Purpose: Fecal microbiota transplantation (FMT) is an effective treatment option for patients with recurrent Clostridioides difficile infection (rCDI). However, there is a paucity of evidence regarding its efficacy and safety in patients with rCDI and concurrent inflammatory bowel disease (IBD). Here, we present a single-center experience of FMT for treatment of rCDI in Iranian patients with IBD.

Patients and Methods: Eight patients with established IBD (7 with ulcerative colitis and 1 with Crohn's disease) who underwent at least one FMT via colonoscopy for treatment of rCDI were enrolled in this study. Demographics, pre-FMT and post-FMT IBD activity, efficacy for rCDI and adverse events (AEs) were assessed during a 6-month follow-up period. All patients had experienced 3 episodes of rCDI and were refractory to conventional therapies with metronidazole and vancomycin. Primary cure and secondary cure rates were assessed after FMT treatments.

Results: A total of 10 FMTs were performed via colonoscopy in 8 patients (6/8; 75% men) with a median age of 35 years (range: 22-60). Two patients received a second FMT. Overall, the primary and secondary cure rates were 75% and 100%, respectively. Two patients developed CPE-producing C. perfringens diagnoses after second FMTs. There were no other AEs, and no patient experienced IBD flare.

Conclusion: We demonstrated that FMT appears to be an effective, safe and rational therapeutic alternative for resolution of rCDI in patients with underlying IBD. Furthermore, we suggest implementing the CPE-producing C. perfringens testing in the screening of FMT donors.}, } @article {pmid32981762, year = {2020}, author = {Martínez Pizarro, S}, title = {Transplantation of fecal microbiota in multidrug-resistant Klebsiella pneumoniae colonization and infection.}, journal = {Gastroenterologia y hepatologia}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.gastrohep.2020.06.009}, pmid = {32981762}, issn = {0210-5705}, } @article {pmid32981509, year = {2020}, author = {Gulati, M and Singh, SK and Corrie, L and Chandwani, L and Singh, A and Kapoor, B and Kumar, R and Pandey, NK and Kumar, B and Awasthi, A and Khursheed, R}, title = {Fecal Microbiota Transplant: Latest Addition to Arsenal Against Recurrent Clostridium Difficile Infection.}, journal = {Recent patents on anti-infective drug discovery}, volume = {}, number = {}, pages = {}, doi = {10.2174/1574891X15666200925092354}, pmid = {32981509}, issn = {2212-4071}, abstract = {An infectious disease of colon, recurrent Clostridium difficile infection (RCDI) is hitherto considered insurmountable leading to significant morbidity and mortality. Gut dysbiosis, generally resulting from frequent use of antibiotics is considered to be responsible for the etiopathogenesis of rCDI. Ironically, the conventional treatment strategies for the disease also include the use of anti-infective drugs such as metronidazole, vancomycin and fidaxomycin. As a result of the efforts to overcome the limitations of these treatment options to control recurrence of disease, Fecal Microbiota Transplant (FMT) has emerged as an effective and safe alternative. It is pertinent to add here that FMT is defined as the process of engraftment of fecal suspension from the healthy person into the gastrointestinal tract of the diseased individual aiming at the restoration of gut microbiota. FMT has proved to be quite successful in the treatment of recurrent and resistant Clostridium difficile infections (RCDI). In last three decades a lot of information has been generated on the use of FMT for RCDI. A number of clinical trials have been reported with generally very high success rates. However, very small number of patents could be found in the area indicating that there still exists lacuna in the knowledge about FMT with respect to its preparation, regulation, mode of delivery and safety. The current review attempts to dive deeper to discuss the patents available in the area while supporting the information contained therein with the non-patent literature.}, } @article {pmid32980389, year = {2020}, author = {Shaffer, SR and Witt, J and Targownik, LE and Kao, D and Lee, C and Smieliauskas, F and Rubin, DT and Singh, H and Bernstein, CN}, title = {Cost-effectiveness analysis of a fecal microbiota transplant center for treating recurrent C.difficile infection.}, journal = {The Journal of infection}, volume = {81}, number = {5}, pages = {758-765}, doi = {10.1016/j.jinf.2020.09.025}, pmid = {32980389}, issn = {1532-2742}, abstract = {OBJECTIVE: We assessed the cost-effectiveness of establishing a fecal microbial transplant (FMT) unit in Canada for the treatment of recurrent CDI.

DESIGN: We performed a cost-effectiveness analysis to determine the number of patients with recurrent CDI needed to treat (NNT) annually to make establishing a FMT unit cost-effective. We compared treating patients for their second recurrence of CDI with FMT in a jurisdiction with a FMT unit, compared to being treated with antibiotics; then sent to a medical center with FMT available for the third recurrence. We used a willingness to pay threshold of $50,000 per quality-adjusted-life-year gained.

RESULTS: The minimum annual NNT was 15 for FMT via colonoscopy, 17 for FMT via capsule, and 44 for FMT via enema compared with vancomycin, and 16, 18, and 47 compared with fidaxomicin, respectively. A medical center's minimum catchment area when establishing a FMT unit would have to be 56,849 if using FMT via colonoscopy, or 64,429 if using capsules.

CONCLUSION: We report the minimum number of patients requiring treatment annually with FMT to achieve cost-effectiveness, when including start-up and ongoing costs. FMT is cost-effective in Canada in populations with a sufficient number of eligible patients, ranging from 15 to 47 depending on the FMT modality used. This is crucial for medical jurisdictions making decisions about establishing a FMT unit for the treatment of recurrent CDI. The cost-effectiveness can be generalized in other countries.}, } @article {pmid32979504, year = {2020}, author = {Coman, V and Vodnar, DC}, title = {Gut microbiota and old age: Modulating factors and interventions for healthy longevity.}, journal = {Experimental gerontology}, volume = {141}, number = {}, pages = {111095}, pmid = {32979504}, issn = {1873-6815}, abstract = {Our gut microbiota is a complex and dynamic ecosystem with a paramount role in shaping our metabolic and immunological functions. Recent research suggests that aging may negatively affect the composition, diversity, and function of our microbiota mainly due to alterations in diet and immunologic reactivity (i.e. immunosenescence), and increased incidence of certain diseases and, therefore, increased exposure to certain medication (e.g. antibiotics, proton pump inhibitors). In turn, this aging-related gut dysbiosis may contribute to the initiation and/or progress of other metabolic diseases, and consequently, to a decrease in healthy longevity. On the positive side, promising therapeutic interventions, such as diet supplementation with prebiotics, probiotics and synbiotics, or fecal microbiota transplantation, aimed to counteract these aging-related deleterious consequences, could improve our health, and extend our healthy lifespan. In this context, the current review aims to assess the latest progress in identifying the key elements affecting the gut microbiota of the older adults and their mechanism of action, and the effectiveness of the therapeutic interventions aimed at restoring the diversity and healthy functions of the gut microbiota in older individuals.}, } @article {pmid32976567, year = {2020}, author = {Saha, S and Mara, K and Pardi, DS and Khanna, S}, title = {Durability Of Response To Fecal Microbiota Transplantation After Exposure to Risk Factors for Recurrence In Patients With Clostridioides difficile Infection.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa1457}, pmid = {32976567}, issn = {1537-6591}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is highly effective for preventing recurrent Clostridioides difficile infection (CDI). Durability (no recurrence despite additional risk factor exposure) of FMT protection is largely unknown. We studied the durability of FMT in patients with recurrent CDI.

METHODS: A retrospective study of adults undergoing FMT for recurrent CDI was conducted. Data collected included demographics, CDI risk factors (comorbidities, healthcare exposure, systemic non-CDI antibiotic use, acid suppressant medications) and future CDI episodes. Durable response to FMT was defined as lack of CDI episodes within 1 year post-FMT despite risk factor exposure. Descriptive statistics, univariate and multivariable Cox proportional hazards regression were used as applicable. Two tailed p<0.05 was considered statistically significant.

RESULTS: Overall 460 patients were included [median age 57 (18-94) years, 65.2% female]. Comorbidities included chronic liver disease, 12.8% (n=59), cancer, 11.7% (n=54), chronic kidney disease, 3.9% (n=18) and inflammatory bowel disease, 21.9% (n=101). Overall, 31.3% (n=144) received antibiotics, 21.7% (n=100) received acid suppressants, 76.8% (n=350) had healthcare exposure after FMT. Of 374 patients with risk factor exposure, 78.1% [95% confidence interval (CI) 72.7%-84.0%] had durable response to FMT at one year. On multivariable analysis, antibiotic use was independently associated with decreased durability of FMT [hazard ratio 0.27 (95% CI, 0.15-0.49), p<0.001].

CONCLUSION: Majority of patients had a durable response to FMT despite exposure to CDI risk factors. Antibiotic exposure after FMT independently predicted loss of durability of FMT. Larger studies are needed to define predictors of durable response in patients with and without exposure to antibiotics.}, } @article {pmid32973502, year = {2020}, author = {Cai, TT and Ye, XL and Li, RR and Chen, H and Wang, YY and Yong, HJ and Pan, ML and Lu, W and Tang, Y and Miao, H and Snijders, AM and Mao, JH and Liu, XY and Lu, YB and Ding, DF}, title = {Resveratrol Modulates the Gut Microbiota and Inflammation to Protect Against Diabetic Nephropathy in Mice.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {1249}, pmid = {32973502}, issn = {1663-9812}, abstract = {Oral administration of resveratrol is able to ameliorate the progression of diabetic nephropathy (DN); however, its mechanisms of action remain unclear. Recent evidence suggested that the gut microbiota is involved in the metabolism therapeutics. In the current study, we sought to determine whether the anti-DN effects of resveratrol are mediated through modulation of the gut microbiota using the genetic db/db mouse model of DN. We demonstrate that resveratrol treatment of db/db mice relieves a series of clinical indicators of DN. We then show that resveratrol improves intestinal barrier function and ameliorates intestinal permeability and inflammation. The composition of the gut microbiome was significantly altered in db/db mice compared to control db/m mice. Dysbiosis in db/db mice characterized by low abundance levels of Bacteroides, Alistipes, Rikenella, Odoribacter, Parabacteroides, and Alloprevotella genera were reversed by resveratrol treatment, suggesting a potential role for the microbiome in DN progression. Furthermore, fecal microbiota transplantation, derived from healthy resveratrol-treated db/m mice, was sufficient to antagonize the renal dysfunction, rebalance the gut microbiome and improve intestinal permeability and inflammation in recipient db/db mice. These results indicate that resveratrol-mediated changes in the gut microbiome may play an important role in the mechanism of action of resveratrol, which provides supporting evidence for the gut-kidney axis in DN.}, } @article {pmid32971101, year = {2020}, author = {Wang, L and An, J and Song, S and Mei, M and Li, W and Ding, F and Liu, S}, title = {Electroacupuncture preserves intestinal barrier integrity through modulating the gut microbiota in DSS-induced chronic colitis.}, journal = {Life sciences}, volume = {261}, number = {}, pages = {118473}, doi = {10.1016/j.lfs.2020.118473}, pmid = {32971101}, issn = {1879-0631}, mesh = {Animals ; Colitis/chemically induced/metabolism/pathology/*therapy ; Dextran Sulfate ; *Electroacupuncture ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Intestinal Mucosa/metabolism/pathology ; Intestines/*pathology ; Male ; Mice, Inbred C57BL ; Permeability ; }, abstract = {AIMS: Electroacupuncture (EA) at ST36 has been verified to ameliorate experimental acute colitis. However, the effect of EA on chronic colitis and its mechanism has not yet been explored. This study aimed to assess the protective effect of EA against chronic colitis and the related mechanisms.

MAIN METHODS: Chronic colitis was induced by dextran sulfate sodium (DSS) in C57BL/6 mice, and EA was applied throughout the entire experiment. Colonic inflammation and intestinal barrier integrity were evaluated. Alterations in the gut microbiota were analyzed by 16S rRNA gene sequencing. The fecal microbiota transplantation (FMT) experiment was used to further confirm the effect of the gut microbiota on the barrier protective effect of EA. The potential molecular mechanisms were explored by western blotting.

KEY FINDINGS: (1) EA lowered the disease activity index (DAI) and histological scores, decreased the levels of TNFα, IL1β, IL6 and iNOS, and increased the IL10 level in DSS-induced chronic colitis. (2) EA upregulated the protein expression of ZO-1, Occludin, E-Cadherin and mucin2 (MUC2), reduced the apoptosis and proliferation of intestinal epithelial cells (IECs) and intestinal permeability. (3) EA enhanced the gut microbiota diversity and restored the community structure. (4) Both the low-frequency EA (LEA) FMT and high-frequency EA (HEA) FMT maintained the intestinal barrier integrity. (5) EA promoted activation of the mitogen activated protein kinase (MAPK) signaling pathway.

SIGNIFICANCE: EA can relieve chronic experimental colitis, and this effect may depend on activation of the MAPK signaling pathway through modulation of the gut microbiota to preserve the intestinal barrier.}, } @article {pmid32970852, year = {2020}, author = {Ross, CN and Reveles, KR}, title = {Feasibility of fecal microbiota transplantation via oral gavage to safely alter gut microbiome composition in marmosets.}, journal = {American journal of primatology}, volume = {82}, number = {12}, pages = {e23196}, pmid = {32970852}, issn = {1098-2345}, support = {P30 AG044271/AG/NIA NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Animals, Zoo/microbiology ; Bacteria/*classification ; Bacterial Physiological Phenomena ; Callithrix/*microbiology ; Feasibility Studies ; Fecal Microbiota Transplantation/*veterinary ; *Gastrointestinal Microbiome ; Male ; Texas ; }, abstract = {Disruption of microbial communities within human hosts has been associated with infection, obesity, cognitive decline, cancer risk and frailty, suggesting that microbiome-targeted therapies may be an option for improving healthspan and lifespan. The objectives of this study were to determine the feasibility of delivering fecal microbiota transplants (FMTs) to marmosets via oral gavage and to evaluate if alteration of the gut microbiome post-FMT could be achieved. This was a prospective study of marmosets housed at the Barshop Institute for Longevity and Aging Studies in San Antonio, Texas. Eligible animals included healthy young adult males (age 2-5 years) with no recent medication use. Stool from two donors was combined and administered in 0.5 ml doses to five young recipients once weekly for 3 weeks. Safety outcomes and alterations in the gut microbiome composition via 16S ribosomal RNA sequencing were compared at baseline and monthly up to 6 months post-FMT. Overall, significant differences in the percent relative abundance was seen in FMT recipients at the phylum and family levels from baseline to 1 month and baseline to 6 months post-FMT. In permutational multivariate analysis of variance analyses, treatment status (donor vs. recipient) (p = .056) and time course (p = .019) predicted β diversity (p = .056). The FMT recipients did not experience any negative health outcomes over the course of the treatment. FMT via oral gavage was safe to administer to young adult marmosets. The marmoset microbiome may be altered by FMT; however, progressive changes in the microbiome are strongly driven by the host and its baseline microbiome composition.}, } @article {pmid32962069, year = {2020}, author = {Cold, F and Kousgaard, SJ and Halkjaer, SI and Petersen, AM and Nielsen, HL and Thorlacius-Ussing, O and Hansen, LH}, title = {Fecal Microbiota Transplantation in the Treatment of Chronic Pouchitis: A Systematic Review.}, journal = {Microorganisms}, volume = {8}, number = {9}, pages = {}, pmid = {32962069}, issn = {2076-2607}, support = {7076-00129B//Danish Innovation Fund/ ; }, abstract = {The objective was to evaluate available literature on treatment of chronic pouchitis with fecal microbiota transplantation (FMT) focusing on clinical outcomes, safety, and different approaches to FMT preparation and delivery. A systematic review of electronic databases was conducted using Medline, EMBASE, and the Cochrane Central Register of Controlled Trials Library from inception through April 2020. Human studies of all study types reporting results of FMT to treat chronic pouchitis were included. Nine studies, reporting FMT treatment of 69 patients with chronic pouchitis were found eligible for the review. Most studies were case series and cohort studies rated as having fair to poor quality due to high risk of bias and small sample size. Only one randomized controlled trial was included, finding no beneficial effect of FMT. In total clinical response after FMT was reported in 14 (31.8%) out of 44 evaluated patients at various timepoints after FMT, and clinical remission in ten (22.7%) patients. Only minor self-limiting adverse events were reported. FMT varied greatly regarding preparation, length of treatment, and route of delivery. The effects of FMT on symptoms of chronic pouchitis are not established, though some studies show promising results. Future controlled well-designed studies are warranted.}, } @article {pmid32957333, year = {2020}, author = {Mao, D and Jiang, Q and Sun, Y and Mao, Y and Guo, L and Zhang, Y and Man, M and Ouyang, G and Sheng, L}, title = {Treatment of intestinal graft-versus-host disease with unrelated donor fecal microbiota transplantation capsules: A case report.}, journal = {Medicine}, volume = {99}, number = {38}, pages = {e22129}, doi = {10.1097/MD.0000000000022129}, pmid = {32957333}, issn = {1536-5964}, mesh = {Adult ; Capsules ; *Fecal Microbiota Transplantation ; Graft vs Host Disease/*therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Intestinal Diseases/*therapy ; Male ; Myelodysplastic Syndromes/therapy ; Unrelated Donors ; }, abstract = {INTRODUCTION: Fecal microbiota transplantation (FMT), administering fecal suspensions via a nasoduodenal tube, has achieved a promising effect in the treatment of intestinal graft-versus-host disease (GvHD) in some pilot studies. In this study, oral FMT capsules from unrelated donor were used for the first time in the treatment of intestinal GvHD. Patient concerns: A 31-year-old male who was diagnosed as "myelodysplastic syndromes with excess blasts II" (intermediate risk 2 of international prognostic scoring system) received human leukocyte antigen -matched sibling donor allogeneic hematopoietic stem cell transplantation. The patient developed diarrhea, vomiting, and bloody stool on 28 days after transplantation.

DIAGNOSIS: Intestinal acute GvHD was diagnosed clinically with histological confirmation by colonoscopy and pathological biopsy.

INTERVENTIONS: This patient was treated with first cycle of oral FMT capsules after failure to initial treatment of methylprednisolone (2 mg/kg/d) combined with recombinant human tumor necrosis factor-α receptorII: IgG Fc fusion protein (25 mg, biw). The symptoms of intestinal GvHD were relieved but recurred 11 days later. Second cycle of oral FMT capsules was carried out.

OUTCOMES: After 2 cycles of fecal bacteria transplantation, intestinal GvHD was gradually controlled and did not recur again during the 2-month follow-up. The diversity and structure of the intestinal flora after FMT was closer to that of healthy donors than that before.

CONCLUSION: Our case showed oral FMT capsules could be used as a treatment option for corticosteroid refractory intestinal GvHD. Further studies are warranted to assess the clinical efficacy and safety of oral FMT capsules in the treatment of intestinal GvHD.

RATIONALE: Fecal microbiota transplantation (FMT), administering fecal suspensions via a nasoduodenal tube, has achieved a promising effect in the treatment of intestinal graft-versus-host disease (GvHD) in some pilot studies. In this study, oral FMT capsules from unrelated donor were used for the first time in the treatment of intestinal GvHD.

PATIENT CONCERNS: A 31-year-old male who was diagnosed as "myelodysplastic syndromes with excess blasts II" (intermediate risk 2 of international prognostic scoring system) received human leukocyte antigen -matched sibling donor allogeneic hematopoietic stem cell transplantation. The patient developed diarrhea, vomiting, and bloody stool on 28 days after transplantation.

DIAGNOSES: Intestinal acute GvHD was diagnosed clinically with histological confirmation by colonoscopy and pathological biopsy.

INTERVENTIONS: This patient was treated with first cycle of oral FMT capsules after failure to initial treatment of methylprednisolone (2 mg/kg/d) combined with recombinant human tumor necrosis factor-a receptorII: IgG Fc fusion protein (25 mg, biw). The symptoms of intestinal GvHD were relieved but recurred 11 days later. Second cycle of oral FMT capsules was carried out.

OUTCOMES: After 2 cycles of fecal bacteria transplantation, intestinal GvHD was gradually controlled and did not recur again during the 2-month follow-up. The diversity and structure of the intestinal flora after FMT was closer to that of healthy donors than that before.

CONCLUSION: Our case showed oral FMT capsules could be used as a treatment option for corticosteroid refractory intestinal GvHD. Further studies are warranted to assess the clinical efficacy and safety of oral FMT capsules in the treatment of intestinal GvHD.

LESSONS: There is still a possibility of recurrence after the treatment of GvHD with capsule fecal microbiota transplantation. How to optimize the dosage and treatment course of fecal microbiota capsule administration needs further exploration.}, } @article {pmid32955197, year = {2020}, author = {Li, Q and Ding, X and Liu, K and Marcella, C and Liu, X and Zhang, T and Liu, Y and Li, P and Xiang, L and Cui, B and Wang, J and Bai, J and Zhang, F}, title = {Fecal Microbiota Transplantation for Ulcerative Colitis: The Optimum Timing and Gut Microbiota as Predictors for Long-Term Clinical Outcomes.}, journal = {Clinical and translational gastroenterology}, volume = {11}, number = {8}, pages = {e00224}, pmid = {32955197}, issn = {2155-384X}, abstract = {INTRODUCTION: The previous researches aimed to evaluate the efficacy and safety of fecal microbiota transplantation (FMT) for ulcerative colitis (UC) in a short-term observation. The present study aimed to explore the optimum timing of FMT for maintaining the long-term clinical benefits and to target the gut microbiota that may help to predict the long-term success or failure of FMT in UC.

METHODS: Two hundred two patients with UC were recruited from November 2012 to September 2018. The primary endpoint of this study was the maintaining time of the first and second courses of FMT. Relapse was defined as partial Mayo score ≥2 after achieving clinical remission and an increase of partial Mayo score ≥1 after achieving clinical response. The stool samples were analyzed by 16S rRNA gene sequencing.

RESULTS: The median maintaining time of the efficacy was 120 days (IQR, 45-180) and 182.5 days (IQR, 105-311.25) from the first course and second course of FMT, respectively. No FMT-related serious adverse events were observed. The differences of the relative abundance in Eggerthella, Lactobacillus, and Ruminococcus between pre-FMT and 5 days post-FMT were remarkably correlated with the long-term clinical remission (P < 0.05).

DISCUSSION: This study demonstrated that patients with UC should undergo the second course of FMT within 4 months after the first course of FMT for maintaining the long-term clinical benefits. The short-term alterations of microbiota after FMT may be conducive to predicting the long-term efficacy of FMT in UC (see Visual Abstract, Supplementary Digital Content, http://links.lww.com/CTG/A363).}, } @article {pmid32954843, year = {2020}, author = {Ianiro, G and Segal, JP and Mullish, BH and Quraishi, MN and Porcari, S and Fabiani, G and Gasbarrini, A and Cammarota, G}, title = {Fecal microbiota transplantation in gastrointestinal and extraintestinal disorders.}, journal = {Future microbiology}, volume = {15}, number = {}, pages = {1173-1183}, doi = {10.2217/fmb-2020-0061}, pmid = {32954843}, issn = {1746-0921}, abstract = {Fecal microbiota transplantation (FMT) is the infusion of feces from a healthy donor into the gut of a recipient to treat a dysbiosis-related disease. FMT has been proven to be a safe and effective treatment for Clostridioides difficile infection, but increasing evidence supports the role of FMT in other gastrointestinal and extraintestinal diseases. The aim of this review is to paint the landscape of current evidence of FMT in different fields of application (including irritable bowel syndrome, inflammatory bowel disease, liver disorders, decolonization of multidrug-resistant bacteria, metabolic disorders and neurological disorders), as well as to discuss the current regulatory scenario of FMT, and hypothesize future directions of FMT.}, } @article {pmid32953854, year = {2020}, author = {Zhong, M and Sun, Y and Wang, HG and Marcella, C and Cui, BT and Miao, YL and Zhang, FM}, title = {Awareness and attitude of fecal microbiota transplantation through transendoscopic enteral tubing among inflammatory bowel disease patients.}, journal = {World journal of clinical cases}, volume = {8}, number = {17}, pages = {3786-3796}, pmid = {32953854}, issn = {2307-8960}, abstract = {BACKGROUND: Transendoscopic enteral tubing (TET) has been used in China as a novel delivery route for fecal microbiota transplantation (FMT) into the whole colon with a high degree of patient satisfaction among adults.

AIM: To explore the recognition and attitudes of FMT through TET in patients with inflammatory bowel disease (IBD).

METHODS: An anonymous questionnaire, evaluating their awareness and attitudes toward FMT and TET was distributed among IBD patients in two provinces of Eastern and Southwestern China. Question formats included single-choice questions, multiple-choice questions and sorting questions. Patients who had not undergone FMT were mainly investigated for their cognition and acceptance of FMT and TET. Patients who had experience of FMT, the way they underwent FMT and acceptance of TET were the main interest. Then all the patients were asked whether they would recommend FMT and TET. This study also analyzed the preference of FMT delivery in IBD patients and the patient-related factors associated with it.

RESULTS: A total of 620 eligible questionnaires were included in the analysis. The survey showed that 44.6% (228/511) of patients did not know that FMT is a therapeutic option in IBD, and 80.6% (412/511) of them did not know the concept of TET. More than half (63.2%, 323/511) of the participants stated that they would agree to undergo FMT through TET. Of the patients who underwent FMT via TET [62.4% (68/109)], the majority [95.6% (65/68)] of them were satisfied with TET. Patients who had undergone FMT and TET were more likely to recommend FMT than patients who had not (94.5% vs 86.3%, P = 0.018 and 98.5% vs 87.8%, P = 0.017). Patients' choice for the delivery way of FMT would be affected by the type of disease and whether the patient had the experience of FMT. When compared to patients without experience of FMT, Crohn's disease and ulcerative colitis patients who had experience of FMT preferred mid-gut TET (P < 0.001) and colonic TET (P < 0.001), respectively.

CONCLUSION: Patients' experience of FMT through TET lead them to maintain a positive attitude towards FMT. The present findings highlighted the significance of patient education on FMT and TET.}, } @article {pmid32946509, year = {2020}, author = {Caldeira, LF and Borba, HH and Tonin, FS and Wiens, A and Fernandez-Llimos, F and Pontarolo, R}, title = {Fecal microbiota transplantation in inflammatory bowel disease patients: A systematic review and meta-analysis.}, journal = {PloS one}, volume = {15}, number = {9}, pages = {e0238910}, pmid = {32946509}, issn = {1932-6203}, mesh = {Fecal Microbiota Transplantation/adverse effects/*methods ; Humans ; Inflammatory Bowel Diseases/*therapy ; Randomized Controlled Trials as Topic ; Remission Induction ; Treatment Outcome ; }, abstract = {OBJECTIVES: Current evidence on fecal microbiota transplantation for inflammatory bowel disease is inconclusive. We conducted a systematic review to gather evidence on the efficacy and safety of fecal microbiota transplantation for inflammatory bowel disease.

METHODS: Systematic searches were conducted in PubMed, Scopus, and Web of Science. Clinical remission was considered as the primary endpoint. Pairwise meta-analyses were performed for the randomized controlled studies (Mantel Haenszel, random effects model). Proportion meta-analyses, accounting for weighted pooled rates reported in the interventional studies, were conducted using the mixed effects model. Subgroup analyses considering the type of stool, donor type, and disease subtype were also performed. Cumulative meta-analyses to assess further needs of evidence were conducted.

RESULTS: Sixty studies were included, from which 36 could be synthesized in the quantitative analyses. Pairwise meta-analyses of six controlled trials showed significant differences in favor of fecal microbiota transplantation compared with placebo (clinical remission: RR 1.70 [95% CI 1.12, 2.56]; clinical response: RR 1.68 [95% CI 1.04, 2.72]). An overall clinical remission of 37%, overall clinical response of 54%, and a prevalence of 29% of adverse events were found for the interventional studies. Frozen fecal material and universal donors were related to better efficacy outcomes. In addition, Crohn's disease patients seemed to benefit more from the procedure.

CONCLUSIONS: The comparative analyses demonstrated that frozen fecal material from universal donors may be related to a higher rate of clinical remission, especially for Crohn's disease.}, } @article {pmid32945066, year = {2021}, author = {El-Salhy, M and Valeur, J and Hausken, T and Gunnar Hatlebakk, J}, title = {Changes in fecal short-chain fatty acids following fecal microbiota transplantation in patients with irritable bowel syndrome.}, journal = {Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society}, volume = {33}, number = {2}, pages = {e13983}, doi = {10.1111/nmo.13983}, pmid = {32945066}, issn = {1365-2982}, support = {40415//Helse Fonna/ ; }, abstract = {BACKGROUND: Short-chain fatty acids (SCFAs) may play a role in the pathophysiology of irritable bowel syndrome (IBS). This study analyzed fecal SCFAs after performing fecal microbiota transplantation (FMT) in the IBS patients who were included in our previous study of the efficacy of FMT.

METHODS: This study included 142 of the 164 IBS patients who participated in our previous study. They were belonging to three groups: placebo (own feces), 30-g (superdonor feces), and 60-g (superdonor feces) FMT. The patients completed the IBS Severity Scoring System (IBS-SSS) Birmingham IBS Symptom, Fatigue Assessment Scale (FAS), the IBS Quality of Life (IBS-QoL) and Short-Form Nepean Dyspepsia Index (SF-NDI) questionnaires and delivered fecal samples at the baseline and 1 month after FMT. The SCFA levels were determined by vacuum distillation followed by gas chromatography.

KEY RESULTS: The fecal butyric acid level was significantly increased after FMT in both the 30-g and 60-g groups (both P ≤ 0.001). In the 60-g group, the levels of total SCFAs and isobutyric, isovaleric, and valeric acids increased after FMT. Butyric acid levels in the responders in both the 30-g and 60-g FMT groups were significantly inversely correlated with IBS-SSS and FAS scores (P = 0.001, r = -0.3 and P = 0.0001. r=- 0.3, respectively). There were no differences in the SCFA levels in the placebo group after FMT.

CONCLUSION AND INFERENCES: FMT increases the fecal SCFA levels in IBS patients. The increase in the butyric acid level is inversely correlated with symptoms in IBS patients following FMT, suggesting that SCFAs might play a role in the pathophysiology of IBS. www.clini​caltr​ials.gov (NCT03822299).}, } @article {pmid32943612, year = {2020}, author = {Xie, Z and Jiang, H and Liu, W and Zhang, X and Chen, D and Sun, S and Zhou, C and Liu, J and Bao, S and Wang, X and Zhang, Y and Li, J and Hu, L and Li, J}, title = {The triterpenoid sapogenin (2α-OH-Protopanoxadiol) ameliorates metabolic syndrome via the intestinal FXR/GLP-1 axis through gut microbiota remodelling.}, journal = {Cell death & disease}, volume = {11}, number = {9}, pages = {770}, pmid = {32943612}, issn = {2041-4889}, abstract = {Gypenosides, extracts of Gynostemma yixingense, have been traditionally prescribed to improve metabolic syndrome in Asian folk and local traditional medicine hospitals. However, the mechanism of its action remains unclarified. In this work, our results indicated that chronic administration of 2α-OH-protopanoxadiol (GP2), a metabolite of gypenosides in vivo, protected mice from high-fat diet-induced obesity and improved glucose tolerance by improving intestinal L-cell function. Mechanistically, GP2 treatment inhibited the enzymatic activity of bile salt hydrolase and modulated the proportions of the gut microbiota, which led to an increase in the accumulation of tauro-β-muricholic acid (TβMCA) in the intestine. TβMCA induced GLP-1 production and secretion by reducing the transcriptional activity of nuclear receptor farnesoid X receptor (FXR). Transplantation of GP2-remodelled fecal microbiota into antibiotic-treated mice also increased the intestinal TβMCA content and improved intestinal L-cell function. These findings demonstrate that GP2 ameliorates metabolic syndrome at least partly through the intestinal FXR/GLP-1 axis via gut microbiota remodelling and also suggest that GP2 may serve as a promising oral therapeutic agent for metabolic syndrome.}, } @article {pmid32942889, year = {2020}, author = {Stebel, R and Vojtilová, L and Husa, P}, title = {Clostridium difficile Infection: an update on treatment and prevention.}, journal = {Vnitrni lekarstvi}, volume = {66}, number = {2}, pages = {58-62}, pmid = {32942889}, issn = {0042-773X}, mesh = {Anti-Bacterial Agents/therapeutic use ; *Clostridioides difficile ; *Clostridium Infections/epidemiology/prevention & control ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Disruption of the colonic microflora is one of the most significant adverse effects of antibiotic (ATB) therapy. Excessive multiplication of toxigenic Clostridioides difficile strains is responsible for about 20 % of cases of post-antibiotic diarrhoea. The global trend of Clostridium colitis incidence, severity, mortality and in particular therapeutic failure keeps rising. At the Department of Infectious Diseases we work on long-term monitoring of the most important colitis-associated risk factors and evaluation of individual therapeutic and preventive procedures (selective ATB therapy, faecal bacteriotherapy). A diligent analysis of risk factors and knowledge of pathogenesis are a prerequisite to practical implementation of effective and rational precautions to curb spreading of this illness. In the future, we anticipate increased use of fecal microbiota transplant, improvements in faecal transplant administration, wider use of probiotics and selective ATBs and further introduction of passive and active immunization into practice.}, } @article {pmid32939928, year = {2020}, author = {Masetti, R and Zama, D and Leardini, D and Muratore, E and Turroni, S and Prete, A and Brigidi, P and Pession, A}, title = {The gut microbiome in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation.}, journal = {Pediatric blood & cancer}, volume = {67}, number = {12}, pages = {e28711}, doi = {10.1002/pbc.28711}, pmid = {32939928}, issn = {1545-5017}, mesh = {Gastrointestinal Microbiome/*immunology ; Graft vs Host Disease/*etiology/pathology ; Hematologic Neoplasms/*therapy ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Transplantation, Homologous ; }, abstract = {The gut microbiome (GM) has been associated with different clinical outcomes in the context of allogeneic hematopoietic stem cell transplantation (HSCT). Large multicenter cohort studies in adults have found significant correlations with overall survival, relapse, and incidence of complications. Moreover, GM is already a promising target for therapeutic interventions. However, few data are available in children, a population presenting unique features and challenges. During childhood, the GM evolves rapidly with large structural fluctuations, alongside with the maturation of the immune system. Furthermore, the HSCT procedure presents significant differences in children. These considerations underline the importance of a specific focus on the pediatric setting, and the role of GM and its age-dependent trajectory in influencing the immunity reconstitution and clinical outcomes. This review provides a comprehensive overview of the available evidence in the field of GM and pediatric HSCT, highlighting age-specific issues and discussing GM-based therapeutic approaches.}, } @article {pmid32929373, year = {2020}, author = {Wu, J and Wei, Z and Cheng, P and Qian, C and Xu, F and Yang, Y and Wang, A and Chen, W and Sun, Z and Lu, Y}, title = {Rhein modulates host purine metabolism in intestine through gut microbiota and ameliorates experimental colitis.}, journal = {Theranostics}, volume = {10}, number = {23}, pages = {10665-10679}, pmid = {32929373}, issn = {1838-7640}, abstract = {Background: Gut microbiota, which plays a crucial role in inflammatory bowel diseases (IBD), might have therapeutic benefits for ulcerative colitis or Crohn's disease. Targeting gut microbiota represents a new treatment strategy for IBD patients. Rhein is one of the main components of rhubarb and exhibits poor oral bioavailability but still exerts anti-inflammatory effects in some diseases. Therefore, we investigated the effect of rhein on colitis and studied its possible mechanisms. Methods: The chronic mouse colitis model was induced by four rounds of 2% dextran sulfate sodium (DSS) treatment. The mice were treated with 50 mg/kg and 100 mg/kg rhein daily, body weight, colon length, histological score, inflammatory cytokines in serum or intestine, and fecal lipocalin 2 concentration were determined. Th17 cell, Th1 cell and Th2 cell infiltration in the mesenteric lymph node were analyzed by flow cytometry. Metabolic profiles were collected by non-targeted metabolomics and key metabolic pathways were identified using MetaboAnalyst 4.0. We also assessed intestinal barrier permeability and performed 16s rDNA sequencing. Lactobacillus sp. was cultured, and fecal microbiota transplantation (FMT) was employed to evaluate the contribution of gut microbiota. Results: Rhein could significantly alleviate DSS-induced chronic colitis. Uric acid was identified as a crucial modulator of colitis and rhein treatment led to decreased uric acid levels. We determined that rhein changed purine metabolism indirectly, while the probiotic Lactobacillus was involved in the regulation of host metabolism. Uric acid resulted in a worsened intestinal barrier, which could be rescued by rhein. We further confirmed that rhein-treated gut microbiota was sufficient to relieve DSS-induced colitis by FMT. Conclusion: We showed that rhein could modulate gut microbiota, which indirectly changed purine metabolism in the intestine and subsequently alleviated colitis. Our study has identified a new approach to the clinical treatment of colitis.}, } @article {pmid32925627, year = {2020}, author = {Jeney, SES and Lane, F and Oliver, A and Whiteson, K and Dutta, S}, title = {Fecal Microbiota Transplantation for the Treatment of Refractory Recurrent Urinary Tract Infection.}, journal = {Obstetrics and gynecology}, volume = {136}, number = {4}, pages = {771-773}, doi = {10.1097/AOG.0000000000004052}, pmid = {32925627}, issn = {1873-233X}, mesh = {Adult ; Drug Resistance, Bacterial ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Recurrence ; Secondary Prevention/*methods ; Treatment Outcome ; *Urinary Tract Infections/microbiology/physiopathology/prevention & control ; }, } @article {pmid32924908, year = {2020}, author = {Liu, Y and Qin, S and Feng, Y and Song, Y and Lv, N and Liu, F and Zhang, X and Wang, S and Wei, Y and Li, S and Su, S and Zhang, W and Xue, Y and Hao, Y and Zhu, B and Ma, J and Yang, H}, title = {Perturbations of gut microbiota in gestational diabetes mellitus patients induce hyperglycemia in germ-free mice.}, journal = {Journal of developmental origins of health and disease}, volume = {11}, number = {6}, pages = {580-588}, doi = {10.1017/S2040174420000768}, pmid = {32924908}, issn = {2040-1752}, abstract = {Shifts in the maternal gut microbiota have been implicated in the development of gestational diabetes mellitus (GDM). Understanding the interaction between gut microbiota and host glucose metabolism will provide a new target of prediction and treatment. In this nested case-control study, we aimed to investigate the causal effects of gut microbiota from GDM patients on the glucose metabolism of germ-free (GF) mice. Stool and peripheral blood samples, as well as clinical information, were collected from 45 GDM patients and 45 healthy controls (matched by age and prepregnancy body mass index (BMI)) in the first and second trimester. Gut microbiota profiles were explored by next-generation sequencing of the 16S rRNA gene, and inflammatory factors in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Fecal samples from GDM and non-GDM donors were transferred to GF mice. The gut microbiota of women with GDM showed reduced richness, specifically decreased Bacteroides and Akkermansia, as well as increased Faecalibacterium. The relative abundance of Akkermansia was negatively associated with blood glucose levels, and the relative abundance of Faecalibacterium was positively related to inflammatory factor concentrations. The transfer of fecal microbiota from GDM and non-GDM donors to GF mice resulted in different gut microbiota colonization patterns, and hyperglycemia was induced in mice that received GDM donor microbiota. These results suggested that the shifting pattern of gut microbiota in GDM patients contributed to disease pathogenesis.}, } @article {pmid32923252, year = {2020}, author = {Lin, Z and Iqbal, Z and Ortiz, JF and Khan, SA and Jahan, N}, title = {Fecal Microbiota Transplantation in Recurrent Clostridium Difficile Infection: Is it Superior to Other Conventional Methods?.}, journal = {Cureus}, volume = {12}, number = {8}, pages = {e9653}, pmid = {32923252}, issn = {2168-8184}, abstract = {Clostridium difficile (C. difficile) is a gram-positive species of spore-forming bacteria. C. difficile infection (CDI) is one of the most common hospital-acquired infections in the United States, mainly caused by the use of recent antibiotics that leads to intestinal dysbiosis. Recurrent C. difficile infection (rCDI) often occurs after the successful treatment of CDI. Approximately, 30% of patients experience a clinical recurrence of prior symptoms within eight weeks of antibiotic cessation. This present literature review covers the current pathophysiology of CDI, risk factors for infection, diagnostic methods, several treatment modalities, and the potential use of fecal microbial transplant (FMT) for patients with multiple recurrent CDIs. Recent studies have focused on FMT, with an efficacy rate of nearly 90% in multiple recurrent CDI settings. Despite its efficacy, it is not commonly used as first-line treatment. More studies are needed to establish this therapy as the first option in patients with rCDI.}, } @article {pmid32922400, year = {2020}, author = {Kreft, L and Hoffmann, C and Ohnmacht, C}, title = {Therapeutic Potential of the Intestinal Microbiota for Immunomodulation of Food Allergies.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1853}, pmid = {32922400}, issn = {1664-3224}, abstract = {Food allergy is an atopic disease that is caused by the immune system targeting harmless food antigens that can result in life-threatening anaphylaxis. As humans and microbes have co-evolved, inevitably commensal microbes have a tremendous impact on our health. As such, the gut with its enormous microbial richness reflects a highly tolerogenic environment at steady state, in which immune cells are educated to react in a well-calibrated manner to food and microbial antigens. Recent evidence indicates that the susceptibility to food allergy is critically linked to microbial dysbiosis and can be transmitted by microbial transfer from humans to mice. Experimental work and epidemiological studies further point toward a critical time window in early childhood during which the immune system is imprinted by microbial colonization. Particularly, Foxp3-expressing regulatory T cells turn out to be key players, acting as rheostats for controlling the magnitude of food allergic reactions. An increasing number of bacterial metabolites has recently been shown to regulate directly or indirectly the differentiation of peripherally induced Tregs, most of which co-express the RAR-related orphan receptor gamma t (RORγt). Genetic ablation provided additional direct evidence for the importance of RORγt+ Tregs in food allergy. Future strategies for the stratification of food allergic patients with the aim to manipulate the intestinal microbiota by means of fecal transplantation efforts, pre- or probiotic regimens or for boosting oral immunotherapy may improve diagnosis and therapy. In this review some of the key underlying mechanisms are summarized and future directions for potential microbial therapy are explored.}, } @article {pmid32920548, year = {2020}, author = {Zhang, L and Zhou, W and Zhan, L and Hou, S and Zhao, C and Bi, T and Lu, X}, title = {Fecal microbiota transplantation alters the susceptibility of obese rats to type 2 diabetes mellitus.}, journal = {Aging}, volume = {12}, number = {17}, pages = {17480-17502}, pmid = {32920548}, issn = {1945-4589}, abstract = {Obesity is one of the susceptibility factors for type 2 diabetes (T2DM), both of which could accelerate the aging of the body and bring many hazards. A causal relationship is present between intestinal microbiota and body metabolism, but how the microbiota play a role in the progression of obesity to T2DM has not been elucidated. In this study, we transplanted healthy or obese-T2DM intestinal microbiota to ZDF and LZ rats, and used 16S rRNA and targeted metabonomics to evaluate the directional effect of the microbiota on the susceptibility of obese rats to T2DM. The glycolipid metabolism phenotype could be changed bidirectionally in obese rats instead of in lean ones. One possible mechanism is that the microbiota and metabolites alter the structure of the intestinal tract, and improve insulin and leptin resistance through JAK2 / IRS / Akt pathway. It is worth noting that 7 genera, such as Lactobacillus, Clostridium and Roche, can regulate 15 metabolites, such as 3-indolpropionic acid, acetic acid and docosahexaenoic acid, and have a significant improvement on glycolipid metabolism phenotype. Attention to intestinal homeostasis may be the key to controlling obesity and preventing T2DM.}, } @article {pmid32920061, year = {2020}, author = {Seong, H and Lee, SK and Cheon, JH and Yong, DE and Koh, H and Kang, YK and Jeong, WY and Lee, WJ and Sohn, Y and Cho, Y and Hyun, JH and Baek, YJ and Kim, MH and Kim, JH and Ahn, JY and Ku, NS and Jeong, SJ and Yeom, JS and Cho, MS and Lee, JH and Kim, BY and Choi, JY}, title = {Fecal Microbiota Transplantation for multidrug-resistant organism: Efficacy and Response prediction.}, journal = {The Journal of infection}, volume = {81}, number = {5}, pages = {719-725}, doi = {10.1016/j.jinf.2020.09.003}, pmid = {32920061}, issn = {1532-2742}, abstract = {OBJECTIVES: The increasing prevalence of multidrug-resistant microorganisms (MDRO) is increasing the frequency of poor clinical outcomes, prolonging hospitalizations, and raising healthcare costs. This study evaluated the eradication efficacy of fecal microbiota transplantation (FMT) and identified microbial and functional biomarkers of MDRO decolonization.

METHODS: Fecal solution obtained from healthy unrelated donors was infused in the participants' guts which had been colonized with carbapenemase-producing enterobacteriacea (CPE), vancomycin-resistant enterococci (VRE), or both CPE and VRE. Fecal samples from recipients were collected and microbiome changes before and after FMT were assessed.

RESULTS: Twenty-four (68.6%) out of 35 patients were decolonized within one year of receiving FMT. Multivariate analysis showed that FMT (FMT: hazard ratio (HR) = 5.343, 95% confidence interval (CI) = 1.877-15.212, p = 0.002) and MDRO types (CPE: HR = 11.146, 95% CI = 2.420-51.340, p = 0.002; CPE/VRE: HR = 2.948, 95% CI = 1.200-7.246, p = 0.018; VRE served as the reference) were significant independent factors associated with time to decolonization. Microbiota analysis showed higher richness and biodiversity before FMT resulted in VRE decolonization. The species Clostridium ramosum and the genuses Anaerostipes and Eisenbergiella could serve as taxonomic biomarkers and K02017 could serve as a functional biomarker for VRE clearance.

CONCLUSION: FMT is an effective way to decolonize MDRO and its effectiveness may be predicted by microbiome analysis.}, } @article {pmid32917563, year = {2020}, author = {Apartsin, K and Smirnova, V}, title = {Convalescent fecal microbiota transplantation as a possible treatment for COVID-19.}, journal = {Clinics and research in hepatology and gastroenterology}, volume = {44}, number = {5}, pages = {e113-e114}, pmid = {32917563}, issn = {2210-741X}, mesh = {*Betacoronavirus ; COVID-19 ; Coronavirus Infections/*therapy ; *Fecal Microbiota Transplantation ; Humans ; Immunization, Passive ; Pandemics ; Pneumonia, Viral/*therapy ; SARS-CoV-2 ; }, } @article {pmid32913089, year = {2020}, author = {Wargo, JA}, title = {Modulating gut microbes.}, journal = {Science (New York, N.Y.)}, volume = {369}, number = {6509}, pages = {1302-1303}, doi = {10.1126/science.abc3965}, pmid = {32913089}, issn = {1095-9203}, support = {R01 CA219896/CA/NCI NIH HHS/United States ; }, mesh = {Clostridioides difficile ; Diet ; Dysbiosis/therapy ; Enterocolitis, Pseudomembranous/therapy ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Inflammatory Bowel Diseases/therapy ; Prebiotics/administration & dosage ; }, } @article {pmid32911536, year = {2020}, author = {Vicente-Dueñas, C and Janssen, S and Oldenburg, M and Auer, F and González-Herrero, I and Casado-García, A and Isidro-Hernández, M and Raboso-Gallego, J and Westhoff, P and Pandyra, AA and Hein, D and Gössling, KL and Alonso-López, D and De Las Rivas, J and Bhatia, S and García-Criado, FJ and García-Cenador, MB and Weber, APM and Köhrer, K and Hauer, J and Fischer, U and Sánchez-García, I and Borkhardt, A}, title = {An intact gut microbiome protects genetically predisposed mice against leukemia.}, journal = {Blood}, volume = {136}, number = {18}, pages = {2003-2017}, pmid = {32911536}, issn = {1528-0020}, abstract = {The majority of childhood leukemias are precursor B-cell acute lymphoblastic leukemias (pB-ALLs) caused by a combination of prenatal genetic predispositions and oncogenic events occurring after birth. Although genetic predispositions are frequent in children (>1% to 5%), fewer than 1% of genetically predisposed carriers will develop pB-ALL. Although infectious stimuli are believed to play a major role in leukemogenesis, the critical determinants are not well defined. Here, by using murine models of pB-ALL, we show that microbiome disturbances incurred by antibiotic treatment early in life were sufficient to induce leukemia in genetically predisposed mice, even in the absence of infectious stimuli and independent of T cells. By using V4 and full-length 16S ribosomal RNA sequencing of a series of fecal samples, we found that genetic predisposition to pB-ALL (Pax5 heterozygosity or ETV6-RUNX1 fusion) shaped a distinct gut microbiome. Machine learning accurately (96.8%) predicted genetic predisposition using 40 of 3983 amplicon sequence variants as proxies for bacterial species. Transplantation of either wild-type (WT) or Pax5+/- hematopoietic bone marrow cells into WT recipient mice revealed that the microbiome is shaped and determined in a donor genotype-specific manner. Gas chromatography-mass spectrometry (GC-MS) analyses of sera from WT and Pax5+/- mice demonstrated the presence of a genotype-specific distinct metabolomic profile. Taken together, our data indicate that it is a lack of commensal microbiota rather than the presence of specific bacteria that promotes leukemia in genetically predisposed mice. Future large-scale longitudinal studies are required to determine whether targeted microbiome modification in children predisposed to pB-ALL could become a successful prevention strategy.}, } @article {pmid32909356, year = {2020}, author = {Chen, M and Liu, XL and Zhang, YJ and Nie, YZ and Wu, KC and Shi, YQ}, title = {Efficacy and safety of fecal microbiota transplantation by washed preparation in patients with moderate to severely active ulcerative colitis.}, journal = {Journal of digestive diseases}, volume = {21}, number = {11}, pages = {621-628}, pmid = {32909356}, issn = {1751-2980}, support = {81600443//National Natural Science Foundation of China/ ; 81873554//National Natural Science Foundation of China/ ; }, abstract = {OBJECTIVE: We aimed to evaluate the short-term efficacy and safety of fecal microbiota transplantation (FMT) by washed preparation for moderate to severely active UC.

METHODS: An open-label prospective trial was conducted in an inflammatory bowel disease (IBD) tertiary referral center from April 2016 to March 2018. Patients with moderate to severely active UC were randomly assigned to undergo FMT thrice on day 1, 3 and 5 by nasojejunal tube (NJT) or transendoscopic enteral tubing (TET). The primary end-point was a clinical response at week 2 post-FMT. The secondary end-points were clinical and endoscopic remission at week 12 post-FMT, safety and disease progression.

RESULTS: Of the nine patients included, 77.8% (7/9) achieved a clinical response at week 2. And 55.6% (5/9) and 33.3% (3/9), respectively, achieved clinical remission and endoscopic remission at week 12. In two patients who had no response to FMT, one switched to anti-tumor necrosis factor-α therapy, and the other underwent a colectomy. FMT was delivered through NJT in 44.4% (4/9) of the patients, while TET was used in 55.6% (5/9). The clinical outcomes did not differ significantly based on the delivery route (P > 0.05). Adverse events, all mild and self-limiting, were observed in 33.3% (3/9) of the patients.

CONCLUSIONS: FMT by washed preparation appears to be a safe and effective adjunct therapy for moderate to severely active UC during a short-term follow-up. The efficacy did not differ significantly between the NJT or TET delivery routes. Further randomized controlled studies are needed to confirm these findings.}, } @article {pmid32908211, year = {2020}, author = {Park, JC and Im, SH}, title = {Of men in mice: the development and application of a humanized gnotobiotic mouse model for microbiome therapeutics.}, journal = {Experimental & molecular medicine}, volume = {52}, number = {9}, pages = {1383-1396}, doi = {10.1038/s12276-020-0473-2}, pmid = {32908211}, issn = {2092-6413}, abstract = {Considerable evidence points to the critical role of the gut microbiota in physiology and disease. The administration of live microbes as a therapeutic modality is increasingly being considered. However, key questions such as how to identify candidate microorganisms and which preclinical models are relevant to recapitulate human microbiota remain largely unanswered. The establishment of a humanized gnotobiotic mouse model through the fecal microbiota transplantation of human feces into germ-free mice provides an innovative and powerful tool to mimic the human microbial system. However, numerous considerations are required in designing such a model, as various elements, ranging from the factors pertaining to human donors to the mouse genetic background, affect how microbes colonize the gut. Thus, it is critical to match the murine context to that of human donors to provide a continuous and faithful progression of human flora in mice. This is of even greater importance when the need for accuracy and reproducibility across global research groups are taken into account. Here, we review the key factors that affect the formulation of a humanized mouse model representative of the human gut flora and propose several approaches as to how researchers can effectively design such models for clinical relevance.}, } @article {pmid32906656, year = {2020}, author = {Roussin, L and Prince, N and Perez-Pardo, P and Kraneveld, AD and Rabot, S and Naudon, L}, title = {Role of the Gut Microbiota in the Pathophysiology of Autism Spectrum Disorder: Clinical and Preclinical Evidence.}, journal = {Microorganisms}, volume = {8}, number = {9}, pages = {}, pmid = {32906656}, issn = {2076-2607}, abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 160 people in the world. Although there is a strong genetic heritability to ASD, it is now accepted that environmental factors can play a role in its onset. As the prevalence of gastrointestinal (GI) symptoms is four-times higher in ASD patients, the potential implication of the gut microbiota in this disorder is being increasingly studied. A disturbed microbiota composition has been demonstrated in ASD patients, accompanied by altered production of bacterial metabolites. Clinical studies as well as preclinical studies conducted in rodents have started to investigate the physiological functions that gut microbiota might disturb and thus underlie the pathophysiology of ASD. The first data support an involvement of the immune system and tryptophan metabolism, both in the gut and central nervous system. In addition, a few clinical studies and a larger number of preclinical studies found that modulation of the microbiota through antibiotic and probiotic treatments, or fecal microbiota transplantation, could improve behavior. Although the understanding of the role of the gut microbiota in the physiopathology of ASD is only in its early stages, the data gathered in this review highlight that this role should be taken in consideration.}, } @article {pmid32905484, year = {2020}, author = {Cheung, MK and Yue, GGL and Tsui, KY and Gomes, AJ and Kwan, HS and Chiu, PWY and Lau, CBS}, title = {Discovery of an interplay between the gut microbiota and esophageal squamous cell carcinoma in mice.}, journal = {American journal of cancer research}, volume = {10}, number = {8}, pages = {2409-2427}, pmid = {32905484}, issn = {2156-6976}, abstract = {Esophageal squamous cell carcinoma (ESCC) is the main type of esophageal cancer (EC) worldwide, causing half a million deaths each year. Recent evidence has demonstrated the role of the gut microbiota in health and disease. However, our current understanding of the gut microbiome in EC remains scarce. Here, we characterized the gut and esophageal microbiome in a metastatic mouse model of ESCC and examined the functional roles of the gut microbiota in EC development in fecal microbiota transplantation (FMT) experiments. Nude mice intraperitoneally xenografted with human EC-109 cells showed significant alterations in the overall structure, but not alpha diversity, of the gut and esophageal microbiome as compared to naïve control mice. Xenograft of EC cells depleted the order Pasteurellales in the gut microbiome, and enriched multiple predicted metabolic pathways, including those involved in carbohydrate and lipid metabolism, in the esophageal microbiome. FMT of stool from healthy mice to antibiotic-treated xenograft-bearing mice significantly attenuated liver metastasis, suggesting a protective role of the commensal gut microbiota in EC. Moreover, we showed that combination chemotherapy with cisplatin and 5-fluorouracil, and the anti-EC medicinal herb Andrographis paniculata (AP) differentially affected the gut and esophageal microbiome in EC. FMT experiment revealed a reduced anti-metastatic efficacy of AP on liver metastasis in antibiotic-treated xenograft-bearing mice, suggesting a role of the commensal gut microbiota in the anti-metastatic efficacy of the herb. In conclusion, our findings reveal for the first time an interplay between the gut microbiota and EC and provide insights into the treatment strategies for EC.}, } @article {pmid32901505, year = {2020}, author = {Lozupone, M and D'Urso, F and Piccininni, C and Montagna, M and Sardone, R and Resta, E and Dibello, V and Daniele, A and Giannelli, G and Bellomo, A and Panza, F}, title = {The relationship between epigenetics and microbiota in neuropsychiatric diseases.}, journal = {Epigenomics}, volume = {12}, number = {17}, pages = {1559-1568}, doi = {10.2217/epi-2020-0053}, pmid = {32901505}, issn = {1750-192X}, abstract = {Microbiota might be considered as a pool for environmental epigenetic factors. Evidence is accumulating that environmental exposures - including microbes, diet, drugs - play a role in the pathogenesis of many neuropsychiatric disorders. Underlying mechanisms are complex, involving the sensitive interplay of genetics with epigenetics, neuroinflammation and the innate immune system. Modifications of microbiota affect neurogenesis and the maturation of microglia, influencing social behavior, stress-related responses and fear learning mechanisms. The excitatory neurons in the medial prefrontal cortex appear to play a key role. The mechanisms through which antibiotics administration may modulate microbiota and, therefore, behavior and neuropsychiatric disorders, may be influenced by several variables such as pre-existing gastrointestinal inflammation, the baseline microbiota composition, diet and stress perception. Probiotics, individualized diet, antibiotics and fecal transplantation could positively modulate the effects of epigenetic factors on neuropsychiatric disorders.}, } @article {pmid32899236, year = {2020}, author = {Wang, SC and Chen, YC and Chen, SJ and Lee, CH and Cheng, CM}, title = {Alcohol Addiction, Gut Microbiota, and Alcoholism Treatment: A Review.}, journal = {International journal of molecular sciences}, volume = {21}, number = {17}, pages = {}, pmid = {32899236}, issn = {1422-0067}, support = {108-2314-B-695 -002 -//Ministry of Science and Technology, Taiwan/ ; }, abstract = {Alcohol addiction is a leading risk factor for personal death and disability. In 2016, alcohol use caused 2.2% of female deaths and 6.8% of male deaths, and disability-adjusted life years (DALYs) were 2.3% in female and 8.9% in male. Individuals with alcohol use disorder are at high risk of anxiety, depression, impaired cognition performance, and illicit drug use and are comorbid with liver disease, such as alcoholic hepatitis and liver cirrhosis, which is a major cause of personal death and disability worldwide. Psychological interventions, such as cognitive behavior therapy and motivational interviewing, as well as medical treatments, such as disulfiram, naltrexone, acamprosate, and nalmefene, are used for the treatment of alcohol addiction in Europe and the United States. However, the effect of current interventions is limited, and the need for additional interventions is substantial. Alcohol use impairs the intestinal barrier and causes changes to the intestinal permeability as well as the gut microbiota composition. Emerging studies have tried to reveal the role of the gut-brain axis among individuals with alcohol use disorder with or without alcohol liver disease. Bacterial products penetrate the impaired intestinal barrier and cause central inflammation; changes to the gut microbiota impair enterohepatic circulation of bile acids; alcohol abuse causes shortage of vital nutrients such as thiamine. Several studies have suggested that probiotics, through either oral administration or fecal microbiota transplantation, increased intestinal levels of potentially beneficial bacteria such as bifidobacteria and lactobacilli, improving the levels of liver-associated enzymes in patients with mild alcoholic hepatitis, and demonstrating beneficial psychotropic effects on anxiety and depression. In addition to medications for alcohol addiction, gene editing therapy such as clustered regularly interspaced short palindromic repeats (CRISPRs) may be another potential research target. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), which are associated with ADH and ALDH genes, are major enzymes involved in alcohol metabolism, and gene editing approaches may have the potential to directly modify specific genes to treat alcoholism caused by genetic defects. Further research is needed to study the effect of the combined treatment for alcohol addiction.}, } @article {pmid32896201, year = {2020}, author = {Galan-Ros, J and Ramos-Arenas, V and Conesa-Zamora, P}, title = {Predictive values of colon microbiota in the treatment response to colorectal cancer.}, journal = {Pharmacogenomics}, volume = {21}, number = {14}, pages = {1045-1059}, doi = {10.2217/pgs-2020-0044}, pmid = {32896201}, issn = {1744-8042}, abstract = {The crosstalk between the colon mucosa and the microbiota represents a complex and delicate equilibrium. Gastrointestinal diseases such as inflammatory bowel disease and colorectal cancer (CRC) are associated with a state of altered microbiota composition known as dysbiosis, which seems to play a causative role in some of these illnesses. Recent reports have shown that the colorectal microbiome is responsible for the response and safety to treatments against CRC, especially immunotherapy, hence opening the possibility to use bacteria as a predictive marker and also as a therapeutic agent. The review objective is to summarize updated reports about the the implication of the colorectal microbiome in the development of CRC, in treatment response and its potential as a therapeutic approach.}, } @article {pmid32893721, year = {2020}, author = {Martinez-Gili, L and McDonald, JAK and Liu, Z and Kao, D and Allegretti, JR and Monaghan, TM and Barker, GF and Miguéns Blanco, J and Williams, HRT and Holmes, E and Thursz, MR and Marchesi, JR and Mullish, BH}, title = {Understanding the mechanisms of efficacy of fecal microbiota transplant in treating recurrent Clostridioides difficile infection and beyond: the contribution of gut microbial-derived metabolites.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1810531}, pmid = {32893721}, issn = {1949-0984}, support = {MC_PC_12025/MRC_/Medical Research Council/United Kingdom ; MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Fecal microbiota transplant (FMT) is a highly-effective therapy for recurrent Clostridioides difficile infection (rCDI), and shows promise for certain non-CDI indications. However, at present, its mechanisms of efficacy have remained poorly understood. Recent studies by our laboratory have noted the particular key importance of restoration of gut microbe-metabolite interactions in the ability of FMT to treat rCDI, including the impact of FMT upon short chain fatty acid (SCFAs) and bile acid metabolism. This includes a significant impact of these metabolites upon the life cycle of C. difficile directly, along with potential postulated additional benefits, including effects upon host immune response. In this Addendum, we first present an overview of these recent advancements in this field, and then describe additional novel data from our laboratory on the impact of FMT for rCDI upon several gut microbial-derived metabolites which had not previously been implicated as being of relevance.}, } @article {pmid32889369, year = {2020}, author = {Lee, KA and Shaw, HM and Bataille, V and Nathan, P and Spector, TD}, title = {Role of the gut microbiome for cancer patients receiving immunotherapy: Dietary and treatment implications.}, journal = {European journal of cancer (Oxford, England : 1990)}, volume = {138}, number = {}, pages = {149-155}, doi = {10.1016/j.ejca.2020.07.026}, pmid = {32889369}, issn = {1879-0852}, mesh = {Animals ; Anti-Bacterial Agents/adverse effects ; Bacteria/*drug effects/immunology ; *Diet/adverse effects ; Dietary Supplements ; Dysbiosis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*drug effects ; Host-Pathogen Interactions ; Humans ; Immune Checkpoint Inhibitors/adverse effects/*therapeutic use ; *Immunotherapy/adverse effects ; Neoplasms/*drug therapy/immunology/microbiology ; Nutritional Status ; Proton Pump Inhibitors/adverse effects ; }, abstract = {Immune-checkpoint inhibitors (ICIs) have revolutionised the therapeutic landscape for multiple malignancies and the health of the gut microbiome (GM) is strongly linked with therapeutic responses to ICI. This review explores the implications of diet and medication on the GM for patients receiving ICI. Clinical trials are underway to explore the impact of factors such as faecal microbiota transfer, probiotics, prebiotics, bacteria consortia and a number of dietary interventions on patients receiving ICI. Randomised controlled trials are lacking, and inferences are currently based on short-term clinical and observational studies. Antibiotics should be avoided before ICI initiation, and depending on prospective data, future consideration may be given to temporary delay of initiation of non-urgent ICI if patient has had broad spectrum antibiotics within 1 month of planned treatment initiation. Proton pump inhibitor use should be discontinued when not clearly indicated and potential switch to a histamine H2-receptor antagonist considered. Patients should be advised to minimise animal meat intake and maximise plants, aiming to consume ≥30 plant types weekly. A high fibre intake (>30 g/day) has been seen to be beneficial in increasing the chance of ICI response. Fermented foods may have a beneficial effect on the GM and should be introduced where possible. Ideally, all patients should be referred to a nutritionist or dietician with knowledge of GM before commencing ICI.}, } @article {pmid32881759, year = {2020}, author = {Dawoodbhoy, FM and Patel, BK and Patel, K and Bhatia, M and Lee, CN and Moochhala, SM}, title = {Gut Microbiota Dysbiosis as a Target for Improved Post-Surgical Outcomes and Improved Patient Care. A Review of Current Literature.}, journal = {Shock (Augusta, Ga.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/SHK.0000000000001654}, pmid = {32881759}, issn = {1540-0514}, abstract = {Critical illness results in significant changes in the human gut microbiota, leading to the breakdown of the intestinal barrier function, which plays a role in the pathogenesis of multiple organ dysfunction. Patients with sepsis/acute respiratory distress syndrome (ARDS) have a profoundly distorted intestinal microbiota rhythm, which plays a considerable role in the development of gut-derived infections and intestinal dysbiosis. Despite recent medical developments, post-surgical complications are associated with a high morbidity and mortality rate. Bacterial translocation (BT), which is the movement of bacteria and bacterial products across the intestinal barrier, was shown to be a mechanism behind sepsis. Current research is focusing on a solution by addressing significant factors that contribute to intestinal dysbiosis, which subsequently leads to multiple organ failure and, thus, mortality. It may, however, be challenging to manipulate the microbiota in critically ill patients for enhanced therapeutic gain. Probiotic manipulation is advantageous for maintaining the gut-barrier defense and for modulating the immune response. Based on available published research, this review aims to address the application of potential strategies in the intensive care unit (ICU), supplemented with current therapeutics by the administration of probiotics, prebiotics, and fecal microbiota transplant, to reduce post-surgical complications of sepsis/ARDS in critically ill patients.}, } @article {pmid32880314, year = {2020}, author = {Labuschaigne, M and Slabbert, M and Budree, S and Hoosien, E and Brink, A and Blockman, M}, title = {The ethicolegal framework relevant to human faecal microbiota transplants in South Africa: Part 3. Stool as a 'drug' or medicine.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {110}, number = {8}, pages = {819-821}, doi = {10.7196/SAMJ.2020.v110i8.15070}, pmid = {32880314}, issn = {2078-5135}, mesh = {Biological Specimen Banks/legislation & jurisprudence ; *Fecal Microbiota Transplantation ; Feces ; Humans ; South Africa ; *Therapeutic Human Experimentation/ethics/legislation & jurisprudence ; Tissue and Organ Procurement/*legislation & jurisprudence ; }, abstract = {The purpose of this article, the last in a series of three exploring the legal framework for the regulation of faecal microbiota transplantation (FMT) in South Africa (SA), is to determine the regulatory framework that applies to microbial-based treatments involving a level of manipulation that exceeds that of basic stool transplantation, e.g. processed FMT-derived products in capsule form. The article highlights the legal requirements for the registration of these products as biological medicines in SA law. Although human stool banks are not regulated in terms of the National Health Act 61 of 2003 (NHA) and regulations, the earlier articles point out that human stool fits the definition of human tissue and human biological material as defined by the NHA. For this reason, stool banks should be considered tissue banks in terms of the NHA and regulations. Healthcare practitioners and researchers involved in FMT banking and transplantation should strive to comply with these regulations in the absence of clear legal direction at present.}, } @article {pmid32880313, year = {2020}, author = {Labuschaigne, M and Slabbert, M and Budree, S and Hoosien, E and Brink, A and Blockman, M}, title = {The ethicolegal framework relevant to human faecal microbiota transplants in South Africa: Part 2. Human stool as tissue?.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {110}, number = {8}, pages = {816-818}, doi = {10.7196/SAMJ.2020.v110i8.15069}, pmid = {32880313}, issn = {2078-5135}, mesh = {Biological Specimen Banks/legislation & jurisprudence ; *Fecal Microbiota Transplantation ; Feces ; Humans ; South Africa ; Therapeutic Human Experimentation/ethics/legislation & jurisprudence ; Tissue and Organ Procurement/ethics/*legislation & jurisprudence ; }, abstract = {Faecal microbiota transplantation (FMT) has been shown to be an effective treatment for recurrent Clostridioides difficile infection. The purpose of this article, the second of a series of three articles, is to explore the legal framework governing human FMT in South Africa (SA). FMT involves different modes of administration that require different regulatory considerations. The focus of this article is to explore the legal classification of human stool as tissue in terms of the National Health Act 61 of 2003, as well as the regulation of human stool banks as tissue banks. The article concludes with specific recommendations aimed at improving the current regulatory vacuum relating to the regulation of FMT in SA.}, } @article {pmid32880312, year = {2020}, author = {Labuschaigne, M and Slabbert, M and Budree, S and Hoosien, E and Brink, A and Blockman, M}, title = {The ethicolegal framework relevant to human faecal microbiota transplants in South Africa: Part 1. A legal vacuum.}, journal = {South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde}, volume = {110}, number = {8}, pages = {812-815}, doi = {10.7196/SAMJ.2020.v110i8.14563}, pmid = {32880312}, issn = {2078-5135}, mesh = {Biological Specimen Banks/legislation & jurisprudence ; *Fecal Microbiota Transplantation ; Feces ; Gastrointestinal Microbiome ; Humans ; *Legislation, Medical ; South Africa ; }, abstract = {The legal regulation of faecal microbiota transplantation (FMT) in South Africa (SA) is currently unclear. The purpose of this article, the first of three in a series, is to explore the nature, role and clinical application of FMT in SA in order to determine, from a legal perspective, the appropriate regulatory pathways governing FMT as a procedure that may combine approaches for the treatment of drugs, human tissue for transplantation, or clinical treatment as part of the practice of medicine. FMT has been shown to be a novel, safe and effective treatment for recurrent Clostridioides difficile infection (CDI). Stool banks are instrumental in enabling access to FMT for patients and clinicians and help to catalyse research in the microbiome. However, the regulatory landscape in SA remains unclear. Microbial therapies such as FMT are necessary, especially in a time of rising microbiome-associated inflammatory diseases and increasing resistance to traditional antibiotics. FMT is now considered as part of the standard of care for recurrent CDI overseas, but is currently only being used for research purposes in a minority of clinical cases of CDI in SA. This article, which lays the foundation for consideration of this question in three parts, suggests that the relevant regulatory system would depend on the categorisation of human stool as tissue, the exact composition of the FMT, how it is administered to patients, and the relevant levels of manipulation of the stool for FMT-derived products.}, } @article {pmid32874052, year = {2020}, author = {Yue, B and Yu, ZL and Lv, C and Geng, XL and Wang, ZT and Dou, W}, title = {Regulation of the intestinal microbiota: An emerging therapeutic strategy for inflammatory bowel disease.}, journal = {World journal of gastroenterology}, volume = {26}, number = {30}, pages = {4378-4393}, pmid = {32874052}, issn = {2219-2840}, abstract = {The rapid development of metagenomics, metabolomics, and metatranscriptomics provides novel insights into the intestinal microbiota factors linked to inflammatory bowel disease (IBD). Multiple microorganisms play a role in intestinal health; these include bacteria, fungi, and viruses that exist in a dynamic balance to maintain mucosal homeostasis. Perturbations in the intestinal microbiota disrupt mucosal homeostasis and are closely related to IBD in humans and colitis in mice. Therefore, preventing or correcting the imbalance of microbiota may serve as a novel prevention or treatment strategy for IBD. We review the most recent evidence for direct or indirect interventions targeting intestinal microbiota for treatment of IBD in order to overcome the current limitations of IBD therapies and shed light on personalized treatment options.}, } @article {pmid32871960, year = {2020}, author = {Xue, LJ and Yang, XZ and Tong, Q and Shen, P and Ma, SJ and Wu, SN and Zheng, JL and Wang, HG}, title = {Fecal microbiota transplantation therapy for Parkinson's disease: A preliminary study.}, journal = {Medicine}, volume = {99}, number = {35}, pages = {e22035}, doi = {10.1097/MD.0000000000022035}, pmid = {32871960}, issn = {1536-5964}, mesh = {Aged ; Colonoscopy ; Fecal Microbiota Transplantation/adverse effects/methods/*statistics & numerical data ; Female ; Humans ; Intubation, Gastrointestinal ; Male ; Middle Aged ; Parkinson Disease/*therapy ; Patient Satisfaction ; Pilot Projects ; Young Adult ; }, abstract = {Imbalances in the gut microbiota mediate the progression of neurodegenerative diseases such as Parkinson's disease (PD). Fecal microbiota transplantation (FMT) is currently being explored as a potential therapy for PD. The objective of this study was to assess the efficacy and safety of FMT on PD. Fifteen PD patients were included, 10 of them received FMT via colonoscopy (colonic FMT group) and 5 received FMT via nasal-jejunal tube (nasointestinal FMT group). The score of PSQI, HAMD, HAMA, PDQ-39, NMSQ and UPDRS-III significantly decreased after FMT treatment (all P < .05). Colonic FMT group showed significant improvement and longer maintenance of efficacy compared with nasointestinal FMT (P = .002). Two patients achieved self-satisfying outcomes that last for more than 24 months. However, nasointestinal FMT group had no significant therapeutic effect, although UPDRS-III score slightly reduced. There were no patients were satisfied with nasointestinal FMT for more than 3 months. Among 15 PD patients, there were 5 cases had adverse events (AEs), including diarrhea (2 cases), abdominal pain (2 cases) and flatulence (1 case). These AEs were mild and self-limiting. We conclude that FMT can relieve the motor and non-motor symptoms with acceptable safety in PD. Compared with nasointestinal FMT, colonic FMT seems better and preferable.}, } @article {pmid32866799, year = {2020}, author = {Marcondes Ávila, PR and Fiorot, M and Michels, M and Dominguini, D and Abatti, M and Vieira, A and de Moura, AB and Behenck, JP and Borba, LA and Botelho, MEM and Réus, GZ and Dal-Pizzol, F and Ritter, C}, title = {Effects of microbiota transplantation and the role of the vagus nerve in gut-brain axis in animals subjected to chronic mild stress.}, journal = {Journal of affective disorders}, volume = {277}, number = {}, pages = {410-416}, doi = {10.1016/j.jad.2020.08.013}, pmid = {32866799}, issn = {1573-2517}, abstract = {INTRODUCTION: Currently, there is a growing emphasis on the study of intestinal signaling as an influencer in the pathophysiology of neuropsychiatric diseases, and the gut-brain axis is recognized as a communication route through endocrine, immune, and neural pathways (vagus nerve). Studies have shown that diets that modify the microbiota can reduce stress-related behavior and hypothalamic-pituitary-adrenal axis activation. Investigators have used fecal microbiota transplantation (FMT) approaches to demonstrate that stress-related microbiota composition plays a causal role in behavioral changes.

AIM: We hypothesized that FMT may present immunomodulatory, biochemical, endocrine, cognitive, and behavioral benefits in stress situations and that these changes can be mediated via the vagus nerve.

METHODS: Animals were subjected to a chronic mild stress (CMS) protocol. In one experiment, animals were divided into five groups: control, control + FMT, control + FMT + CMS, CMS + saline, and CMS + FMT. The animals received FMT, and behavioral tests were performed; cytokine and carbonyl levels were measured. In a second experiment, animals were submitted to vagotomy and divided into two groups: CMS + FMT and CMS + vagotomy + FMT.

RESULTS: Animals submitted to the CMS protocol or that received FMT from stressed animals showed behavioral changes and changes in neuroactive substances (increased IL-6 and TNF-α levels and carbonyl proteins). The FMT of healthy donors improved the analyzed parameters. In addition, vagotomy influenced beneficial FMT results, confirmed by behavioral testing and protein carbonyl in the hippocampus.

CONCLUSION: Manipulation of the microbiota reversed the behavioral and biochemical changes induced by the CMS protocol, and the vagus nerve influenced the gut-brain axis response.}, } @article {pmid32865119, year = {2020}, author = {Magruder, M and Edusei, E and Zhang, L and Albakry, S and Satlin, MJ and Westblade, LF and Malha, L and Sze, C and Lubetzky, M and Dadhania, DM and Lee, JR}, title = {Gut commensal microbiota and decreased risk for Enterobacteriaceae bacteriuria and urinary tract infection.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1805281}, pmid = {32865119}, issn = {1949-0984}, abstract = {Urinary tract infection (UTI) is a common complication in kidney transplant recipients and can lead to significant morbidity and mortality. Recent evidence supports a role for the gut as a source for UTIs but little is known about the relationship between gut commensal bacteria and UTI development. We hypothesized that the abundance of gut commensal bacteria is associated with a lower risk of developing bacteriuria and UTIs. We performed gut microbiome profiling using 16S rRNA gene sequencing of the V4-V5 hypervariable region on 510 fecal specimens in 168 kidney transplant recipients. Fifty-one kidney transplant recipients (30%) developed Enterobacteriaceae bacteriuria within the first 6 months after transplantation (Enterobacteriaceae Bacteriuria Group) and 117 did not (No Enterobacteriaceae Bacteriuria Group). The relative abundances of Faecalibacterium and Romboutsia were significantly higher in the fecal specimens from the No Enterobacteriaceae Bacteriuria Group than those from the Enterobacteriaceae Bacteriuria Group (Adjusted P value<.01). The combined relative abundance of Faecalibacterium and Romboutsia was inversely correlated with the relative abundance of Enterobacteriaceae (r = -0.13, P = .003). In a multivariable Cox Regression, a top tercile cutoff of the combined relative abundance of Faecalibacterium and Romboutsia of ≥13.7% was independently associated with a decreased risk for Enterobacteriaceae bacteriuria (hazard ratio 0.3, P = .02) and Enterobacteriaceae UTI (hazard ratio 0.4, P = .09). In conclusion, we identify bacterial taxa associated with decreased risk for Enterobacteriaceae bacteriuria and Enterobacteriaceae UTI in kidney transplant recipients, which supports future studies on modulating the gut microbiota as a novel treatment for preventing UTIs.}, } @article {pmid32864024, year = {2020}, author = {Raghu Subramanian, C and Talluri, S and Khan, SU and Katz, JA and Georgetson, M and Sinh, P}, title = {Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in Patients With Multiple Comorbidities: Long-Term Safety and Efficacy Results From a Tertiary Care Community Hospital.}, journal = {Gastroenterology research}, volume = {13}, number = {4}, pages = {138-145}, pmid = {32864024}, issn = {1918-2805}, abstract = {Background: Cure rates of Clostridium difficile infection (CDI) with fecal microbiota transplant (FMT) have been promising. However, there is debate regarding success of FMT in patients with comorbidities.

Methods: Electronic chart review was done to collect data on patients who underwent FMT from January 2015 to August 2017. Charts were analyzed in November 2018 with a median follow-up of 25.4 months (interquartile range 20 - 31 months).

Results: Twenty patients underwent FMT. The primary success rate at our institution was 90% and overall success rate was 100%. Six patients (43%) had FMT failure (two early and four late).

Conclusions: This case series is a description of our center's initial experience with FMT for treatment of recurrent CDI. Our high success rate reiterates the efficacy and safety of FMT in this population including patients with comorbidities.}, } @article {pmid32862830, year = {2020}, author = {Kwak, S and Choi, J and Hink, T and Reske, KA and Blount, K and Jones, C and Bost, MH and Sun, X and Burnham, CD and Dubberke, ER and Dantas, G and , }, title = {Impact of investigational microbiota therapeutic RBX2660 on the gut microbiome and resistome revealed by a placebo-controlled clinical trial.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {125}, pmid = {32862830}, issn = {2049-2618}, support = {U54 CK000162/CK/NCEZID CDC HHS/United States ; }, abstract = {BACKGROUND: Intestinal microbiota restoration can be achieved by complementing a subject's perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key application of such treatment. Another emerging application of interest is reducing antibiotic-resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome.

RESULTS: All patients exhibited significant recovery of gut microbiome diversity and a decrease of ARG relative abundance during the first 7 days post-treatment. However, the microbiome and resistome shifts toward average configurations from unperturbed individuals were more significant and longer-lasting in RBX2660 recipients compared to placebo. We quantified microbiome and resistome modification by RBX2660 using a novel "transplantation index" metric. We identified taxonomic and metabolic features distinguishing the baseline microbiome of non-transplanted patients and taxa specifically enriched during the process of transplantation. We elucidated the correlation between resistome and taxonomic transplantations and post-treatment dynamics of patient-specific and RBX2660-specific ARGs. Whole genome sequencing of AROs cultured from RBX2660 product and patient samples indicate ARO eradication in patients via RBX2660 administration, but also, to a lesser extent, introduction of RBX2660-derived AROs.

CONCLUSIONS: Through shotgun metagenomic sequencing, we elucidated the effects of RBX2660 in the microbiome and resistome. Antibiotic discontinuation alone resulted in significant recovery of gut microbial diversity and reduced ARG relative abundance, but RBX2660 administration more rapidly and completely changed the composition of patients' microbiome, resistome, and ARO colonization by transplanting RBX2660 microbiota into the recipients. Although ARGs and AROs were transmitted through RBX2660, the resistome post-RBX2660 more closely resembled that of the administered product-a proxy for the donor-than an antibiotic perturbed state.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299570 . Registered 19 November 2014 Video Abstract.}, } @article {pmid32861068, year = {2020}, author = {Zhang, F and Zhang, X and Yu, J and Tan, Y and Guo, P and Wu, C}, title = {The gut microbiota confers the lipid-lowering effect of bitter melon (Momordica charantia L.) In high-fat diet (HFD)-Induced hyperlipidemic mice.}, journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie}, volume = {131}, number = {}, pages = {110667}, doi = {10.1016/j.biopha.2020.110667}, pmid = {32861068}, issn = {1950-6007}, abstract = {The bitter melon (Momordica charantia) is a medical food with well-documented hypoglycemic and anti-hyperlipidemic activities. Previous studies showed that the M. charantia fruit (MC) could modulate the gut microbiota, but whether this modulation is essential for MC's pharmacological effects is largely unknown. Here, we assessed the causality of gut microbes in MC-elicited anti-hyperlipidemic effects for the first time. Oral administration of MC significantly prevented hyperlipidemia, but this amelioration substantially diminished when co-treated with antibiotics. Transplantation of gut flora from MC-treated donor mice also significantly decreased serum lipids. The microbiological analysis revealed that MC moderately increased diversity and shifted the overall structure of gut microbiota. It selectively enhanced the relative abundance of short-chain fatty acid (SCFAs)-producing genera and increased fecal SCFAs content. These results demonstrate that M. charantia fruit (MC) may exert an anti-hyperlipidemic effect through modulating gut microbes and increasing SCFAs production.}, } @article {pmid32860791, year = {2021}, author = {Rinott, E and Youngster, I and Yaskolka Meir, A and Tsaban, G and Zelicha, H and Kaplan, A and Knights, D and Tuohy, K and Fava, F and Scholz, MU and Ziv, O and Reuven, E and Tirosh, A and Rudich, A and Blüher, M and Stumvoll, M and Ceglarek, U and Clement, K and Koren, O and Wang, DD and Hu, FB and Stampfer, MJ and Shai, I}, title = {Effects of Diet-Modulated Autologous Fecal Microbiota Transplantation on Weight Regain.}, journal = {Gastroenterology}, volume = {160}, number = {1}, pages = {158-173.e10}, pmid = {32860791}, issn = {1528-0012}, support = {K99 DK119412/DK/NIDDK NIH HHS/United States ; P30 DK046200/DK/NIDDK NIH HHS/United States ; R00 DK119412/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND & AIMS: We evaluated the efficacy and safety of diet-modulated autologous fecal microbiota transplantation (aFMT) for treatment of weight regain after the weight-loss phase.

METHODS: In the DIRECT PLUS (Dietary Intervention Randomized Controlled Trial Polyphenols-Unprocessed) weight-loss trial (May 2017 through July 2018), abdominally obese or dyslipidemic participants in Israel were randomly assigned to healthy dietary guidelines, Mediterranean diet, and green-Mediterranean diet weight-loss groups. All groups received free gym membership and physical activity guidelines. Both isocaloric Mediterranean groups consumed 28 g/d walnuts (+440 mg/d polyphenols provided). The green-Mediterranean dieters also consumed green tea (3-4 cups/d) and a Wolffia globosa (Mankai strain, 100 g/d) green shake (+800 mg/d polyphenols provided). After 6 months (weight-loss phase), 90 eligible participants (mean age, 52 years; mean weight loss, 8.3 kg) provided a fecal sample that was processed into aFMT by frozen, opaque, and odorless capsules. The participants were then randomly assigned to groups that received 100 capsules containing their own fecal microbiota or placebo until month 14. The primary outcome was regain of the lost weight over the expected weight-regain phase (months 6-14). Secondary outcomes were gastrointestinal symptoms, waist circumference, glycemic status, and changes in the gut microbiome, as measured by metagenomic sequencing and 16s ribosomal RNA. We validated the results in a parallel in vivo study of mice specifically fed with Mankai compared with control chow diet.

RESULTS: Of the 90 participants in the aFMT trial, 96% ingested at least 80 of 100 oral aFMT or placebo frozen capsules during the transplantation period. No aFMT-related adverse events or symptoms were observed. For the primary outcome, although no significant differences in weight regain were observed among the participants in the different lifestyle interventions during months 6-14 (aFMT, 30.4% vs placebo, 40.6%; P = .28), aFMT significantly attenuated weight regain in the green-Mediterranean group (aFMT, 17.1%, vs placebo, 50%; P = .02), but not in the dietary guidelines (P = .57) or Mediterranean diet (P = .64) groups (P for the interaction = .03). Accordingly, aFMT attenuated waist circumference gain (aFMT, 1.89 cm vs placebo, 5.05 cm; P = .01) and insulin rebound (aFMT, -1.46 ± 3.6 μIU/mL vs placebo, 1.64 ± 4.7 μIU/mL; P = .04) in the green-Mediterranean group but not in the dietary guidelines or Mediterranean diet (P for the interaction = .04 and .03, respectively). The green-Mediterranean diet was the only intervention to induce a significant change in microbiome composition during the weight-loss phase, and to prompt preservation of weight-loss-associated specific bacteria and microbial metabolic pathways (mainly microbial sugar transport) after the aFMT. In mice, Mankai-modulated aFMT in the weight-loss phase compared with control diet aFMT, significantly prevented weight regain and resulted in better glucose tolerance during a high-fat diet-induced regain phase (all, P < .05).

CONCLUSIONS: Autologous FMT, collected during the weight-loss phase and administrated in the regain phase, might preserve weight loss and glycemic control, and is associated with specific microbiome signatures. A high-polyphenols, green plant-based or Mankai diet better optimizes the microbiome for an aFMT procedure. ClinicalTrials.gov number, NCT03020186.}, } @article {pmid32860788, year = {2020}, author = {Kong, L and Lloyd-Price, J and Vatanen, T and Seksik, P and Beaugerie, L and Simon, T and Vlamakis, H and Sokol, H and Xavier, RJ}, title = {Linking Strain Engraftment in Fecal Microbiota Transplantation With Maintenance of Remission in Crohn's Disease.}, journal = {Gastroenterology}, volume = {159}, number = {6}, pages = {2193-2202.e5}, pmid = {32860788}, issn = {1528-0012}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 AT009708/AT/NCCIH NIH HHS/United States ; }, abstract = {BACKGROUND & AIMS: Crohn's disease (CD) is a chronic gastrointestinal disease resulting from the dysfunctional interplay between genetic susceptibility, the immune system, and commensal intestinal microbiota. Emerging evidence suggests that treatment by suppression of the immune response and replacement of the microbiota through fecal microbiota transplantation (FMT) is a promising approach for the treatment of CD.

METHODS: We obtained stool metagenomes from CD patients in remission and assessed gut microbiome composition before and after FMT at the species and strain levels. Longitudinal follow-up evaluation allowed us to identify the gain, loss, and strain replacement of specific species and link these events to the maintenance of remission in CD.

RESULTS: We found that FMT had a significant long-term effect on patient microbial compositions, although this was primarily driven by the engraftment of donor species, which remained at low abundance. Thirty-eight percent of FMT-driven changes were strain replacements, emphasizing the importance of detailed profiling methods, such as metagenomics. Several instances of long-term coexistence between donor and patient strains were also observed. Engraftment of some Actinobacteria, and engraftment or loss of Proteobacteria, were related to better disease outcomes in CD patients who received FMT, and transmission of Bacteroidetes was deleterious.

CONCLUSIONS: Our results suggest clades that may be beneficial to transmit/eliminate through FMT, and provide criteria that may help identify personalized FMT donors to more effectively maintain remission in CD patients. The framework established here creates a foundation for future studies centered around the application of FMT and defined microbial communities as a therapeutic approach for treating CD.}, } @article {pmid32859933, year = {2020}, author = {Ianiro, G and Rossi, E and Thomas, AM and Schinzari, G and Masucci, L and Quaranta, G and Settanni, CR and Lopetuso, LR and Armanini, F and Blanco-Miguez, A and Asnicar, F and Consolandi, C and Iacovelli, R and Sanguinetti, M and Tortora, G and Gasbarrini, A and Segata, N and Cammarota, G}, title = {Faecal microbiota transplantation for the treatment of diarrhoea induced by tyrosine-kinase inhibitors in patients with metastatic renal cell carcinoma.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {4333}, pmid = {32859933}, issn = {2041-1723}, mesh = {Aged ; Carcinoma, Renal Cell/*complications ; Diarrhea/*therapy ; Double-Blind Method ; Drug Therapy ; Dysbiosis ; Enzyme Inhibitors/*metabolism ; Fecal Microbiota Transplantation/*methods ; Feces ; Female ; Gastrointestinal Microbiome ; Humans ; Kidney Neoplasms/*complications ; Male ; Middle Aged ; Tissue Donors ; Tyrosine/*metabolism ; }, abstract = {Diarrhoea is one of the most burdensome and common adverse events of chemotherapeutics, and has no standardised therapy to date. Increasing evidence suggests that the gut microbiome can influence the development of chemotherapy-induced diarrhoea. Here we report findings from a randomised clinical trial of faecal microbiota transplantation (FMT) to treat diarrhoea induced by tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (ClinicalTrials.gov number: NCT04040712). The primary outcome is the resolution of diarrhoea four weeks after the end of treatments. Twenty patients are randomised to receive FMT from healthy donors or placebo FMT (vehicle only). Donor FMT is more effective than placebo FMT in treating TKI-induced diarrhoea, and a successful engraftment is observed in subjects receiving donor faeces. No serious adverse events are observed in both treatment arms. The trial meets pre-specified endpoints. Our findings suggest that the therapeutic manipulation of gut microbiota may become a promising treatment option to manage TKI-dependent diarrhoea.}, } @article {pmid32857289, year = {2020}, author = {Wang, Y and Liu, F and Zhang, G and Su, Y and Sun, X and Chen, Q and Wang, C and Fu, H and He, Y and Zhu, X and Liu, X and Lv, M and Zhao, X and Zhao, X and Li, Y and Wang, Q and Huang, X and Zhang, X}, title = {Gut microbiome alterations and its link to corticosteroid resistance in immune thrombocytopenia.}, journal = {Science China. Life sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11427-020-1788-2}, pmid = {32857289}, issn = {1869-1889}, abstract = {Quantitative metagenomic studies have linked the gut microbiota to autoimmune disorders. Here, we performed deep shotgun metagenomic sequencing of fecal samples from 99 immune thrombocytopenia (ITP) patients and 52 healthy controls. Dysbiosis in the gut microbiome of ITP was detected phylogenetically and functionally, and classifier based on species markers distinguished individuals with ITP from healthy controls. In particular, the abundance of Ruminococcus gnavus, Bifidobacterium longum and Akkermansia muciniphila was markedly increased in treatment-naïve ITP patients, and the alterations of microbial species were correlated with clinical indices. Functionally, the secondary bile acid biosynthesis and flagellar assembly were depleted in the gut microbiota of ITP, which may contribute to the onset of ITP by affecting the immune system. Furthermore, we found that corticosteroid treatment affected the gut microbiome of ITP. Compared with corticosteroid-sensitive ITP patients, we identified that the corticosteroid-resistant ITP patients displayed a distinct gut microbiome, which was different from that of the treatment-naïve ITP patients. Together, we provided support for the critical role of gut microbiota in the development of ITP and established a foundation for further research characterizing gut microbiota in relation to corticosteroid resistance of ITP.}, } @article {pmid32856048, year = {2020}, author = {Ahn, IS and Lang, JM and Olson, CA and Diamante, G and Zhang, G and Ying, Z and Byun, HR and Cely, I and Ding, J and Cohn, P and Kurtz, I and Gomez-Pinilla, F and Lusis, AJ and Hsiao, EY and Yang, X}, title = {Host Genetic Background and Gut Microbiota Contribute to Differential Metabolic Responses to Fructose Consumption in Mice.}, journal = {The Journal of nutrition}, volume = {150}, number = {10}, pages = {2716-2728}, pmid = {32856048}, issn = {1541-6100}, support = {T32 DK007789/DK/NIDDK NIH HHS/United States ; T32 ES015457/ES/NIEHS NIH HHS/United States ; F31 AG064844/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*drug effects ; Cecum/microbiology ; Energy Metabolism/*drug effects/*genetics ; Fecal Microbiota Transplantation ; Feces/microbiology ; Fructose/*pharmacology ; Gastrointestinal Microbiome/*drug effects ; Male ; Mice ; Mice, Inbred Strains ; Random Allocation ; }, abstract = {BACKGROUND: It is unclear how high fructose consumption induces disparate metabolic responses in genetically diverse mouse strains.

OBJECTIVE: We aimed to investigate whether the gut microbiota contributes to differential metabolic responses to fructose.

METHODS: Eight-week-old male C57BL/6J (B6), DBA/2J (DBA), and FVB/NJ (FVB) mice were given 8% fructose solution or regular water (control) for 12 wk. The gut microbiota composition in cecum and feces was analyzed using 16S ribosomal DNA sequencing, and permutational multivariate ANOVA (PERMANOVA) was used to compare community across mouse strains, treatments, and time points. Microbiota abundance was correlated with metabolic phenotypes and host gene expression in hypothalamus, liver, and adipose tissues using Biweight midcorrelation. To test the causal role of the gut microbiota in determining fructose response, we conducted fecal transplants from B6 to DBA mice and vice versa for 4 wk, as well as gavaged antibiotic-treated DBA mice with Akkermansia for 9 wk, accompanied with or without fructose treatment.

RESULTS: Compared with B6 and FVB, DBA mice had significantly higher Firmicutes to Bacteroidetes ratio and lower baseline abundance of Akkermansia and S24-7 (P < 0.05), accompanied by metabolic dysregulation after fructose consumption. Fructose altered specific microbial taxa in individual mouse strains, such as a 7.27-fold increase in Akkermansia in B6 and 0.374-fold change in Rikenellaceae in DBA (false discovery rate <5%), which demonstrated strain-specific correlations with host metabolic and transcriptomic phenotypes. Fecal transplant experiments indicated that B6 microbes conferred resistance to fructose-induced weight gain in DBA mice (F = 43.1, P < 0.001), and Akkermansia colonization abrogated the fructose-induced weight gain (F = 17.8, P < 0.001) and glycemic dysfunctions (F = 11.8, P = 0.004) in DBA mice.

CONCLUSIONS: Our findings support that differential microbiota composition between mouse strains is partially responsible for host metabolic sensitivity to fructose, and that Akkermansia is a key bacterium that confers resistance to fructose-induced metabolic dysregulation.}, } @article {pmid32852834, year = {2020}, author = {Ianiro, G and Porcari, S and Ford, AC and Gasbarrini, A and Cammarota, G}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome-room for improvement.}, journal = {Alimentary pharmacology & therapeutics}, volume = {52}, number = {5}, pages = {923-924}, doi = {10.1111/apt.15923}, pmid = {32852834}, issn = {1365-2036}, mesh = {Colonoscopy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome/therapy ; }, } @article {pmid32852821, year = {2020}, author = {Lahtinen, P and Jalanka, J and Hartikainen, A and Mattila, E and Hillilä, M and Punkkinen, J and Koskenpato, J and Anttila, VJ and Tillonen, J and Satokari, R and Arkkila, P}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome-room for improvement. Authors' reply.}, journal = {Alimentary pharmacology & therapeutics}, volume = {52}, number = {5}, pages = {925-926}, doi = {10.1111/apt.15942}, pmid = {32852821}, issn = {1365-2036}, mesh = {Colonoscopy ; Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome/therapy ; }, } @article {pmid32850913, year = {2020}, author = {Ouyang, J and Isnard, S and Lin, J and Fombuena, B and Peng, X and Nair Parvathy, S and Chen, Y and Silverman, MS and Routy, JP}, title = {Treating From the Inside Out: Relevance of Fecal Microbiota Transplantation to Counteract Gut Damage in GVHD and HIV Infection.}, journal = {Frontiers in medicine}, volume = {7}, number = {}, pages = {421}, pmid = {32850913}, issn = {2296-858X}, abstract = {The gastrointestinal (GI) tract is a complex and well-balanced milieu of anatomic and immunological barriers. The epithelial surface of the GI tract is colonized by trillions of microorganisms, known as the gut microbiota, which is considered an "organ" with distinctive endocrine and immunoregulatory functions. Dysregulation of the gut microbiota composition, termed dysbiosis, has been associated with epithelial damage and translocation of microbial products into the circulating blood. Dysbiosis, increased gut permeability and chronic inflammation play a major role on the clinical outcome of inflammatory bowel diseases, graft-vs.-host disease (GVHD) and HIV infection. In this review, we focus on GVHD and HIV infection, conditions sharing gut immune damage leading to dysbiosis. The degree of dysbiosis and level of epithelial gut damage predict poor clinical outcome in both conditions. Emerging interventions are therefore warranted to promote gut microbiota homeostasis and improve intestinal barrier function. Interventions such as anti-inflammatory medications, and probiotics have toxicity and/or limited transitory effects, justifying innovative approaches. Fecal microbiota transplantation (FMT) is one such approach where fecal microorganisms are transferred from healthy donors into the GI tract of the recipient to restore microbiota composition in patients with Clostridium difficile-induced colitis or inflammatory bowel diseases. Preliminary findings point toward a beneficial effect of FMT to improve GVHD and HIV-related outcomes through the engraftment of beneficial donor bacteria, notably those producing anti-inflammatory metabolites. Herein, we critically review the potential for FMT in alleviating dysbiosis and gut damage in patients with GVHD or HIV-infection. Understanding the underlying mechanism by which FMT restores gut function will pave the way toward novel scalable and targeted interventions.}, } @article {pmid32850467, year = {2020}, author = {Sehgal, R and Bedi, O and Trehanpati, N}, title = {Role of Microbiota in Pathogenesis and Management of Viral Hepatitis.}, journal = {Frontiers in cellular and infection microbiology}, volume = {10}, number = {}, pages = {341}, pmid = {32850467}, issn = {2235-2988}, abstract = {Hepatitis is a condition that can be self-limiting or can progress to fibrosis (scarring), cirrhosis, or liver cancer. These days, gut microbiota becomes an important part of our immune system, which is important for disease progression or recovery. Translocation of gut microbial and metabolic products causes intestinal inflammation by modulating immune cells leading to impairment of the primary barrier. But there are limited studies discussing pathogenesis and management of hepatitis with gut microbiota. In this review, we have discussed the role of gut microbiota in pathogenesis and management of various hepatitis, especially hepatitis B and C. We have discussed the role of bacterial products, LPS-TLR4 pathway, and unmethylated CpG DNA, which ultimately affects downstream NF-kB signaling in hepatitis. Finally, we have discussed the role of fecal microbiota transplantation in the management of hepatitis.}, } @article {pmid32849912, year = {2020}, author = {Barberio, B and Massimi, D and Bonfante, L and Facchin, S and Calò, L and Trevenzoli, M and Savarino, EV and Cattelan, AM}, title = {Fecal microbiota transplantation for norovirus infection: a clinical and microbiological success.}, journal = {Therapeutic advances in gastroenterology}, volume = {13}, number = {}, pages = {1756284820934589}, pmid = {32849912}, issn = {1756-283X}, } @article {pmid32849279, year = {2020}, author = {Sfera, A and Osorio, C and Diaz, EL and Maguire, G and Cummings, M}, title = {The Other Obesity Epidemic-Of Drugs and Bugs.}, journal = {Frontiers in endocrinology}, volume = {11}, number = {}, pages = {488}, pmid = {32849279}, issn = {1664-2392}, abstract = {Chronic psychiatric patients with schizophrenia and related disorders are frequently treatment-resistant and may require higher doses of psychotropic drugs to remain stable. Prolonged exposure to these agents increases the risk of weight gain and cardiometabolic disorders, leading to poorer outcomes and higher medical cost. It is well-established that obesity has reached epidemic proportions throughout the world, however it is less known that its rates are two to three times higher in mentally ill patients compared to the general population. Psychotropic drugs have emerged as a major cause of weight gain, pointing to an urgent need for novel interventions to attenuate this unintended consequence. Recently, the gut microbial community has been linked to psychotropic drugs-induced obesity as these agents were found to possess antimicrobial properties and trigger intestinal dysbiosis, depleting Bacteroidetes phylum. Since germ-free animals exposed to psychotropics have not demonstrated weight gain, altered commensal flora composition is believed to be necessary and sufficient to induce dysmetabolism. Conversely, not only do psychotropics disrupt the composition of gut microbiota but the later alter the metabolism of the former. Here we review the role of gut bacterial community in psychotropic drugs metabolism and dysbiosis. We discuss potential biomarkers reflecting the status of Bacteroidetes phylum and take a closer look at nutritional interventions, fecal microbiota transplantation, and transcranial magnetic stimulation, strategies that may lower obesity rates in chronic psychiatric patients.}, } @article {pmid32846251, year = {2021}, author = {Li, L and Wang, Q and Gao, Y and Liu, L and Duan, Y and Mao, D and Luo, Y}, title = {Colistin and amoxicillin combinatorial exposure alters the human intestinal microbiota and antibiotic resistome in the simulated human intestinal microbiota.}, journal = {The Science of the total environment}, volume = {750}, number = {}, pages = {141415}, doi = {10.1016/j.scitotenv.2020.141415}, pmid = {32846251}, issn = {1879-1026}, mesh = {Amoxicillin ; Anti-Bacterial Agents ; *Colistin ; Dysbiosis ; *Gastrointestinal Microbiome ; Humans ; }, abstract = {Antibiotics treatment could cause the dysbiosis of human intestinal microbiota and antibiotic resistome. Fecal microbiota transplantation (FMT) has been an efficacious treatment to restore the dysbiosis of intestinal microbiota in a variety of intestinal diseases. However, to data, the effect of the combinatorial antibiotic treatment on microbiota, antibiotic resistome and the FMT for restoration affected by combinatorial antibiotic exposure in the human intestinal microbiota remain unclear. In this study, we systematically investigated the effect of the colistin and amoxicillin combinatorial exposure in the simulator of the human intestinal microbial ecosystem (SHIME) and found that this combinatorial exposure significantly altered (p < 0.05) the human intestinal microbiota and antibiotic resistome. The shift of bacterial community and antibiotic resistome could incompletely recovery to baseline by FMT treatment after combinatorial antibiotic exposure. Additionally, the variance of antibiotic resistome was dominantly driven by the bacterial community (41.18%-68.03%) after the combinatorial antibiotic exposure. Overall, this study first to investigate the influence of the colistin and amoxicillin combinatorial exposure on the intestinal microbiota and antibiotic resistome, and assess the FMT recovery in the simulated human intestinal microbiota, which may potentially provide a correct administration of antibiotics and application of FMT in the clinic.}, } @article {pmid32842435, year = {2020}, author = {Zhang, W and Jiang, KW}, title = {[Role of gut microbiota in carcinogenesis and treatment for colorectal cancer].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {5}, pages = {516-520}, doi = {10.3760/cma.j.cn.441530-20190820-00314}, pmid = {32842435}, issn = {1671-0274}, support = {2016YFC0106000//National Key Research and Development Plan/ ; }, mesh = {*Carcinogenesis/genetics/immunology/metabolism/pathology ; Colorectal Neoplasms/*microbiology/pathology/physiopathology/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestines/*microbiology/pathology/physiopathology ; Probiotics/therapeutic use ; Tumor Microenvironment/physiology ; }, abstract = {Colorectal cancer is one of the most common malignant tumors of digestive tract. There are a large number of microorganisms in the digestive tract. Under normal physiological conditions, intestinal microorganisms can help with digestion and absorption, resist pathogen invasion and regulate the proliferation of intestinal mucosal cells. However, intestinal microflora imbalance will affect the intestinal microenvironment and intestinal cell function, and is closely related to the incidence and progression of colorectal cancer. Firstly, this paper introduces the changes of intestinal flora in patients with colorectal cancer, and then summarizes the mode of intestinal flora participating in the occurrence of colorectal cancer from the macro level. Then, we elaborate the involvement of intestinal flora in colorectal cancer from the aspects of cytokine-dependent chronic inflammation, DNA damage of intestinal epithelial cells, carcinogenic metabolites of intestinal flora and cellular enzymes, and changes of intestinal immune system. The pathogenesis of colorectal cancer provides a reference for further study of the pathogenesis of colorectal cancer. Finally, from the perspective of intestinal flora and colorectal cancer treatment, we analyze the significance of probiotics and bacterial flora transplantation for the treatment of colorectal cancer, and provide some new treatment ideas and methods that may be useful for the treatment of colorectal cancer.}, } @article {pmid32842434, year = {2020}, author = {Zhang, XY and Chen, QY and Li, N and Qin, HL}, title = {[Indication selection and clinical application strategies of fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {5}, pages = {509-515}, doi = {10.3760/cma.j.cn.441530-20200110-00015}, pmid = {32842434}, issn = {1671-0274}, support = {SHDC12017112, SHDC12019114//Emerging Cutting-Edge Technology Joint Research Projects of Shanghai/ ; }, mesh = {Clostridioides difficile/*isolation & purification ; Clostridium Infections/*therapy ; Donor Selection ; Fecal Microbiota Transplantation/adverse effects/*methods/standards ; Feces/microbiology ; Humans ; Treatment Outcome ; }, abstract = {Fecal microbiota transplant (FMT) has become an effective method for the treatment of recurrent C. difficile infection. In addition, it has shown certain effects in other diseases inside and outside the intestine. A large number of clinical trials have been carried out. However, there is still lack of uniform standard for strategies of FMT. In this paper, we discussed the current hot and controversial issues of FMT from the aspects of indication, donor screening, fecal suspension quality control, methodology, follow-up and efficacy judgment, treatment of adverse reaction and ethical supervision based on our team's clinical experience.}, } @article {pmid32841976, year = {2020}, author = {Collins, M and DeWitt, M}, title = {Fecal microbiota transplantation in the treatment of Crohn disease.}, journal = {JAAPA : official journal of the American Academy of Physician Assistants}, volume = {33}, number = {9}, pages = {34-37}, doi = {10.1097/01.JAA.0000694964.31958.b9}, pmid = {32841976}, issn = {1547-1896}, abstract = {Fecal microbiota transplantation (FMT) is an alternative treatment option with minimal risk for patients with Crohn disease. This article explains FMT and how it effectively targets the gut microbiota changes associated with the pathogenesis of Crohn disease.}, } @article {pmid32841646, year = {2020}, author = {Kelly, CR and Laine, LA and Wu, GD}, title = {Monitoring Fecal Microbiota Transplantation Practice in a Rapidly Evolving Health and Regulatory Environment.}, journal = {Gastroenterology}, volume = {159}, number = {6}, pages = {2004-2006}, pmid = {32841646}, issn = {1528-0012}, } @article {pmid32839368, year = {2020}, author = {Song, DS}, title = {[Medical Treatment of Alcoholic Liver Disease].}, journal = {The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi}, volume = {76}, number = {2}, pages = {65-70}, doi = {10.4166/kjg.2020.76.2.65}, pmid = {32839368}, issn = {2233-6869}, abstract = {Alcoholic liver disease is a major cause of liver disease that results in significant morbidity and mortality in Korea. Abstinence is the most important strategy to prevent disease progression. Corticosteroids improve the one-month survival in patients with severe alcoholic hepatitis, but it was not effective on long-term survival. An N-acetylcysteine treatment combined with corticosteroids may provide a short-term survival benefit than corticosteroids alone. Pentoxifylline is unlikely to affect short-term survival. Hence, studies on new therapies, such as granulocyte colony-stimulating factor and fecal microbiota transplantation, are ongoing. This paper briefly reviews the current knowledge of the medical treatment of alcoholic liver disease.}, } @article {pmid32839363, year = {2021}, author = {Yoon, H and Shim, HI and Seol, M and Shin, CM and Park, YS and Kim, N and Lee, DH}, title = {Factors Related to Outcomes of Fecal Microbiota Transplantation in Patients with Clostridioides difficile Infection.}, journal = {Gut and liver}, volume = {15}, number = {1}, pages = {61-69}, pmid = {32839363}, issn = {2005-1212}, abstract = {Background/Aims: The aim of this study was to evaluate factors related to outcomes of fecal microbiota transplantation (FMT) in patients with Clostridioides difficile infection (CDI) and viability of frozen stock for FMT.

Methods: Clinical data of patients who had received FMT for CDI were prospectively collected. Next-generation 16S rRNA gene sequencing of bacteria was performed from donors' and recipients' stool. Colony-forming units (CFUs) of cultures from frozen stock solutions for FMT were measured at 0, 4, 8, 12, 24, 48 weeks after preparation of the solutions.

Results: In total, 25 FMT procedures were performed in 20 cases (14 fresh and 11 frozen FMT). Forty-five percent of cases involved fulminant CDI. The overall success rate was 55% after the 1st FMT and 75% after the 2nd FMT. The success rate was significantly higher in partially treated CDI than in refractory CDI (100% vs 71.4%; p=0.001). In successful cases only, the decrease in alpha-diversity in the recipient stool microbiomes was recovered after FMT to a level similar to that in donor stools. There was a significant difference in the microbiome composition in pre-FMT recipients' stool between successful and failed cases (p=0.001). The CFUs of frozen solution for FMT did not decrease for 48 weeks in both aerobic and anaerobic cultures.

Conclusions: FMT is highly effective in partially treated CDI but not in refractory CDI. The microbiome differs between failed and successful cases. Frozen stock for FMT is viable up to 48 weeks.}, } @article {pmid32835916, year = {2020}, author = {Zhan, J and Ma, X and Liu, D and Liang, Y and Li, P and Cui, J and Zhou, Z and Wang, P}, title = {Gut microbiome alterations induced by tributyltin exposure are associated with increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {266}, number = {Pt 3}, pages = {115276}, doi = {10.1016/j.envpol.2020.115276}, pmid = {32835916}, issn = {1873-6424}, mesh = {Animals ; Body Weight ; *Gastrointestinal Microbiome ; Glucose ; Homeostasis ; Insulin ; Mice ; Mice, Inbred ICR ; Trialkyltin Compounds ; }, abstract = {Tributyltin (TBT), an organotin compound once widely used in agriculture and industry, has been reported to induce obesity and endocrine disruption. Gut microbiota has a strong connection with the host's physiology. Nevertheless, the influences of TBT exposure on gut microbiota and whether TBT-influenced gut microbiota is related to TBT-induced toxicity remain unclear. To fill these gaps, ICR (CD-1) mice were respectively exposed to TBT at NOEL (L-TBT) and tenfold NOEL (H-TBT) daily by gavage for 8 weeks in the current study. The results showed that TBT exposure significantly increased body weight as well as epididymal fat, and led to adipocyte hypertrophy, dyslipidemia and impaired glucose and insulin homeostasis in mice. Additionally, TBT exposure significantly decreased the levels of T4, T3 and testosterone in serum. Also of note, TBT exposure changed gut microbiota composition mainly by decreasing Bacteroidetes and increasing Firmicutes proportions. To confirm the role of gut microbiota in TBT-induced overweight and hormonal disorders, fecal microbiota transplantation was performed and the mice receiving gut microbiota from H-TBT mice had similar phenotypes with their donor mice including significant body weight and epididymal fat gain, glucose and insulin dysbiosis and hormonal disorders. These results suggested that gut microbiome altered by TBT exposure was involved in the TBT-induced increased body weight, impaired glucose and insulin homeostasis and endocrine disruption in mice, providing significant evidence and a novel perspective for better understanding the mechanism by which TBT induces toxicity.}, } @article {pmid32835671, year = {2020}, author = {Badran, M and Khalyfa, A and Ericsson, A and Gozal, D}, title = {Fecal microbiota transplantation from mice exposed to chronic intermittent hypoxia elicits sleep disturbances in naïve mice.}, journal = {Experimental neurology}, volume = {334}, number = {}, pages = {113439}, doi = {10.1016/j.expneurol.2020.113439}, pmid = {32835671}, issn = {1090-2430}, support = {R01 HL130984/HL/NHLBI NIH HHS/United States ; R56 HL140548/HL/NHLBI NIH HHS/United States ; RF1 AG061824/AG/NIA NIH HHS/United States ; U42 OD010918/OD/NIH HHS/United States ; }, abstract = {Obstructive sleep apnea (OSA) is a chronic prevalent condition characterized by intermittent hypoxia (IH) and sleep fragmentation (SF). Evidence suggests that OSA can alter the gut microbiome (GM) diversity and composition that may then promote the occurrence of some of the OSA-associated morbidities. However, it is unclear whether perturbations in the GM caused by IH can elicit sleep disturbances that underlie the increased sleep propensity that occurs in IH-exposed mice. To evaluate this issue, we exposed C57Bl/6 J mice to IH or room air (RA) for 6 weeks, and fecal matter was collected and frozen. C57Bl/6 J naïve mice were then randomly assigned to a fecal microbiota transfer (FMT) protocol for 3 weeks with either IH or RA fecal slur, and their GM was then analyzed using 16 s rRNA sequencing. In addition, FMT recipients underwent sleep recordings using piezoelectric approaches for 3 consecutive days. As anticipated, FMT-IH and FMT-RA mice showed different taxonomic profiles that corresponded to previous effects of IH on GM. Furthermore, FMT-IH mice exhibited increased sleep duration and the frequency of longer sleep bouts during the dark cycle, suggesting increased sleepiness (p < 0.0001 vs. FMT-RA mice). Thus, alterations of GM diversity induced by IH exposures can elicit sleep disturbances in the absence of concurrent IH, suggesting that sleep disturbances can be mediated, at least in part, by IH-induced alterations in GM.}, } @article {pmid32831634, year = {2020}, author = {Li, K and Wei, S and Hu, L and Yin, X and Mai, Y and Jiang, C and Peng, X and Cao, X and Huang, Z and Zhou, H and Ma, G and Liu, Z and Li, H and Zhao, B}, title = {Protection of Fecal Microbiota Transplantation in a Mouse Model of Multiple Sclerosis.}, journal = {Mediators of inflammation}, volume = {2020}, number = {}, pages = {2058272}, pmid = {32831634}, issn = {1466-1861}, abstract = {Given the growing evidence of a link between gut microbiota (GM) dysbiosis and multiple sclerosis (MS), fecal microbiota transplantation (FMT), aimed at rebuilding GM, has been proposed as a new therapeutic approach to MS treatment. To evaluate the viability of FMT for MS treatment and its impact on MS pathology, we tested FMT in mice with experimental autoimmune encephalomyelitis (EAE), a mouse model of MS. We provide evidence that FMT can rectify altered GM to some extent with a therapeutic effect on EAE. We also found that FMT led to reduced activation of microglia and astrocytes and conferred protection on the blood-brain barrier (BBB), myelin, and axons in EAE. Taken together, our data suggest that FMT, as a GM-based therapy, has the potential to be an effective treatment for MS.}, } @article {pmid32830227, year = {2020}, author = {Zou, J and Zhao, X and Shi, Z and Zhang, Z and Vijay-Kumar, M and Chassaing, B and Gewirtz, AT}, title = {Critical role of innate immunity to flagellin in absence of adaptive immunity.}, journal = {The Journal of infectious diseases}, volume = {}, number = {}, pages = {}, doi = {10.1093/infdis/jiaa521}, pmid = {32830227}, issn = {1537-6613}, abstract = {BACKGROUND: Bacterial flagellin is a major target of innate and adaptive immunity, both of which can promote and/or compensate for deficiencies in each other's function.

AIM/METHODS: To investigate the role of innate immune detection of flagellin irrespective of adaptive immunity, we examined the consequences of loss of toll-like receptor 5 (T5) and/or Nod-like receptor 4 (N4) upon a Rag1-deficient background.

RESULTS: Mice lacking TLR5 and Rag1 (T5/Rag-DKO) exhibited frequent lethal Pasteurellaceae-containing abscesses that prevented breeding of these mice. Mice lacking TLR5, NLRC4, and Rag1 (T5/N4/Rag-TKO) also resulted in sporadic lethal abdominal abscesses caused by similar Pasteurellaceae. In the absence of such infections, relative to Rag1-KO, T5/N4/Rag-TKO mice exhibited microbiota encroachment, low-grade inflammation, microbiota dysbiosis, and, moreover were highly prone to Citrobacter infection and developed severe colitis when adoptively transferred with colitogenic T-cells. Relative proneness of T5/N4/Rag-TKO mice to T-cell colitis was ablated by antibiotics while fecal microbiota transplant from T5/N4/Rag-TKO mice to WT mice transferred proneness to Citrobacter infection, indicating that dysbiosis in T5/N4/Rag-TKO mice contributed to these phenotypes.

CONCLUSIONS: These results demonstrate a critical role for innate immune detection of flagellin, especially in the intestinal tract and particularly in hosts deficient in adaptive immunity.}, } @article {pmid32821439, year = {2020}, author = {Chen, H and Chen, Z and Shen, L and Wu, X and Ma, X and Lin, D and Zhang, M and Ma, X and Liu, Y and Wang, Z and Zhang, Y and Kuang, Z and Lu, Z and Li, X and Ma, L and Lin, X and Si, L and Chen, X}, title = {Fecal microbiota transplantation from patients with autoimmune encephalitis modulates Th17 response and relevant behaviors in mice.}, journal = {Cell death discovery}, volume = {6}, number = {}, pages = {75}, pmid = {32821439}, issn = {2058-7716}, abstract = {The significance of the microbiota-gut-brain axis has been increasingly recognized as a major modulator of autoimmunity. Here, we aim to characterize the gut microbiota of a large cohort of treatment-naïve anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis patients relative to that of healthy controls (HCs). Relative to HCs, anti-NMDAR encephalitis patients had a decreased microbiome alpha-diversity index, marked disturbances of gut microbial composition and intestinal permeability damage. Disturbed microbiota in anti-NMDAR encephalitis patients might be linked with different clinical characteristics. Imputed KEGG analysis revealed perturbations of functional modules in the gut microbiomes of anti-NMDAR encephalitis. Compared to HCs, microbiota-depleted mice receiving fecal microbiota transplantation (FMT) from anti-NMDAR encephalitis patients had hypersensitivity and cognitive impairment. Furthermore, anti-NMDAR encephalitis FMT mice showed altered T cells in the spleen and small intestine lamina propria with an increased Th17 cells. Overall, this study first suggests that the anti-NMDAR encephalitis microbiome itself can influence neurologic, Th17 response and behavioral function. The gut microbiota is a potential therapeutic target for anti-NMDAR encephalitis.}, } @article {pmid32821067, year = {2020}, author = {Ghouri, YA and Tahan, V and Shen, B}, title = {Secondary causes of inflammatory bowel diseases.}, journal = {World journal of gastroenterology}, volume = {26}, number = {28}, pages = {3998-4017}, pmid = {32821067}, issn = {2219-2840}, abstract = {Inflammatory bowel diseases (IBD), conventionally consist of Crohn's disease (CD) and ulcerative colitis. They occur in individuals with high risk genotype for the disease in the setting of appropriate environmental factors. The pathogenesis of IBD involves a dysregulated autoimmune response to gut dysbiosis, which in turn is triggered due to exposure to various inciting environmental factors. But there is no clearly defined etiology of IBD and this type of disease is termed as "idiopathic IBD", "classic IBD", or "primary IBD". We reviewed the current medical literature and found that certain etiological factors may be responsible for the development of IBD or IBD-like conditions, and we consider this form of de novo IBD as "secondary IBD". Currently known factors that are potentially responsible for giving rise to secondary IBD are medications; bowel altering surgeries and transplantation of organs, stem cells or fecal microbiome. Medications associated with the development of secondary IBD include; immunomodulators, anti-tumor necrosis factor alpha agents, anti-interleukin agents, interferons, immune stimulating agents and checkpoint inhibitors. Colectomy can in some cases give rise to de novo CD, pouchitis of the ileal pouch, or postcolectomy enteritis syndrome. After solid organ transplantation or hematopoietic stem cell transplantation, the recipient may develop de novo IBD or IBD flare. Fecal microbiota transplantation has been widely used to treat patients suffering from recurrent Clostridium difficile infection but can also causes IBD flares.}, } @article {pmid32820707, year = {2020}, author = {Yiu, JHC and Chan, KS and Cheung, J and Li, J and Liu, Y and Wang, Y and Fung, WWL and Cai, J and Cheung, SWM and Dorweiler, B and Wan, EYF and Tso, P and Xu, A and Woo, CW}, title = {Gut Microbiota-Associated Activation of TLR5 Induces Apolipoprotein A1 Production in the Liver.}, journal = {Circulation research}, volume = {127}, number = {10}, pages = {1236-1252}, pmid = {32820707}, issn = {1524-4571}, abstract = {RATIONALE: Dysbiosis of gut microbiota plays an important role in cardiovascular diseases but the molecular mechanisms are complex. An association between gut microbiome and the variance in HDL-C (high-density lipoprotein-cholesterol) level was suggested in a human study. Besides, dietary fat was shown to increase both HDL-C and LDL-C (low-density lipoprotein-cholesterol) levels. We speculate that certain types of gut bacteria responding to dietary fat may help to regulate HDL-C level and potentially affect atherosclerotic development.

OBJECTIVE: We aimed to investigate whether and how high-fat diet (HFD)-associated gut microbiota regulated HDL-C level.

METHODS AND RESULTS: We found that HFD increased gut flagellated bacteria population in mice. The increase in HDL-C level was adopted by mice receiving fecal microbiome transplantation from HFD-fed mouse donors. HFD led to increased hepatic but not circulating flagellin, and deletion of TLR5 (Toll-like receptor 5), a receptor sensing flagellin, suppressed HFD-stimulated HDL-C and ApoA1 (apolipoprotein A1) levels. Overexpression of TLR5 in the liver of TLR5-knockout mice was able to partially restore the production of ApoA1 and HDL-C levels. Mechanistically, TLR5 activation by flagellin in primary hepatocytes stimulated ApoA1 production through the transcriptional activation responding to the binding of NF-κB (nuclear factor-κB) on Apoa1 promoter region. Furthermore, oral supplementation of flagellin was able to stimulate hepatic ApoA1 production and HDL-C level and decrease atherosclerotic lesion size in apolipoprotein E-deficient (Apoe-/-) mice without triggering hepatic and systemic inflammation. The stimulation of ApoA1 production was also seen in human ApoA1-transgenic mice treated with oral flagellin.

CONCLUSIONS: Our finding suggests that commensal flagellated bacteria in gut can facilitate ApoA1 and HDL-C productions in liver through activation of TLR5 in hepatocytes. Hepatic TLR5 may be a potential drug target to increase ApoA1.}, } @article {pmid32819434, year = {2020}, author = {Li, Y and Luo, ZY and Hu, YY and Bi, YW and Yang, JM and Zou, WJ and Song, YL and Li, S and Shen, T and Li, SJ and Huang, L and Zhou, AJ and Gao, TM and Li, JM}, title = {The gut microbiota regulates autism-like behavior by mediating vitamin B6 homeostasis in EphB6-deficient mice.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {120}, pmid = {32819434}, issn = {2049-2618}, abstract = {BACKGROUND: Autism spectrum disorder (ASD) is a developmental disorder, and the effective pharmacological treatments for the core autistic symptoms are currently limited. Increasing evidence, particularly that from clinical studies on ASD patients, suggests a functional link between the gut microbiota and the development of ASD. However, the mechanisms linking the gut microbiota with brain dysfunctions (gut-brain axis) in ASD have not yet been full elucidated. Due to its genetic mutations and downregulated expression in patients with ASD, EPHB6, which also plays important roles in gut homeostasis, is generally considered a candidate gene for ASD. Nonetheless, the role and mechanism of EPHB6 in regulating the gut microbiota and the development of ASD are unclear.

RESULTS: Here, we found that the deletion of EphB6 induced autism-like behavior and disturbed the gut microbiota in mice. More importantly, transplantation of the fecal microbiota from EphB6-deficient mice resulted in autism-like behavior in antibiotic-treated C57BL/6J mice, and transplantation of the fecal microbiota from wild-type mice ameliorated the autism-like behavior in EphB6-deficient mice. At the metabolic level, the disturbed gut microbiota in EphB6-deficient mice led to vitamin B6 and dopamine defects. At the cellular level, the excitation/inhibition (E/I) balance in the medial prefrontal cortex was regulated by gut microbiota-mediated vitamin B6 in EphB6-deficient mice.

CONCLUSIONS: Our study uncovers a key role for the gut microbiota in the regulation of autism-like social behavior by vitamin B6, dopamine, and the E/I balance in EphB6-deficient mice, and these findings suggest new strategies for understanding and treating ASD. Video abstract.}, } @article {pmid32817490, year = {2020}, author = {Britton, GJ and Contijoch, EJ and Spindler, MP and Aggarwala, V and Dogan, B and Bongers, G and San Mateo, L and Baltus, A and Das, A and Gevers, D and Borody, TJ and Kaakoush, NO and Kamm, MA and Mitchell, H and Paramsothy, S and Clemente, JC and Colombel, JF and Simpson, KW and Dubinsky, MC and Grinspan, A and Faith, JJ}, title = {Defined microbiota transplant restores Th17/RORγt+ regulatory T cell balance in mice colonized with inflammatory bowel disease microbiotas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {117}, number = {35}, pages = {21536-21545}, pmid = {32817490}, issn = {1091-6490}, support = {R01 DK112296/DK/NIDDK NIH HHS/United States ; R01 DK112978/DK/NIDDK NIH HHS/United States ; R01 DK124133/DK/NIDDK NIH HHS/United States ; R01 GM108505/GM/NIGMS NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; R01 DK123749/DK/NIDDK NIH HHS/United States ; F31 DK112679/DK/NIDDK NIH HHS/United States ; T32 AI078892/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Colitis/prevention & control ; Colon/microbiology ; Crohn Disease/metabolism/microbiology ; Cytokines/immunology ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/immunology ; Humans ; Inflammatory Bowel Diseases/immunology/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Nuclear Receptor Subfamily 1, Group F, Member 3/*immunology ; T-Lymphocytes, Regulatory/*immunology/microbiology ; Th17 Cells/*immunology/microbiology ; }, abstract = {The building evidence for the contribution of microbiota to human disease has spurred an effort to develop therapies that target the gut microbiota. This is particularly evident in inflammatory bowel diseases (IBDs), where clinical trials of fecal microbiota transplantation have shown some efficacy. To aid the development of novel microbiota-targeted therapies and to better understand the biology underpinning such treatments, we have used gnotobiotic mice to model microbiota manipulations in the context of microbiotas from humans with inflammatory bowel disease. Mice colonized with IBD donor-derived microbiotas exhibit a stereotypical set of phenotypes, characterized by abundant mucosal Th17 cells, a deficit in the tolerogenic RORγt+ regulatory T (Treg) cell subset, and susceptibility to disease in colitis models. Transplanting healthy donor-derived microbiotas into mice colonized with human IBD microbiotas led to induction of RORγt+ Treg cells, which was associated with an increase in the density of the microbiotas following transplant. Microbiota transplant reduced gut Th17 cells in mice colonized with a microbiota from a donor with Crohn's disease. By culturing strains from this microbiota and screening them in vivo, we identified a specific strain that potently induces Th17 cells. Microbiota transplants reduced the relative abundance of this strain in the gut microbiota, which was correlated with a reduction in Th17 cells and protection from colitis.}, } @article {pmid32816876, year = {2020}, author = {Zhang, L and Roy, S}, title = {Opioid Modulation of the Gut-Brain Axis in Opioid-Associated Comorbidities.}, journal = {Cold Spring Harbor perspectives in medicine}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a040485}, pmid = {32816876}, issn = {2157-1422}, abstract = {Growing evidence from animal and human studies show that opioids have a major impact on the composition and function of gut microbiota. This leads to disruption in gut permeability and altered microbial metabolites, driving both systemic and neuroinflammation, which in turn impacts central nervous system (CNS) homeostasis. Tolerance and dependence are the major comorbidities associated with prolonged opioid use. Inflammatory mediators and signaling pathways have been implicated in both opioid tolerance and dependence. We provide evidence that targeting the gut microbiome during opioid use through prebiotics, probiotics, antibiotics, and fecal microbial transplantation holds the greatest promise for novel treatments for opioid abuse. Basic research and clinical trials are required to examine what is more efficacious to yield new insights into the role of the gut-brain axis in opioid abuse.}, } @article {pmid32814133, year = {2021}, author = {Yu, Z and Shi, Z and Zheng, Z and Han, J and Yang, W and Lu, R and Lin, W and Zheng, Y and Nie, D and Chen, G}, title = {DEHP induce cholesterol imbalance via disturbing bile acid metabolism by altering the composition of gut microbiota in rats.}, journal = {Chemosphere}, volume = {263}, number = {}, pages = {127959}, doi = {10.1016/j.chemosphere.2020.127959}, pmid = {32814133}, issn = {1879-1298}, mesh = {Animals ; Bacteroidetes/genetics ; Bile Acids and Salts/metabolism ; Cecum ; Cholesterol/*metabolism ; Diethylhexyl Phthalate/metabolism/*toxicity ; Firmicutes/genetics ; Gastrointestinal Microbiome/*drug effects ; Lipid Metabolism/genetics ; Liver/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/metabolism ; Rats ; }, abstract = {Di(2-ethylhexyl) phthalate (DEHP) is one of the most widespread environmental contaminants worldwide because of its massive production, extensive use in common products, and liability to leach from products. This study investigated the mechanisms of DEHP mediated alteration of lipid metabolism. Rats were treated with 0.5 mg kg-1 d-1 of DEHP for 23 weeks. Results showed that the treatment induced cholesterol imbalance. Further fecal transplantation experiments corroborated the involvement of gut microbiota in DEHP-induced cholesterol imbalance. In addition, 16S rRNA gene sequencing analysis of cecal contents showed that DEHP disrupted the gut microbiota diversity in rats and increased the ratio of Firmicutes to Bacteroidetes. Further cecal metabolomic analyses, bile salt hydrolase enzyme activity, and gene expression examination revealed that chronic DEHP exposure generated a bile acid profile in the gut that is a more potent activator of farnesoid X receptor (FXR). The activation of FXR in the gut induced the expression of fibroblast growth factor 15, which subsequently suppressed cytochrome P450 family 7 subfamily A member 1 in the liver and bile acid synthesis. These results suggest that DEHP might induce cholesterol imbalance by regulating bile acid metabolism via the remodeling of the gut microbiota.}, } @article {pmid32814026, year = {2020}, author = {Stephen-Victor, E and Crestani, E and Chatila, TA}, title = {Dietary and Microbial Determinants in Food Allergy.}, journal = {Immunity}, volume = {53}, number = {2}, pages = {277-289}, pmid = {32814026}, issn = {1097-4180}, support = {R01 AI126915/AI/NIAID NIH HHS/United States ; R21 AI132843/AI/NIAID NIH HHS/United States ; }, abstract = {The steep rise in food allergy (FA) has evoked environmental factors involved in disease pathogenesis, including the gut microbiota, diet, and their metabolites. Early introduction of solid foods synchronizes with the "weaning reaction," a time during which the microbiota imprints durable oral tolerance. Recent work has shown that children with FA manifest an early onset dysbiosis with the loss of Clostridiales species, which promotes the differentiation of ROR-γt+ regulatory T cells to suppress FA. This process can be reversed in pre-clinical mouse models by targeted bacteriotherapy. Here, we review the dominant tolerance mechanisms enforced by the microbiota to suppress FA and discuss therapeutic intervention strategies that act to recapitulate the early life window of opportunity in stemming the FA epidemic.}, } @article {pmid32808030, year = {2020}, author = {Olesen, SW and Gerardin, Y}, title = {Re-evaluating the evidence for fecal microbiota transplantation "super-donors" in inflammatory bowel disease.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjaa170}, pmid = {32808030}, issn = {1876-4479}, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is a recommended treatment for recurrent Clostridioides difficile infection, and there is promise that FMT may be effective for conditions like inflammatory bowel disease (IBD). Previous FMT clinical trials have considered the possibility of a "donor effect", that is, that FMT material from different donors has different clinical efficacies.

AIM & METHODS: Here we re-evaluate evidence for donor effects in published FMT clinical trials for IBD.

RESULTS: In 10 of 12 published studies, no statistically significant donor effect was detected when rigorously re-evaluating the original analyses. One study had statistically significant separation of microbiota composition of pools of donor stool when stratified by patient outcome. One study reported a significant effect but did not have underlying data available for re-evaluation. When quantifying the uncertainty on the magnitude of the donor effect, confidence intervals were large, including both zero donor effect and very substantial donor effects.

CONCLUSION: Although we found very little evidence for donor effects, the existing data also cannot rule out the possibility that donor effects are clinically important. Large clinical trials prospectively designed to detect donor effects are likely necessary to determine if donor effects are clinically relevant for IBD.}, } @article {pmid32805128, year = {2020}, author = {Vandekerckhove, E and Janssens, F and Tate, D and De Looze, D}, title = {Treatment of Gut Fermentation Syndrome With Fecal Microbiota Transplantation.}, journal = {Annals of internal medicine}, volume = {173}, number = {10}, pages = {855}, doi = {10.7326/L20-0341}, pmid = {32805128}, issn = {1539-3704}, mesh = {Alcoholic Intoxication/etiology ; Anti-Bacterial Agents/*adverse effects ; Blood Alcohol Content ; Dietary Carbohydrates/*metabolism ; Ethanol/*metabolism ; *Fecal Microbiota Transplantation ; *Fermentation ; Gastric Bypass ; Gastrointestinal Diseases/chemically induced/microbiology/*therapy ; Gastrointestinal Microbiome/*drug effects ; Humans ; Liver Function Tests ; Male ; Middle Aged ; Syndrome ; }, } @article {pmid32801142, year = {2020}, author = {van Lier, YF and Davids, M and Haverkate, NJE and de Groot, PF and Donker, ML and Meijer, E and Heubel-Moenen, FCJI and Nur, E and Zeerleder, SS and Nieuwdorp, M and Blom, B and Hazenberg, MD}, title = {Donor fecal microbiota transplantation ameliorates intestinal graft-versus-host disease in allogeneic hematopoietic cell transplant recipients.}, journal = {Science translational medicine}, volume = {12}, number = {556}, pages = {}, doi = {10.1126/scitranslmed.aaz8926}, pmid = {32801142}, issn = {1946-6242}, abstract = {Disruption of the intestinal microbiota occurs frequently in allogeneic hematopoietic cell transplantation (allo-HCT) recipients and predisposes them to development of graft-versus-host disease (GvHD). In a prospective, single-center, single-arm study, we investigated the effect of donor fecal microbiota transplantation (FMT) on symptoms of steroid-refractory or steroid-dependent, acute or late-onset acute intestinal GvHD in 15 individuals who had undergone allo-HCT. Study participants received a fecal suspension from an unrelated healthy donor via nasoduodenal infusion. Donor FMT was well tolerated, and infection-related adverse events did not seem to be related to the FMT procedure. In 10 of 15 study participants, a complete clinical response was observed within 1 month after FMT, without additional interventions to alleviate GvHD symptoms. This response was accompanied by an increase in gut microbial α-diversity, a partial engraftment of donor bacterial species, and increased abundance of butyrate-producing bacteria, including Clostridiales and Blautia species. In 6 of the 10 responding donor FMT recipients, immunosuppressant drug therapy was successfully tapered. Durable remission of steroid-refractory or steroid-dependent GvHD after donor FMT was associated with improved survival at 24 weeks after donor FMT. This study highlights the potential of donor FMT as a treatment for steroid-refractory or steroid-dependent GvHD, but larger clinical trials are needed to confirm the safety and efficacy of this procedure.}, } @article {pmid32799901, year = {2020}, author = {Wang, S and Ishima, T and Zhang, J and Qu, Y and Chang, L and Pu, Y and Fujita, Y and Tan, Y and Wang, X and Hashimoto, K}, title = {Ingestion of Lactobacillus intestinalis and Lactobacillus reuteri causes depression- and anhedonia-like phenotypes in antibiotic-treated mice via the vagus nerve.}, journal = {Journal of neuroinflammation}, volume = {17}, number = {1}, pages = {241}, pmid = {32799901}, issn = {1742-2094}, support = {none//Smoking Research Foundation/ ; JP19dm0107119//Japan Agency for Medical Research and Development/ ; }, abstract = {BACKGROUND: The brain-gut-microbiota axis plays a role in the pathogenesis of stress-related disorders such as depression. In this study, we examined the effects of fecal microbiota transplantation (FMT) in mice with antibiotic-treated microbiota depletion.

METHODS: The fecal microbiota was obtained from mice subjected to chronic social defeat stress (CSDS) and control (no CSDS) mice. FMT from these two groups was performed to antibiotic-treated mice. 16S rRNA analysis was performed to examine the composition of gut microbiota. Furthermore, the effects of subdiaphragmatic vagotomy in depression-like phenotypes after ingestion of microbes were examined.

RESULTS: The ingestion of fecal microbiota from CSDS-susceptible mice resulted in an anhedonia-like phenotype, higher plasma levels of interleukin-6 (IL-6), and decreased expression of synaptic proteins in the prefrontal cortex (PFC) in antibiotic-treated mice but not in water-treated mice. 16S rRNA analysis suggested that two microbes (Lactobacillus intestinalis and Lactobacillus reuteri) may be responsible for the anhedonia-like phenotype in antibiotic-treated mice after FMT. Ingestion of these two microbes for 14 days led to depression- and anhedonia-like phenotypes, higher plasma IL-6 levels, and decreased expression of synaptic proteins in the PFC of antibiotic-treated mice. Interestingly, subdiaphragmatic vagotomy significantly blocked the development of behavioral abnormalities, elevation of plasma IL-6 levels, and downregulation of synaptic proteins in the PFC after ingestion of these two microbes.

CONCLUSIONS: These findings suggest that microbiota depletion using an antibiotic cocktail is essential for the development of FMT-induced behavioral changes and that the vagus nerve plays a key role in behavioral abnormalities in antibiotic-treated mice after the ingestion of L. intestinalis and L. reuteri. Therefore, it is likely that the brain-gut-microbiota axis participates in the pathogenesis of depression via the vagus nerve.}, } @article {pmid32785703, year = {2020}, author = {Su, X and Yin, X and Liu, Y and Yan, X and Zhang, S and Wang, X and Lin, Z and Zhou, X and Gao, J and Wang, Z and Zhang, Q}, title = {Gut Dysbiosis Contributes to the Imbalance of Treg and Th17 Cells in Graves' Disease Patients by Propionic Acid.}, journal = {The Journal of clinical endocrinology and metabolism}, volume = {105}, number = {11}, pages = {}, doi = {10.1210/clinem/dgaa511}, pmid = {32785703}, issn = {1945-7197}, abstract = {BACKGROUND: Graves' disease (GD) is a typical organ-specific autoimmune disease. Intestinal flora plays a pivotal role in immune homeostasis and autoimmune disease development. However, the association and mechanism between intestinal flora and GD remain elusive.

OBJECTIVE: To investigate the association and mechanism between intestinal flora and GD.

METHODS: We recruited 58 initially untreated GD patients and 63 healthy individuals in the study. The composition and metabolic characteristics of the intestinal flora in GD patients and the causal relationship between intestinal flora and GD pathogenesis were assessed using 16S rRNA gene sequencing, targeted/untargeted metabolomics, and fecal microbiota transplantation.

RESULTS: The composition, metabolism, and inter-relationships of the intestinal flora were also changed, particularly the significantly reduced short-chain fatty acid (SCFA)-producing bacteria and SCFAs. The YCH46 strain of Bacteroides fragilis could produce propionic acid and increase Treg cell numbers while decreasing Th17 cell numbers. Transplanting the intestinal flora of GD patients significantly increased GD incidence in the GD mouse model. Additionally, there were 3 intestinal bacteria genera (Bacteroides, Alistipes, Prevotella) could distinguish GD patients from healthy individuals with 85% accuracy.

CONCLUSIONS: Gut dysbiosis contributes to a Treg/Th17 imbalance through the pathway regulated by propionic acid and promotes the occurrence of GD, together with other pathogenic factors. Bacteroides, Alistipes, and Prevotella have great potential to serve as adjunct markers for GD diagnosis. This study provided valuable clues for improving immune dysfunction of GD patients using B. fragilis and illuminated the prospects of microecological therapy for GD as an adjunct treatment.}, } @article {pmid32773765, year = {2020}, author = {Zhang, Q and Lu, Q and Luo, Y}, title = {Fecal Microbiota Transplantation and Detection of Prevalence of IgA-Coated Bacteria in the Gut.}, journal = {Journal of visualized experiments : JoVE}, volume = {}, number = {161}, pages = {}, doi = {10.3791/60772}, pmid = {32773765}, issn = {1940-087X}, mesh = {Animals ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunoglobulin A/*metabolism ; Mice ; Prevalence ; }, abstract = {Gut microbiota exert pleiotropic roles in human health and disease. Fecal microbiota transplantation (FMT) is an effective method to investigate the biological function of intestinal bacteria as a whole or at the species level. Several different FMT methods have been published. Here, we present an FMT protocol that successfully depletes gut microbiota in a matter of days, followed by transplantation of fecal microbiota from fresh or frozen donor intestinal contents to conventional mice. Real time-PCR is applied to test the efficacy of bacterial depletion. Sequencing of the 16S ribosomal RNA (rRNA) is then applied to test the relative abundance and identity of gut microbiota in recipient mice. We also present a flow cytometry-based detection method of immunoglobulin A (IgA)-coated bacteria in the gut.}, } @article {pmid32772093, year = {2020}, author = {Sood, A and Singh, A and Mahajan, R and Midha, V and Kaur, K and Singh, D and Bansal, N and Dharni, K}, title = {Clinical Predictors of response to Faecal Microbiota Transplantation in patients with active ulcerative colitis.}, journal = {Journal of Crohn's & colitis}, volume = {}, number = {}, pages = {}, doi = {10.1093/ecco-jcc/jjaa163}, pmid = {32772093}, issn = {1876-4479}, abstract = {BACKGROUND: Fecal Microbiota Transplantation (FMT) has been shown to be effective for induction of remission in patients with active ulcerative colitis (UC). At present, clinical factors impacting the response to FMT in UC remain unclear.

METHODS: Patients with active UC treated with multisession FMT via colonoscopy at weeks 0, 2, 6, 10, 14, 18, and 22, were analysed. Response to FMT was defined as achievement of corticosteroid free clinical remission at week 30. Patient and disease characteristics were evaluated to determine the predictors of response to FMT.

RESULTS: Out of 140 patients with active UC treated with FMT, 93 patients [mean age 34.96±11.27 years, 62.36% males (n=58), mean Mayo clinic score 8.07±2.00] who completed the multi-session FMT protocol were analysed. Fifty-seven (61.29%) patients achieved clinical remission. Younger age (OR for age 0.93, 95% CI 0.89-0.97, p=0.001), moderate (Mayo clinic score 6-9) disease severity (OR 3.01, 95% CI 1.12 to 8.06, p=0.025) and endoscopic Mayo score 2 (OR 5.55, 95% CI 2.18-14.06, p<0.001) were significant predictors of remission on univariate analysis. Younger age, disease extent E2 and endoscopic mayo score 2 (OR 0.925, 95% CI 0.88-0.97, p=0.002; OR 2.89, 95% CI 1.01-8.25, p=0.04 and OR 8.43, 95% CI 2.38-29.84, p=0.001, respectively) were associated with clinical remission on multivariate logistic regression. A mathematical model (nomogram) was developed for estimating the probability of remission with FMT protocol.

CONCLUSION: Younger age, disease extent E2, and endoscopic mayo score 2 significantly predict achievement of clinical remission with FMT in active UC. The prediction model can help in selecting individuals for FMT. Validation in larger cohorts is needed.}, } @article {pmid32769886, year = {2020}, author = {He, Y and Xu, R and Wang, W and Zhang, J and Hu, X}, title = {Probiotics, prebiotics, antibiotic, Chinese herbal medicine, and fecal microbiota transplantation in irritable bowel syndrome: Protocol for a systematic review and network meta-analysis.}, journal = {Medicine}, volume = {99}, number = {32}, pages = {e21502}, doi = {10.1097/MD.0000000000021502}, pmid = {32769886}, issn = {1536-5964}, mesh = {Adolescent ; Adult ; Aged ; Anti-Bacterial Agents/*therapeutic use ; Bayes Theorem ; Drugs, Chinese Herbal/*therapeutic use ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/microbiology/*therapy ; Male ; Middle Aged ; Network Meta-Analysis ; Prebiotics/*administration & dosage ; Probiotics/*therapeutic use ; Randomized Controlled Trials as Topic ; Research Design ; Systematic Reviews as Topic ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disease, with a high global incidence, which seriously influences the quality of life and work efficiency of patients. Extensive research showed that IBS is related to changes in the intestinal microenvironment. The novel treatment strategy targeting the gut microbiota is being actively implemented. Probiotics, antibiotics, prebiotics, fecal microbiota transplantation, and Chinese Herbal Medicine have been proven to be effective in the treatment of IBS, and all have an impact on the intestinal flora of patients. However, these 5 treatments have their own pros and cons and have not been systematically evaluated and compared. Therefore, this study will indirectly compare the safety and effectiveness of these 5 methods in the treatment of IBS through network meta-analysis.

METHODS: The following databases including Embase, Pubmed, Cochrane Central Register of Controlled Trials, Chinese Biomedical Literature Database, WHO International Clinical Trials Registry Platform and ClinicalTrials.gov will be retrieved from inception to June 2020 without language restrictions. Literature selection, data extraction, and bias analysis will be done by 2 researchers. The primary outcome is global symptoms improvement. The secondary outcomes will include individual IBS symptom scores, emotional response, and adverse events. The conventional pair-wise meta-analysis will be performed using Stata V.14.0 and be pooled using a random-effects model. We will use WinBUGS V.1.4.3 (Cambridge, United Kingdom) with a Bayesian hierarchical random-effects model to conduct the network meta-analysis.

RESULTS: This study will provide systematic reviews and indirect network comparison results about treatments of IBS.

CONCLUSIONS: This study will systematically evaluate and compare 5 intestinal flora-related therapies for IBS and to provide an evidence-based medical decision-making basis for clinicians.

TRIAL REGISTRATION NUMBER: INPLASY202050047.}, } @article {pmid32767183, year = {2020}, author = {Tan, GSE and Tay, HL and Tan, SH and Lee, TH and Ng, TM and Lye, DC}, title = {Gut Microbiota Modulation: Implications for Infection Control and Antimicrobial Stewardship.}, journal = {Advances in therapy}, volume = {37}, number = {10}, pages = {4054-4067}, pmid = {32767183}, issn = {1865-8652}, abstract = {The human microbiome comprises a complex ecosystem of microbial communities that exist within the human body, the largest and most diverse of which are found within the human intestine. It has been increasingly implicated in human health and diseases, demonstrably playing a critical role in influencing host immune response, protection against pathogen overgrowth, biosynthesis, and metabolism. As our understanding of the links between the gut microbiota with host immunity and infectious diseases deepens, there is a greater need to incorporate methods of modulating it as a means of therapy or infection prevention in daily clinical practice. Traditional antimicrobial stewardship principles have been evaluated to assess their impact on the gut microbiota diversity and the consequent repercussions, taking into consideration antibiotic pharmacokinetic and pharmacodynamic properties. Novel strategies of selective digestive decontamination and fecal microbiota transplantation to regulate the gut microbiota have also been tested in different conditions with variable results. This review seeks to provide an overview of the available literature on the modulation of the gut microbiota and its implications for infection control and antimicrobial stewardship. With increased understanding, gut microbiota profiling through metataxonomic analysis may provide further insight into modulating microbial communities in the context of infection prevention and control.}, } @article {pmid32765600, year = {2020}, author = {Yang, CQ and Guo, XS and Ji-Li, and Wei, ZB and Zhao, L and Zhao, GT and Sheng, ST}, title = {Rifaximin Improves Visceral Hyperalgesia via TRPV1 by Modulating Intestinal Flora in the Water Avoidance Stressed Rat.}, journal = {Gastroenterology research and practice}, volume = {2020}, number = {}, pages = {4078681}, pmid = {32765600}, issn = {1687-6121}, abstract = {Background: Rifaximin is effective in relieving pain symptoms with IBS patients, although the mechanisms were not clear. The aims of the research were to investigate whether the visceral hyperalgesia was alleviated by rifaximin via TRPV1 channel in rats.

Methods: Rats were subjected to water avoidance stress (WAS) and were pretreated with rifaximin by oral gavage. The visceromotor response to colorectal distension was measured. The changes of TRPV1 in peripheral and central neurons of rats were detected by immunofluorescence, western blot method, and RT-PCR. Bacterial 16S ribosomal DNA in ileal contents was assessed using the Illumina MiSeq platform. The effect of intestinal flora on TRPV1 channel was observed by fecal microbiota transplantation (FMT) methods.

Results: Rifaximin could relieve the visceral hyperalgesia and reduce the TRPV1 expression of neurons and ileum mucosa in rats induced by WAS. The reduced relative abundance of intestinal flora induced by WAS could be partly prevented by rifaximin. The electromyographical activities and immunoreactivity of TRPV1 in rats could be changed after FMT.

Conclusions: Rifaximin could improve visceral hyperalgesia via TRPV1 channels of peripheral and central neurons by modulating intestinal flora in rats.}, } @article {pmid32764526, year = {2020}, author = {Alagna, L and Palomba, E and Mangioni, D and Bozzi, G and Lombardi, A and Ungaro, R and Castelli, V and Prati, D and Vecchi, M and Muscatello, A and Bandera, A and Gori, A}, title = {Multidrug-Resistant Gram-Negative Bacteria Decolonization in Immunocompromised Patients: A Focus on Fecal Microbiota Transplantation.}, journal = {International journal of molecular sciences}, volume = {21}, number = {16}, pages = {}, pmid = {32764526}, issn = {1422-0067}, abstract = {Antimicrobial resistance is an important issue for global health; in immunocompromised patients, such as solid organ and hematological transplant recipients, it poses an even bigger threat. Colonization by multidrug-resistant (MDR) bacteria was acknowledged as a strong risk factor to subsequent infections, especially in individuals with a compromised immune system. A growing pile of studies has linked the imbalance caused by the dominance of certain taxa populating the gut, also known as intestinal microbiota dysbiosis, to an increased risk of MDR bacteria colonization. Several attempts were proposed to modulate the gut microbiota. Particularly, fecal microbiota transplantation (FMT) was successfully applied to treat conditions like Clostridioides difficile infection and other diseases linked to gut microbiota dysbiosis. In this review we aimed to provide a look at the data gathered so far on FMT, focusing on its possible role in treating MDR colonization in the setting of immunocompromised patients and analyzing its efficacy and safety.}, } @article {pmid32764281, year = {2020}, author = {Arias, N and Arboleya, S and Allison, J and Kaliszewska, A and Higarza, SG and Gueimonde, M and Arias, JL}, title = {The Relationship between Choline Bioavailability from Diet, Intestinal Microbiota Composition, and Its Modulation of Human Diseases.}, journal = {Nutrients}, volume = {12}, number = {8}, pages = {}, pmid = {32764281}, issn = {2072-6643}, support = {PSI2017-83893-R//Ministerio de Ciencia e Innovación/ ; PSI2015-73111-EXP//Ministerio de Economía y Competitividad/ ; PSI2017-90806-REDT//Ministerio de Economía y Competitividad/ ; AGL2017-83653R//Ministerio de Economía y Competitividad/ ; IJCI-2017-32156//Ministerio de Ciencia e Innovación/ ; }, abstract = {Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which, upon absorption by the host is converted into trimethylamine-N-oxide (TMAO) in the liver. A high accumulation of both components is related to cardiovascular disease, inflammatory bowel disease, non-alcoholic fatty liver disease, and chronic kidney disease. However, the relationship between the microbiota production of these components and its impact on these diseases still remains unknown. In this review, we will address which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., the genotype) and diet affect TMA production, and the colonization of these microbes and the reversal of dysbiosis as a therapy for these diseases.}, } @article {pmid32762536, year = {2020}, author = {Witkowski, M and Weeks, TL and Hazen, SL}, title = {Gut Microbiota and Cardiovascular Disease.}, journal = {Circulation research}, volume = {127}, number = {4}, pages = {553-570}, pmid = {32762536}, issn = {1524-4571}, support = {P01 HL147823/HL/NHLBI NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; }, abstract = {Fecal microbial community changes are associated with numerous disease states, including cardiovascular disease (CVD). However, such data are merely associative. A causal contribution for gut microbiota in CVD has been further supported by a multitude of more direct experimental evidence. Indeed, gut microbiota transplantation studies, specific gut microbiota-dependent pathways, and downstream metabolites have all been shown to influence host metabolism and CVD, sometimes through specific identified host receptors. Multiple metaorganismal pathways (involving both microbe and host) both impact CVD in animal models and show striking clinical associations in human studies. For example, trimethylamine N-oxide and, more recently, phenylacetylglutamine are gut microbiota-dependent metabolites whose blood levels are associated with incident CVD risks in large-scale clinical studies. Importantly, a causal link to CVD for these and other specific gut microbial metabolites/pathways has been shown through numerous mechanistic animal model studies. Phenylacetylglutamine, for example, was recently shown to promote adverse cardiovascular phenotypes in the host via interaction with multiple ARs (adrenergic receptors)-a class of key receptors that regulate cardiovascular homeostasis. In this review, we summarize recent advances of microbiome research in CVD and related cardiometabolic phenotypes that have helped to move the field forward from associative to causative results. We focus on microbiota and metaorganismal compounds/pathways, with specific attention paid to short-chain fatty acids, secondary bile acids, trimethylamine N-oxide, and phenylacetylglutamine. We also discuss novel therapeutic strategies for directly targeting the gut microbiome to improve cardiovascular outcomes.}, } @article {pmid32760391, year = {2020}, author = {Jouhten, H and Ronkainen, A and Aakko, J and Salminen, S and Mattila, E and Arkkila, P and Satokari, R}, title = {Cultivation and Genomics Prove Long-Term Colonization of Donor's Bifidobacteria in Recurrent Clostridioides difficile Patients Treated With Fecal Microbiota Transplantation.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1663}, pmid = {32760391}, issn = {1664-302X}, abstract = {Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (rCDI) and it's also considered for treating other indications. Metagenomic studies have indicated that commensal donor bacteria may colonize FMT recipients, but cultivation has not been employed to verify strain-level colonization. We combined molecular profiling of Bifidobacterium populations with cultivation, molecular typing, and whole genome sequencing (WGS) to isolate and identify strains that were transferred from donors to recipients. Several Bifidobacterium strains from two donors were recovered from 13 recipients during the 1-year follow-up period after FMT. The strain identities were confirmed by WGS and comparative genomics. Our results show that specific donor-derived bifidobacteria can colonize rCDI patients for at least 1 year, and thus FMT may have long-term consequences for the recipient's microbiota and health. Conceptually, we demonstrate that FMT trials combined with microbial profiling can be used as a platform for discovering and isolating commensal strains with proven colonization capacity for potential therapeutic use.}, } @article {pmid32756350, year = {2020}, author = {Mańkowska-Wierzbicka, D and Stelmach-Mardas, M and Gabryel, M and Tomczak, H and Skrzypczak-Zielińska, M and Zakerska-Banaszak, O and Sowińska, A and Mahadea, D and Baturo, A and Wolko, Ł and Słomski, R and Dobrowolska, A}, title = {The Effectiveness of Multi-Session FMT Treatment in Active Ulcerative Colitis Patients: A Pilot Study.}, journal = {Biomedicines}, volume = {8}, number = {8}, pages = {}, pmid = {32756350}, issn = {2227-9059}, support = {502-01-222-38-000//grant for young scientists from Poznan University of Medical Sciences, Poznan, Poland/ ; }, abstract = {The modification of the microbiome through fecal microbiota transplantation (FMT) is becoming a very promising therapeutic option for inflammatory bowel disease (IBD) patients. Our pilot study aimed to assess the effectiveness of multi-session FMT treatment in active ulcerative colitis (UC) patients. Ten patients with UC were treated with multi-session FMT (200 mL) from healthy donors, via colonoscopy/gastroscopy. Patients were evaluated as follows: at baseline, at week 7, and after 6 months, routine blood tests (including C reactive protein (CRP) and calprotectin) were performed. 16S rRNA gene (V3V4) sequencing was used for metagenomic analysis. The severity of UC was classified based on the Truelove-Witts index. The assessment of microbial diversity showed significant differences between recipients and healthy donors. FMT contributed to long-term, significant clinical and biochemical improvement. Metagenomic analysis revealed an increase in the amount of Lactobacillaceaea, Micrococcaceae, Prevotellaceae, and TM7 phylumsp.oral clone EW055 during FMT, whereas Staphylococcaceae and Bacillaceae declined significantly. A positive increase in the proportion of the genera Bifidobacterium, Lactobacillus, Rothia, Streptococcus, and Veillonella and a decrease in Bacillus, Bacteroides, and Staphylococcus were observed based on the correlation between calprotectin and Bacillus and Staphylococcus; ferritin and Lactobacillus, Veillonella, and Bifidobacterium abundance was indicated. A positive change in the abundance of Firmicutes was observed during FMT and after 6 months. The application of multi-session FMT led to the restoration of recipients' microbiota and resulted in the remission of patients with active UC.}, } @article {pmid32755639, year = {2020}, author = {Holmes, A and Finger, C and Morales-Scheihing, D and Lee, J and McCullough, LD}, title = {Gut dysbiosis and age-related neurological diseases; an innovative approach for therapeutic interventions.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {226}, number = {}, pages = {39-56}, pmid = {32755639}, issn = {1878-1810}, support = {R01 NS077769/NS/NINDS NIH HHS/United States ; R01 NS094543/NS/NINDS NIH HHS/United States ; R01 NS103592/NS/NINDS NIH HHS/United States ; RF1 AG058463/AG/NIA NIH HHS/United States ; }, mesh = {Aging/*pathology ; Brain/pathology ; Dysbiosis/*microbiology/therapy ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Nervous System Diseases/*microbiology/pathology ; }, abstract = {The gut microbiota is a complex ecosystem of bacteria, fungi, and viruses that acts as a critical regulator in microbial, metabolic, and immune responses in the host organism. Imbalances in the gut microbiota, termed "dysbiosis," often induce aberrant immune responses, which in turn disrupt the local and systemic homeostasis of the host. Emerging evidence has highlighted the importance of gut microbiota in intestinal diseases, and more recently, in age-related central nervous systems diseases, for example, stroke and Alzheimer's disease. It is now generally recognized that gut microbiota significantly influences host behaviors and modulates the interaction between microbiota, gut, and brain, via the "microbiota-gut-brain axis." Several approaches have been utilized to reduce age-related dysbiosis in experimental models and in clinical studies. These include strategies to manipulate the microbiome via fecal microbiota transplantation, administration of prebiotics and probiotics, and dietary interventions. In this review, we explore both clinical and preclinical therapies for treating age-related dysbiosis.}, } @article {pmid32755385, year = {2020}, author = {Bernardazzi, C and Xu, H and Tong, H and Laubitz, D and Figliuolo da Paz, V and Curiel, L and Ghishan, FK}, title = {An indisputable role of NHE8 in mucosal protection.}, journal = {American journal of physiology. Gastrointestinal and liver physiology}, volume = {319}, number = {4}, pages = {G421-G431}, pmid = {32755385}, issn = {1522-1547}, support = {R01DK3023890/GF/NIH HHS/United States ; }, mesh = {Animals ; Butyrates/metabolism ; Butyric Acid/administration & dosage ; Colon/microbiology ; Dysbiosis/etiology/microbiology/therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/physiology ; Goblet Cells/drug effects/physiology ; HT29 Cells ; Humans ; Intestinal Mucosa/*physiology ; Lactobacillus/physiology ; Mice ; Mice, Knockout ; Mucins/biosynthesis ; Probiotics/administration & dosage ; Sodium-Hydrogen Exchangers/deficiency/*physiology ; }, abstract = {The loss of the intestinal Na+/H+ exchanger isoform 8 (NHE8) results in an ulcerative colitis-like condition with reduction of mucin production and dysbiosis, indicating that NHE8 plays an important role in intestinal mucosal protection. The aim of this study was to investigate the potential rebalance of the altered microbiota community of NHE8-deficient mice via fecal microbiota transplantation (FMT) and feeding probiotic VSL#3. We also aimed to stimulate mucin production by sodium butyrate administration via enema. Data from 16S rRNA sequencing showed that loss of NHE8 contributes to colonic microbial dysbiosis with reduction of butyrate-producing bacteria. FMT increased bacterial adhesion in the colon in NHE8 knockout (NHE8KO) mice. Periodic-acid Schiff reagent (PAS) stain and quantitative PCR showed no changes in mucin production during FMT. In mice treated with the probiotic VSL#3, a reduction of Lactobacillus and segmented filamentous bacteria (SFB) in NHE8KO mouse colon was detected and an increase in goblet cell theca was observed. In NHE8KO mice receiving sodium butyrate (NaB), 1 mM NaB stimulated Muc2 expression without changing goblet cell theca, but 10 mM NaB induced a significant reduction of goblet cell theca without altering Muc2 expression. Furthermore, 5 mM and 10 mM NaB-treated HT29-MTX cells displayed increased apoptosis, while 0.5 mM NaB stimulated Muc2 gene expression. These data showed that loss of NHE8 leads to dysbiosis with reduction of butyrate-producing bacteria and FMT and VSL#3 failed to rebalance the microbiota in NHE8KO mice. Therefore, FMT, VSL#3, and NaB are not able to restore mucin production in the absence of NHE8 in the intestine.NEW & NOTEWORTHY Loss of Na+/H+ exchanger isoform 8 (NHE8), a Slc9 family of exchanger that contributes to sodium uptake, cell volume regulation, and intracellular pH homeostasis, resulted in dysbiosis with reduction of butyrate-producing bacteria and decrease of Muc2 production in the intestine in mice. Introducing fecal microbiota transplantation (FMT) and VSL#3 in NHE8 knockout (NHE8KO) mice failed to rebalance the microbiota in these mice. Furthermore, administration of FMT, VSL#3, and sodium butyrate was unable to restore mucin production in the absence of NHE8 in the intestine.}, } @article {pmid32751239, year = {2020}, author = {Perillo, F and Amoroso, C and Strati, F and Giuffrè, MR and Díaz-Basabe, A and Lattanzi, G and Facciotti, F}, title = {Gut Microbiota Manipulation as a Tool for Colorectal Cancer Management: Recent Advances in Its Use for Therapeutic Purposes.}, journal = {International journal of molecular sciences}, volume = {21}, number = {15}, pages = {}, pmid = {32751239}, issn = {1422-0067}, support = {IG-2019 22923//Associazione Italiana per la Ricerca sul Cancro/ ; }, abstract = {Colorectal cancer (CRC) is a multifaceted disease influenced by both environmental and genetic factors. A large body of literature has demonstrated the role of gut microbes in promoting inflammatory responses, creating a suitable microenvironment for the development of skewed interactions between the host and the gut microbiota and cancer initiation. Even if surgery is the primary therapeutic strategy, patients with advanced disease or cancer recurrence after surgery remain difficult to cure. Therefore, the gut microbiota has been proposed as a novel therapeutic target in light of recent promising data in which it seems to modulate the response to cancer immunotherapy. The use of microbe-targeted therapies, including antibiotics, prebiotics, live biotherapeutics, and fecal microbiota transplantation, is therefore considered to support current therapies in CRC management. In this review, we will discuss the importance of host-microbe interactions in CRC and how promoting homeostatic immune responses through microbe-targeted therapies may be useful in preventing/treating CRC development.}, } @article {pmid32750174, year = {2020}, author = {Bajaj, JS and Gavis, EA and Fagan, A and Wade, JB and Thacker, LR and Fuchs, M and Patel, S and Davis, B and Meador, J and Puri, P and Sikaroodi, M and Gillevet, PM}, title = {A Randomized Clinical Trial of Fecal Microbiota Transplant for Alcohol Use Disorder.}, journal = {Hepatology (Baltimore, Md.)}, volume = {}, number = {}, pages = {}, doi = {10.1002/hep.31496}, pmid = {32750174}, issn = {1527-3350}, abstract = {BACKGROUND & AIMS: Alcohol use disorder (AUD) is associated with microbial alterations that worsen with cirrhosis. Fecal microbiota transplant (FMT) could be a promising approach.

APPROACH & RESULTS: In this phase 1, double-blind, randomized clinical trial, AUD-related cirrhosis patients with problem drinking (AUDIT-10>8) were randomized 1:1 into receiving one placebo or FMT enema from a donor enriched in Lachnospiraceae and Ruminococcaceae. 6-month safety was the primary outcome. Alcohol craving questionnaire, alcohol consumption (urinary ethylglucuronide/creatinine, Etg), quality of life (QOL), cognition, serum IL-6 and lipopolysaccharide-binding protein (LBP), plasma/stool short-chain fatty acids (SCFA) and stool microbiota were tested at baseline and day 15. A 6-month follow-up with serious adverse events (SAE) analysis was performed. 20 patients with AUD-related cirrhosis [65±6.4 years, all men, MELD 8.9±2.7] with similar demographics, cirrhosis and AUD severity were included. Craving reduced significantly in 90% of FMT versus 30% in placebo at day15(p=0.02) with lower urinary Etg (p=0.03), improved cognition and psychosocial QOL. There was reduction in serum IL-6 and LBP and increased butyrate/isobutyrate compared to baseline in FMT but not placebo. Microbial diversity increased with higher Ruminococcaceae and other SCFA producing taxa post-FMT but not placebo, which were linked with SCFA levels. At 6 months, patients with any SAEs (8 vs 2, p=0.02), AUD-related SAEs (7 vs 1, p=0.02) and SAEs/patient [median(IQR),1.5(1.25) vs 0(0.25) in FMT,p=0.02] were higher in placebo versus FMT.

CONCLUSIONS: This phase 1 trial shows that FMT is safe and associated with short-term reduction in alcohol craving and consumption with favorable microbial changes versus placebo in patients with alcohol-related cirrhosis with alcohol misuse. There was also a reduction in AUD-related events over 6 months in patients assigned to FMT.}, } @article {pmid32742991, year = {2020}, author = {Yue, YY and Fan, XY and Zhang, Q and Lu, YP and Wu, S and Wang, S and Yu, M and Cui, CW and Sun, ZR}, title = {Bibliometric analysis of subject trends and knowledge structures of gut microbiota.}, journal = {World journal of clinical cases}, volume = {8}, number = {13}, pages = {2817-2832}, pmid = {32742991}, issn = {2307-8960}, abstract = {BACKGROUND: Gut microbiota is an emerging field of research, with related research having breakthrough development in the past 15 years. Bibliometric analysis can be applied to analyze the evolutionary trends and emerging hotspots in this field.

AIM: To study the subject trends and knowledge structures of gut microbiota related research fields from 2004 to 2018.

METHODS: The literature data on gut microbiota were identified and downloaded from the PubMed database. Through biclustering analysis, strategic diagrams, and social network analysis diagrams, the main trend and knowledge structure of research fields concerning gut microbiota were analyzed to obtain and compare the research hotspots in each period.

RESULTS: According to the strategic coordinates and social relationship network map, Clostridium Infections/microbiology, Clostridium Infections/therapy, RNA, Ribosomal, 16S/genetics, Microbiota/genetics, Microbiota/immunology, Dysbiosis/immunology, Infla-mmation/immunology, Fecal Microbiota Transplantation/methods, Fecal Microbiota Transplantation can be used as an emerging research hotspot in the past 5 years (2014-2018).

CONCLUSION: Some subjects were not yet fully studied according to the strategic coordinates; and the emerging hotspots in the social network map can be considered as directions of future research.}, } @article {pmid32742177, year = {2020}, author = {Abhyankar, D and McKee, KT and Vukojevic, P}, title = {Gut Microbiota and Response to Immunotherapeutic Drugs in Oncology: More Questions Than Answers.}, journal = {Clinical Medicine Insights. Oncology}, volume = {14}, number = {}, pages = {1179554920933868}, pmid = {32742177}, issn = {1179-5549}, abstract = {Immuno-oncology drugs (IODs) have revolutionized the treatment of some cancers. Although IODs are enabling some patients with cancer to become long-time survivors, only 30% to 40% respond to these drugs. There is experimental and clinical evidence that the gut microbiome may play a role in IOD response, leading to speculation that manipulation of the gut microenvironment might improve the response rate to IODs. We review the evidence relating to how gut microorganisms may affect response to IODs and discuss the implications of targeting the microbiome to improve IOD response, including the challenges to refine and translate the findings to practical clinical use.}, } @article {pmid32739967, year = {2020}, author = {Guery, B and Barbut, F and Tschudin-Sutter, S}, title = {Diagnostic and therapy of severe Clostridioides difficile infections in the ICU.}, journal = {Current opinion in critical care}, volume = {26}, number = {5}, pages = {450-458}, doi = {10.1097/MCC.0000000000000753}, pmid = {32739967}, issn = {1531-7072}, mesh = {Anti-Bacterial Agents/therapeutic use ; Clostridioides ; *Clostridioides difficile ; *Clostridium Infections/diagnosis/therapy ; Humans ; Intensive Care Units ; }, abstract = {PURPOSE OF REVIEW: The purpose of the review is to provide all the recent data focusing on the diagnostic and treatment of Clostridioides difficile infection in patients admitted in the ICU.

RECENT FINDINGS: In the ICU, diagnosis remains complicated with a large number of alternative diagnosis. The treatment classically relies on vancomycin but fidaxomicin and fecal microbiota transplantation are now potential solutions in selected indications.

SUMMARY: Data on ICU-related CDI remain limited and conflicting. To date, there is no unique and simple way to obtain a diagnosis for CDI, the combination of clinical signs and a two-step testing algorithm remains the recommended gold-standard. Two molecules can be proposed for first line treatment: vancomycin and fidaxomicin. Although metronidazole may still be discussed as a treatment option for mild CDI in low-risk patients, its use for ICU-patients does not seem reasonable. Several reports suggest that fecal microbiota transplantation could be discussed, as it is well tolerated and associated with a high rate of clinical cure. CDI is a dynamic and active area of research with new diagnostic techniques, molecules, and management concepts likely changing our approach to this old disease in the near future.}, } @article {pmid32738249, year = {2020}, author = {Allegretti, JR and Kelly, CR and Grinspan, A and Mullish, BH and Kassam, Z and Fischer, M}, title = {Outcomes of Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Diseases and Recurrent Clostridioides difficile Infection.}, journal = {Gastroenterology}, volume = {159}, number = {5}, pages = {1982-1984}, doi = {10.1053/j.gastro.2020.07.045}, pmid = {32738249}, issn = {1528-0012}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, } @article {pmid32737354, year = {2020}, author = {Wasinger, VC and Lu, K and Yau, YY and Nash, J and Lee, J and Chang, J and Paramsothy, S and Kaakoush, NO and Mitchell, HM and Leong, RWL}, title = {Spp24 is associated with endocytic signalling, lipid metabolism, and discrimination of tissue integrity for 'leaky-gut' in inflammatory bowel disease.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {12932}, pmid = {32737354}, issn = {2045-2322}, mesh = {Adolescent ; Adult ; Aged ; Biomarkers ; Colitis, Ulcerative/*blood/pathology/therapy ; *Endocytosis ; Fecal Microbiota Transplantation ; Female ; Humans ; Intestinal Mucosa/*metabolism/pathology ; *Lipid Metabolism ; Male ; Middle Aged ; Phosphoproteins/*blood ; *Signal Transduction ; }, abstract = {Epithelial barrier injury allows contaminants to cross-over into the blood stream and trigger an inflammatory response, contributing to inflammatory bowel disease (IBD). Currently there is no single test that can reliably diagnose intestinal mucosal barrier function or measure impaired epithelial cell integrity associated with increasing permeability. Here, we assess the association between serum proteins and small intestinal permeability as detected by confocal laser endomicroscopy (CLE); in particular the known IBD marker-secreted phosphoprotein 24 (SPP24) and its binding partners; and use developed monoclonal antibodies to assess the role of SPP24 in mucosal healing. Sera were obtained from 28 IBD patients and non-IBD controls undergoing CLE with scores ranging from low to high permeability, as well as active ulcerative colitis from 53 patients undergoing fecal microbiota transplant therapy (FMT). Higher permeability associated with altered lipid metabolism, heightened innate immune response and junctional protein signalling in UC patients. A correlation between increasing leak and SPP24 peptide was observed. There is a strong indication of the novel role of SPP24 in gut barrier dysfunction particularly in ulcerative colitis. Its correlation to the established CLE for monitoring permeability has the potential to provide a blood based parallel to monitor and guide therapy more readily across a broad spectrum of illnesses for which 'leak' dominates the pathology.}, } @article {pmid32729978, year = {2020}, author = {Lu, JF and Zhu, MQ and Zhang, H and Liu, H and Xia, B and Wang, YL and Shi, X and Peng, L and Wu, JW}, title = {Neohesperidin attenuates obesity by altering the composition of the gut microbiota in high-fat diet-fed mice.}, journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology}, volume = {34}, number = {9}, pages = {12053-12071}, doi = {10.1096/fj.201903102RR}, pmid = {32729978}, issn = {1530-6860}, support = {81670758//National Natural Science Foundation of China (NSFC)/ ; 81970713//National Natural Science Foundation of China (NSFC)/ ; 7182147//Beijing Municipal Natural Science Foundation/ ; 2018-2-4062//Capital's Funds for Health Improvement and Research/ ; 2018RC310023//Fundamental Research Funds of the Chinese Academy of Medical Science/ ; //Programs for Shaanxi Science & Technology: 2020NY-01/ ; //Special Talent Recruitment Fund of China to JWW/ ; }, abstract = {Obesity and related metabolic disorders are associated with intestinal microbiota dysbiosis, disrupted intestinal barrier, and chronic inflammation. Neohesperidin (Neo), a natural polyphenol abundant in citrus fruits, is known for its preventative and therapeutic effects on numerous diseases. Here, we report that Neo administration attenuates weight gain, low-grade inflammation, and insulin resistance in mice fed high-fat diet (HFD). Also, Neo administration substantially restores gut barrier damage, metabolic endotoxemia, and systemic inflammation. Sequencing of 16S rRNA genes in fecal samples revealed that Neo administration reverses HFD-induced intestinal microbiota dysbiosis: an increase in the diversity of gut microbiota and alteration in the composition of intestinal microbiota (particularly in the relative abundances of Bacteroidetes and Firmicutes). Furthermore, systemic antibiotic treatment abolishes the beneficial effects of Neo in body weight control, suggesting that the effect of Neo on obesity attenuation largely depends on the gut microbiota. More importantly, we demonstrate that the impact of Neo on the regulation of obesity could be transferred from Neo-treated mice to HFD-fed mice via fecal microbiota transplantation. Collectively, our data highlight the efficacy of Neo as a prebiotic agent for attenuating obesity, implying a potential mechanism for gut microbiota mediated the beneficial effect of Neo.}, } @article {pmid32727864, year = {2020}, author = {Bhattacharjee, D and Seekatz, AM}, title = {Dilution as a Solution: Targeting Microbial Populations with a Simplified Dilution Strategy.}, journal = {mSphere}, volume = {5}, number = {4}, pages = {}, pmid = {32727864}, issn = {2379-5042}, mesh = {*Clostridioides difficile ; *Clostridium Infections ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {The gut microbiota is an integral part of maintaining resistance against infection by Clostridioides (Clostridium) difficile, a pathogen of increasing concern in both health care and community settings. The recent article by J. M. Auchtung, E. C. Preisner, J. Collins, A. I. Lerma, and R. A. Britton (mSphere 5:e00387-20, 2020, https://doi.org/10.1128/mSphere.00387-20) demonstrates an innovative approach to identify microbes that inhibit C. difficile by employing a dilution scheme to test different microbial mixtures in vitro and in vivo This type of approach can advance the identification and validation of specific microbes that elicit functions of interest for many conditions involving the microbiota, of which the complexity and variability can often complicate causality.}, } @article {pmid32727857, year = {2020}, author = {Auchtung, JM and Preisner, EC and Collins, J and Lerma, AI and Britton, RA}, title = {Identification of Simplified Microbial Communities That Inhibit Clostridioides difficile Infection through Dilution/Extinction.}, journal = {mSphere}, volume = {5}, number = {4}, pages = {}, pmid = {32727857}, issn = {2379-5042}, support = {R01 AI123278/AI/NIAID NIH HHS/United States ; }, abstract = {The gastrointestinal microbiome plays an important role in limiting susceptibility to infection with Clostridioides difficile To better understand the ecology of bacteria important for C. difficile colonization resistance, we developed an experimental platform to simplify complex communities of fecal bacteria through dilution and rapidly screen for their ability to resist C. difficile colonization after challenge, as measured by >100-fold reduction in levels of C. difficile in challenged communities. We screened 76 simplified communities diluted from cultures of six fecal donors and identified 24 simplified communities that inhibited C. difficile colonization in vitro Sequencing revealed that simplified communities were composed of 19 to 67 operational taxonomic units (OTUs) and could be partitioned into four distinct community types. One simplified community could be further simplified from 56 to 28 OTUs through dilution and retain the ability to inhibit C. difficile We tested the efficacy of seven simplified communities in a humanized microbiota mouse model. We found that four communities were able to significantly reduce the severity of the initial C. difficile infection and limit susceptibility to disease relapse. Analysis of fecal microbiomes from treated mice demonstrated that simplified communities accelerated recovery of indigenous bacteria and led to stable engraftment of 19 to 22 OTUs from simplified communities. Overall, the insights gained through the identification and characterization of these simplified communities increase our understanding of the microbial dynamics of C. difficile infection and recovery.IMPORTANCEClostridioides difficile is the leading cause of antibiotic-associated diarrhea and a significant health care burden. Fecal microbiota transplantation is highly effective at treating recurrent C. difficile disease; however, uncertainties about the undefined composition of fecal material and potential long-term unintended health consequences remain. These concerns have motivated studies to identify new communities of microbes with a simpler composition that will be effective at treating disease. This work describes a platform for rapidly identifying and screening new simplified communities for efficacy in treating C. difficile infection. Four new simplified communities of microbes with potential for development of new therapies to treat C. difficile disease are identified. While this platform was developed and validated to model infection with C. difficile, the underlying principles described in the paper could be easily modified to develop therapeutics to treat other gastrointestinal diseases.}, } @article {pmid32726437, year = {2020}, author = {Trivedi, R and Barve, K}, title = {Gut microbiome a promising target for management of respiratory diseases.}, journal = {The Biochemical journal}, volume = {477}, number = {14}, pages = {2679-2696}, doi = {10.1042/BCJ20200426}, pmid = {32726437}, issn = {1470-8728}, mesh = {Anti-Bacterial Agents/therapeutic use ; Asthma/etiology/microbiology ; Cystic Fibrosis/microbiology ; Dysbiosis/complications ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome/physiology ; Humans ; Lab-On-A-Chip Devices ; Lung Diseases/drug therapy/*etiology ; Prebiotics/administration & dosage ; Probiotics/administration & dosage/*therapeutic use ; Respiratory Tract Infections/drug therapy/*etiology ; Spray Drying ; Synbiotics/administration & dosage ; }, abstract = {The intestinal microbial flora has risen to be one of the important etiological factors in the development of diseases like colorectal cancer, obesity, diabetes, inflammatory bowel disease, anxiety and Parkinson's. The emergence of the association between bacterial flora and lungs led to the discovery of the gut-lung axis. Dysbiosis of several species of colonic bacteria such as Firmicutes and Bacteroidetes and transfer of these bacteria from gut to lungs via lymphatic and systemic circulation are associated with several respiratory diseases such as lung cancer, asthma, tuberculosis, cystic fibrosis, etc. Current therapies for dysbiosis include use of probiotics, prebiotics and synbiotics to restore the balance between various species of beneficial bacteria. Various approaches like nanotechnology and microencapsulation have been explored to increase the permeability and viability of probiotics in the body. The need of the day is comprehensive study of mechanisms behind dysbiosis, translocation of microbiota from gut to lung through various channels and new technology for evaluating treatment to correct this dysbiosis which in turn can be used to manage various respiratory diseases. Microfluidics and organ on chip model are emerging technologies that can satisfy these needs. This review gives an overview of colonic commensals in lung pathology and novel systems that help in alleviating symptoms of lung diseases. We have also hypothesized new models to help in understanding bacterial pathways involved in the gut-lung axis as well as act as a futuristic approach in finding treatment of respiratory diseases caused by dysbiosis.}, } @article {pmid32724908, year = {2020}, author = {Zukauckas, K and Vandiver, J and Biehle, L}, title = {It's time to rethink your approach to C diff infection.}, journal = {The Journal of family practice}, volume = {69}, number = {6}, pages = {293-300}, pmid = {32724908}, issn = {1533-7294}, mesh = {Abdominal Pain/etiology/physiopathology ; Anti-Bacterial Agents/therapeutic use ; Clostridioides difficile/drug effects/*pathogenicity ; Clostridium Infections/*drug therapy ; Cross Infection ; Diarrhea/etiology/physiopathology ; Female ; Humans ; Middle Aged ; Risk Factors ; Vancomycin/therapeutic use ; }, abstract = {Metronidazole is no longer the drug of choice for first-line therapy. And fecal microbiota transplantation has proven effective for certain patients.}, } @article {pmid32718072, year = {2020}, author = {Wagner-Skacel, J and Dalkner, N and Moerkl, S and Kreuzer, K and Farzi, A and Lackner, S and Painold, A and Reininghaus, EZ and Butler, MI and Bengesser, S}, title = {Sleep and Microbiome in Psychiatric Diseases.}, journal = {Nutrients}, volume = {12}, number = {8}, pages = {}, pmid = {32718072}, issn = {2072-6643}, abstract = {OBJECTIVES: Disturbances in the gut-brain barrier play an essential role in the development of mental disorders. There is considerable evidence showing that the gut microbiome not only affects digestive, metabolic and immune functions of the host but also regulates host sleep and mental states through the microbiota-gut-brain axis. The present review summarizes the role of the gut microbiome in the context of circadian rhythms, nutrition and sleep in psychiatric disorders.

METHODS: A PubMed search (studies published between April 2015-April 2020) was conducted with the keywords: "sleep, microbiome and psychiatry"; "sleep, microbiome and depression"; "sleep, microbiome and bipolar disorder", "sleep, microbiome and schizophrenia", "sleep, microbiome and anorexia nervosa", "sleep, microbiome and substance use disorder", "sleep, microbiome and anxiety"; "clock gene expression and microbiome", "clock gene expression and nutrition". Only studies investigating the relationship between sleep and microbiome in psychiatric patients were included in the review.

RESULTS: Search results yielded two cross-sectional studies analyzing sleep and gut microbiome in 154 individuals with bipolar disorder and one interventional study analyzing the effect of fecal microbiota transplantation in 17 individuals with irritable bowel syndrome on sleep. In patients with bipolar disorder, Faecalibacterium was significantly associated with improved sleep quality scores and a significant correlation between Lactobacillus counts and sleep.

CONCLUSION: Translational research on this important field is limited and further investigation of the bidirectional pathways on sleep and the gut microbiome in mood disorders is warranted.}, } @article {pmid32717434, year = {2020}, author = {Murthy, HS and Gharaibeh, RZ and Al-Mansour, Z and Kozlov, A and Trikha, G and Newsome, RC and Gauthier, J and Farhadfar, N and Wang, Y and Kelly, DL and Lybarger, J and Jobin, C and Wang, GP and Wingard, JR}, title = {Baseline Gut Microbiota Composition Is Associated with Major Infections Early after Hematopoietic Cell Transplantation.}, journal = {Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation}, volume = {26}, number = {11}, pages = {2001-2010}, doi = {10.1016/j.bbmt.2020.07.023}, pmid = {32717434}, issn = {1523-6536}, abstract = {Infection is a major cause of morbidity and mortality after hematopoietic cell transplantation (HCT). Gut microbiota (GM) composition and metabolites provide colonization resistance against dominance of potential pathogens, and GM dysbiosis following HCT can be deleterious to immune reconstitution. Little is known about the composition, diversity, and evolution of GM communities in HCT patients and their association with subsequent febrile neutropenia (FN) and infection. Identification of markers before HCT that predict subsequent infection could be useful in developing individualized antimicrobial strategies. Fecal samples were collected prospectively from 33 HCT recipients at serial time points: baseline, post-conditioning regimen, neutropenia onset, FN onset (if present), and hematologic recovery. GM was assessed by 16S rRNA sequencing. FN and major infections (ie, bloodstream infection, typhlitis, invasive fungal infection, pneumonia, and Clostridium difficile enterocolitis) were identified. Significant shifts in GM composition and diversity were observed during HCT, with the largest alterations occurring after initiation of antibiotics. Loss of diversity persisted without a return to baseline at hematologic recovery. GM in patients with FN was enriched in Mogibacterium, Bacteroides fragilis, and Parabacteroides distasonis, whereas increased abundance of Prevotella, Ruminococcus, Dorea, Blautia, and Collinsella was observed in patients without fever. A baseline protective GM profile (BPGMP) was predictive of protection from major infection. The BPGMP was associated with subsequent major infections with 77% accuracy and an area under the curve of 79%, with sensitivity, specificity, and positive and negative predictive values of 0.71, 0.91, 0.77, and 0.87, respectively. Our data show that large shifts in GM composition occur early after HCT, and differences in baseline GM composition are associated with the development of subsequent major infections.}, } @article {pmid32713786, year = {2021}, author = {Chiu, CH and Tsai, MC and Cheng, HT and Le, PH and Kuo, CJ and Chiu, CT}, title = {Fecal microbiota transplantation and donor screening for Clostridioides difficile infection during COVID-19 pandemic.}, journal = {Journal of the Formosan Medical Association = Taiwan yi zhi}, volume = {120}, number = {2}, pages = {791-793}, pmid = {32713786}, issn = {0929-6646}, mesh = {*COVID-19 ; Clostridioides difficile/*isolation & purification ; *Donor Selection ; *Fecal Microbiota Transplantation ; Humans ; Pandemics ; }, } @article {pmid32712721, year = {2021}, author = {Reyes-Castillo, Z and Valdés-Miramontes, E and Llamas-Covarrubias, M and Muñoz-Valle, JF}, title = {Troublesome friends within us: the role of gut microbiota on rheumatoid arthritis etiopathogenesis and its clinical and therapeutic relevance.}, journal = {Clinical and experimental medicine}, volume = {21}, number = {1}, pages = {1-13}, pmid = {32712721}, issn = {1591-9528}, abstract = {The role of gut microbiota on immune regulation and the development of autoimmune diseases such as rheumatoid arthritis (RA) is an emerging research topic. Multiple studies have demonstrated alterations on gut microbiota composition and/or function (referred to as dysbiosis) both in early and established RA patients. Still, research delineating the molecular mechanisms by which gut microorganisms induce the loss of immune tolerance or contribute to disease progression is scarce. Available data indicate that gut microbiota alterations are involved in RA autoimmune response by several mechanisms including the post-translational modification of host proteins, molecular mimicry between bacterial and host epitopes, activation of immune system and polarization toward inflammatory phenotypes, as well as induction of intestinal permeability. Therefore, in this review we analyze recent clinical and molecular evidence linking gut microbiota with the etiopathogenesis of RA. The potential of the gut microbiota as a diagnostic or severity biomarker is discussed, as well as the opportunity areas for the development of complementary therapeutic strategies based on the modulation of gut microbiota in the rheumatic patient.}, } @article {pmid32711581, year = {2020}, author = {Zhang, P and Liu, J and Xiong, B and Zhang, C and Kang, B and Gao, Y and Li, Z and Ge, W and Cheng, S and Hao, Y and Shen, W and Yu, S and Chen, L and Tang, X and Zhao, Y and Zhang, H}, title = {Microbiota from alginate oligosaccharide-dosed mice successfully mitigated small intestinal mucositis.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {112}, pmid = {32711581}, issn = {2049-2618}, abstract = {BACKGROUND: The increasing incidence of cancer and intestinal mucositis induced by chemotherapeutics are causing worldwide concern. Many approaches such as fecal microbiota transplantation (FMT) have been used to minimize mucositis. However, it is still unknown whether FMT from a donor with beneficial gut microbiota results in more effective intestinal function in the recipient. Recently, we found that alginate oligosaccharides (AOS) benefit murine gut microbiota through increasing "beneficial" microbes to rescue busulfan induced mucositis.

RESULTS: In the current investigation, FMT from AOS-dosed mice improved small intestine function over FMT from control mice through the recovery of gene expression and an increase in the levels of cell junction proteins. FMT from AOS-dosed mice showed superior benefits over FMT from control mice on recipient gut microbiotas through an increase in "beneficial" microbes such as Leuconostocaceae and recovery in blood metabolome. Furthermore, the correlation of gut microbiota and blood metabolites suggested that the "beneficial" microbe Lactobacillales helped with the recovery of blood metabolites, while the "harmful" microbe Mycoplasmatales did not.

CONCLUSION: The data confirm our hypothesis that FMT from a donor with superior microbes leads to a more profound recovery of small intestinal function. We propose that gut microbiota from naturally produced AOS-treated donor may be used to prevent small intestinal mucositis induced by chemotherapeutics or other factors in recipients. Video Abstract.}, } @article {pmid32702186, year = {2020}, author = {Zhao, D and Dai, W and Tao, H and Zhuang, W and Qu, M and Chang, YN}, title = {Polysaccharide isolated from Auricularia auricular-judae (Bull.) prevents dextran sulfate sodium-induced colitis in mice through modulating the composition of the gut microbiota.}, journal = {Journal of food science}, volume = {85}, number = {9}, pages = {2943-2951}, doi = {10.1111/1750-3841.15319}, pmid = {32702186}, issn = {1750-3841}, mesh = {Animals ; Basidiomycota/*chemistry ; Colitis, Ulcerative/chemically induced/*microbiology/*prevention & control ; Dextran Sulfate/adverse effects ; Disease Models, Animal ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects ; Humans ; Mice ; Mice, Inbred C57BL ; Plant Extracts/*administration & dosage/isolation & purification ; Polysaccharides/*administration & dosage/isolation & purification ; }, abstract = {Inflammatory bowel disease (IBD) is a chronic intestinal disease, which was commonly found in westerners whereas is increasingly prevalent in Asia because of the changing eating habits. In previous research, we found that a water-soluble polysaccharide isolated from Auricularia auricular-judae (Bull.)-a kind of edible mushroom (Aap)-is composed of β-1,3 glycosidic bonds, which is regarded as therapeutic or protective substance in enteritis. We therefore aimed to find the preventing effect of Aap on IBD. Here, we reported that pre-administration of Aap not only ameliorated weight loss, colon damage, and mucosal inflammation in colitis mice, but also prevented the damage of intestinal barrier by reducing the D-lactic acid and diamine oxidase level in plasma. Through high-throughput sequencing, we found that Aap changed gut microbiota composition. Furthermore, the preventing effect was transmissible via horizontal feces transfer from Aap-treated mice to normal mice. Our results indicated that oral administration of Aap is a promising protective substance of IBD. PRACTICAL APPLICATION: Our study proved that Auricularia auricula polysaccharide had substantial preventing effect on DSS-induced colitis in mice. This research might lay the theoretical foundation and technical support for the development of related functional foods. People could also enhance their gut immunity by eating Auricularia auricular in their daily life. Auricularia auricular as a highly nutritious agricultural product showed the broad significance in nutrition and food function.}, } @article {pmid32701563, year = {2020}, author = {Tariq, R and Saha, S and Solanky, D and Pardi, DS and Khanna, S}, title = {Predictors and Management of Failed Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.}, journal = {Journal of clinical gastroenterology}, volume = {}, number = {}, pages = {}, doi = {10.1097/MCG.0000000000001398}, pmid = {32701563}, issn = {1539-2031}, abstract = {BACKGROUND AND GOALS: Clostridioides difficile infection (CDI) recurs in 10% to 15% after fecal microbiota transplantation (FMT). We identify predictors, and describe management and outcome of patients with recurrent CDI after FMT in a predominantly outpatient cohort.

METHODS: A nested case-control study of patients undergoing FMT for recurrent CDI from August 2012 to January 2017 was performed. FMT failure was defined as recurrent diarrhea with positive C. difficile stool test during follow-up (≥2 mo). Controls (patients without FMT failures) were matched to cases 1:1 for sex and timing of FMT±1 month.

RESULTS: Overall, 522 patients underwent FMT; 70 [13.4%; median age 53.8 years (range, 18 to 89 y), 54.3% females] recurred within a median 5.6 months (range, 0.2 to 34.9 mo). Number of prior CDI episodes, prior CDI treatment, and prior CDI-related hospitalizations were similar in cases and controls. Systemic antibiotics after FMT (54.3% vs. 21.4%, P<0.0001), inflammatory bowel disease (IBD) (34.3% vs. 15.7%, P=0.01), pseudomembranes at FMT (4.3% vs. 0%, P=0.03), and poor bowel preparation (68.5% vs. 31.4%, P=0.01) were associated with FMT failure. On multivariate analysis, IBD [odds ratio (OR) 4.34; 95% confidence interval (CI), 1.24-15.15], systemic antibiotics (OR 7.39; 95% CI, 3.02-18.07), and poor bowel preparation (OR 3.84; 95% CI, 1.59-9.28) predicted FMT failure with an area under the curve of 0.78. Among FMT failures, 37 (52.8%) were managed with antibiotics, 32 (45.7%) with repeat FMT after antibiotics and 1 with colectomy.

CONCLUSIONS: Use of systemic antibiotics, IBD, and poor bowel preparation predict FMT failure. Patients with FMT failure can be managed with antibiotics and/or repeat FMT.}, } @article {pmid32697259, year = {2020}, author = {Jing, N and Liu, X and Jin, M and Yang, X and Hu, X and Li, C and Zhao, K}, title = {Fubrick tea attenuates high-fat diet induced fat deposition and metabolic disorder by regulating gut microbiota and caffeine metabolism.}, journal = {Food & function}, volume = {11}, number = {8}, pages = {6971-6986}, doi = {10.1039/d0fo01282c}, pmid = {32697259}, issn = {2042-650X}, abstract = {Fubrick tea aqueous extract (FTEs) has been reported to improve lipid metabolism and gut microbiota communities in mice and humans. However, it is still unclear how FTEs prevents obesity through gut microbiota, and whether some other regulatory mechanisms are involved in the process. Here, we found that FTEs supplementation effectively alleviated the body weight gain, visceral fat accumulation, dyslipidemia, and impaired glucose tolerance induced by a high-fat diet (HFD), and fecal microbiota transplantation (FMT) from FTEs-treated mice showed similar protective effects as FTEs supplementation in mice fed with a HFD. The results confirmed that gut microbiota played key roles in attenuating HFD-induced fat deposition and metabolic disorder. In particular, FTEs reversed HFD-induced gut microbiota dysbiosis via increasing the relative abundances of Bacteroides, Adlercreutzia, Alistipes, Parabacteroides, and norank_f_Lachnospiraceae, and reducing that of Staphylococcus. Interestingly, FTEs could still alleviate HFD-induced lipid accumulation in mice treated with antibiotics, which had increased relative abundances of Bacteroidetes, Bacteroides, and Bacteroides_uniformis sp. In addition, supplementation with FTEs also modified the serum metabolome, especially the "caffeine metabolism" pathway. Furthermore, FTEs supplementation increased the concentrations of caffeine, theophylline, and theobromine in serum, which were positively correlated with an abundance of norank_f_Lachnospiraceae. Overall, FTEs exerts beneficial effects against obesity induced by HFD, and the underlying mechanism is partially related to the reprogramming of intestinal microbiota, while the metabolism of caffeine in FTEs also played an important role in the process. This study provides a theoretical basis for the further study of the anti-obesity effects of FTEs and the consideration of gut microbiota as a potential target for the treatment of obesity induced by a HFD.}, } @article {pmid32690139, year = {2020}, author = {Halsey, T and Ologun, G and Wargo, J and Jenq, RR}, title = {Uncovering the role of the gut microbiota in immune checkpoint blockade therapy: A mini-review.}, journal = {Seminars in hematology}, volume = {57}, number = {1}, pages = {13-18}, pmid = {32690139}, issn = {1532-8686}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 HL124112/HL/NHLBI NIH HHS/United States ; T32 CA009599/CA/NCI NIH HHS/United States ; }, abstract = {In recent years, the microbiota has been implicated as a key factor associated with both response and toxicity from immune checkpoint blockade therapy. Numerous studies have been published that specifically highlight the importance of the microbiome as a distinct influencer of anti-PD-1/PD-L1 and anti-CTLA-4 activity in cancer patients, but a full understanding of mechanisms behind these interactions has yet to be achieved. With greater insight into how the microbiome can modulate immune checkpoint blockade comes the potential to target the microbiome to improve response rates and minimize toxicities. This mini-review looks at noteworthy studies that have explored the relationship between the microbiome and immune checkpoint blockade response and toxicity in both preclinical and clinical studies, with an emphasis on current hypotheses regarding mechanisms of action and potential microbiome-targeted therapeutic strategies under development.}, } @article {pmid32687975, year = {2020}, author = {Siddiqui, MT and Cresci, GAM}, title = {Microbiota reprogramming for treatment of alcohol-related liver disease.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {226}, number = {}, pages = {26-38}, pmid = {32687975}, issn = {1878-1810}, support = {R00 AA023266/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Disease Models, Animal ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Liver Diseases, Alcoholic/physiopathology/*therapy ; Probiotics ; }, abstract = {In the past decade knowledge has expanded regarding the importance of the gut microbiota in maintaining intestinal homeostasis and overall health. During this same time, we have also gained appreciation for the role of the gut-liver axis in the development of liver diseases. Alcohol overconsumption is one of the leading causes of liver failure globally. However, not all people with alcohol use disorder progress to advanced stages of liver disease. With advances in technology to investigate the gut microbiome and metabolome, we are now beginning to delineate alcohol's effects on the gut microbiome in relation to liver disease. This review presents our current understanding on the role of the gut microbiota during alcohol exposure, and various therapeutic attempts that have been made to reprogram the gut microbiota with the goal of alleviating alcoholic-related liver disease.}, } @article {pmid32686598, year = {2020}, author = {Zhu, Z and Huang, J and Li, X and Xing, J and Chen, Q and Liu, R and Hua, F and Qiu, Z and Song, Y and Bai, C and Mo, YY and Zhang, Z}, title = {Gut microbiota regulate tumor metastasis via circRNA/miRNA networks.}, journal = {Gut microbes}, volume = {12}, number = {1}, pages = {1788891}, pmid = {32686598}, issn = {1949-0984}, abstract = {BACKGROUND: Increasing evidence indicates that gut microbiota plays an important role in cancer progression. However, the underlying mechanism remains largely unknown. Here, we report that broad-spectrum antibiotics (ABX) treatment leads to enhanced metastasis by the alteration of gut microbiome composition.

METHODS: Cancer LLC and B16-F10 cell metastasis mouse models, and microarray/RNA sequencing analysis were used to reveal the regulatory functions of microbiota-mediated circular RNA (circRNA)/microRNA (miRNA) networks that may contribute to cancer metastasis.

RESULTS: The specific pathogen-free (SPF) mice with ABX treatment demonstrated enhanced lung metastasis. Fecal microbiota transplantation (FMT) from SPF mice or Bifidobacterium into germ-free mice significantly suppressed lung metastasis. Mechanistically, gut microbiota impacts circRNA expression to regulate levels of corresponding miRNAs. Specifically, such modulations of gut microbiota inhibit mmu_circ_0000730 expression in an IL-11-dependent manner. Bioinformatics analysis combined with luciferase reporter assays revealed reciprocal repression between mmu_circ_0000730 and mmu-miR-466i-3p. We further showed that both mmu-miR-466i-3p and mmu-miR-466 f-3p suppresses a number of genes involved in epithelial-mesenchymal transition (EMT) and stemness of cancer stem cells such as SOX9.

CONCLUSIONS: These results provide evidence of a previously unrecognized regulatory role of non-coding RNAs in microbiota-mediated cancer metastasis, and thus, the microbiome may serve as a therapeutic target.}, } @article {pmid32685087, year = {2020}, author = {Wei, Z and Shen, P and Cheng, P and Lu, Y and Wang, A and Sun, Z}, title = {Gut Bacteria Selectively Altered by Sennoside A Alleviate Type 2 Diabetes and Obesity Traits.}, journal = {Oxidative medicine and cellular longevity}, volume = {2020}, number = {}, pages = {2375676}, pmid = {32685087}, issn = {1942-0994}, abstract = {Accumulating evidences implicate that gut microbiota play an important role in the onset and prolongation of fat inflammation and diabetes. Sennoside A, the main active ingredient of Rhizoma Rhei (rhubarb), is widely used for constipation as a kind of anthranoid laxative (e.g., senna). Here, we put forward the hypothesis that the structural alteration of gut microbiota in obesity mice may be involved in the pathogenesis of type 2 diabetes (T2D) which may be ameliorated by Sennoside A. We investigated the appearance of obesity, insulin resistance, host inflammation, and leaky gut phenotype with or without Sennoside A in db/db mice. Horizontal fecal microbiota transplantation (FMT) was used to confirm the critical roles of gut microbiota in the amelioration of the indices in T2D mice after Sennoside A treatment. As a result, we found that Sennoside A administration markedly improved the indices in T2D mice and obesity-related traits including blood glucose level, body weight, lipid metabolism disorder, and insulin resistance. The gut microbiota changed quickly during the onset of T2D in db/db mice, which confirmed the hypothesis that gut microbiota was involved in the pathogenesis of T2D. Sennoside A altered gut microbial composition which might mediate the antiobesogenic effects in T2D remission. Sennoside A also reduced inflammation and increased tight junction proteins in the ileum in gene-deficient mice via gut microbiota alteration. FMT lowered the blood glucose level and improved insulin resistance, corroborating that Sennoside A perhaps exerted its antiobesogenic effects through gut microbiota alteration. Chemical Compounds Studied in This Article. Compounds studied in this article include Sennoside A (PubChem CID: 73111) and metformin hydrochloride (PubChem CID: 14219).}, } @article {pmid32684346, year = {2020}, author = {Martínez-González, AE and Andreo-Martínez, P}, title = {Prebiotics, probiotics and fecal microbiota transplantation in autism: A systematic review.}, journal = {Revista de psiquiatria y salud mental}, volume = {13}, number = {3}, pages = {150-164}, doi = {10.1016/j.rpsm.2020.06.002}, pmid = {32684346}, issn = {1989-4600}, abstract = {In recent years, there has been an increase in studies of the implications of the gut microbiota (GM) in children with autism spectrum disorder (ASD). There is a hypothesis which propose a relationship between the emotional state and the abundance of intestinal microbes through the so-called microbiota-intestine-brain axis. In this sense, dysbiotic GM could be a contributing factor to the appearance of ASD. This systematic review article analyzes the results of the intervention using prebiotics (carrot powder, vitamin A, partially hydrolyzed guar gum, galactooligosaccharides, etc.), probiotics (mainly: Lactobacillus, Bifidobacterium, etc.) and transplantation of fecal microbiota in ASD children. In conclusion, the results of the initial studies suggest changes in ASD symptoms, gastro-intestinal symptoms and GM composition after the interventions. However, the results should be taken with caution because there are very few studies that analyze the efficacy of long-term treatments and the different combinations of them.}, } @article {pmid32681922, year = {2021}, author = {Holvoet, T and Joossens, M and Vázquez-Castellanos, JF and Christiaens, E and Heyerick, L and Boelens, J and Verhasselt, B and van Vlierberghe, H and De Vos, M and Raes, J and De Looze, D}, title = {Fecal Microbiota Transplantation Reduces Symptoms in Some Patients With Irritable Bowel Syndrome With Predominant Abdominal Bloating: Short- and Long-term Results From a Placebo-Controlled Randomized Trial.}, journal = {Gastroenterology}, volume = {160}, number = {1}, pages = {145-157.e8}, doi = {10.1053/j.gastro.2020.07.013}, pmid = {32681922}, issn = {1528-0012}, abstract = {BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with intestinal dysbiosis. Given the reported promising results of open-label fecal microbiota transplantation (FMT) therapy in patients with predominant abdominal bloating, we studied efficacy of this treatment in a randomized, placebo-controlled trial.

METHODS: Patients with refractory IBS, defined as failure of ≥3 conventional therapies, were randomly assigned to single-dose nasojejunal administration of donor stools (n = 43) or autologous stools (n = 19) in a double-blind study, performed from December 2015 through October 2017, and were followed up for 1 year. IBS-related symptoms were assessed by using a daily symptom diary to determine general abdominal discomfort, abdominal bloating, abdominal pain, and flatulence on a scale of 1-6. Number of daily bowel movements, consistency of the stools, and abdominal circumference were also recorded. Patients completed the IBS-specific quality of life questionnaire. Primary endpoints were improvement of IBS symptoms and bloating at 12 weeks (response). Secondary endpoints were changes in IBS symptom scores and quality of life. Stool samples were collected for microbiota amplicon sequencing. Open-label retransplantation was offered after the trial.

RESULTS: At week 12, 56% of patients given donor stool reported improvement in both primary endpoints compared with 26% of patients given placebo (P = .03). Patients given donor stool had significant improvements in level of discomfort (mean reduction, 19%; median score before FMT, 3.98; range, 2.13-6.00; median score after FMT, 3.1; range, 951.29-5.90), stool frequency (mean reduction, 13%; median score before FMT, 2.10; range, 0.57-14.29; median score after FMT 1.7; range, 0.71-4.29), urgency (mean reduction, 38%; median score before FMT, 0.61; range, 0.00-1.00; median score after FMT, 0.37; range, 0.00-1.00), abdominal pain (mean reduction, 26%; median score before FMT, 3.88; range, 1.57-5.17; median score after FMT, 2.80; range, 1.14-4.94), flatulence (mean reduction, 10%; median score before FMT, 3.42; range, 0.71-6.00; median score after FMT, 3.07; range, 0.79-4.23), and quality of life (mean increase, 16%; median score before FMT 32.6; range, 11-119; median score after FMT, 43.1; range, 32.25-99). A significantly higher proportion of women given donor stool (69%) had a response than men (29%) (P = .01). Fecal samples from responders had higher diversity of microbiomes before administration of donor material than fecal samples from nonresponders (P = .04) and distinct baseline composition (P = .04), but no specific marker taxa were associated with response. After single FMT, 21% of patients given donor stool reported effects that lasted for longer than 1 year compared with 5% of patients given placebo stool. A second FMT reduced symptoms in 67% of patients with an initial response to donor stool but not in patients with a prior nonresponse.

CONCLUSIONS: In a randomized trial of patients with treatment-refractory IBS with predominant bloating, FMT relieved symptoms compared with placebo (autologous transplant), although the effects decreased over 1 year. A second FMT restored the response patients with a prior response. Response was associated with composition of the fecal microbiomes before FMT; this might be used to as a biomarker to select patients for this treatment. ClinicalTrials.gov, Number: NCT02299973.}, } @article {pmid32681643, year = {2020}, author = {Ghani, R and Mullish, BH and McDonald, JAK and Ghazy, A and Williams, HRT and Brannigan, ET and Mookerjee, S and Satta, G and Gilchrist, M and Duncan, N and Corbett, R and Innes, AJ and Pavlů, J and Thursz, MR and Davies, F and Marchesi, JR}, title = {Disease prevention not decolonization - a model for fecal microbiota transplantation in patients colonized with multidrug-resistant organisms.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa948}, pmid = {32681643}, issn = {1537-6591}, support = {MR/R000875/1/MRC_/Medical Research Council/United Kingdom ; }, abstract = {Fecal microbiota transplantation (FMT) yields variable intestinal decolonization results for multidrug-resistant organisms (MDROs). This study showed significant reductions in antibiotic duration, bacteremia and length of stay in 20 patients colonized/ infected with MDRO receiving FMT (compared to pre-FMT history, and a matched group not receiving FMT), despite modest decolonization rates.}, } @article {pmid32681029, year = {2020}, author = {Jang, YO and Lee, SH and Choi, JJ and Kim, DH and Choi, JM and Kang, MJ and Oh, YM and Park, YJ and Shin, Y and Lee, SW}, title = {Fecal microbial transplantation and a high fiber diet attenuates emphysema development by suppressing inflammation and apoptosis.}, journal = {Experimental & molecular medicine}, volume = {52}, number = {7}, pages = {1128-1139}, doi = {10.1038/s12276-020-0469-y}, pmid = {32681029}, issn = {2092-6413}, support = {2019R1F1A1057875//National Research Foundation of Korea (NRF)/International ; 2016R1A6A3A11932575//National Research Foundation of Korea (NRF)/International ; }, abstract = {Recent work has suggested a microbial dysbiosis association between the lung and gut in respiratory diseases. Here, we demonstrated that gut microbiome modulation attenuated emphysema development. To modulate the gut microbiome, fecal microbiota transplantation (FMT) and diet modification were adopted in mice exposed to smoking and poly I:C for the emphysema model. We analyzed the severity of emphysema by the mean linear intercept (MLI) and apoptosis by the fluorescent TUNEL assay. Microbiome analysis was also performed in feces and fecal extracellular vesicles (EVs). The MLI was significantly increased with smoking exposure. FMT or a high-fiber diet (HFD) attenuated the increase. Weight loss, combined with smoking exposure, was not noted in mice with FMT. HFD significantly decreased macrophages and lymphocytes in bronchoalveolar lavage fluid. Furthermore, IL-6 and IFN-γ were decreased in the bronchoalveolar lavage fluid and serum. The TUNEL score was significantly lower in mice with FMT or HFD, suggesting decreased cell apoptosis. In the microbiome analysis, Bacteroidaceae and Lachnospiraceae, which are alleged to metabolize fiber into short-chain fatty acids (SCFAs), increased at the family level with FMT and HFD. FMT and HFD attenuated emphysema development via local and systemic inhibition of inflammation and changes in gut microbiota composition, which could provide a new paradigm in COPD treatment.}, } @article {pmid32677955, year = {2020}, author = {Sui, H and Zhang, L and Gu, K and Chai, N and Ji, Q and Zhou, L and Wang, Y and Ren, J and Yang, L and Zhang, B and Hu, J and Li, Q}, title = {YYFZBJS ameliorates colorectal cancer progression in ApcMin/+ mice by remodeling gut microbiota and inhibiting regulatory T-cell generation.}, journal = {Cell communication and signaling : CCS}, volume = {18}, number = {1}, pages = {113}, pmid = {32677955}, issn = {1478-811X}, abstract = {BACKGROUND: Progression of Colorectal cancer (CRC) is influenced by single or compounded environmental factors. Accumulating evidence shows that microbiota can influence the outcome of cancer immunotherapy. T cell, one of the main populations of effector immune cells in antitumor immunity, has been considered as a double-edged sword during the progression of CRC. Our previous studies indicate that traditional Chinese herbs (TCM) have potential anticancer effects in improving quality of life and therapeutic effect. However, little is known about the mechanism of TCM formula in cancer prevention.

METHODS: Here, we used C57BL/6 J ApcMin/+ mice, an animal model of human intestinal tumorigenesis, to investigate the gut bacterial diversity and their mechanisms of action in gastrointestinal adenomas, and to evaluate the effects of Yi-Yi-Fu-Zi-Bai-Jiang-San (YYFZBJS) on of colon carcinogenesis in vivo and in vitro. Through human-into-mice fecal microbiota transplantation (FMT) experiments from YYFZBJS volunteers or control donors, we were able to differentially modulate the tumor microbiome and affect tumor growth as well as tumor immune infiltration.

RESULTS: We report herein, YYFZBJS treatment blocked tumor initiation and progression in ApcMin/+ mice with less change of body weight and increased immune function. Moreover, diversity analysis of fecal samples demonstrated that YYFZBJS regulated animal's natural gut flora, including Bacteroides fragilis, Lachnospiraceae and so on. Intestinal tumors from conventional and germ-free mice fed with stool from YYFZBJS volunteers had been decreased. Some inflammation' expression also have been regulated by the gut microbiota mediated immune cells. Intestinal lymphatic, and mesenteric lymph nodes (MLN), accumulated CD4+ CD25+ Foxp3 positive Treg cells were reduced by YYFZBJS treatment in ApcMin/+ mice. Although YYFZBJS had no inhibition on CRC cell proliferation by itself, the altered Tregs mediated by YYFZBJS repressed CRC cancer cell growth, along with reduction of the phosphorylation of β-catenin.

CONCLUSIONS: In conclusion, we demonstrated that gut microbiota and Treg were involved in CRC development and progression, and we propose YYFZBJS as a new potential drug option for the treatment of CRC. Video abstract.}, } @article {pmid32677453, year = {2020}, author = {Khanna, S}, title = {Fecal transplant clinical trials for Clostridioides difficile: an interview with Sahil Khanna.}, journal = {Future microbiology}, volume = {15}, number = {}, pages = {709-712}, doi = {10.2217/fmb-2020-0102}, pmid = {32677453}, issn = {1746-0921}, abstract = {This interview was conducted by Atiya Henry, Commissioning Editor of Future Microbiology. Sahil Khanna is an Associate Professor of Medicine in the Division of Gastroenterology and Hepatology at Mayo Clinic, Rochester (MN, USA). He currently directs the Comprehensive Gastroenterology Interest group, Clostridioides difficile clinic, Fecal Microbiota Transplantation program and C. difficile related clinical trials at Mayo Clinic. He completed Medical School at the All India Institute of Medical Sciences, New Delhi; followed by Post Doctoral Research at University of California, San Diego (CA, USA); residency in Internal Medicine and Fellowship in Gastroenterology and Hepatology at Mayo Clinic, before joining the Faculty. He also completed Masters in Clinical and Translational Sciences during his fellowship. His research and clinical interests include epidemiology, outcomes and emerging therapeutics for C. difficile infection, an arena in which he has had numerous publications and presentations. He has over 100 peer-reviewed publications, serves as reviewer, is on the editorial board of several journals and has won numerous awards.}, } @article {pmid32677450, year = {2021}, author = {Dubois, NE and Read, CY and O'Brien, K and Ling, K}, title = {Challenges of Screening Prospective Stool Donors for Fecal Microbiota Transplantation.}, journal = {Biological research for nursing}, volume = {23}, number = {1}, pages = {21-30}, doi = {10.1177/1099800420941185}, pmid = {32677450}, issn = {1552-4175}, abstract = {Despite high efficacy rates, significant costs and logistical challenges associated with procuring stool from healthy donors for fecal microbiota transplantation (FMT) have presented barriers to broader institutional adoption and limited the availability of this life-saving treatment. Published outcomes for donor screening programs report donor deferral rates between 90% and 96%. Due to the paucity of FMT donor screening data, a secondary analysis on a cohort of previously screened donors (n = 7,968) was conducted to provide a synopsis of the observed trends and rationales for prospective stool donor deferrals. Upon completion of the evaluation, 1.7% of prospective donors (n = 134) qualified for stool donation. Over 50% of donors who completed the online pre-screen were deferred, primarily for a body mass index of 30 kg/m2 or greater (n = 1,516, 37.0%), logistics (n = 841, 20.5%), and travel history (n = 638, 15.5%). Despite pre-screening, 569 donors (72.8%) who completed the in-person clinical assessment were ultimately deferred due primarily to potentially microbiome-mediated diseases (n = 187, 32.9%). A notably small portion of donors (n = 46, 25.6%) were deferred during the laboratory assessment process suggesting the clinical assessment was effective at deferring donors at higher risk for transmissible diseases. Donors lost to follow-up throughout the screening process presented a significant challenge and contributed to a notable (n = 3,117; 39.1%) portion of donor attrition. Findings were used to support recommendations for improving prospective stool donor screening programs and to provide suggestions for future research.}, } @article {pmid32675857, year = {2020}, author = {Dupont, HL and Jiang, ZD and Dupont, AW and Utay, NS}, title = {THE INTESTINAL MICROBIOME IN HUMAN HEALTH AND DISEASE.}, journal = {Transactions of the American Clinical and Climatological Association}, volume = {131}, number = {}, pages = {178-197}, pmid = {32675857}, issn = {0065-7778}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; }, abstract = {The Human Microbiome Initiative of NIH, begun in 2007, has opened the door to the power of the intestinal microbiome in health and disease. The 100 trillion gut microbes influence body function through three pathways: (1) via the neural route where 500 million neurons of the enteric nervous system (the body's second brain) connect to the brain and spinal cord, (2) via the immune route where the gut-immune capacity prevents infection and elicits immune response to vaccines, and (3) by the hormonal route wherein biologically active chemicals are released from enteroendocrine cells to control mood and body functions. Through research, the identification of diseases and disorders associated with abnormal microbiome ("dysbiosis") has increased in number with potential for reversibility. Our team has developed an orally administered fecal microbiota transplantation product that is effective in reversing dysbiosis in recurrent Clostridioides difficile (C. difficile) and is being used to reverse abnormal microbiomes in chronic dysbiotic disorders.}, } @article {pmid32675782, year = {2021}, author = {Touchefeu, Y and Duchalais, E and Bruley des Varannes, S and Alameddine, J and Mirallie, E and Matysiak-Budnik, T and Le Bastard, Q and Javaudin, F and Rimbert, M and Jotereau, F and Montassier, E}, title = {Concomitant decrease of double-positive lymphocyte population CD4CD8αα and Faecalibacterium prausnitzii in patients with colorectal cancer.}, journal = {European journal of gastroenterology & hepatology}, volume = {32}, number = {2}, pages = {149-156}, doi = {10.1097/MEG.0000000000001842}, pmid = {32675782}, issn = {1473-5687}, abstract = {INTRODUCTION AND AIMS: Changes in the composition of the gut microbiota in patients with colorectal cancer (CRC) compatible with a contribution of the gut microbiota in carcinogenesis have been reported. In particular, a decrease Faecalibacterium prausnitzii has been identified. A CD4CD8αα, double-positive lymphocyte population (DP8α) has recently been demonstrated in the human colon and blood with regulatory functions and specificity for F. prausnitzii. Here, we aimed to detect dysbiosis in the fecal microbiome of patients with CRC by metagenomic analysis, and to look for changes in the levels of DP8α circulating T cells specific for F. prausnitzii in these patients.

PATIENTS AND METHODS: Patients with CRC and control subjects were prospectively included. None had received antibiotics in the previous month or any anti-tumor treatment. A stool sample was collected for each participant, and analyzed by shotgun sequencing. The DP8α T cell population was identified and quantified on fresh whole blood by flow cytometry with anti-CD45, anti-CD3, anti-CD4 and anti-CD8α co-labeling.

RESULTS: Twenty-one patients with CRC and 20 controls subjects were included. We found that mean relative abundance of five species was significantly decreased in CRC patients compared with controls, including F. prausnitzii, Barnesiella intestinihominis, Alistipes finegoldii, Bacteroides eggerthii and Eubacterium siraeum. We also found that the DP8α T cell population was significantly decreased in the blood of CRC patients compared with controls.

CONCLUSION: In our work, we showed that a reduced abundance of F. prausnitzii in CRC patients was associated to a significant decrease in the circulating DP8α Treg population, suggesting a potential involvement of reduced activity of DP8α T cells in colonic carcinogenesis. These findings open new diagnostic and therapeutic strategies for CRC.}, } @article {pmid32671773, year = {2020}, author = {Wang, T and Liu, K and Wen, L and Yang, Y and Yin, X and Liu, K and Chen, Y and He, Y and Yang, M and Wei, Y and Wang, B and Chen, D}, title = {Autophagy and Gastrointestinal Diseases.}, journal = {Advances in experimental medicine and biology}, volume = {1207}, number = {}, pages = {529-556}, doi = {10.1007/978-981-15-4272-5_38}, pmid = {32671773}, issn = {0065-2598}, mesh = {*Autophagy/drug effects ; Cholera ; Crohn Disease ; Gastritis, Atrophic ; *Gastrointestinal Diseases/drug therapy ; Gastrointestinal Neoplasms ; Helicobacter Infections ; Humans ; }, abstract = {Normal gastrointestinal physiology is fundamental for all the living beings. Gastrointestinal diseases mainly include gastrointestinal motility disorders, infectious inflammation (such as Helicobacter pylori infection, cholera, and intestinal parasites), non-infectious inflammation (such as chronic gastritis and Crohn's disease), and gastrointestinal cancers. In addition, intestinal microbial disorder is also an important cause of intestinal diseases, so intestinal microecological treatment (fecal microbiota transplantation) is an important mean of treating gastrointestinal diseases. In recent years, the role of autophagy in gastrointestinal diseases has been studied extensively. Autophagy is observed under various pathological processes of the gastrointestinal tract. For example, it has been demonstrated that autophagy plays an important role in maintaining the homeostasis and integrity of intestinal epithelium. Additionally, autophagy regulates host response to H. pylori infection and development of gastrointestinal cancers. Therefore, we will discuss pivotal roles of autophagy in various gastrointestinal diseases and analyze the underlying molecular mechanisms, which may provide new therapeutic targets applicable for the treatment of gastrointestinal diseases.}, } @article {pmid32670347, year = {2020}, author = {Qi, X and Zhong, X and Xu, S and Zeng, B and Chen, J and Zang, G and Zeng, L and Bai, S and Zhou, C and Wei, H and Xie, P}, title = {Extracellular Matrix and Oxidative Phosphorylation: Important Role in the Regulation of Hypothalamic Function by Gut Microbiota.}, journal = {Frontiers in genetics}, volume = {11}, number = {}, pages = {520}, pmid = {32670347}, issn = {1664-8021}, abstract = {Background: In previous studies, our team examined the gut microbiota of healthy individuals and depressed patients using fecal microbiota transplantation of germ-free (GF) mice. Our results showed that depression-like and anxiety-like behavioral phenotypes of host mice were increased, but the molecular mechanism by which gut microbiota regulate host behavioral phenotypes is still unclear.

Methods: To investigate the molecular mechanism by which gut microbiota regulate host brain function, adult GF mice were colonized with fecal samples derived from healthy control (HC) individuals or patients with major depressive disorder (MDD). Transcriptomic profiling of hypothalamus samples was performed to detect differentially expressed genes (DEGs). qRT-PCR was used for validation experiments.

Results: Colonization germ-free (CGF) mice had 243 DEGs compared with GF mice. The most enriched KEGG pathways associated with upregulated genes were "protein digestion and absorption," "extracellular matrix (ECM)-receptor interaction," and "focal adhesion." MDD mice had 642 DEGs compared with HC mice. The most enriched KEGG pathways associated with upregulated genes in MDD mice were also "protein digestion and absorption," "ECM-receptor interaction," and "focal adhesion." Meanwhile, the most enriched KEGG pathway associated with downregulated genes in these mice was "oxidative phosphorylation," and genes related to this pathway were found to be highly correlated in PPI network analysis.

Conclusion: In summary, our findings suggested that regulation of ECM is a key mechanism shared by different gut microbiota and that inhibition of energy metabolism in the hypothalamus by gut microbiota derived from MDD patients is a potential mechanism of behavioral regulation and depression.}, } @article {pmid32667590, year = {2020}, author = {Generoso, JS and Giridharan, VV and Lee, J and Macedo, D and Barichello, T}, title = {The role of the microbiota-gut-brain axis in neuropsychiatric disorders.}, journal = {Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999)}, volume = {}, number = {}, pages = {}, doi = {10.1590/1516-4446-2020-0987}, pmid = {32667590}, issn = {1809-452X}, abstract = {The microbiota-gut-brain axis is a bidirectional signaling mechanism between the gastrointestinal tract and the central nervous system. The complexity of the intestinal ecosystem is extraordinary; it comprises more than 100 trillion microbial cells that inhabit the small and large intestine, and this interaction between microbiota and intestinal epithelium can cause physiological changes in the brain and influence mood and behavior. Currently, there has been an emphasis on how such interactions affect mental health. Evidence indicates that intestinal microbiota are involved in neurological and psychiatric disorders. This review covers evidence for the influence of gut microbiota on the brain and behavior in Alzheimer disease, dementia, anxiety, autism spectrum disorder, bipolar disorder, major depressive disorder, Parkinson's disease, and schizophrenia. The primary focus is on the pathways involved in intestinal metabolites of microbial origin, including short-chain fatty acids, tryptophan metabolites, and bacterial components that can activate the host's immune system. We also list clinical evidence regarding prebiotics, probiotics, and fecal microbiota transplantation as adjuvant therapies for neuropsychiatric disorders.}, } @article {pmid32664182, year = {2020}, author = {Zhang, S and Lv, J and Ren, X and Hao, X and Zhou, P and Wang, Y}, title = {The efficacy and safety of fecal microbiota transplantation in the treatment of systemic sclerosis: A protocol for systematic review and meta analysis.}, journal = {Medicine}, volume = {99}, number = {28}, pages = {e21267}, doi = {10.1097/MD.0000000000021267}, pmid = {32664182}, issn = {1536-5964}, mesh = {Adolescent ; Adult ; Fecal Microbiota Transplantation/*methods ; Female ; Gastrointestinal Microbiome/physiology ; Humans ; Male ; Meta-Analysis as Topic ; Middle Aged ; Research Design ; Scleroderma, Systemic/microbiology/*therapy ; Systematic Reviews as Topic ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Systemic sclerosis (SSc) is 1 of the most complex systemic autoimmune diseases.Accumulating evidence suggests that gut microbiota affect the development and function of the immune system and may play a role in the pathogenesis of autoimmune diseases. This new paradigm raises the possibility that many diseases result, at least partially, from microbiota-related dysfunction. This understanding invites the investigation of fecal microbiota transplantation (FMT) in the treatment of SSc. However, no study has specifically and systematically investigated the efficacy and safety of FMT in the treatment of SSc. Thus, this study will systematically and comprehensively appraise the efficacy and safety of FMT in the treatment of SSc.

METHODS: We will search the following sources without restrictions for date, language, or publication status: PubMed, Web of Science,Cochrane Central Register of Controlled Trials (CENTRAL) Cochrane Library, EMBASE and China National Knowledge Infrastructure. We will apply a combination of Medical Subject Heading (MeSH) and free-text terms incorporating database-specific controlled vocabularies and text words to implement search strategies. We will also search the ongoing trials registered in the World Health Organization's International Clinical Trials Registry Platform. Besides, the previous relevant reviews conducted on FMT for SSc and reference lists of included studies will also be searched.

RESULTS: This study will provide a reliable basis for the treatment of SSc with FMT.

CONCLUSIONS: The findings will be an available reference to evaluate the efficacy and safety of FMT in the treatment of SSc.

REGISTRATION NUMBER: INPLASY202060019.}, } @article {pmid32663372, year = {2020}, author = {Lim, YY and Lee, YS and Ooi, DSQ}, title = {Engineering the Gut Microbiome for Treatment of Obesity: A Review of Current Understanding and Progress.}, journal = {Biotechnology journal}, volume = {15}, number = {10}, pages = {e2000013}, doi = {10.1002/biot.202000013}, pmid = {32663372}, issn = {1860-7314}, abstract = {Obesity is a complex, multifactorial disease that is increasing in prevalence despite extensive research and efforts to curb it. Over the last decade, gut microbiome has emerged as an important contributor to the pathogenesis of obesity. Microbiome profile is altered in obese phenotype and the causative role of microbiome in obesity is demonstrated in fecal microbiota transplantation studies. Herein, recent evidences supporting the role of gut microbiome in obesity and the current therapies designed to engineer gut microbiome for treatment of obesity will be reviewed. The microbial enterotypes associated with obesity is outlined, and the gut microbiota-driven metabolism and low-grade inflammation linking gut microbiome and obesity is examined. How the different intrinsic and extrinsic factors such as host genetics, mode of childbirth delivery, diet, lifestyle habits and use of antibiotics influence the composition of the gut microbiome in the development of obesity is evaluated. Also, the efficacy of current microbiome-based therapies in the forms of prebiotics, probiotics and engineered microbes that are used to manipulate gut microbiome in treating obesity is discussed.}, } @article {pmid32663072, year = {2020}, author = {Matsuoka, K}, title = {Fecal microbiota transplantation for ulcerative colitis.}, journal = {Immunological medicine}, volume = {}, number = {}, pages = {1-5}, doi = {10.1080/25785826.2020.1792040}, pmid = {32663072}, issn = {2578-5826}, abstract = {Altered abundance and composition of the gut microbiota, i.e., dysbiosis, is reported to be involved in the pathogenesis of various diseases including not only gastrointestinal diseases but also metabolic, neurological, and autoimmune disorders. Fecal microbiota transplantation (FMT) aims to correct dysbiosis by administrating feces collected from donors and thus treat the underlying disease. Ulcerative colitis (UC) is a disease characterized by chronic inflammation in the large intestine. Patients with UC have been reported to have dysbiosis, and more specifically, reduced diversity and abundance of the gut microbiota. FMT has been tried as a treatment for UC. Favorable effects of FMT on UC had been reported in case reports or case series. Recently, four randomized controlled trials of FMT for UC were published. Three of the four studies reported that FMT was more effective than control treatment. Thus, FMT is considered as a promising treatment for UC; however, there are many issues to solve before FMT can become a standard therapy for UC including donor selection, administration routes, frequencies, easy-to-administer formulation development, and optimal patient population.}, } @article {pmid32658171, year = {2020}, author = {Blanco, C}, title = {The influence of the gut microbiome on obesity.}, journal = {Journal of the American Association of Nurse Practitioners}, volume = {32}, number = {7}, pages = {504-510}, doi = {10.1097/JXX.0000000000000480}, pmid = {32658171}, issn = {2327-6924}, abstract = {Obesity is a disease with multiple environmental and genetic factors, which when combined contribute to the maintenance of an elevated body weight, thereby reducing long-term success of weight loss. The human gut microbiome is becoming a new potential contributor to obesity. Specifically, gut bacteria and their metabolites are known to affect dysbiosis, metabolism, endotoxemia, and inflammation. Many environmental and lifestyle factors can alter the gut microbiota affecting obesity. Potential therapies to alter the gut microbiota include supplementation with probiotic organisms and the use of fecal microbiota transplantation. This review will examine the growing evidence supporting the mechanisms with which the human gut microbiota may influence obesity, various influences on the microbiota, and potential therapies.}, } @article {pmid32657282, year = {2020}, author = {Huang, GQ and Bai, Y and Sun, ZQ and Liu, J}, title = {Successful Treatment of Pseudomembranous Colitis with Fecal Microbiota Transplantation - A Case Study on A Patient Rescued by Extracorporeal Cardiopulmonary Resuscitation After Cardiac Arrest.}, journal = {Annals of transplantation}, volume = {25}, number = {}, pages = {e923283}, pmid = {32657282}, issn = {2329-0358}, abstract = {BACKGROUND Pseudomembranous colitis (PMC) is an opportunistic, nosocomial infection caused by Clostridium difficile. CASE REPORT Here we described a patient who developed PMC during her recovery from cardiac arrest. A 16-year-old female high school student experienced sudden cardiac arrest. Spontaneous circulation was not returned by standard cardiopulmonary resuscitation. After her admission to the emergency unit, her cardiac function and neurologic function were finally resumed by extracorporeal cardiopulmonary resuscitation (ECPR); however, after 14 days, her recovery was complicated with excessive diarrhea and shock. Colonoscopy confirmed the diagnosis of PMC. Metronidazole and vancomycin were immediately administered; however, the treatment did not result in any improvement. Fecal microbiota transplantation was then performed, and after 4 transplantations, her diarrhea was significantly ameliorated. After hospital stay for 135 days, the patient was finally discharged with grade II brain function. She later recovered self-care ability in follow-up. CONCLUSIONS The patient suffered from a long-term gastrointestinal ischemia-hypoxia resulting from cardiac arrest. The use of broad-spectrum antibiotics in the later treatment led to refractory PMC, which was successfully managed by multiple fecal microbiota transplantation.}, } @article {pmid32656839, year = {2020}, author = {Lahtinen, P and Jalanka, J and Hartikainen, A and Mattila, E and Hillilä, M and Punkkinen, J and Koskenpato, J and Anttila, VJ and Tillonen, J and Satokari, R and Arkkila, P}, title = {Letter: faecal microbiota transplantation for irritable bowel syndrome. Authors' reply.}, journal = {Alimentary pharmacology & therapeutics}, volume = {52}, number = {3}, pages = {557-558}, doi = {10.1111/apt.15875}, pmid = {32656839}, issn = {1365-2036}, mesh = {*Anemia ; Azathioprine ; Fecal Microbiota Transplantation ; Humans ; *Irritable Bowel Syndrome ; *Leukopenia ; }, } @article {pmid32656836, year = {2020}, author = {Segal, JP and Mullish, BH and Quraishi, MN and Iqbal, TH}, title = {Letter: faecal microbiota transplantation for IBS.}, journal = {Alimentary pharmacology & therapeutics}, volume = {52}, number = {3}, pages = {556-557}, doi = {10.1111/apt.15824}, pmid = {32656836}, issn = {1365-2036}, mesh = {Azathioprine ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; *Irritable Bowel Syndrome ; }, } @article {pmid32656604, year = {2020}, author = {Agarwal, A and Maheshwari, A and Verma, S and Arrup, D and Phillips, L and Vinayek, R and Nair, P and Hagan, M and Dutta, S}, title = {Superiority of Higher-Volume Fresh Feces Compared to Lower-Volume Frozen Feces in Fecal Microbiota Transplantation for Recurrent Clostridioides Difficile Colitis.}, journal = {Digestive diseases and sciences}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10620-020-06459-0}, pmid = {32656604}, issn = {1573-2568}, abstract = {GOALS: To compare the clinical outcomes of different protocols for fecal microbiota transplantation (FMT) in two community hospitals with similar patient demographics.

BACKGROUND: FMT is commonly performed for recurrent or refractory Clostridioides difficile infection (rCDI). The clinical efficacy of FMT for this indication has been well established. However, there has been no standardization or optimization of the amount of fecal material, method of feces preparation, or route of delivery for FMT.

STUDY: In this retrospective study, patients with rCDI received FMT using commercially available frozen fecal preparation (22.7 g) at Center A and locally prepared fresh fecal filtrate (30-50 g) at Center B. The primary outcome was defined as complete resolution of clinical symptoms related to rCDI after at least 8 weeks of follow-up.

RESULTS: Fifty patients from each center were included in the study. Clinical success after initial FMT with lower-volume frozen fecal preparation at Center A was 32/50 (64.0%) compared to 49/50 (98.0%) with higher-volume fresh fecal filtrate at Center B (p < 0.0001). Seventeen patients in Center A and 1 patient in Center B underwent at least one repeat FMT. Overall clinical success was achieved in 43/50 (86%) of patients in Center A and 50/50 (100%) in Center B (p = 0.012).

CONCLUSIONS: Our results suggest superior clinical efficacy of a larger amount of fresh fecal filtrate over a smaller amount of commercially available frozen fecal preparation. Further studies are needed to examine the effect of varying amounts of feces and the optimal protocol for FMT in patients with rCDI.}, } @article {pmid32655675, year = {2020}, author = {Zhu, Y and Zhang, JY and Wei, YL and Hao, JY and Lei, YQ and Zhao, WB and Xiao, YH and Sun, AD}, title = {The polyphenol-rich extract from chokeberry (Aronia melanocarpa L.) modulates gut microbiota and improves lipid metabolism in diet-induced obese rats.}, journal = {Nutrition & metabolism}, volume = {17}, number = {}, pages = {54}, pmid = {32655675}, issn = {1743-7075}, abstract = {The gut microbiota plays a critical role in obesity and lipid metabolism disorder. Chokeberry (Aronia melanocarpa L.) are rich in polyphenols with various physiological and pharmacological activities. We determined serum physiological parameters and fecal microbial components by using related kits, liquid chromatography-mass spectrometry (LC-MS) and 16S rRNA gene sequencing every 10 days. Real-time PCR analysis was used to measure gene expression of bile acids (BAs) and lipid metabolism in liver and adipose tissues. We analyzed the effects of different Chokeberry polyphenol (CBPs) treatment time on obesity and lipid metabolism in high fat diet (HFD)-fed rats. The results indicated that CBPs treatment prevents obesity, liver steatosis and improves dyslipidemia in HFD-fed rats. CBPs modulated the composition of the gut microbiota with the extended treatment time, reducing the Firmicutes/Bacteroidetes ratio (F/B ratio) and increasing the relative abundance of Bacteroides, Prevotella, Akkermansia and other bacterial species associated with anti-obesity properties. We found that CBPs treatment gradually decreased the total BAs pool and particularly reduced the relative content of cholic acid (CA), deoxycholic acid (DCA) and enhanced the relative content of chenodeoxycholic acid (CDCA). These changes were positively correlated Bacteroides, Prevotella and negatively correlated with Clostridium, Eubacterium, Ruminococcaceae. In liver and white adipose tissues, the gene expression of lipogenesis, lipolysis and BAs metabolism were regulated after CBPs treatment in HFD-fed rats, which was most likely mediated through FXR and TGR-5 signaling pathway to improve lipid metabolism. In addition, the mRNA expression of PPARγ, UCP1 and PGC-1α were upregulated markedly in interscapular brown adipose tissue (iBAT) after CBPs treatment. We confirmed that CBPs could reduce the body weight of HFD-fed rats by accelerating energy homeostasis and thermogenesis in iBAT. Finally, the fecal microbiota transplantation (FMT) experiment results demonstrated that FMT from CBPs-treated rats failed to reduce the weight of HFD-fed rats. However, FMT from CBPs-treated rats improved dyslipidemia and reshaped gut microbiota in HFD-fed rats. In conclusion, CBPs treatment improved obesity and complications by regulating gut microbiota in HFD-fed rats. The gut microbiota plays an important role in BAs metabolism after CBPs treatment, and BAs have therefore emerged as major effectors in microbe-host signaling events that influence host lipid metabolism, energy metabolism and thermogenesis.}, } @article {pmid32655239, year = {2020}, author = {Ryu, AJ and Rahimi, RS and Leise, MD}, title = {The Current Hepatic Encephalopathy Pipeline.}, journal = {Journal of clinical and experimental hepatology}, volume = {10}, number = {4}, pages = {377-385}, pmid = {32655239}, issn = {0973-6883}, abstract = {Hepatic encephalopathy (HE) is a complication of acute or chronic liver failure; its mechanism is complex, involving multiple organ systems, and is still being elucidated. The standard of care, lactulose, has remained generally unchanged for decades. However, in recent years, better understanding of the pathophysiology has yielded new therapeutic targets for this reversible condition. These novel treatments act both on traditional pathways established in the ammonia hypothesis and through more recently discovered mechanisms. Here, we review contemporary investigational therapies for HE. We used narrative reviews and searched ClinicalTrials.gov database for the condition "hepatic encephalopathy" through August 29, 2019. Our review yielded six key areas of therapeutic focus: (1) antibiotics against urease-producing gut bacteria, (2) intravenous ammonia scavengers, (3) modified synthetic probiotics, (4) fecal microbiota transplant, (5) brain steroid-modulating agents, and 6) nonlactulose laxatives. Active trials are ongoing in each of these therapeutic areas.}, } @article {pmid32649987, year = {2020}, author = {Keskey, R and Cone, JT and DeFazio, JR and Alverdy, JC}, title = {The use of fecal microbiota transplant in sepsis.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {226}, number = {}, pages = {12-25}, pmid = {32649987}, issn = {1878-1810}, support = {R01 GM062344/GM/NIGMS NIH HHS/United States ; }, mesh = {Brain/physiopathology ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; Immunophenotyping ; Sepsis/immunology/*therapy ; }, abstract = {Sepsis is defined as a dysregulated inflammatory response, which ultimately results from a perturbed interaction of both an altered immune system and the biomass and virulence of involved pathogens. This response has been tied to the intestinal microbiota, as the microbiota and its associated metabolites play an essential role in regulating the host immune response to infection. In turn, critical illness as well as necessary health care treatments result in a collapse of the intestinal microbiota diversity and a subsequent loss of health-promoting short chain fatty acids, such as butyrate, leading to the development of a maladaptive pathobiome. These perturbations of the microbiota contribute to the dysregulated immune response and organ failure associated with sepsis. Several case series have reported the ability of fecal microbiota transplant (FMT) to restore the host immune response and aid in recovery of septic patients. Additionally, animal studies have revealed the mechanism of FMT rescue in sepsis is likely related to the ability of FMT to restore butyrate producing bacteria and alter the innate immune response aiding in pathogen clearance. However, several studies have reported lethal complications associated with FMT, including bacteremia. Therefore, FMT in the treatment of sepsis is and should remain investigational until a more detailed mechanism of how FMT restores the host immune response in sepsis is determined, allowing for the development of more fine-tuned microbiota therapies.}, } @article {pmid32645991, year = {2020}, author = {Shin, YC and Shin, W and Koh, D and Wu, A and Ambrosini, YM and Min, S and Eckhardt, SG and Fleming, RYD and Kim, S and Park, S and Koh, H and Yoo, TK and Kim, HJ}, title = {Three-Dimensional Regeneration of Patient-Derived Intestinal Organoid Epithelium in a Physiodynamic Mucosal Interface-on-a-Chip.}, journal = {Micromachines}, volume = {11}, number = {7}, pages = {}, pmid = {32645991}, issn = {2072-666X}, support = {RR160093//Cancer Prevention and Research Institute of Texas/ ; 1912-03604//Leona M. and Harry B. Helmsley Charitable Trust/ ; F99 CA245801/CA/NCI NIH HHS/United States ; UTA18-000889/CRI/Cancer Research Institute/United States ; R21CA236690//National Cancer Institute of the National Institutes of Health/ ; BWF 1019990.01//Burroughs Wellcome Fund Collaborative Research Travel Grant/ ; F99CA245801//National Cancer Institute of the National Institutes of Health (NIH/NCI)/ ; 771066//American College of Veterinary Internal Medicine Advance Research Fellowships/ ; 2018M3A9H3025030//Ministry of Science and ICT, South Korea/ ; }, abstract = {The regeneration of the mucosal interface of the human intestine is critical in the host-gut microbiome crosstalk associated with gastrointestinal diseases. The biopsy-derived intestinal organoids provide genetic information of patients with physiological cytodifferentiation. However, the enclosed lumen and static culture condition substantially limit the utility of patient-derived organoids for microbiome-associated disease modeling. Here, we report a patient-specific three-dimensional (3D) physiodynamic mucosal interface-on-a-chip (PMI Chip) that provides a microphysiological intestinal milieu under defined biomechanics. The real-time imaging and computational simulation of the PMI Chip verified the recapitulation of non-linear luminal and microvascular flow that simulates the hydrodynamics in a living human gut. The multiaxial deformations in a convoluted microchannel not only induced dynamic cell strains but also enhanced particle mixing in the lumen microchannel. Under this physiodynamic condition, an organoid-derived epithelium obtained from the patients diagnosed with Crohn's disease, ulcerative colitis, or colorectal cancer independently formed 3D epithelial layers with disease-specific differentiations. Moreover, co-culture with the human fecal microbiome in an anoxic-oxic interface resulted in the formation of stochastic microcolonies without a loss of epithelial barrier function. We envision that the patient-specific PMI Chip that conveys genetic, epigenetic, and environmental factors of individual patients will potentially demonstrate the pathophysiological dynamics and complex host-microbiome crosstalk to target a patient-specific disease modeling.}, } @article {pmid32645451, year = {2020}, author = {Cheng, YW and Alhaffar, D and Saha, S and Khanna, S and Bohm, M and Phelps, E and Ghabril, M and Orman, E and Sashidhar, S and Rogers, N and Xu, H and Khoruts, A and Vaughn, B and Kao, D and Wong, K and Cammarota, G and Ianiro, G and Dhere, T and Kraft, CS and Mehta, N and Woodworth, MH and Allegretti, JR and Nativ, L and Marcus, J and El-Nachef, N and Fischer, M}, title = {Fecal Microbiota Transplantation Is Safe and Effective in Patients With Clostridioides difficile Infection and Cirrhosis.}, journal = {Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.cgh.2020.06.051}, pmid = {32645451}, issn = {1542-7714}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND & AIMS: Clostridioides difficile infection (CDI) harms a large proportion of patients with cirrhosis. Fecal microbiota transplantation (FMT) is recommended for recurrent CDI, but its effects in patients with cirrhosis have not been established. We performed a multicenter observational study to evaluate the efficacy and safety of FMT for CDI in patients with cirrhosis.

METHODS: We performed a retrospective study of 63 adults with cirrhosis (median model for end-stage liver disease score, 14.5; 24 patients with decompensated cirrhosis) who underwent FMT for CDI from January 2012 through November 2018 at 8 academic centers in the United States, Canada, and Italy. We collected data on patient demographics and characteristics of cirrhosis, CDI, and FMT from medical records and compared differences among patients with different severities of cirrhosis, and FMT successes vs failures at the 8-week follow-up evaluation. We also obtained data on adverse events (AEs) and severe AEs within 12 weeks of FMT.

RESULTS: Patients underwent FMT for recurrent CDI (55 of 63; 87.3%), severe CDI (6 of 63; 9.5%), or fulminant CDI (2 of 63; 3.2%) primarily via colonoscopy (59 of 63; 93.7%) as outpatients (47 of 63; 76.8%). FMT success was achieved for 54 patients (85.7%). Among FMT failures, a higher proportion used non-CDI antibiotics at the time of FMT (44.4% vs 5.6%; P < .001), had Child-Pugh scores of B or C (100% vs 37.7%; P < .001), used probiotics (77.8% vs 24.1%; P = .003), had pseudomembranes (22.2% vs 0; P = .018), and underwent FMT as inpatients (45.5% vs 19%; P = .039), compared with FMT successes. In multivariable analysis, use of non-CDI antibiotics at the time of FMT (odds ratio, 17.43; 95% CI, 2.00-152.03; P = .01) and use of probiotics (odds ratio, 11.9; 95% CI, 1.81-78.3; P = .01) were associated with a greater risk of FMT failure. FMT-related AEs occurred in 33.3% of patients (21 of 63)-most were self-limited abdominal cramps or diarrhea. There were only 5 severe AEs that possibly were related to FMT; none involved infection or death.

CONCLUSIONS: In a retrospective study, we found FMT to be safe and effective for the treatment of CDI in patients with cirrhosis.}, } @article {pmid32641428, year = {2020}, author = {Seekatz, AM}, title = {mSphere of Influence: Translating Gut Microbiome Studies To Benefit Human Health.}, journal = {mSphere}, volume = {5}, number = {4}, pages = {}, pmid = {32641428}, issn = {2379-5042}, abstract = {Anna M. Seekatz works in the field of the gut microbiome as it related to infectious diseases. In this "mSphere of Influence" article, she reflects on how two studies, "The impact of a consortium of fermented milk strains on the gut microbiome of gnotobiotic mice and monozygotic twins" (N. P. McNulty, T. Yatsunenko, A. Hsiao, et al., Sci Transl Med 3:106ra106, 2011) and "High-throughput DNA sequence analysis reveals stable engraftment of gut microbiota following transplantation of previously frozen fecal bacteria" (M. J. Hamilton, A. R. Weingarden, T. Unno, A. Khoruts, and M. J. Sadowsky, Gut Microbes 4:125-135, 2013), shaped how she approaches interpreting microbiome studies.}, } @article {pmid32639360, year = {2020}, author = {Van den Houte, K and Colomier, E and Schol, J and Carbone, F and Tack, J}, title = {Recent advances in diagnosis and management of irritable bowel syndrome.}, journal = {Current opinion in psychiatry}, volume = {33}, number = {5}, pages = {460-466}, pmid = {32639360}, issn = {1473-6578}, abstract = {PURPOSE OF REVIEW: This review summarizes recent progress in the diagnosis and management of irritable bowel syndrome, with a focus on dietary and microbiota aspects.

RECENT FINDINGS: From a pathophysiological point of view, IBS is a multifactorial condition with both peripheral (transit) as central (visceral hypersensitivity, anxiety, depression) contribution in a cumulative fashion to the symptom pattern and severity. More recently, the focus has shifted to diet and microbiota. The number of dietary options that can be used for IBS and the understanding of determinants of their efficacy is rapidly increasing. Several studies have confirmed the efficacy of the low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet. Sucrose-isomaltase deficiency has emerged as pathogenetic mechanisms in a subset of patients, who do not respond to low FODMAP diet but may respond to starch and sucrose elimination. Herbal remedies, probiotics and secretagogues have been the topic of additional treatment trials. The efficacy of fecal microbiota transplantation in IBS is variable across studies, but donor selection is emerging as a critical factor.

SUMMARY: Irritable bowel syndrome has evolved into a disorder of interaction between dietary factors and gut microbiota, with impact on bowel symptoms as well as extra-intestinal, central, symptoms. Dietary adjustments and treatments targeting the gut microbiota are areas of active research and clinical progress.}, } @article {pmid32636823, year = {2020}, author = {Moreno-Indias, I and Lundberg, R and Krych, L and Metzdorff, SB and Kot, W and Sørensen, DB and Nielsen, DS and Hansen, CHF and Hansen, AK}, title = {A Humanized Diet Profile May Facilitate Colonization and Immune Stimulation in Human Microbiota-Colonized Mice.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1336}, pmid = {32636823}, issn = {1664-302X}, abstract = {Background: In spite of the importance of the use of gnotobiotic mice for human fecal transfer, colonization efficiency and immune stimulation after human microbiota inoculation in mice are poorly studied compared to mouse microbiota inoculation. We tested the colonization efficiency and immune responses in mice bred for one additional generation after inoculating the parent generation with either a human (HM) or a mouse microbiota (MM). Furthermore, we tested if colonization efficiency and immune stimulation could be improved in HM-colonized mice by dietary approaches: if these were fed a diet closer to the human diet either in its sources of animal fat and protein [the "animal source" (AS) diet] or in its proportions of macronutrients from the normal sources of a mouse diet [the "human profile" (HP) diet].

Results: Although significantly lower in mice with a human microbiota (30-40% vs. 61-70%) the colonization efficiency was significantly higher in HM mice fed the HP diet (40%), and in MM mice fed AS (70%). The microbiota of mice fed HP was comparable to the microbiota of mice fed a standard rodent chow, while the microbiota of mice fed the animal source diet (AS) clustered separately. Mice inoculated with mouse fecal matter had significantly more CD4+ T cells and Cd4 expression and significantly fewer regulatory T cells (Tregs) and FoxP3 expression than human microbiota inoculated mice, but cell proportions differences were mostly apparent between mice fed the AS diet. Mice fed the HP diet had significantly higher expression of Cd8a.

Conclusion: It is concluded that a diet with a humanized profile could support the establishment of a human microbiota in mice, which will, however, still elicit a lower colonization efficiency compared to mice inoculated with a mouse microbiota.}, } @article {pmid32631492, year = {2020}, author = {Alavi, S and Mitchell, JD and Cho, JY and Liu, R and Macbeth, JC and Hsiao, A}, title = {Interpersonal Gut Microbiome Variation Drives Susceptibility and Resistance to Cholera Infection.}, journal = {Cell}, volume = {181}, number = {7}, pages = {1533-1546.e13}, pmid = {32631492}, issn = {1097-4172}, support = {R35 GM124724/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Animals ; Bile Acids and Salts ; Cholera/*metabolism/microbiology ; Disease Models, Animal ; Disease Susceptibility/*microbiology ; Fecal Microbiota Transplantation/methods ; Female ; Gastrointestinal Microbiome/*physiology ; Host-Pathogen Interactions/physiology ; Humans ; Hydrolases/analysis ; Male ; Mice ; Mice, Inbred C57BL ; Microbiota ; Taurocholic Acid/metabolism ; Vibrio cholerae/pathogenicity/physiology ; Virulence ; }, abstract = {The gut microbiome is the resident microbial community of the gastrointestinal tract. This community is highly diverse, but how microbial diversity confers resistance or susceptibility to intestinal pathogens is poorly understood. Using transplantation of human microbiomes into several animal models of infection, we show that key microbiome species shape the chemical environment of the gut through the activity of the enzyme bile salt hydrolase. The activity of this enzyme reduced colonization by the major human diarrheal pathogen Vibrio cholerae by degrading the bile salt taurocholate that activates the expression of virulence genes. The absence of these functions and species permits increased infection loads on a personal microbiome-specific basis. These findings suggest new targets for individualized preventative strategies of V. cholerae infection through modulating the structure and function of the gut microbiome.}, } @article {pmid32629118, year = {2020}, author = {Su, CW and Chen, CY and Jiao, L and Long, SR and Mao, T and Ji, Q and O'Donnell, S and Stanton, C and Zheng, S and Walker, WA and Cherayil, BJ and Shi, HN}, title = {Helminth-Induced and Th2-Dependent Alterations of the Gut Microbiota Attenuate Obesity Caused by High-Fat Diet.}, journal = {Cellular and molecular gastroenterology and hepatology}, volume = {10}, number = {4}, pages = {763-778}, pmid = {32629118}, issn = {2352-345X}, support = {P30 DK040561/DK/NIDDK NIH HHS/United States ; R21 AI144738/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND & AIMS: Epidemiological and animal studies have indicated an inverse correlation between the rising prevalence of obesity and metabolic syndrome and exposure to helminths. Whether helminth-induced immune response contributes to microbiota remodeling in obesity remains unknown. The aim of this study is to explore the immune-regulatory role of helminth in the prevention of HFD-induced obesity through remodeling gut microbiome.

METHODS: C57BL/6J WT and STAT6-/- mice were infected with Heligmosomoides polygyrus and followed by high fat diet (HFD) feeding for 6 weeks. The host immune response, body weight, and fecal microbiota composition were analyzed. We used adoptive transfer of M2 macrophages and microbiota transplantation approaches to determine the impact of these factors on HFD-obesity. We also examined stool microbiota composition and short chain fatty acids (SCFAs) concentration and determined the expression of SCFA-relevant receptors in the recipient mice.

RESULTS: Helminth infection of STAT6-/- (Th2-deficient) mice and adoptive transfer of helminth-induced alternatively activated (M2) macrophages demonstrated that the helminth-associated Th2 immune response plays an important role in the protection against obesity and induces changes in microbiota composition. Microbiota transplantation showed that helminth-induced, Th2-dependent alterations of the gut microbiota are sufficient to confer protection against obesity. Collectively, these results indicate that helminth infection protects against HFD-induced obesity by Th2-dependent, M2 macrophage-mediated alterations of the intestinal microbiota.

CONCLUSION: Our findings provide new mechanistic insights into the complex interplay between helminth infection, the immune system and the gut microbiota in a HFD-induced obesity model and holds promise for gut microbiome-targeted immunotherapy in obesity prevention.}, } @article {pmid32620839, year = {2020}, author = {Xiao, Y and Angulo, MT and Lao, S and Weiss, ST and Liu, YY}, title = {An ecological framework to understand the efficacy of fecal microbiota transplantation.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {3329}, pmid = {32620839}, issn = {2041-1723}, support = {R01 AI141529/AI/NIAID NIH HHS/United States ; R01 HD093761/HD/NICHD NIH HHS/United States ; UH3 OD023268/OD/NIH HHS/United States ; U19 AI095219/AI/NIAID NIH HHS/United States ; U01 HL089856/HL/NHLBI NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; Clostridioides difficile/physiology ; Clostridium Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Mice ; Models, Theoretical ; Recurrence ; Treatment Outcome ; }, abstract = {Human gut microbiota plays critical roles in physiology and disease. Our understanding of ecological principles that govern the dynamics and resilience of this highly complex ecosystem remains rudimentary. This knowledge gap becomes more problematic as new approaches to modifying this ecosystem, such as fecal microbiota transplantation (FMT), are being developed as therapeutic interventions. Here we present an ecological framework to understand the efficacy of FMT in treating conditions associated with a disrupted gut microbiota, using the recurrent Clostridioides difficile infection as a prototype disease. This framework predicts several key factors that determine the efficacy of FMT. Moreover, it offers an efficient algorithm for the rational design of personalized probiotic cocktails to decolonize pathogens. We analyze data from both preclinical mouse experiments and a clinical trial of FMT to validate our theoretical framework. The presented results significantly improve our understanding of the ecological principles of FMT and have a positive translational impact on the rational design of general microbiota-based therapeutics.}, } @article {pmid32620549, year = {2020}, author = {Ianiro, G and Mullish, BH and Kelly, CR and Kassam, Z and Kuijper, EJ and Ng, SC and Iqbal, TH and Allegretti, JR and Bibbò, S and Sokol, H and Zhang, F and Fischer, M and Costello, SP and Keller, JJ and Masucci, L and van Prehn, J and Quaranta, G and Quraishi, MN and Segal, J and Kao, D and Satokari, R and Sanguinetti, M and Tilg, H and Gasbarrini, A and Cammarota, G}, title = {Reorganisation of faecal microbiota transplant services during the COVID-19 pandemic.}, journal = {Gut}, volume = {69}, number = {9}, pages = {1555-1563}, pmid = {32620549}, issn = {1468-3288}, mesh = {Betacoronavirus ; COVID-19 ; Change Management ; Clostridium Infections/microbiology/*therapy ; *Coronavirus Infections/epidemiology/prevention & control ; *Donor Selection ; Fecal Microbiota Transplantation/*methods ; *Gastroenterology/organization & administration/trends ; Gastrointestinal Microbiome ; Humans ; Infection Control/methods/standards ; *Pandemics/prevention & control ; *Patient Selection ; *Pneumonia, Viral/epidemiology/prevention & control ; Risk Adjustment/methods/standards ; SARS-CoV-2 ; }, abstract = {The COVID-19 pandemic has led to an exponential increase in SARS-CoV-2 infections and associated deaths, and represents a significant challenge to healthcare professionals and facilities. Individual countries have taken several prevention and containment actions to control the spread of infection, including measures to guarantee safety of both healthcare professionals and patients who are at increased risk of infection from COVID-19. Faecal microbiota transplantation (FMT) has a well-established role in the treatment of Clostridioides difficile infection. In the time of the pandemic, FMT centres and stool banks are required to adopt a workflow that continues to ensure reliable patient access to FMT while maintaining safety and quality of procedures. In this position paper, based on the best available evidence, worldwide FMT experts provide guidance on issues relating to the impact of COVID-19 on FMT, including patient selection, donor recruitment and selection, stool manufacturing, FMT procedures, patient follow-up and research activities.}, } @article {pmid32618725, year = {2020}, author = {Claytor, JD and El-Nachef, N}, title = {Fecal microbial transplant for inflammatory bowel disease.}, journal = {Current opinion in clinical nutrition and metabolic care}, volume = {23}, number = {5}, pages = {355-360}, doi = {10.1097/MCO.0000000000000676}, pmid = {32618725}, issn = {1473-6519}, abstract = {PURPOSE OF REVIEW: The purpose of this brief review is to investigate the current utility of fecal microbial transplantation (FMT) to ameliorate dysbiosis contributing to inflammatory bowel disease pathogenesis.

RECENT FINDINGS: Increasing data from randomized, controlled trials support a role for multiple FMT administrations in the induction of remission and even as a maintenance therapy in mild-to-moderate Ulcerative Colitis. Small series and one small randomized controlled trial among patients with Crohn's Disease and with pouchitis continue to produce conflicting clinical results and microbial profile data on the host and donor levels. It is not clear whether patients with Crohn's disease are more susceptible to disease flare after FMT. Novel FMT delivery systems, including oral, and early-intensity colonoscopic devices, are under investigation.

SUMMARY: The allure of minimizing the risks and cost of long-term immunosuppression via modulation of patient microbiota remains enticing, and the most recent randomized controlled data in ulcerative colitis reveals acceptable clinical remission rates. However, prior to wide adoption of FMT within the inflammatory bowel disease treatment armamentarium, large clinical trials identifying biomarkers of treatment success, ensuring safety across all indications, and cultivating optimized donor and host selection are needed.}, } @article {pmid32618715, year = {2020}, author = {Wong, D and Nanda, N}, title = {Clostridium difficile disease in solid organ transplant recipients: a recommended treatment paradigm.}, journal = {Current opinion in organ transplantation}, volume = {25}, number = {4}, pages = {357-363}, pmid = {32618715}, issn = {1531-7013}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Broadly Neutralizing Antibodies/therapeutic use ; Clostridioides difficile/isolation & purification ; Clostridium Infections/drug therapy/*epidemiology/*therapy ; Fecal Microbiota Transplantation ; Humans ; Incidence ; Organ Transplantation/*methods/*statistics & numerical data ; Randomized Controlled Trials as Topic ; Transplant Recipients/statistics & numerical data ; }, abstract = {PURPOSE OF REVIEW: Organ transplant recipients have an increased incidence of Clostridium difficile disease and lower clinical response rates compared with the general population. Transplant specific treatment approaches are not defined. Therefore, a review of therapeutics in the transplant population is needed.

RECENT FINDINGS: A literature review on the current therapies for C. difficile was performed focusing on the evidence in transplant recipients and immunosuppressed populations.

SUMMARY: Transplant patients warrant an aggressive approach to treatment. The authors propose a suggested treatment paradigm for therapy.}, } @article {pmid32618656, year = {2020}, author = {Craven, L and Rahman, A and Nair Parvathy, S and Beaton, M and Silverman, J and Qumosani, K and Hramiak, I and Hegele, R and Joy, T and Meddings, J and Urquhart, B and Harvie, R and McKenzie, C and Summers, K and Reid, G and Burton, JP and Silverman, M}, title = {Allogenic Fecal Microbiota Transplantation in Patients With Nonalcoholic Fatty Liver Disease Improves Abnormal Small Intestinal Permeability: A Randomized Control Trial.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {7}, pages = {1055-1065}, doi = {10.14309/ajg.0000000000000661}, pmid = {32618656}, issn = {1572-0241}, mesh = {Double-Blind Method ; Duodenoscopy ; *Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; *Intestine, Small ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*therapy ; Permeability ; }, abstract = {INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an obesity-related disorder that is rapidly increasing in incidence and is considered the hepatic manifestation of the metabolic syndrome. The gut microbiome plays a role in metabolism and maintaining gut barrier integrity. Studies have found differences in the microbiota between NAFLD and healthy patients and increased intestinal permeability in patients with NAFLD. Fecal microbiota transplantation (FMT) can be used to alter the gut microbiome. It was hypothesized that an FMT from a thin and healthy donor given to patients with NAFLD would improve insulin resistance (IR), hepatic proton density fat fraction (PDFF), and intestinal permeability.

METHODS: Twenty-one patients with NAFLD were recruited and randomized in a ratio of 3:1 to either an allogenic (n = 15) or an autologous (n = 6) FMT delivered by using an endoscope to the distal duodenum. IR was calculated by HOMA-IR, hepatic PDFF was measured by MRI, and intestinal permeability was tested using the lactulose:mannitol urine test. Additional markers of metabolic syndrome and the gut microbiota were examined. Patient visits occurred at baseline, 2, 6 weeks, and 6 months post-FMT.

RESULTS: There were no significant changes in HOMA-IR or hepatic PDFF in patients who received the allogenic or autologous FMT. Allogenic FMT patients with elevated small intestinal permeability (>0.025 lactulose:mannitol, n = 7) at baseline had a significant reduction 6 weeks after allogenic FMT.

DISCUSSION: FMT did not improve IR as measured by HOMA-IR or hepatic PDFF but did have the potential to reduce small intestinal permeability in patients with NAFLD.}, } @article {pmid32618640, year = {2020}, author = {Khanna, S and Pardi, D}, title = {Fecal Microbiota Transplantation for Recurrent Clostridioides difficile infection: The COVID-19 Era.}, journal = {The American journal of gastroenterology}, volume = {115}, number = {7}, pages = {971-974}, pmid = {32618640}, issn = {1572-0241}, mesh = {Anti-Bacterial Agents/therapeutic use ; Biological Specimen Banks/standards ; COVID-19 ; Clostridioides difficile/isolation & purification ; Clostridium Infections/diagnosis/microbiology/*therapy ; *Coronavirus Infections/diagnosis ; Donor Selection ; *Fecal Microbiota Transplantation ; Humans ; Mass Screening ; *Pandemics ; *Pneumonia, Viral/diagnosis ; Recurrence ; }, } @article {pmid32617914, year = {2020}, author = {Floyd, JL and Grant, MB}, title = {The Gut-Eye Axis: Lessons Learned from Murine Models.}, journal = {Ophthalmology and therapy}, volume = {9}, number = {3}, pages = {499-513}, pmid = {32617914}, issn = {2193-8245}, support = {R01EY028858/NH/NIH HHS/United States ; R01 EY012601/EY/NEI NIH HHS/United States ; T32 HL105349/HL/NHLBI NIH HHS/United States ; R01 EY025383/EY/NEI NIH HHS/United States ; R01EY028037/NH/NIH HHS/United States ; R01EY025383/NH/NIH HHS/United States ; R01EY012601/NH/NIH HHS/United States ; R01 EY028037/EY/NEI NIH HHS/United States ; R01 EY028858/EY/NEI NIH HHS/United States ; }, abstract = {A healthy gut microbiota is essential in maintaining the human body in a homeostatic state by its functions in digestion and immune tolerance. Under states of aberrant microbial composition or function (dysbiosis), the gut microbiota induces systemic inflammation that can lead to the onset of many diseases. In this review, we describe some evidence, largely from rodent studies, that supports the possible role of a dysbiotic gut microbiota in the onset and exacerbation of ocular diseases, primarily diabetic retinopathy, age-related macular degeneration, choroidal neovascularization, and uveitis. Furthermore, we examine several potential therapeutic measures that show promise in restoring the gut microbiota to a eubiotic state, preventing the aforementioned disease pathologies.}, } @article {pmid32611702, year = {2020}, author = {Woodworth, MH}, title = {mSphere of Influence: Microbiome-Associated Phenotypes Are Modifiable.}, journal = {mSphere}, volume = {5}, number = {4}, pages = {}, pmid = {32611702}, issn = {2379-5042}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; }, abstract = {Michael Woodworth focuses on translational microbiome therapeutic research. In this mSphere of Influence article, he reflects on how "Gut microbiomes of Malawian twin pairs discordant for kwashiorkor" by Michelle Smith et al. (M. I. Smith, T. Yatsunenko, M. J. Manary, I. Trehan, et al., Science 339:548-554, 2013, https://doi.org/10.1126/science.1229000) made an impact on him by revealing the causal influence of microbial communities in the development of severe malnutrition.}, } @article {pmid32610522, year = {2020}, author = {Bilinski, J and Dziurzynski, M and Grzesiowski, P and Podsiadly, E and Stelmaszczyk-Emmel, A and Dzieciatkowski, T and Dziewit, L and Basak, GW}, title = {Multimodal Approach to Assessment of Fecal Microbiota Donors based on Three Complementary Methods.}, journal = {Journal of clinical medicine}, volume = {9}, number = {7}, pages = {}, pmid = {32610522}, issn = {2077-0383}, support = {1WP/FS200/ZW2/17//Ministerstwo Nauki i Szkolnictwa Wyższego/ ; }, abstract = {Methods of stool assessment are mostly focused on next-generation sequencing (NGS) or classical culturing, but only rarely both. We conducted a series of experiments using a multi-method approach to trace the stability of gut microbiota in various donors over time, to find the best method for the proper selection of fecal donors and to find "super-donor" indicators. Ten consecutive stools donated by each of three donors were used for the experiments (30 stools in total). The experiments assessed bacterial viability measured by flow cytometry, stool culturing on different media and in various conditions, and NGS (90 samples in total). There were no statistically significant differences between live and dead cell numbers; however, we found a group of cells classified as not-dead-not-alive, which may be possibly important in selection of "good" donors. Donor C, being a regular stool donor, was characterized by the largest number of cultivable species (64). Cultivable core microbiota (shared by all donors) was composed of only 16 species. ANCOM analysis of NGS data highlighted particular genera to be more abundant in one donor vs. the others. There was a correlation between the not-dead-not-alive group found in flow cytometry and Anaeroplasma found by NGS, and we could distinguish a regular stool donor from the others. In this work, we showed that combining various methods of microbiota assessment gives more information than each method separately.}, } @article {pmid32607098, year = {2020}, author = {Park, R and Umar, S and Kasi, A}, title = {Immunotherapy in Colorectal Cancer: Potential of Fecal Transplant and Microbiota-augmented Clinical Trials.}, journal = {Current colorectal cancer reports}, volume = {16}, number = {4}, pages = {81-88}, pmid = {32607098}, issn = {1556-3790}, support = {R01 CA185322/CA/NCI NIH HHS/United States ; }, abstract = {Purpose of review: This review summarizes the role of the microbiome in colorectal cancer (CRC) in the setting of immunotherapy and emphasizes the potential of microbiota-influencing strategies with a focus on the use of fecal microbiota transplant (FMT).

Recent findings: Observations from preclinical and clinical studies suggest that the human gut microbiome is implicated in the CRC carcinogenesis and is integral in determining the clinical response and toxicity to immunotherapy. Among the therapeutic methods devised to exploit the microbiome, FMT is the most direct method and is backed by the highest level of evidence of efficacy in nonneoplastic disease settings. Furthermore, a favorable microbiome has the potential to overcome immunotherapy resistance and ameliorate immune-related adverse events (irAEs). To this end, clinical trials are underway to evaluate the potential of FMT and microbiota-augmented methods in the setting of immunotherapy in CRC.

Summary: Evidence from animal studies, retrospective studies, and smaller-scale prospective human studies have led to initiation of a number of microbiota-augmented clinical trials in CRC. Given the intimate relationship between the gut microbiota and the immune system as well as antitumor immune responses, potentiating immunotherapy and managing its toxicity are major areas of research in microbiota-augmented therapies in cancer. Therefore, evaluation of the patient microbiome as a routine part of clinical outcome analysis is warranted in future clinical trials.}, } @article {pmid32605650, year = {2020}, author = {Benech, N and Sokol, H}, title = {Fecal microbiota transplantation in gastrointestinal disorders: time for precision medicine.}, journal = {Genome medicine}, volume = {12}, number = {1}, pages = {58}, pmid = {32605650}, issn = {1756-994X}, abstract = {Fecal microbiota transplantation (FMT) has demonstrated efficacy in treating inflammatory bowel diseases and irritable bowel syndrome in an increasing number of randomized controlled trials. Recently published data gives striking insights into the factors associated with FMT success paving the road for the use of precision medicine in gastrointestinal disorders.}, } @article {pmid32601752, year = {2020}, author = {Meyer, DC and Hill, SS and Bebinger, DM and McDade, JA and Davids, JS and Alavi, K and Maykel, JA}, title = {Resolution of multiply recurrent and multifocal diverticulitis after fecal microbiota transplantation.}, journal = {Techniques in coloproctology}, volume = {24}, number = {9}, pages = {971-975}, doi = {10.1007/s10151-020-02275-w}, pmid = {32601752}, issn = {1128-045X}, abstract = {BACKGROUND: The exact pathophysiology of diverticulitis is not well understood and may be multifactorial. Recent studies highlight dysbiosis as a plausible mechanism. FMT is a safe strategy to restore commensal colon microbiota and has proven to be an effective treatment for gastrointestinal dysbiosis such as Clostridium difficile infection (CDI). There have been no studies reporting the treatment of diverticulitis with FMT. Our aim was to describe the novel application of fecal microbiota transplantation (FMT) for the treatment of recurrent diverticulitis.

CASE: We report a case of a 63-year-old woman who had a 13-year history of multiply recurrent and multifocal diverticulitis previously treated with numerous short courses of intravenous and oral antibiotics for acute flares, two segmental colon resections, and suppressive antibiotic therapy for recurrent disease. Secondary to multiple courses of antibiotics , the patient developed CDI. She was treated with a single round of FMT and subsequently stopped all antibiotics at the time of FMT.

RESULTS: In 20 months of follow-up, the patient has had no further recurrence of diverticulitis or CDI.

CONCLUSIONS: FMT could prove to be a novel therapy for refractory diverticulitis but requires further investigation.}, } @article {pmid32601270, year = {2020}, author = {Fremin, BJ and Sberro, H and Bhatt, AS}, title = {MetaRibo-Seq measures translation in microbiomes.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {3268}, pmid = {32601270}, issn = {2041-1723}, support = {P30 AG066515/AG/NIA NIH HHS/United States ; P50 AG047366/AG/NIA NIH HHS/United States ; }, mesh = {Metagenomics ; Microbiota/*genetics ; Protein Biosynthesis/genetics ; RNA-Seq/*methods ; }, abstract = {No method exists to measure large-scale translation of genes in uncultured organisms in microbiomes. To overcome this limitation, we develop MetaRibo-Seq, a method for simultaneous ribosome profiling of tens to hundreds of organisms in microbiome samples. MetaRibo-Seq was benchmarked against gold-standard Ribo-Seq in a mock microbial community and applied to five different human fecal samples. Unlike RNA-Seq, Ribo-Seq signal of a predicted gene suggests it encodes a translated protein. We demonstrate two applications of this technique: First, MetaRibo-Seq identifies small genes, whose identification until now has been challenging. For example, MetaRibo-Seq identifies 2,091 translated, previously unannotated small protein families from five fecal samples, more than doubling the number of small proteins predicted to exist in this niche. Second, the combined application of RNA-Seq and MetaRibo-Seq identifies differences in the translation of transcripts. In summary, MetaRibo-Seq enables comprehensive translational profiling in microbiomes and identifies previously unannotated small proteins.}, } @article {pmid32600151, year = {2020}, author = {Hazan, S}, title = {Rapid improvement in Alzheimer's disease symptoms following fecal microbiota transplantation: a case report.}, journal = {The Journal of international medical research}, volume = {48}, number = {6}, pages = {300060520925930}, pmid = {32600151}, issn = {1473-2300}, abstract = {Alzheimer's disease (AD), the most common form of dementia, is a leading cause of death and a major cause of morbidity in older people. The disease is characterized by progressive memory loss, cognitive impairment, and the cerebral accumulation of amyloid-β peptide. Given the health and economic impacts of AD, treatments that target the underlying etiology of AD or modify the course of the disease are of significant interest. The gut microbiome has been increasingly implicated in the pathogenesis of several neurological diseases, including multiple sclerosis and Parkinson's disease. Furthermore, emerging evidence has demonstrated that there are alterations in gut microbiome composition in patients with AD, suggesting involvement of the microbiome-gut-brain axis. We present symptom improvement in a patient with AD following fecal microbiota transplantation for a Clostridioides difficile infection.}, } @article {pmid32594732, year = {2020}, author = {Chen, QY and Tian, HL and Yang, B and Qin, HL and Li, N}, title = {[A case report of refractory methemoglobinemia after nitrite poisoning treated by fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {90-92}, doi = {10.3760/cma.j.cn.441530-20200416-00218}, pmid = {32594732}, issn = {1671-0274}, mesh = {Fecal Microbiota Transplantation/*methods ; Humans ; Methemoglobinemia/*chemically induced/*therapy ; Nitrites/*poisoning ; }, } @article {pmid32594731, year = {2020}, author = {Yang, B and Chen, QY and Tian, HL and Lin, ZL and Zhao, D and Ye, C and Zhang, XY and Qin, HL and Li, N}, title = {[Application of modified blind nasojejunal tube technique in fecal microbiota transplantation - report of 2267 cases].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {86-89}, doi = {10.3760/cma.j.cn.441530-20200414-00209}, pmid = {32594731}, issn = {1671-0274}, mesh = {Enteral Nutrition ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Humans ; Intubation, Gastrointestinal/*methods ; Jejunum ; Treatment Outcome ; }, } @article {pmid32594729, year = {2020}, author = {Chen, QY and Yang, B and Tian, HL and Lin, ZL and Zhao, D and Ye, C and Zhang, XY and Qin, HL and Li, N}, title = {[Association between the clinical efficacy of fecal microbiota transplantation in recipients and the choice of donor].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {69-76}, doi = {10.3760/cma.j.cn.441530-20200417-00222}, pmid = {32594729}, issn = {1671-0274}, support = {81670493//National Natural Science Fundation of China/ ; }, mesh = {Autistic Disorder/*therapy ; Butyrates/analysis ; Case-Control Studies ; *Donor Selection ; Fatty Acids, Volatile/analysis ; Fecal Microbiota Transplantation/*methods ; Feces/chemistry/microbiology ; Humans ; Intestinal Diseases/*therapy ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Objective: To examine the association between the clinical efficacy of fecal microbiota transplantation (FMT) in recipients and the choice of donor, and to observe the characteristics of intestinal flora and metabolites among different donors. Methods: A retrospective case-control study was conducted. Donor whose feces was administrated for more than 30 recipients was enrolled. Data of 20 FMT donors and corresponding recipients at Intestinal Microecology Diagnosis and Treatment Center of the Tenth People's Hospital from October 2018 to December 2019 were collected retrospectively. During follow-up, the efficacy of each recipient 8-week after FMT treatment was recorded and analyzed. Based on the efficacy of each donor, the donors were divided into three groups: high efficacy group (effective rate >60%, 10 donors), moderate efficacy group (effective rate 30%-60%, 6 donors) and low efficacy group (effective rate <30%, 4 donors). The structure of the bacterial flora and the content of fecal short-chain fatty acids in each group of donors were detected and compared among groups. Association of the efficacy of each donor group with the morbidity of complications, and association of efficacy of recipients with donors were analyzed. The evaluation indicators of FMT efficacy included objective clinical effectiveness and/or subjective effectiveness. Objective effectiveness indicated clinical cure plus clinical improvement, and subjective effectiveness indicated marked effectiveness plus medium effectiveness through questionnaire during follow-up. Results: A total of 1387 recipients were treated by 20 donors, including 749 cases of chronic constipation, 141 cases of chronic diarrhea, 107 cases of inflammatory bowel disease (IBD), 121 cases of irritable bowel syndrome (IBS), 83 cases of autism, and 186 cases of other diseases, such as radiation bowel injury, intestinal pseudo-obstruction, paralytic intestinal obstruction, functional bloating and allergic diseases. There were 829 cases, 403 cases, and 155 cases in high efficacy group, moderate efficacy group and low efficacy group respectively. Baseline data among 3 groups were not significantly different (all P> 0.05). In comparison of bacterial abundance (operational taxonomic unit, OTU) among different effective donor groups, the high efficacy group was the highest (330.68±57.28), the moderate efficacy group was the second (237.79±41.89), and the low efficacy group was the lowest (160.60±49.61), whose difference was statistically significant (F=16.910, P<0.001). In comparison of bacterial diversity (Shannon index), the high efficacy group and the moderate efficacy group were higher (2.96±0.36 and 2.67±0.54, respectively), and the low efficacy group was lower (2.09±0.55), whose difference was statistically significant (F=5.255, P=0.017). In comparison of butyric acid content among three groups, the high efficacy group had the highest [(59.20±9.00) μmol/g], followed by middle efficacy group [(46.92±9.48) μmol/g], and the low efficacy group had the lowest [(37.23±5.03) μmol/g], whose difference was statistically significant (F=10.383, P=0.001). The differences of acetic acid and propionic acid among three groups were not statistically significant (all P>0.05). A total of 418 cases developed complications (30.1%). Morbidity of complication in low efficacy group, moderate efficacy group and high efficacy group was 40.6% (63/155), 30.0% (121/403) and 28.2% (243/829) respectively, and the difference was statistically significant (χ(2)=9.568, P=0.008). The incidence of diarrhea in low efficacy group, moderate efficacy group and high efficacy group was 7.1% (11/155), 4.0% (16/403) and 2.8% (23/829) respectively, and the difference was statistically significant (χ(2)=7.239, P=0.027). Comparing the incidences of other types of complications, no statistically significant differences were found (all P>0.05). Follow up began 8 weeks after the FMT treatment. The total follow-up rate was 83.6% (1160/1387). The overall effective rate 58.3% (676/1160). Effective rates of various diseases were as follows: chronic constipation 54.3% (328/604), chronic diarrhea 88.5% (115/130), IBD 56.1% (55/98), IBS 55.1% (59/107), autism 61.6% (45/73), and other diseases 50.0% (74/148). Comparing the effective rate of three groups of donors for different diseases, there was no statistically significant difference in chronic diarrhea (P>0.05); there was a positive correlation trend in IBD, IBS and autism, but the differences were not statistically significant (all P>0.05). For chronic constipation and other diseases, high efficacy group had the highest effective rate [65.0% (243/374) and 63.2% (55/87)], followed by moderate efficacy group [49.4% (86/174) and 38.1% (16/42)], and low efficacy group had the lowest [16.1% (9/56) and 15.8% (3/19)], whose differences were significant (all P<0.05). Conclusions: Different donors have different efficacy in different diseases. Chronic constipation, radiation bowel injury, etc. need to choose donors with high efficacy. IBD, IBS and autism may also be related to the effectiveness of donors, while chronic diarrhea is not associated to the donor. The efficiency of the donor is negatively correlated to the morbidity of complications. The abundance and diversity of intestinal flora and the content of butyric acid may affect the efficacy of the donor.}, } @article {pmid32594728, year = {2020}, author = {Tian, HL and Chen, QY and Yang, B and Ma, CL and Lin, ZL and Zhang, XY and Zhou, SL and Qin, HL and Li, N}, title = {[Effects of fecal microbiota transplantation in different routes on the clinical efficacy of slow transit constipation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {63-68}, doi = {10.3760/cma.j.cn.441530-20200415-00212}, pmid = {32594728}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; 04.99.18001//Special fund for the construction of the clinical center of Tenth People's Hospital of Tongji University/ ; }, mesh = {Adult ; Constipation/physiopathology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Gastrointestinal Transit/*physiology ; Humans ; Retrospective Studies ; Treatment Outcome ; }, abstract = {Objective: To evaluate the efficacy and safety of the fecal microbiota transplantation (FMT) in the different route administration for slow transit constipation (STC). Methods: A retrospective cohort study was conducted. The clinical data of 270 STC patients who voluntarily received FMT treatment in the Tenth People's Hospital of Tongji University from May 2018 to May 2019 were collected. Non-relative healthy adult standard donors were applied. The treatment routes of bacterial flora transplantation included nasojejunal tube (nasal enteral tube group, 120 cases), oral enterobacterial capsule treatment (oral capsule group, 120 cases), and colonoscopy infusion (colonoscopy group, 30 cases). The efficacy and safety of treatment among the three groups were compared. Results: Transplanted bacteria of three groups were extracted from 100 g of fresh feces. All the patients successfully completed the transplantation. The waiting time for the nasal enteral tube group, oral capsule group and colonoscopy group was (1.5±0.5) d, (0.4±0.3) d and (3.6±0.8) d respectively; the cost of establishing the transplantation path was (495±20) yuan, (25±10) yuan and (1420±45) yuan respectively, whose differences were statistically significant (F=9.210, P=0.03; F=10.600,P=0.01). The clinical improvement rates at 1 month after FMT treatment in the nasojejunal tube group, oral capsule group and colonoscopy group were 74.2% (89/120), 60.0% (72/120) and 53.3% (16/30) respectively, whose difference was statistically significant (χ(2)=5.990, P<0.05). The clinical improvement rates at 3 months after treatment were 71.1% (69/97), 53.6% (45/84), and 44.0% (11/25) respectively, whose difference was statistically significant (χ(2)=7.620, P<0.05). The incidence of adverse reactions in the colonoscopy group was 76.7% (23/30), which was higher than that in the nasal nasojejunal group (39.2%, 47/120) and oral capsule group (21.7%, 26/120). The most common adverse reactions in the nasojejunal tube group, oral capsule group and colonoscopy group were respiratory discomfort (17.5%, 21/120), nausea and vomiting (10.0%, 12/120), and diarrhea (36.7%, 11/30). During the 3-month follow-up after treatment, no FMT-related adverse reactions were reported. Conclusions: The nasojejunal tube route has stable clinical efficacy and operability, while the oral capsule route has shorter waiting time and less cost. However, the adverse reactions caused by different transplantation methods are different, thus personalized transplantation method should be recommended.}, } @article {pmid32594727, year = {2020}, author = {Lin, ZL and Chen, QY and Tian, HL and Yang, B and Zhao, D and Ye, C and Zhang, XY and Ma, CL and Qin, HL and Li, N}, title = {[Effect of fecal bacterial preservation time on the outcomes of fecal microbiota transplantation for slow transit constipation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {56-62}, doi = {10.3760/cma.j.cn.441530-20200414-00207}, pmid = {32594727}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; 04.99.18001//Special Fund for the Construction of the Clinical Center of Tenth People's Hospital of Tongji University/ ; }, mesh = {Constipation/physiopathology/*therapy ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Transit/*physiology ; Humans ; Quality of Life ; Retrospective Studies ; Time Factors ; Treatment Outcome ; }, abstract = {Objective: To investigate the effect of different fecal bacterial preservation time on the efficacy and complications of FMT. Methods: A retrospective cohort study was carried out. Clinical data of 483 patients with slow transit constipation undergoing voluntary FMT at Intestinal Microecology Diagnosis and Treatment Center from August 2017 to October 2019 were retrospectively collected. According to the storage time of fecal bacterial samples used in FMT treatment, the cases were divided into fresh bacterial solution (n=29), bacterial solution stored at -80℃ for 1 week (n=187), 1 month (n=121), 3 months (n=89), 6 months (n=38), and 12 months (n=19). The total number of complete bowel movement, Wexner constipation score, gastrointestinal quality of life index (GIQLI), FMT satisfaction score and related adverse reactions were summarized and compared among groups 1 week and 1 month after FMT treatment. Results: There were no statistically significant differences in the baseline data of patients among different bacterial solution storage time (all P>0.05). After 1 month of treatment, the overall frequency of defecation of all the patients was (3.83 ± 1.22) times/week, Wexner constipation score was (6.74 ± 3.56) points, GIQLI score was (108.76 ± 15.38) points, clinical cure rate was 57.8% (279/483). The improvement rate was 66.3% (320/483), and the treatment satisfaction was (3.85 ± 0.93) points. No severe FMT-associated complication and death were observed during treatment and follow-up period. FMT-related adverse events occurred in 115 cases (23.8%), including nausea in 25 cases (5.2%), vomiting in 13 (2.7%), diarrhea in 21 (4.3%), abdominal pain in 16 (3.3%), abdominal distension in 33 (6.8%), sore throat in 56 (11.6%) and fever in 16(3.3%), all of which relieved after symptomatic treatment. There were no statistically significant differences in the number of defecations, Wexner constipation scores, and GIQLI scores before FMT, 1 week and 1 month after FMT treatment among different bacterial solution storage groups (all P>0.05). Differences of clinical cure rate, clinical improvement rate, and treatment satisfaction of patients 1 week and 1 month after treatment were not statistically significant (all P>0.05). Among the groups, differences in the overall complications and types of complications after FMT treatment were not statistically significant (all P>0.05). Conclusions: FMT is safe and effective in the treatment of slow transit constipation. Fresh fecal bacterial samples or fecal bacterial samples frozen at -80℃ for 1 year can be safely applied to FMT for the treatment of slow transit constipation, with stable short-term efficacy and without serious adverse reactions.}, } @article {pmid32594726, year = {2020}, author = {Chen, QY and Tian, HL and Yang, B and Lin, ZL and Zhao, D and Ye, C and Zhang, XY and Qin, HL and Li, N}, title = {[Effect of intestinal preparation on the efficacy and safety of fecal microbiota transplantation treatment].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {48-55}, doi = {10.3760/cma.j.cn.441530-20200418-00225}, pmid = {32594726}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; }, mesh = {Adult ; Anti-Bacterial Agents/administration & dosage ; Autistic Disorder/*therapy ; Cathartics/administration & dosage ; Enema ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; Humans ; Intestinal Diseases/*therapy ; Male ; Middle Aged ; Preoperative Care/methods ; Recurrence ; Retrospective Studies ; Time Factors ; Treatment Outcome ; }, abstract = {Objective: To investigate the effect of intestinal preparation on the efficacy and complications of fecal microbiota transplantation (FMT). Methods: A retrospective cohort study was performed. Clinical and follow-up data of 1501 patients who received FMT in the department of Colorectal Disease Specialty, Intestinal Microecology Diagnosis and Treatment Center, the Tenth People's Hospital, Tongji University from February 2018 to June 2019 were collected retrospectively. According to the intestinal preparation before FMT treatment, patients were divided into non-intestinal preparation group (n=216), antibiotic pretreatment group (n=383), intestinal cleansing group (n=267), and antibiotic combined with intestinal cleansing group (n=635). The adverse reactions after FMT treatment and the effective rates at 4-week and 8-week after treatment among the groups were compared. Patients, who repeated FMT treatment in the 3rd month and the 6th month due to reduced efficacy or ineffectiveness were divided into two subgroups: without intestinal preparation group and with intestinal preparation group. The effective rates of the two subgroups were compared. Results: Of the 1501 cases, 588 were male and 913 were female with mean age of (43.3±13.7) years and body mass index of (20.2±2.1) kg/m(2). Transplantation course was (3.3±1.7) weeks. The underlying diseases mainly included constipation (n=564), Crohn's disease (n=157), ulcerative colitis (n=142), irritable bowel syndrome (n=158), recurrent C. difficile infection (CDI) (n=106), autism (n=84), radiation intestinal injury (n=133), radiation enteritis (n=133), and non-CDI chronic diarrhea (n=60); the remaining cases (n=155). Baseline data among the 4 groups were not significantly different (all P>0.05). The overall morbidity of complication was 31.1% (467/1501), including 41 cases of vomiting (2.7%), 91 of nausea (6.1%), 49 of diarrhea (3.3%), 41 of abdominal pain (2.7%), 79 of bloating (5.3%), 72 of throat pain (4.8%), 38 of dizziness (2.5%), 51 of fever (3.4%), 3 of pulmonary infection (0.2%) and 2 of intestinal infection (0.1%). The above symptoms disappeared after symptomatic treatment. There was no statistically significant difference in the incidence of adverse reactions among the 4 groups (P>0.05). After 4-week of FMT treatment, the overall effective rate was 63.5% (902/1420); the effective rate of non-intestinal preparation group, antibiotic pretreatment group, intestinal cleaning group, and antibiotic combined with intestinal cleansing groupwas 57.6% (114/198), 64.2% (231/360), 60.2% (154/265) and 66.5% (403/606), respectively, with no statistically significant difference (χ(2)=6.659, P=0.084). After 8-week of FMT treatment, the overall effective rate was 61.3% (729/1293); the effective rate of non-intestinal preparation group, antibiotic pretreatment group, intestinal cleaning group, and antibiotic combined with intestinal cleansing group was 54.0% (88/163), 62.2% (202/325), 57.4% (132/230) and 64.4% (370/575), respectively, with no statistically significant difference (χ(2)=13.620, P=0.003). The effective rates of antibiotic combined with intestinal cleansing group and antibiotic pretreatment group were obviously higher than that of non-intestinal preparation group (χ(2)=5.789, P=0.016; χ(2)=10.117, P=0.001). Subgroup analysis showed that in the third month, the effective rate at 4-week after treatment was 60.1% (184/306) in the without intestinal preparation group and 61.5% (115/187) in the with intestinal preparation group, whose difference was not significant (χ(2)=0.091, P=0.763); however, in the sixth month, the effective rate at 4-week after treatment was 51.4% (89/173) in the without intestinal preparation group and 61.2% (161/263) in the with intestinal preparationgroup, whose difference was significant (χ(2)=4.229, P=0.040). Conclusions: FMT treatment is safe and effective. The combination of antibiotics and intestinal cleaning can improve overall efficacy of FMT. For patients who need repeated FMT treatment, the combination of antibiotics and intestinal cleaning program within 3 months has no significant effect on the effective rate, but in the sixth month, combinedpreparation is necessary.}, } @article {pmid32594725, year = {2020}, author = {Zhang, FM and Liu, YF}, title = {[Evidence and decision of the choice of delivery way in washed microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {45-47}, doi = {10.3760/cma.j.cn.441530-20200507-00259}, pmid = {32594725}, issn = {1671-0274}, mesh = {Enema ; Enteral Nutrition ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome ; Humans ; Intubation, Gastrointestinal ; }, abstract = {Washed microbiota transplantation (WMT) is a new concept and technique of fecal microbiota transplantation. The delivery routes of WMT include oral capsule, nasogastric tube, nasojejunal tube, gastroscopy, colonic transendoscopic enteral tubing, and anal enema. The research results among different indications or different designs based on the same indication are quite different, partially because of the influence of WMT delivery route. In the process of clinical research design and clinical practice, there are four aspects that affect the decision-making of WMT delivery route: safety, efficacy, cost-effectiveness, and patients' willingness. This article focuses on how to integrate the four aspects mentioned above in the decision-making process of choosing proper delivery of WMT for the final goal of mutual satisfaction between doctors and patients.}, } @article {pmid32594720, year = {2020}, author = {, and , and , and , }, title = {[Chinese experts consensus on clinical practice of the selection and establishment of fecal microbiota transplantation delivery routes].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {14-20}, doi = {10.3760/cma.j.cn.441530-20200420-00228}, pmid = {32594720}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; }, mesh = {China ; Consensus ; Fecal Microbiota Transplantation/adverse effects/*methods/*standards ; Humans ; }, abstract = {Fecal microbiota transplantation (FMT) has gradually shown application prospects in the treatment of intestinal and extraintestinal diseases. In order to standardized FMT operation, based on the clinical experience of the Tenth People's Hospital Affiliated to Tongji University, combined with domestic and foreign literature, Parenteral and Enteral Nutrition Branch of Chinese Medical Association, Enhanced Recovery after Surgery Branch of China International Health Care Promotion Exchange Association, China Microecological Treatment Innovation Alliance, and Microecology Committee of Shanghai Preventive Medicine Association to formulated the" Chinese experts consensus on clinical practice of the selection and establishment of fecal microbiota transplantation delivery routes". It includes four parts: the selection of delivery route, the methodology of transplantation path establishment, the clinical application, and the monitoring of adverse events.}, } @article {pmid32594719, year = {2020}, author = {, and , and , and , }, title = {[Chinese experts consensus on standardized methodology and clinical application of fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {5-13}, doi = {10.3760/cma.j.cn.441530-20200420-00231}, pmid = {32594719}, issn = {1671-0274}, support = {81670493//National Natural Science Foundation of China/ ; }, mesh = {China ; Consensus ; Fecal Microbiota Transplantation/adverse effects/*methods/*standards ; Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Treatment Outcome ; }, abstract = {Fecal microbiota transplantation (FMT) is to transplant the functional bacteria in the feces of healthy people into the patients' intestines, rebuild the new balance of intestinal flora, and achieve the treatment goals of intestinal and extraintestinal diseases. In the past 10 years, FMT has made a breakthrough in the treatment of intestinal and extraintestinal diseases, which is highly expected to treat difficult diseases. However, due to the complexity of FMT methodology and the lack of a unified standard, there is a high heterogeneity in FMT efficacy among various researches, greatly affected its clinical application. Under the initiative of Parenteral and Enteral Nutrition Branch of Chinese Medical Association, Enhanced Recovery after Surgery Branch of China International Health Care Promotion Exchange Association, China Microecological Treatment Innovation Alliance, and Microecology Committee of Shanghai Preventive Medicine Association, the first expert consensus on standardized methodology and clinical application of FMT was established in China, with a view to improving the efficacy of FMT, reducing the incidence of adverse reactions and promoting the clinical application of FMT.}, } @article {pmid32594718, year = {2020}, author = {Li, N}, title = {[Practice and consideration of fecal microbiota transplantation].}, journal = {Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery}, volume = {23}, number = {Z1}, pages = {1-4}, doi = {10.3760/cma.j.cn.441530-20200420-00230}, pmid = {32594718}, issn = {1671-0274}, mesh = {China ; Clostridioides difficile/*isolation & purification ; Clostridium Infections/*therapy ; Fecal Microbiota Transplantation/methods/*standards ; Feces/*microbiology ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestines/*microbiology/physiology/physiopathology ; Recurrence ; Treatment Outcome ; }, abstract = {As an innovative therapy, FMT has made a breakthrough in the treatment of recurrent Clostridium difficile infection (CDI). With the rapid development of biotechnology, the relationship between intestinal microflora and diseases has been gradually eluciated. Great hope has also been given to FMT in other intestinal and extraintestinal diseases with ineffective traditional treatment. However, as a new therapy method, FMT still has many unknown fields, such as the selection of clinical donors, the preparation of standardized bacterial solution and capsule, the selection of indications, the matching of donor and receptor, and the prevention and treatment of complications. Since 2012, our center has carried out treatment research and practice of FMT, so far with more than 60 000 FMTs for more than 3500 cases. Based on large sample data and experience, this special issue reports and discusses the above topics, and focuses on the establishment and clinical application of standardized methodology of FMT, which will undoubtedly play a positive role in promoting the healthy development of FMT treatment in China.}, } @article {pmid32592577, year = {2020}, author = {Jiang, S and Wang, B and Sha, T and Li, X}, title = {Changes in the Intestinal Microbiota in Patients with Stage 5 Chronic Kidney Disease on a Low-Protein Diet and the Effects of Human to Rat Fecal Microbiota Transplantation.}, journal = {Medical science monitor : international medical journal of experimental and clinical research}, volume = {26}, number = {}, pages = {e921557}, pmid = {32592577}, issn = {1643-3750}, abstract = {BACKGROUND Dietary protein restriction is recommended for patients with stage 5 chronic kidney disease (CKD), or end-stage renal disease (ESRD). This study aimed to investigate the changes in the intestinal microbiota due to different dietary regimens in patients with stage 5 CKD and the effects of human to rat fecal microbiota transplantation. MATERIAL AND METHODS Second-generation high-throughput sequencing was used to analyze the amplifiers in the 16S rRNA V4 region in the intestinal microbiota of patients with stage 5 CKD and healthy individuals. The intestinal microbiota of patients with stage 5 CKD in the low-protein group and the healthy individual group was transferred by human to rat fecal microbiota transplantation using Sprague-Dawley rats. Data underwent meta-analysis using Meta-Stat. RESULTS Patients with CKD on a very low-protein diet showed an increase in intestinal Escherichia, Shigella, and Klebsiella, a decrease in Blautia, heat map analysis showed that Christensenellaceae R-7 group rs1 were significantly increased, and MetaStat analysis showed that Bacteroides, Prevotella, and Mitsuokella were significantly increased. Following human to rat fecal microbiota transplantation from patients with stage 5 CKD, the profile of the rat intestinal microbiota became similar to the human donors. The weight of the rats fed a very low-protein diet after fecal microbiota transplantation significantly decreased after six weeks compared with normal rats and rats that received normal fecal microbiota transplantation. CONCLUSIONS Patients with stage 5 CKD on a very low-protein diet showed changes in the intestinal microbiota that could be transferred from humans to rats by fecal microbiota transplantation.}, } @article {pmid32588829, year = {2020}, author = {Zhgun, ES and Kislun, YV and Kalachniuk, TN and Veselovsky, VA and Urban, AS and Tikhonova, PO and Pavlenko, AV and Ilchenko, GN and Ilina, EN}, title = {[Evaluation of metabolites levels in feces of patients with inflammatory bowel diseases].}, journal = {Biomeditsinskaia khimiia}, volume = {66}, number = {3}, pages = {233-240}, doi = {10.18097/PBMC20206603233}, pmid = {32588829}, issn = {2310-6972}, mesh = {Fecal Microbiota Transplantation ; *Feces/chemistry ; *Gastrointestinal Microbiome ; Humans ; *Inflammatory Bowel Diseases/metabolism/therapy ; Quality of Life ; }, abstract = {Inflammatory bowel diseases (IBD), which include ulcerative colitis (UC) and Crohn's disease (CD), are chronic intestinal inflammatory disorders with an unknown etiology. They are characterized by chronic recurrent inflammation of the intestinal mucosa and lead to a significant decrease in the quality of life and death of patients. IBD are associated with suppression of normal intestinal microflora, including a decrease in bacteria, producers of short chain fatty acids (SCFAs), exhibiting anti-inflammatory and protective properties. Among the various methods of intestinal microflora correction, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, is of a particular interest. As a result, a positive therapeutic effect is observed, accompanied by the restoration of the normal intestinal microflora of the patient. A significant drawback of the method is the lack of standardization. Metabolites produced by intestinal microflora, namely SCFAs, allow objective assessment of the functional state of the intestinal microbiota and, consequently, the success of the FMT procedure. Using gas chromatography and nuclear magnetic resonance spectroscopy techniques, we have analyzed concentrations and molar ratios of SCFAs in fecal samples of 60 healthy donors. Results were in good accord when comparing two methods as well as with published data. Analysis of SCFAs in feces of patients with UC (19 patients) and CD (17 patients) revealed a general decrease in the concentration of fatty acids in the experimental groups with significant fluctuations in the values in experimental groups compared to control group of healthy donors. On the limited group of IBD patients (6 patients with UC and 5 patients with CD) concentration of SCFAs before and within 30 days of observation after FMT was determined. It was shown that FMT had a significant impact on the SCFAs levels within 1 month term; tendency to reach characteristics of healthy donors is unambiguously traced for both diseases.}, } @article {pmid32587239, year = {2020}, author = {Li, H and Xu, H and Li, Y and Jiang, Y and Hu, Y and Liu, T and Tian, X and Zhao, X and Zhu, Y and Wang, S and Zhang, C and Ge, J and Wang, X and Wen, H and Bai, C and Sun, Y and Song, L and Zhang, Y and Hui, R and Cai, J and Chen, J}, title = {Alterations of gut microbiota contribute to the progression of unruptured intracranial aneurysms.}, journal = {Nature communications}, volume = {11}, number = {1}, pages = {3218}, pmid = {32587239}, issn = {2041-1723}, mesh = {Animals ; Case-Control Studies ; Clostridiaceae/*metabolism ; Cohort Studies ; Disease Progression ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Humans ; *Intracranial Aneurysm/microbiology/pathology ; Male ; Mice ; Prognosis ; Risk Factors ; Taurine/*metabolism ; }, abstract = {Unruptured intracranial aneurysm (UIA) is a life-threatening cerebrovascular condition. Whether changes in gut microbial composition participate in the development of UIAs remains largely unknown. We perform a case-control metagenome-wide association study in two cohorts of Chinese UIA patients and control individuals and mice that receive fecal transplants from human donors. After fecal transplantation, the UIA microbiota is sufficient to induce UIAs in mice. We identify UIA-associated gut microbial species link to changes in circulating taurine. Specifically, the abundance of Hungatella hathewayi is markedly decreased and positively correlated with the circulating taurine concentration in both humans and mice. Consistently, gavage with H. hathewayi normalizes the taurine levels in serum and protects mice against the formation and rupture of intracranial aneurysms. Taurine supplementation also reverses the progression of intracranial aneurysms. Our findings provide insights into a potential role of H. hathewayi-associated taurine depletion as a key factor in the pathogenesis of UIAs.}, } @article {pmid32585945, year = {2020}, author = {Leo, S and Lazarevic, V and Girard, M and Gaïa, N and Schrenzel, J and de Lastours, V and Fantin, B and Bonten, M and Carmeli, Y and Rondinaud, E and Harbarth, S and Huttner, BD}, title = {Metagenomic Characterization of Gut Microbiota of Carriers of Extended-Spectrum Beta-Lactamase or Carbapenemase-Producing Enterobacteriaceae Following Treatment with Oral Antibiotics and Fecal Microbiota Transplantation: Results from a Multicenter Randomized Trial.}, journal = {Microorganisms}, volume = {8}, number = {6}, pages = {}, pmid = {32585945}, issn = {2076-2607}, support = {282512//European Commission under the Seventh Framework Programme (FP7/2007) for Research and technology/ ; }, abstract = {Background: The R-GNOSIS (Resistance in Gram-Negative Organisms: Studying Intervention Strategies) WP3 study was the first multicenter randomized clinical trial systematically investigating fecal microbiota transplantation (FMT) for intestinal decolonization of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). Here, we characterized the temporal dynamics of fecal microbiota changes in a sub-cohort of the R-GNOSIS WP3 participants before and after antibiotics/FMT using whole metagenome shotgun sequencing. Methods: We sequenced fecal DNA obtained from 16 ESBL-E/CPE carriers having received oral colistin/neomycin followed by FMT and their corresponding seven donors. Ten treatment-naïve controls from the same trial were included. Fecal samples were collected at baseline (V0), after antibiotics but before FMT (V2) and three times after FMT (V3, V4 and V5). Results: Antibiotic treatment transiently decreased species richness and diversity and increased the abundance of antibiotic resistance determinants (ARDs). Bifidobacterium species, together with butyrate- and propionate-producing species from Lachnospiraceae and Ruminococcaceae families were significantly enriched in post-FMT microbiota of treated carriers. After FMT, the proportion of Enterobacteriaceae was lower compared to baseline but without statistical significance. Conclusions: Combined antibiotic and FMT treatment resulted in enrichment of species that are likely to limit the gut colonization by ESBL-E/CPE.}, } @article {pmid32585148, year = {2020}, author = {Basson, AR and Zhou, Y and Seo, B and Rodriguez-Palacios, A and Cominelli, F}, title = {Autologous fecal microbiota transplantation for the treatment of inflammatory bowel disease.}, journal = {Translational research : the journal of laboratory and clinical medicine}, volume = {226}, number = {}, pages = {1-11}, pmid = {32585148}, issn = {1878-1810}, support = {R01 DK055812/DK/NIDDK NIH HHS/United States ; }, mesh = {Clostridium Infections/therapy ; *Fecal Microbiota Transplantation ; Humans ; Inflammatory Bowel Diseases/*therapy ; Transplantation, Autologous ; Treatment Outcome ; }, abstract = {The term autologous fecal microbiota transplantation (a-FMT) refers herein to the use of one's feces during a healthy state for later use to restore gut microbial communities after perturbations. Generally, heterologous fecal microbiota transplantation (h-FMT), where feces from a ``healthy" donor is transplanted into a person with illness, has been used to treat infectious diseases such as recurrent Clostridioides difficile infection (CDI), with cure rates of up to 90%. In humans, due to limited response to medicines, h-FMT has become a hallmark intervention to treat CDI. Extrapolating the benefits from CDI, h-FMT has been attempted in various diseases, including inflammatory bowel disease (IBD), but clinical response has been variable and less effective (ranging between 24% and 50%). Differences in h-FMT clinical response could be because CDI is caused by a Clostridial infection, whereas IBD is a complex, microbiome-driven immunological inflammatory disorder that presents predominantly within the gut wall of genetically-susceptible hosts. FMT response variability could also be due to differences in microbiome composition between donors, recipients, and within individuals, which vary with diet, and environments, across regions. While donor selection has emerged as a key factor in FMT success, the use of heterologous donor stool still places the recipient at risk of exposure to infectious/pathogenic microorganisms. As an implementable solution, herein we review the available literature on a-FMT, and list some considerations on the benefits of a-FMT for IBD.}, } @article {pmid32584703, year = {2020}, author = {Gong, Z and Wang, Y}, title = {Immune Checkpoint Inhibitor-Mediated Diarrhea and Colitis: A Clinical Review.}, journal = {JCO oncology practice}, volume = {16}, number = {8}, pages = {453-461}, doi = {10.1200/OP.20.00002}, pmid = {32584703}, issn = {2688-1535}, abstract = {Immune-mediated diarrhea and colitis (IMDC) is among the most common immune-related adverse events in patients with cancer treated with immune checkpoint inhibitors (ICIs). Many factors will affect the risk of IMDC, including the type of ICI used, the type of underlying cancer, and patient characteristics. A recent study showed that preexisting inflammatory bowel disease significantly increases the risk of diarrhea and colitis with ICI treatment. In terms of management, early endoscopic evaluation improves clinical outcome by identifying high-risk patients who will benefit from early add-on immunosuppressants. Inflammatory markers, including fecal lactoferrin and calprotectin, are good screening tools to predict which patients are at risk for colitis. Calprotectin especially is associated with colitis outcome and can be used as a surrogate marker to follow treatment response. Corticosteroids remain the first-line medical treatment of IMDC management, and add-on therapy with vedolizumab or infliximab should be considered in selected patients. Fecal microbiota transplantation may be considered in refractory cases. The decision to resume ICI should be decided by balancing the risk of recurrent IMDC and the likelihood of benefiting from further ICI treatment. There is no clear evidence about whether the use of immunosuppressants will result in a worse cancer outcome. With emerging evidence, our understanding and management strategies are likely to evolve in the future.}, } @article {pmid32582202, year = {2020}, author = {Yan, Y and Zhou, X and Guo, K and Zhou, F and Yang, H}, title = {Chlorogenic Acid Protects Against Indomethacin-Induced Inflammation and Mucosa Damage by Decreasing Bacteroides-Derived LPS.}, journal = {Frontiers in immunology}, volume = {11}, number = {}, pages = {1125}, pmid = {32582202}, issn = {1664-3224}, abstract = {Background: Chlorogenic acid (CGA), a natural bioactive polyphenol, exerts anti-inflammatory, antioxidant, and antibacterial effects that support the maintenance of intestinal health. However, the influence of CGA on gut microbiota and their metabolites, as well as its potential effects and mechanism of action in inflammatory bowel disease, remain to be elucidated. Methods: First, an oral gavage was used to administer CGA to indomethacin-treated mice. Then, fecal microbiota transplantation was performed to explore the role of intestinal microbiota in indomethacin-induced inflammation. Results: CGA treatment protected against body weight loss, damage to intestinal morphology and integrity, inflammation, and alteration of microbiota composition in indomethacin-treated mice. Interestingly, CGA failed to inhibit inflammation or protect intestine integrity in mice treated with antibiotics. Notably, mice who had been colonized with intestinal microbiota from CGA-treated or CGA-and-indomethacin-treated mice, through the fecal microbiota transplantation program, were protected from indomethacin-induced inflammation, growth of Bacteroides, and the accumulation of Bacteroides-derived LPS, in congruence with those who had been treated with CGA. Conclusion: The results suggest that CGA may protect intestine integrity and alleviate inflammatory responses, primarily by inhibiting the growth of Bacteroides and the accumulation of Bacteroides-derived LPS, in indomethacin-induced colitis. This newly identified mechanism broadens our knowledge of how CGA exerts protective effects on intestinal inflammation and provides strategies for the prevention of gastrointestinal mucosal damage in patients treated with indomethacin.}, } @article {pmid32582121, year = {2020}, author = {Liang, W and Zhao, L and Zhang, J and Fang, X and Zhong, Q and Liao, Z and Wang, J and Guo, Y and Liang, H and Wang, L}, title = {Colonization Potential to Reconstitute a Microbe Community in Pseudo Germ-Free Mice After Fecal Microbe Transplant From Equol Producer.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {1221}, pmid = {32582121}, issn = {1664-302X}, abstract = {Human intestinal microbiota plays a crucial role in the conversion of isoflavones into equol. Usually, human microbiota-associated (HMA) animal models are used, since it is difficult to establish the mechanism and causal relationship between equol and microbiota in human studies. Currently, several groups have successfully established HMA animal models that produce equol through germ-free mice or rats; however, the HMA model of producing equol through pseudo germ-free mice has not been established. The objective of this study is to establish an HMA mice model for equol production through pseudo germ-free mice, mimicking the gut microbiota of an adult human equol producer. First, a higher female equol producer was screened as a donor from 15 volunteers. Then, mice were exposed to vancomycin, neomycin sulfate, metronidazole, and ampicillin for 3 weeks to obtain pseudo germ-free mice. Finally, pseudo germ-free mice were inoculated with fecal microbiota of the equol producer for 3 weeks to establish HMA mice of producing equol. The results showed that (i) the ability to produce equol was partially transferred from the donor to the HMA mice. (ii) Most of the original intestinal microbiota of mice were eliminated after broad-spectrum antibiotic administration. (iii) The taxonomy data from HMA mice revealed similar taxa to the donor sample, and the species richness returned to the level close to the donor. (iv) The family Coriobacteriaceae and genera Collinsella were successfully transferred from the donor to HMA mice. In conclusion, the HMA mice model for equol production, based on pseudo germ-free mice, can replace the model established by germ-free mice. The model also provides a basis for studying microbiota during the conversion from isoflavones into equol.}, } @article {pmid32580023, year = {2020}, author = {Inamura, K}, title = {Gut microbiota contributes towards immunomodulation against cancer: New frontiers in precision cancer therapeutics.}, journal = {Seminars in cancer biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.semcancer.2020.06.006}, pmid = {32580023}, issn = {1096-3650}, abstract = {The microbiota influences human health and the development of diverse diseases, including cancer. Microbes can influence tumor initiation and development in either a positive or negative manner. In addition, the composition of the gut microbiota affects the efficacy and toxicity of cancer therapeutics as well as therapeutic resistance. The striking impact of microbiota on oncogenesis and cancer therapy provides compelling evidence to support the notion that manipulating microbial networks represents a promising strategy for treating and preventing cancer. Specific microbes or the microbial ecosystem can be modified via a multiplicity of processes, and therapeutic methods and approaches have been evolving. Microbial manipulation can be applied as an adjunct to traditional cancer therapies such as chemotherapy and immunotherapy. Furthermore, this approach displays great promise as a stand-alone therapy following the failure of standard therapy. Moreover, such strategies may also benefit patients by avoiding the emergence of toxic side effects that result in treatment discontinuation. A better understanding of the host-microbial ecosystem in patients with cancer, together with the development of methodologies for manipulating the microbiome, will help expand the frontiers of precision cancer therapeutics, thereby improving patient care. This review discusses the roles of the microbiota in oncogenesis and cancer therapy, with a focus on efforts to harness the microbiota to fight cancer.}, } @article {pmid32577835, year = {2020}, author = {McQuade, JL and Ologun, GO and Arora, R and Wargo, JA}, title = {Gut Microbiome Modulation Via Fecal Microbiota Transplant to Augment Immunotherapy in Patients with Melanoma or Other Cancers.}, journal = {Current oncology reports}, volume = {22}, number = {7}, pages = {74}, pmid = {32577835}, issn = {1534-6269}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; T32 CA009599/CA/NCI NIH HHS/United States ; }, abstract = {PURPOSE OF REVIEW: We review emerging evidence regarding the impact of gut microbes on antitumor immunity, and ongoing efforts to translate this in clinical trials.

RECENT FINDINGS: Pre-clinical models and human cohort studies support a role for gut microbes in modulating overall immunity and immunotherapy response, and numerous trials are now underway exploring strategies to modulate gut microbes to enhance responses to cancer therapy. This includes the use of fecal microbiota transplant (FMT), which is being used to treat patients with Clostridium difficile infection among other non-cancer indications. The use of FMT is now being extended to modulate gut microbes in patients being treated with cancer immunotherapy, with the goal of enhancing responses and/or to ameliorate toxicity. However, significant complexities exist with such an approach and will be discussed herein. Data from ongoing studies of FMT in cancer will provide critical insights for optimization of this approach.}, } @article {pmid32575899, year = {2020}, author = {Giannone, G and Ghisoni, E and Genta, S and Scotto, G and Tuninetti, V and Turinetto, M and Valabrega, G}, title = {Immuno-Metabolism and Microenvironment in Cancer: Key Players for Immunotherapy.}, journal = {International journal of molecular sciences}, volume = {21}, number = {12}, pages = {}, pmid = {32575899}, issn = {1422-0067}, mesh = {Animals ; Humans ; Immune Checkpoint Inhibitors/pharmacology/therapeutic use ; Immunotherapy/*methods ; Neoplasms/immunology/metabolism/*therapy ; Signal Transduction/drug effects ; Tumor Microenvironment/drug effects ; Tumor-Associated Macrophages/drug effects/immunology/metabolism ; }, abstract = {Immune checkpoint inhibitors (ICIs) have changed therapeutic algorithms in several malignancies, although intrinsic and secondary resistance is still an issue. In this context, the dysregulation of immuno-metabolism plays a leading role both in the tumor microenvironment (TME) and at the host level. In this review, we summarize the most important immune-metabolic factors and how they could be exploited therapeutically. At the cellular level, an increased concentration of extracellular adenosine as well as the depletion of tryptophan and uncontrolled activation of the PI3K/AKT pathway induces an immune-tolerant TME, reducing the response to ICIs. Moreover, aberrant angiogenesis induces a hypoxic environment by recruiting VEGF, Treg cells and immune-suppressive tumor associated macrophages (TAMs). On the other hand, factors such as gender and body mass index seem to affect the response to ICIs, while the microbiome composition (and its alterations) modulates both the response and the development of immune-related adverse events. Exploiting these complex mechanisms is the next goal in immunotherapy. The most successful strategy to date has been the combination of antiangiogenic drugs and ICIs, which prolonged the survival of patients with non-small-cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC), while results from tryptophan pathway inhibition studies are inconclusive. New exciting strategies include targeting the adenosine pathway, TAMs and the microbiota with fecal microbiome transplantation.}, } @article {pmid32574836, year = {2020}, author = {Zhang, F and Chen, H and Zhang, R and Liu, Y and Kong, N and Guo, Y and Xu, M}, title = {5-Fluorouracil induced dysregulation of the microbiome-gut-brain axis manifesting as depressive like behaviors in rats.}, journal = {Biochimica et biophysica acta. Molecular basis of disease}, volume = {1866}, number = {10}, pages = {165884}, doi = {10.1016/j.bbadis.2020.165884}, pmid = {32574836}, issn = {1879-260X}, mesh = {Animals ; Antimetabolites, Antineoplastic/*adverse effects ; Behavior, Animal/drug effects ; Colorectal Neoplasms/drug therapy ; Depression/*chemically induced/diagnosis/metabolism ; Disease Models, Animal ; Fecal Microbiota Transplantation ; Feces/microbiology ; Fluorouracil/*adverse effects ; Gastrointestinal Microbiome/*drug effects/physiology ; Humans ; Intestinal Mucosa/metabolism/microbiology ; Male ; Prefrontal Cortex/*metabolism ; Rats ; }, abstract = {Disturbances of the gut microbiome have been widely suggested to be associated with 5-fluorouracil (5-Fu) induced digestive pathologies. Furthermore, it has been elucidated that the gut microbiome may play a key role in the pathogenesis of depressive disorders via the microbiota-gut-brain axis. Despite the speculation, there exists no direct evidence proving the causality between disturbances in the gut microbiome induced by 5-Fu and depressive mood dysregulation. Herein, behavioral testing was used to evaluate depressive-like behaviors in 5-Fu treated rats. Subsequently, the gut microbiota and prefrontal cortex (PFC) metabolic were analyzed by 16S rRNA sequencing and 1H nuclear magnetic resonance (1H NMR). To clarify the association between the gut microbiota and their role on depressive-like behaviors caused by 5-Fu, a fecal microbiota transplantation (FMT) experiment was carried out. The results suggested that 5-Fu could significantly alter the diversity and abundance of the gut microbiome, and induce PFC metabolic disorders, as well as depressive behaviors in rats. Transplantation of fecal microbiota from healthy control into 5-Fu treated rats significantly alleviated the PFC metabolic disorder and depressive-like behaviors. In conclusion, this study demonstrated that the gut microbiome was actively involved in the occurrence of 5-Fu induced depressive-like behaviors, and manipulation of specific gut microbiome parameters may serve as a promising novel target for side effects of 5-Fu treatment.}, } @article {pmid32574415, year = {2020}, author = {Bilinski, J and Lis, K and Tomaszewska, A and Pechcinska, A and Grzesiowski, P and Dzieciatkowski, T and Walesiak, A and Gierej, B and Ziarkiewicz-Wróblewska, B and Tyszka, M and Kacprzyk, P and Chmielewska, L and Waszczuk-Gajda, A and Wiktor-Jedrzejczak, W and Basak, GW}, title = {Eosinophilic gastroenteritis and graft-versus-host disease induced by transmission of Norovirus with fecal microbiota transplant.}, journal = {Transplant infectious disease : an official journal of the Transplantation Society}, volume = {}, number = {}, pages = {e13386}, doi = {10.1111/tid.13386}, pmid = {32574415}, issn = {1399-3062}, abstract = {Fecal microbiota transplantation (FMT) was performed to decolonize gastrointestinal tract from antibiotic-resistant bacteria before allogeneic hematopoietic cells transplantation (alloHCT). AlloHCT was complicated by Norovirus gastroenteritis, acute graft-versus-host-disease and eosinophilic pancolitis. Norovirus was identified in samples from FMT material. Symptoms resolved after steroids course and second norovirus-free FMT from another donor.}, } @article {pmid32572461, year = {2020}, author = {Mangioni, D and Alagna, L and Gori, A and Bandera, A}, title = {Fecal Microbiota Transplant: keep calm and carry on, learning from experience.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa846}, pmid = {32572461}, issn = {1537-6591}, } @article {pmid32570299, year = {2020}, author = {Shasthry, SM}, title = {Fecal microbiota transplantation in alcohol related liver diseases.}, journal = {Clinical and molecular hepatology}, volume = {26}, number = {3}, pages = {294-301}, pmid = {32570299}, issn = {2287-285X}, abstract = {The current standard of care for severe alcoholic hepatitis (SAH) has several limitations in that only up to one-third of patients are eligible for steroid therapy. Additionally, steroids have their own issues: a portion of patients do not respond, while there is doubtful long-term benefit in those who do and a large proportion are ineligible to receive steroids entirely and hence have no definitive options for treatment. As such, there is a large gap between the problem and the available solutions. Alcohol causes dysbiosis and also disrupts gut barrier function, consequently promoting the translocation of microbial lipopolysaccharide into the portal circulation and liver. Therefore, probiotics, prebiotics, antibiotics, or transplantation of gut microbiota are likely to attenuate the dysbiosis-related liver insult. Fecal microbiota transplantation (FMT) is expected to have a role in managing alcoholic liver disease in general and SAH in particular by correcting dysbiosis, the primary insult. Results from mouse studies have suggested beyond doubt that alcohol-related liver injury is transferrable and also treatable by adopting FMT from suitable donors. Initial human trials from our center have affirmed benefits in human subjects with SAH as well, with both improvements in disease severity and as well as the rate of survival. Further studies addressing the head-to-head comparison of steroids and FMT are ongoing. Available preliminary data are promising and FMT and/or gut microbial modulation might become the standard of care in the near future for managing alcohol-related liver diseases, especially alcoholic hepatitis, with greater applicability, improved acceptability, and minimal side effects.}, } @article {pmid32564632, year = {2020}, author = {Suraya, R and Nagano, T and Kobayashi, K and Nishimura, Y}, title = {Microbiome as a Target for Cancer Therapy.}, journal = {Integrative cancer therapies}, volume = {19}, number = {}, pages = {1534735420920721}, pmid = {32564632}, issn = {1552-695X}, abstract = {Recently, the microbiome has been gaining traction as a major player regulating various functions that correlate with many pathological conditions, including cancer. The central gut microbiota population has the capability to regulate normal inflammatory, immune, and metabolic functions, and disturbance in the balance of the normal microbiota population can subsequently induce pathological responses that closely relate with the mechanistic development and progression of cancer in various forms and sites. As a disease with major socioeconomic burden partly due to its current therapeutic options, modulating the imbalanced gut microbiota represents a novel option not only as an adjuvant therapy to relieve cancer treatment-related symptoms but also to influence cancer progression itself. In this review, we will discuss how the microbiome, specifically the gut microbiota, could affect cancer pathogenesis and what the effect of gut microbiota-targeting treatment options have on the many aspects of cancer pathologies based on the knowledge of recent years.}, } @article {pmid32563025, year = {2020}, author = {Wang, Y and Ren, R and Sun, G and Peng, L and Tian, Y and Yang, Y}, title = {Pilot study of cytokine changes evaluation after fecal microbiota transplantation in patients with ulcerative colitis.}, journal = {International immunopharmacology}, volume = {85}, number = {}, pages = {106661}, doi = {10.1016/j.intimp.2020.106661}, pmid = {32563025}, issn = {1878-1705}, abstract = {AIMS: To evaluate the changes of serum cytokines levels after fecal microbiota transplantation (FMT) in patients with active ulcerative colitis (UC) and the correlation with UC disease activity.

METHODS: Patients with active UC who meet the inclusion and exclusion criteria were recruited, and received FMT from a single donor for three times with an interval of 2-3 months. Serum samples were collected before every FMT. Clinical responses to FMT were assessed according to the criteria of Mayo score. 41 serum cytokines, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were quantitatively detected. Changes in serum cytokines levels after FMT and their correlation with CRP, ESR and Mayo scores were investigated.

RESULTS: 16 active UC patients were enrolled, and 14(87.5%) patients achieved clinical response to FMT. Compared with those before FMT, serum concentrations of IL-1Ra, IL-6, IP-10 and ENA-78 decreased significantly after the second FMT (P < 0.05), and serum concentrations of MEC, VCAM-1 and G-CSF decreased significantly after both the first and second FMT (P < 0.05). Serum levels of IL-6, IL-1Ra and VCAM-1 were all significantly positively correlated with CRP and ESR. Serum level of IP-10 was significantly positively correlated with CRP, ESR and Mayo score. Serum level of G-CSF was significantly positively correlated with Mayo score.

CONCLUSIONS: FMT may play a therapeutic role partly through modulating the host immune response. IL-6, IL-1Ra, IP-10, VCAM-1 and G-CSF may be biomarkers to evaluate the effect of FMT on UC.}, } @article {pmid32560820, year = {2020}, author = {Udomsopagit, T and Miwa, A and Seki, M and Shimbori, E and Kadota, Y and Tochio, T and Sonoyama, K}, title = {Intestinal microbiota transplantation reveals the role of microbiota in dietary regulation of RegIIIβ and RegIIIγ expression in mouse intestine.}, journal = {Biochemical and biophysical research communications}, volume = {529}, number = {1}, pages = {64-69}, doi = {10.1016/j.bbrc.2020.05.150}, pmid = {32560820}, issn = {1090-2104}, mesh = {Animals ; Diet ; Diet, High-Fat ; *Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Ileum/metabolism ; Interleukins/genetics/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Pancreatitis-Associated Proteins/*blood/*genetics ; RNA, Messenger/genetics/metabolism ; Trisaccharides/administration & dosage ; }, abstract = {RegIIIβ and RegIIIγ are antimicrobial peptides expressed in intestinal epithelial cells. Expression of these peptides is reportedly decreased by high-fat diet (HFD) and increased by indigestible oligosaccharides in mice. Clearly, these dietary regimens change the structure of intestinal microbiota. We employed an intestinal microbiota transplantation (IMT) to test whether diet-induced changes in the expression of these peptides are mediated by gut microbiota. C57BL/6J mice were fed either a normal-fat diet (NFD), a HFD, or a NFD supplemented with or without 1-kestose (KES), an indigestible oligosaccharide. Ileal RegIIIβ and RegIIIγ mRNA levels were lower in mice receiving IMT from HFD-fed mice than in those receiving NFD-fed mice and higher in mice receiving IMT from KES-supplemented mice than in those receiving the mice without KES supplementation. Western blot analysis showed that serum RegIIIβ levels changed in parallel with the ileal mRNA levels. We propose that HFD- and KES-induced changes in the ileal RegIIIβ and RegIIIγ expression and in the circulating RegIIIβ levels are mediated, at least in part, by intestinal microbiota.}, } @article {pmid32553109, year = {2020}, author = {Watterson, WJ and Tanyeri, M and Watson, AR and Cham, CM and Shan, Y and Chang, EB and Eren, AM and Tay, S}, title = {Droplet-based high-throughput cultivation for accurate screening of antibiotic resistant gut microbes.}, journal = {eLife}, volume = {9}, number = {}, pages = {}, pmid = {32553109}, issn = {2050-084X}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; RC2 DK122394/DK/NIDDK NIH HHS/United States ; T32 DK007074/DK/NIDDK NIH HHS/United States ; 2018-2019//Samuel and Emma Winters Foundation/International ; }, abstract = {Traditional cultivation approaches in microbiology are labor-intensive, low-throughput, and yield biased sampling of environmental microbes due to ecological and evolutionary factors. New strategies are needed for ample representation of rare taxa and slow-growers that are often outcompeted by fast-growers in cultivation experiments. Here we describe a microfluidic platform that anaerobically isolates and cultivates microbial cells in millions of picoliter droplets and automatically sorts them based on colony density to enhance slow-growing organisms. We applied our strategy to a fecal microbiota transplant (FMT) donor stool using multiple growth media, and found significant increase in taxonomic richness and larger representation of rare and clinically relevant taxa among droplet-grown cells compared to conventional plates. Furthermore, screening the FMT donor stool for antibiotic resistance revealed 21 populations that evaded detection in plate-based assessment of antibiotic resistance. Our method improves cultivation-based surveys of diverse microbiomes to gain deeper insights into microbial functioning and lifestyles.}, } @article {pmid32552337, year = {2020}, author = {Allegretti, JR and Elliott, RJ and Ladha, A and Njenga, M and Warren, K and O'Brien, K and Budree, S and Osman, M and Fischer, M and Kelly, CR and Kassam, Z}, title = {Stool processing speed and storage duration do not impact the clinical effectiveness of fecal microbiota transplantation.}, journal = {Gut microbes}, volume = {11}, number = {6}, pages = {1806-1808}, pmid = {32552337}, issn = {1949-0984}, } @article {pmid32550753, year = {2020}, author = {Little, R and Wine, E and Kamath, BM and Griffiths, AM and Ricciuto, A}, title = {Gut microbiome in primary sclerosing cholangitis: A review.}, journal = {World journal of gastroenterology}, volume = {26}, number = {21}, pages = {2768-2780}, pmid = {32550753}, issn = {2219-2840}, abstract = {Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by biliary inflammation and stricturing. Exploration of the pathogenesis of PSC in light of its association with inflammatory bowel disease (IBD) and the "gut-liver" axis is an emerging area of interest. A growing number of studies have begun to elucidate the role of the gut microbiota, its metabolites and its influence on host immune responses in the development of PSC and PSC-IBD. Studies of the fecal microbiota have highlighted enriched levels of certain species, including Veillonella, Streptococcus and Enterococcus, among others. A heightened immune response to enteric dysbiosis and bacterial translocation have also been implicated. For example, Klebsiella pneumoniae strains derived from gnotobiotic mice transplanted with PSC-IBD microbiota were found to induce pore formation in human intestinal epithelial cells and enhanced Th17 responses. Gut microbes have additionally been hypothesized to be implicated in PSC pathogenesis through their role in the synthesis of various metabolites, including bile acids (BAs), which function as signaling molecules with important gut and hepatic effects. An expanded knowledge of the gut microbiome as it relates to PSC offers critical insight into the development of microbe-altering therapeutic interventions, such as antibiotics, nutritional interventions and fecal microbial transplantation. Some of these have already shown some preliminary evidence of benefit. Despite exciting progress in the field, much work remains to be done; areas that are particularly lacking include functional characterization of the microbiome and examination of pediatric populations. In this review, we summarize studies that have investigated the microbiome in PSC and PSC-IBD as well as putative mechanisms, including the potential role of metabolites, such as BAs. We then briefly review the evidence for interventions with microbe-altering properties for treating PSC.}, } @article {pmid32548192, year = {2020}, author = {Massaro, M and Vansia, J and McGill, S}, title = {Ulcerative Proctitis in a Patient With a History of Fecal Microbiota Transplant for Clostridioides difficile Infection.}, journal = {ACG case reports journal}, volume = {7}, number = {4}, pages = {e00364}, pmid = {32548192}, issn = {2326-3253}, abstract = {Fecal microbiota transplantation (FMT) effectively treats Clostridioides difficile infection and alters the gut microbiota in the long term, but potential adverse effects are poorly understood. We report a man with a family history of ulcerative colitis who developed ulcerative proctitis within a year of FMT.}, } @article {pmid32548190, year = {2020}, author = {Fasanello, MK and Robillard, KT and Boland, PM and Bain, AJ and Kanehira, K}, title = {Use of Fecal Microbial Transplantation for Immune Checkpoint Inhibitor Colitis.}, journal = {ACG case reports journal}, volume = {7}, number = {4}, pages = {e00360}, pmid = {32548190}, issn = {2326-3253}, abstract = {Immune checkpoint inhibitors (ICIs) can result in immune-related adverse events which require rapid identification and treatment. Gastrointestinal immune-related adverse events are among the most frequent and severe of these events. ICI colitis can be refractory to current therapies such as corticosteroids and biologic therapy. Fecal microbiota transplantation (FMT) is currently used in cases of recurrent Clostridioides difficile colitis. Many investigations are underway to test the utility of FMT for additional indications, including inflammatory bowel disease (IBD). We present a 71-year-old man with ICI colitis that was nonresponsive to currently defined management options and treated with benefit from FMT.}, } @article {pmid32539741, year = {2020}, author = {Chinna Meyyappan, A and Forth, E and Wallace, CJK and Milev, R}, title = {Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review.}, journal = {BMC psychiatry}, volume = {20}, number = {1}, pages = {299}, pmid = {32539741}, issn = {1471-244X}, support = {//CIHR/Canada ; }, mesh = {Anxiety ; *Autism Spectrum Disorder ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; *Microbiota ; }, abstract = {BACKGROUND: The Gut-Brain-Axis is a bidirectional signaling pathway between the gastrointestinal (GI) tract and the brain. The hundreds of trillions of microorganisms populating the gastrointestinal tract are thought to modulate this connection, and have far reaching effects on the immune system, central and autonomic nervous systems, and GI functioning. These interactions Diagnostic and statistical manual of mental disorders have also been linked to various psychiatric illnesses such as depression, anxiety, substance abuse, autism spectrum disorder, and eating disorders. It is hypothesized that techniques aimed at strengthening and repopulating the gut microbiome, such as Fecal Microbiota Transplant (FMT), may be useful in the prevention and treatment of psychiatric illnesses.

METHODS: A systematic search of five databases was conducted using key terms related to FMT and psychiatric illnesses. All results were then evaluated based on specific eligibility criteria.

RESULTS: Twenty-one studies met the eligibility criteria and were analysed for reported changes in mood and behavioural measures indicative of psychiatric wellbeing. The studies included were either entirely clinical (n = 8), preclinical with human donors (n = 9), or entirely preclinical (n = 11). All studies found a decrease in depressive and anxiety-like symptoms and behaviours resulting from the transplantation of healthy microbiota. The inverse was also found, with the transmission of depressive and anxiety-like symptoms and behaviours resulting from the transplantation of microbiota from psychiatrically ill donors to healthy recipients.

CONCLUSION: There appears to be strong evidence for the treatment and transmission of psychiatric illnesses through FMT. Further research with larger sample sizes and stronger scientific design is warranted in order to fully determine the efficacy and safety of this potential treatment. Registered on PROSPERO, IRD: CRD42019126795.}, } @article {pmid32537754, year = {2020}, author = {Wong, SH and Yu, J}, title = {Proton-pump inhibitor use before fecal microbiota transplant: A wonder drug, a necessary evil, or a needless prescription?.}, journal = {Journal of gastroenterology and hepatology}, volume = {35}, number = {6}, pages = {913-914}, doi = {10.1111/jgh.15103}, pmid = {32537754}, issn = {1440-1746}, mesh = {Clostridioides difficile ; Clostridium Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Humans ; Proton Pump Inhibitors/*administration & dosage/*adverse effects ; Recurrence ; *Unnecessary Procedures ; }, } @article {pmid32535631, year = {2020}, author = {Uchiyama, K and Wakino, S and Irie, J and Miyamoto, J and Matsui, A and Tajima, T and Itoh, T and Oshima, Y and Yoshifuji, A and Kimura, I and Itoh, H}, title = {Contribution of uremic dysbiosis to insulin resistance and sarcopenia.}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, volume = {35}, number = {9}, pages = {1501-1517}, doi = {10.1093/ndt/gfaa076}, pmid = {32535631}, issn = {1460-2385}, mesh = {Animals ; Bacteria/*isolation & purification ; Dysbiosis/*complications/microbiology ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; *Insulin Resistance ; Lipids/blood ; Male ; Mice ; Mice, Inbred ICR ; Renal Insufficiency, Chronic/*physiopathology ; Sarcopenia/*etiology/pathology/therapy ; Uremia/*complications ; }, abstract = {BACKGROUND: Chronic kidney disease (CKD) leads to insulin resistance (IR) and sarcopenia, which are associated with a high mortality risk in CKD patients; however, their pathophysiologies remain unclear. Recently, alterations in gut microbiota have been reported to be associated with CKD. We aimed to determine whether uremic dysbiosis contributes to CKD-associated IR and sarcopenia.

METHODS: CKD was induced in specific pathogen-free mice via an adenine-containing diet; control animals were fed a normal diet. Fecal microbiota transplantation (FMT) was performed by oral gavage in healthy germ-free mice using cecal bacterial samples obtained from either control mice (control-FMT) or CKD mice (CKD-FMT). Vehicle mice were gavaged with sterile phosphate-buffered saline. Two weeks after inoculation, mice phenotypes, including IR and sarcopenia, were evaluated.

RESULTS: IR and sarcopenia were evident in CKD mice compared with control mice. These features were reproduced in CKD-FMT mice compared with control-FMT and vehicle mice with attenuated insulin-induced signal transduction and mitochondrial dysfunction in skeletal muscles. Intestinal tight junction protein expression and adipocyte sizes were lower in CKD-FMT mice than in control-FMT mice. Furthermore, CKD-FMT mice showed systemic microinflammation, increased concentrations of serum uremic solutes, fecal bacterial fermentation products and elevated lipid content in skeletal muscle. The differences in gut microbiota between CKD and control mice were mostly consistent between CKD-FMT and control-FMT mice.

CONCLUSIONS: Uremic dysbiosis induces IR and sarcopenia, leaky gut and lipodystrophy.}, } @article {pmid32535405, year = {2020}, author = {Liu, L and Wang, Q and Wu, X and Qi, H and Das, R and Lin, H and Shi, J and Wang, S and Yang, J and Xue, Y and Mao, D and Luo, Y}, title = {Vancomycin exposure caused opportunistic pathogens bloom in intestinal microbiome by simulator of the human intestinal microbial ecosystem (SHIME).}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {265}, number = {Pt B}, pages = {114399}, doi = {10.1016/j.envpol.2020.114399}, pmid = {32535405}, issn = {1873-6424}, mesh = {Dysbiosis ; Ecosystem ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Vancomycin ; }, abstract = {Antibiotics are emerging organic pollutants posing high health risks to humans by causing human intestinal microbial disorders with increasing abundances of opportunistic pathogens, and fecal microbiota transplantation (FMT) has been confirmed to restore the dysbiosis of gut flora in many kinds of intestinal disease. However, to date, few studies have focused on the bloomed opportunistic pathogens associated human disease-related pathways as well as antibiotic resistance genes (ARGs) after vancomycin exposure, and there is limited information on using FMT for restoration of intestinal microbiome affected by antibiotics. Therefore, this study investigated effects of vancomycin on the opportunistic pathogens, human disease-related pathways as well as ARGs in human gut, and the restoration of intestinal microbiome by FMT. Results indicated that vancomycin treatment substantially increased human disease-related pathways and decreased abundances of ARGs. Besides, the bloomed opportunistic pathogens including Achromobacter, Klebsiella, and Pseudomonas, caused by vancomycin exposure, were positively correlated with human disease-related pathways. The microbiota abundance and genes of human disease-related pathways and antibiotic resistance showed a remarkable return towards baseline after FMT, but not for natural recovery. These findings suggest that impacts of vancomycin on human gut are profound and FMT will be a promising strategy in clinical application that can restore the dysbiosis of gut microbiota, which may be valuable for directing future work.}, } @article {pmid32529941, year = {2020}, author = {Li, X and He, C and Li, N and Ding, L and Chen, H and Wan, J and Yang, X and Xia, L and He, W and Xiong, H and Shu, X and Zhu, Y and Lu, N}, title = {The interplay between the gut microbiota and NLRP3 activation affects the severity of acute pancreatitis in mice.}, journal = {Gut microbes}, volume = {11}, number = {6}, pages = {1774-1789}, pmid = {32529941}, issn = {1949-0984}, abstract = {Early dysbiosis of the gut microbiota is associated with the severity of acute pancreatitis (AP), although the underlying mechanism is unclear. Here, we investigated the role of crosstalk between NLRP3 and the gut microbiota in the development of AP utilizing gut microbiota deficient mice, as well as NLRP3 knockout (KO) mouse models. Pancreatic damage and systemic inflammation were improved in antibiotic-treated (Abx) and germ-free (GF) mice, accompanied by weakened activity of the intestinal NLRP3 inflammasome. Interestingly, fecal microbiota transplantation (FMT) reactivated the intestinal NLRP3 inflammasome and exacerbated the disease in Abx and GF mice. Although the gut barrier in GF and Abx mice was disrupted, gut microbiota deficiency ameliorated the severity of AP, probably due to the reduction in bacterial translocation from the gut to the pancreas. The composition of the gut microbiota was significantly different between NLRP3 KO mice and wild-type (WT) mice at baseline, and there were alterations in response to the induction of AP. While a dramatic shift in the gut microbiota with overgrowth of Escherichia-Shigella was observed in WT mice suffering from AP, there was no significant change in NLRP3 KO mice with or without AP, suggesting that NLRP3 deficiency counteracts AP-induced microbial disturbance. With a strengthened gut barrier and decreased systemic inflammation, NLRP3 KO mice showed less severe AP, as revealed by reduced pancreatic neutrophilic infiltration and necrosis. Taken together, these results identified the bidirectional modulation between the gut microbiota and NLRP3 in the progression of AP, which suggests the interplay of the host and microbiome during AP.}, } @article {pmid32527171, year = {2020}, author = {Biernat, MM and Urbaniak-Kujda, D and Dybko, J and Kapelko-Słowik, K and Prajs, I and Wróbel, T}, title = {Fecal microbiota transplantation in the treatment of intestinal steroid-resistant graft-versus-host disease: two case reports and a review of the literature.}, journal = {The Journal of international medical research}, volume = {48}, number = {6}, pages = {300060520925693}, pmid = {32527171}, issn = {1473-2300}, abstract = {Acute graft-versus-host disease (aGvHD) reduces the efficiency and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT). In recent years, attempts have been made to transplant fecal microbiota from healthy donors to treat intestinal GvHD. This study presented two cases of patients undergoing allo-HSCT who were later selected for fecal microbiota transplantation (FMT). In the first patient, FMT resulted in the complete resolution of symptoms, whereas therapeutic efficacy was not achieved in the second patient. FMT eliminated drug-resistant pathogens, namely very drug-resistant Enterococcus spp., but not multidrug-resistant Acinetobacter baumannii or Candida spp. Further research is needed, particularly on the safety of FMT in patients with intestinal steroid-resistant GvHD and on the distant impact of transplanted microflora on the outcomes of allo-HSCT. FMT appears promising for the treatment of patients with steroid-resistant GvHD.}, } @article {pmid32523094, year = {2020}, author = {Pérez-Matute, P and Íñiguez, M and de Toro, M and Recio-Fernández, E and Oteo, JA}, title = {Autologous fecal transplantation from a lean state potentiates caloric restriction effects on body weight and adiposity in obese mice.}, journal = {Scientific reports}, volume = {10}, number = {1}, pages = {9388}, pmid = {32523094}, issn = {2045-2322}, mesh = {Adiposity ; Animals ; Body Weight ; Caloric Restriction ; Disease Models, Animal ; *Fecal Microbiota Transplantation ; Feces/*microbiology ; Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/microbiology/*therapy ; Transplantation, Autologous ; }, abstract = {Autologous fecal transplantation (FT-A) emerges as a promising strategy to modulate gut microbiota with minimal side effects since individual´s own feces are transplanted. With the premise of improving obesity and its associated disorders, we investigated if fecal microbiota transplantation (FMT), heterologous and autologous, potentiates the effects of a moderate caloric restriction (CR) in high-fat diet (HFD)-induced obese mice. Mice were randomized into control, HFD, CR (12 weeks on HFD and 6 weeks under CR), FT-H (similar to CR and FMT carried out with feces from controls, weeks 17 & 18), and FT-A (administration of their own feces before developing obesity at weeks 17 & 18). Our study demonstrated that FMT, and, especially, FT-A potentiates the effects of a moderate CR on weight loss and adiposity in the short term, by decreasing feed efficiency and increasing adipose tissue lipolysis. Although FT-A produced a significant increase in bacterial richness/diversity, FMT did not significantly modify gut microbiota composition compared to the CR at phyla and bacteria genera levels, and only significant increases in Bifidobacterium and Blautia genera were observed. These results could suggest that other mechanisms different from bacterial microbiota engraftment participates in these beneficial effects. Thus, FT-A represents a very positive synergetic approach for obese patients that do not respond well to moderate restrictive diets.}, } @article {pmid32519746, year = {2020}, author = {Su, X and Zhao, Y and Li, Y and Ma, S and Wang, Z}, title = {Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis.}, journal = {Clinical science (London, England : 1979)}, volume = {134}, number = {12}, pages = {1521-1535}, doi = {10.1042/CS20200475}, pmid = {32519746}, issn = {1470-8736}, mesh = {Adult ; Animals ; Case-Control Studies ; Dysbiosis/*complications ; Fatty Acids/metabolism ; Fecal Microbiota Transplantation ; Female ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*pathology ; Humans ; Hypothyroidism/*complications ; Male ; Metagenomics ; Mice, Inbred BALB C ; Phylogeny ; ROC Curve ; Thyroid Gland/*pathology ; }, abstract = {Background Previous studies have shown that the gut microbiome is associated with thyroid diseases, including Graves' disease, Hashimoto's disease, thyroid nodules, and thyroid cancer. However, the association between intestinal flora and primary hypothyroidism remains elusive. We aimed to characterize gut microbiome in primary hypothyroidism patients. Methods Fifty-two primary hypothyroidism patients and 40 healthy controls were recruited. The differences in gut microbiota between the two groups were analyzed by 16S rRNA sequencing technology. Fecal microbiota transplantation (FMT) was performed in mice using flora from both groups; changes in thyroid function were then assessed in the mice. Results There were significant differences in α and β diversities of gut microbiota between primary hypothyroidism patients and healthy individuals. The random forest analysis indicated that four intestinal bacteria (Veillonella, Paraprevotella, Neisseria, and Rheinheimera) could distinguish untreated primary hypothyroidism patients from healthy individuals with the highest accuracy; this was confirmed by receiver operator characteristic curve analysis. The short chain fatty acid producing ability of the primary hypothyroidism patients' gut was significantly decreased, which resulted in the increased serum lipopolysaccharide (LPS) levels. The FMT showed that mice receiving the transplant from primary hypothyroidism patients displayed decreased total thyroxine levels. Conclusions Our study suggests that primary hypothyroidism causes changes in gut microbiome. In turn, an altered flora can affect thyroid function in mice. These findings could help understand the development of primary hypothyroidism and might be further used to develop potential probiotics to facilitate the adjuvant treatment of this disease.}, } @article {pmid32518854, year = {2020}, author = {Kates, AE and Gaulke, I and De Wolfe, T and Zimbric, M and Haight, K and Watson, L and Suen, G and Kim, K and Safdar, N}, title = {Fecal microbiota transplantation for patients on antibiotic treatment with C. difficile infection history (GRAFT): Study protocol for a phase II, randomized, double-blind, placebo-controlled trial to prevent recurrent C. difficile infections.}, journal = {Contemporary clinical trials communications}, volume = {18}, number = {}, pages = {100576}, pmid = {32518854}, issn = {2451-8654}, support = {R03 HS025257/HS/AHRQ HHS/United States ; }, abstract = {Recurrent Clostridiodes difficile infections (rCDIs) are a burdensome problem. Patients with a history of CDI that are prescribed antibiotics are at a high risk for recurrence. Fecal microbiota transplantation (FMT) has been shown to be an effective treatment for rCDI, though there is little information on the impact of FMT with antibiotics on the gut microbiome. We are conducting a clinical trial of FMT to prevent rCDI in patients with a history of CDI currently taking antibiotics. Our primary objective is to determine the effect of FMT on the gut microbiome during antibiotic exposure. Our secondary aim is to assess safety and feasibility of using FMT as a prophylaxis for CDI. We plan to enroll 30 patients into a phase II randomized, double-blind, placebo-controlled trial with three arms: (1) 5 FMT capsules per day during antibiotic treatment and for 7 days post antibiotic cessation, (2) a one-time dose of 30 FMT capsules 48-72 h post cessation of antibiotic treatment, or (3) 5 placebo capsules per day during antibiotic treatment and for 7 days post antibiotic treatment. Patients provide stool samples throughout the duration of the study and are cultured C. difficile. Sequencing of the V4 region of the 16S rRNA gene will be carried out to assess the gut microbiota. Results of this study will provide information on the impact of FMT on the gut microbiome as well as the necessary data to examine whether or not prophylactic FMT should be explored further as a way to prevent CDI recurrence.}, } @article {pmid32517023, year = {2020}, author = {Bibbò, S and Settanni, CR and Porcari, S and Bocchino, E and Ianiro, G and Cammarota, G and Gasbarrini, A}, title = {Fecal Microbiota Transplantation: Screening and Selection to Choose the Optimal Donor.}, journal = {Journal of clinical medicine}, volume = {9}, number = {6}, pages = {}, pmid = {32517023}, issn = {2077-0383}, abstract = {In the past decade, fecal microbiota transplantation (FMT) has rapidly spread worldwide in clinical practice as a highly effective treatment option against recurrent Clostridioides difficile infection. Moreover, new evidence also supports a role for FMT in other conditions, such as inflammatory bowel disease, functional gastrointestinal disorders, or metabolic disorders. Recently, some studies have identified specific microbial characteristics associated with clinical improvement after FMT, in different disorders, paving the way for a microbiota-based precision medicine approach. Moreover, donor screening has become increasingly more complex over years, along with standardization of FMT and the increasing number of stool banks. In this narrative review, we discuss most recent evidence on the screening and selection of the stool donor, with reference to recent studies that have identified specific microbiological features for clinical conditions such as Clostridioides difficile infection, irritable bowel syndrome, inflammatory bowel disease, and metabolic disorders.}, } @article {pmid32516027, year = {2020}, author = {Zoll, J and Read, MN and Heywood, SE and Estevez, E and Marshall, JPS and Kammoun, HL and Allen, TL and Holmes, AJ and Febbraio, MA and Henstridge, DC}, title = {Fecal microbiota transplantation from high caloric-fed donors alters glucose metabolism in recipient mice, independently of adiposity or exercise status.}, journal = {American journal of physiology. Endocrinology and metabolism}, volume = {319}, number = {1}, pages = {E203-E216}, doi = {10.1152/ajpendo.00037.2020}, pmid = {32516027}, issn = {1522-1555}, mesh = {Adiposity ; Animals ; *Diet, High-Fat ; *Dietary Sucrose ; *Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Glucose/metabolism ; Glucose Intolerance/metabolism/*microbiology ; Male ; Mice ; Obesity/metabolism/*microbiology ; *Physical Conditioning, Animal ; Random Allocation ; *Sedentary Behavior ; }, abstract = {Studies suggest the gut microbiota contributes to the development of obesity and metabolic syndrome. Exercise alters microbiota composition and diversity and is protective of these maladies. We tested whether the protective metabolic effects of exercise are mediated through fecal components through assessment of body composition and metabolism in recipients of fecal microbiota transplantation (FMT) from exercise-trained (ET) mice fed normal or high-energy diets. Donor C57BL/6J mice were fed a chow or high-fat, high-sucrose diet (HFHS) for 4 wk to induce obesity and glucose intolerance. Mice were divided into sedentary (Sed) or ET groups (6 wk treadmill-based ET) while maintaining their diets, resulting in four donor groups: chow sedentary (NC-Sed) or ET (NC-ET) and HFHS sedentary (HFHS-Sed) or ET (HFHS-ET). Chow-fed recipient mice were gavaged with feces from the respective donor groups weekly, creating four groups (NC-Sed-R, NC-ET-R, HFHS-Sed-R, HFHS-ET-R), and body composition and metabolism were assessed. The HFHS diet led to glucose intolerance and obesity in the donors, whereas exercise training (ET) restrained adiposity and improved glucose tolerance. No donor group FMT altered recipient body composition. Despite unaltered adiposity, glucose levels were disrupted when challenged in mice receiving feces from HFHS-fed donors, irrespective of donor-ET status, with a decrease in insulin-stimulated glucose clearance into white adipose tissue and large intestine and specific changes in the recipient's microbiota composition observed. FMT can transmit HFHS-induced disrupted glucose metabolism to recipient mice independently of any change in adiposity. However, the protective metabolic effect of ET on glucose metabolism is not mediated through fecal factors.}, } @article {pmid32514151, year = {2020}, author = {Fong, W and Li, Q and Yu, J}, title = {Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer.}, journal = {Oncogene}, volume = {39}, number = {26}, pages = {4925-4943}, pmid = {32514151}, issn = {1476-5594}, support = {81972576//National Natural Science Foundation of China (National Science Foundation of China)/International ; }, mesh = {Colorectal Neoplasms/immunology/microbiology/*therapy ; Dysbiosis/*immunology/microbiology ; Fecal Microbiota Transplantation/*methods ; Gastrointestinal Microbiome/*immunology ; Humans ; Immune System/immunology/microbiology ; Prebiotics/*administration & dosage ; Precision Medicine/methods ; Probiotics/*administration & dosage ; Risk Factors ; }, abstract = {Research about the role of gut microbiome in colorectal cancer (CRC) is a newly emerging field of study. Gut microbiota modulation, with the aim to reverse established microbial dysbiosis, is a novel strategy for prevention and treatment of CRC. Different strategies including probiotics, prebiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT) have been employed. Although these strategies show promising results, mechanistically by correcting microbiota composition, modulating innate immune system, enhancing gut barrier function, preventing pathogen colonization and exerting selective cytotoxicity against tumor cells, it should be noted that they are accompanied by risks and controversies that can potentially introduce clinical complications. During bench-to-bedside translation, evaluation of risk-and-benefit ratio, as well as patient selection, should be carefully performed. In view of the individualized host response to gut microbiome intervention, developing personalized microbiome therapy may be the key to successful clinical treatment.}, } @article {pmid32511695, year = {2020}, author = {Bar-Yoseph, H and Carasso, S and Shklar, S and Korytny, A and Even Dar, R and Daoud, H and Nassar, R and Maharshak, N and Hussein, K and Geffen, Y and Chowers, Y and Geva-Zatorsky, N and Paul, M}, title = {Oral capsulized Fecal microbiota transplantation for eradication of carbapenemase-producing Enterobacteriaceae colonization with a metagenomic perspective.}, journal = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, volume = {}, number = {}, pages = {}, doi = {10.1093/cid/ciaa737}, pmid = {32511695}, issn = {1537-6591}, abstract = {BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) infections lead to considerable morbidity and mortality. We assessed the potential of fecal microbiota transplantation (FMT) to eradicate CPE carriage and aimed to explain failure or success through microbiome analyses.

METHODS: In this prospective cohort study, all consenting eligible CPE carriers were treated with oral capsulized FMT for 2 days. The primary outcome was CPE eradication at 1 month, defined by 3 consecutive negative rectal swabs, the last also negative for carbapenemase gene by PCR. Comprehensive metagenomics analysis of the intestinal microbiome of donors and recipients before and after FMT was performed.

RESULTS: Fifteen CPE carriers received FMT, 13 of which completed 2 days of treatment. CPE eradication at 1 month was successful in 9/15 and 9/13, respectively. Bacterial communities showed significant changes in both beta and alpha diversity metrics among participants achieving CPE eradication that were not observed among failures. Post-FMT samples' beta-diversity clustered according to the treatment outcome, both in taxonomy and in function. We observed a significant decrease in beta diversity in participants who received post-FMT antibiotics. Enterobacteriaceae abundance decreased in post-FMT samples of the responders, but increased among failures. Functionally, a clear demarcation between responders (who were similar to the donors) and failures was shown, driven by antimicrobial resistance genes.

CONCLUSION: Our study provides the biological explanation for the effect of FMT against CPE carriage. Decolonization of CPE by FMT is likely mediated by compositional and functional shifts in the microbiome. Thus, FMT might be an efficient strategy for sustained CPE eradication.}, } @article {pmid32509162, year = {2020}, author = {Wang, H and Zhou, C and Huang, J and Kuai, X and Shao, X}, title = {The potential therapeutic role of Lactobacillus reuteri for treatment of inflammatory bowel disease.}, journal = {American journal of translational research}, volume = {12}, number = {5}, pages = {1569-1583}, pmid = {32509162}, issn = {1943-8141}, abstract = {Inflammatory bowel disease (IBD) is a chronic intestinal disease of unknown etiology. However, recent studies have established a pathological role of disordered intestinal microbiota and immune dysregulation. Clinical studies have suggested that the reconstruction of the normal intestinal flora in patients with IBD can reverse the dysbiosis caused by genetic, environmental, dietary, or antibiotic factors to ameliorate the symptoms of IBD. Lactobacillus reuteri is widely present in the intestines of healthy individuals and regulates the intestinal immune system, reducing inflammation through multiple mechanisms. This review summarizes the current knowledge of the role of L. reuteri in maintaining intestinal homeostasis and considers its possible value as a new therapeutic agent for patients with IBD.}, } @article {pmid32508773, year = {2020}, author = {Liu, H and Wang, HH}, title = {Impact of Microbiota Transplant on Resistome of Gut Microbiota in Gnotobiotic Piglets and Human Subjects.}, journal = {Frontiers in microbiology}, volume = {11}, number = {}, pages = {932}, pmid = {32508773}, issn = {1664-302X}, abstract = {Microbiota transplant is becoming a popular process to restore or initiate "healthy" gut microbiota and immunity. But, the potential risks of the related practices need to be carefully evaluated. This study retrospectively examined the resistomes of donated fecal microbiota for treating intestinal disorders, vaginal microbiota of pregnant women, and infant fecal microbiota from rural and urban communities, as well as the impact of transplants on the fecal resistome of human and animal recipients. Antibiotic resistance (AR) genes were found to be abundant in all donor microbiota. An overall surge of resistomes with higher prevalence and abundance of AR genes was observed in the feces of all transplanted gnotobiotic pigs as well as in the feces of infant subjects, compared to those in donor fecal and maternal vaginal microbiota. Surprisingly, transplants using rural Amish microbiota led to more instead of less AR genes in the fecal microbiota of gnotobiotic pigs than did transplants using urban microbiota. New AR gene subtypes undetected originally also appeared in gnotobiotic pigs, in Crohn's Disease (CD) patients after transplant, and in feces of infant subjects. The data illustrated the key role of the host gastrointestinal tract system in amplifying the ever-increasing AR gene pool, even without antibiotic exposure. The data further suggest that the current approaches of microbiota transplant can introduce significant health risk factor(s) to the recipients, and newborn human and animal hosts with naïve gut microbiota were especially susceptible. Given the illustrated public health risks of microbiota transplant, minimizing massive and unnecessary damages to gut microbiota by oral antibiotics and other gut impacting drugs becomes important. Since eliminating risk factors including AR bacteria and opportunistic pathogens directly from donor microbiota is still difficult to achieve, developing microbial cocktails with defined organisms and functions has further become an urgent need, should microbiota transplantation become necessary.}, } @article {pmid32501140, year = {2020}, author = {Reygner, J and Charrueau, C and Delannoy, J and Mayeur, C and Robert, V and Cuinat, C and Meylheuc, T and Mauras, A and Augustin, J and Nicolis, I and Modoux, M and Joly, F and Waligora-Dupriet, AJ and Thomas, M and Kapel, N}, title = {Freeze-dried fecal samples are biologically active after long-lasting storage and suited to fecal microbiota transplantation in a preclinical murine model of Clostridioides difficile infection.}, journal = {Gut microbes}, volume = {11}, number = {5}, pages = {1405-1422}, pmid = {32501140}, issn = {1949-0984}, abstract = {Fecal microbiota transplantation is now recommended for treating recurrent forms of Clostridioides difficile infection. Recent studies have reported protocols using capsules of either frozen or freeze-dried stool allowing oral administration in in- and out-patient settings. However, a central question remains the viability, engraftment, and efficacy of the microbiome over time during storage life. This study shows that both the freeze-drying and freezing procedures for fecal samples allowed preserving viability, short-chain fatty acids concentration, and anti-Clostridioides difficile properties of microbiota without significant alteration after storage for 12 months. Fecal transplantation with freeze-dried microbiota allowed engraftment of microbiota leading to clearance of Clostridioides difficile infection in a preclinical murine model with a survival rate of 70% versus 53-60% in mice treated with frozen inocula, and 20% in the untreated group. Moreover, the freeze-dried powder can be used to fill oral hard capsules using a very low amount (0.5%) of glidant excipient, allowing oral formulation. Altogether, this study showed that freeze-dried inocula can be used for the treatment of Clostridioides difficile infection with long-lasting stability of the fecal microbiota. This formulation facilitates biobanking and allows the use of hard capsules, an essential step to simplify patient access to treatment.}, } @article {pmid32500988, year = {2020}, author = {Piekarska, A and Panasiuk, A and Stępień, PM}, title = {Clinical practice guidelines for Clostridioides (Clostridium) difficile infection and fecal microbiota transplant protocol - recommendations of the Polish Society od Epidemiology and Infectious Diseases.}, journal = {Przeglad epidemiologiczny}, volume = {74}, number = {1}, pages = {69-87}, doi = {10.32394/pe.74.06}, pmid = {32500988}, issn = {0033-2100}, abstract = {Symptomatic Clostridium difficile infection (CDI) is an acute inflammatory disease of the gastrointestinal tract, manifesting in at least 3 unformed stools within 24 hours. Predicting factors for CDI include contact with medical care (mainly hospitalization), antibiotic therapy in the last 12 weeks, use of proton pump inhibitors (PPI), H2 blockers, cancer chemotherapy, especially in the neutropenia stage, gastrointestinal surgery, advanced age and concomitant chronic diseases (renal failure, liver failure, chronic inflammatory bowel disease - especially ulcerative bowel disease, cancer, HIV infection, cachexia and hypoalbuminaemia) and vitamin D deficiency. Clinical classification distinguishes three types of CDI - mild / moderate, severe, and fulminant. The principles of treatment of the first and subsequent CDI incidents depending on the clinical course are based on oral vancomycin. CDI is recurrent. The basis for treating CDI relapses is vancomycin administered orally at a dose of 4x125 mg for 10 days followed by concomitant vancomycin dose reduction therapy. The use of fecal microbiota transfer (FMT) in the treatment of CDI relapses is considered to be the most effective therapy for recurrent CDI. An indication for FMT is antibiotic-resistant C. difficile infection, regardless of the number of incidents CDI. The panel of tests recommended for a bacterial flora donor is presented in the recommendations.}, } @article {pmid32499711, year = {2020}, author = {Cheung, MK and Yue, GGL and Chiu, PWY and Lau, CBS}, title = {A Review of the Effects of Natural Compounds, Medicinal Plants, and Mushrooms on the Gut Microbiota in Colitis and Cancer.}, journal = {Frontiers in pharmacology}, volume = {11}, number = {}, pages = {744}, pmid = {32499711}, issn = {1663-9812}, abstract = {The human gastrointestinal tract harbors a diverse array of microorganisms that play fundamental roles in health and disease. Imbalance in the gut microbiota, namely dysbiosis, can lead to various diseases, including cancer and gastrointestinal tract disorders. Approaches to improve gut dysbiosis, such as dietary intervention, intake of probiotics, and fecal microbiota transplantation are emerging strategies to treat these diseases. Various medicinal botanicals have reported anti-cancer and/or anti-inflammatory properties. Preclinical studies have illustrated that some of these natural products are also capable to modulate the gut microbiota, suggesting their use as possible alternative approach to improve gut dysbiosis and thereby assist diseases treatment. In this review article, we have summarized the current knowledge on the effects of natural compounds, medicinal plants, and mushrooms on the gut microbiota in various cancers and colitis in preclinical animal models. Challenges towards the clinical use of these medicinal botanicals as modulators of the gut microbiota in cancer and colitis treatment are also discussed.}, } @article {pmid32499362, year = {2020}, author = {Simpson, E and Sanjar, F and Wylie, D and Park, S and Koh, H and Bae, J and Kook, SY and Kim, S and Kim, HJ}, title = {Draft Genome Sequences of Two Strains of Bifidobacterium dentium Isolated from a Crude Fecal Extract Used for Fecal Microbiota Transplantation in the Republic of Korea.}, journal = {Microbiology resource announcements}, volume = {9}, number = {23}, pages = {}, pmid = {32499362}, issn = {2576-098X}, abstract = {We present the draft genome sequences of two Bifidobacterium dentium strains isolated from a fecal extract for fecal microbiota transplantation at a hospital in the Republic of Korea. Phylogenetic and functional analyses were performed to understand the physiological characteristics and functions of Bifidobacterium spp. in the human intestine.}, } @article {pmid32496421, year = {2020}, author = {Assimakopoulos, SF and Papadopoulou, I and Bantouna, D and de Lastic, AL and Rodi, M and Mouzaki, A and Gogos, CA and Zolota, V and Maroulis, I}, title = {Fecal Microbiota Transplantation and Hydrocortisone Ameliorate Intestinal Barrier Dysfunction and Improve Survival in a Rat Model of Cecal Ligation and Puncture-Induced Sepsis.}, journal = {Shock (Augusta, Ga.)}, volume = {}, number = {}, pages = {}, doi = {10.1097/SHK.0000000000001566}, pmid = {32496421}, issn = {1540-0514}, abstract = {INTRODUCTION: Sepsis is a life-threatening syndrome which can progress to multiple organ dysfunction with high mortality. Intestinal barrier failure exerts a central role in the pathophysiological sequence of events that lead from sepsis to multiple organ dysfunction. The present study investigated the role of hydrocortisone (HC) administration and fecal microbiota transplantation (FMT) in several parameters of the gut barrier integrity, immune activation and survival, in a model of polymicrobial sepsis in rats.

METHODS: Forty adults male Wistar rats were randomly divided into four groups: sham (group I), cecal ligation and puncture (CLP) (group II), CLP + HC (2.8 mg/kg, intraperitoneally single dose at 6 hours) (group III) and CLP + FMT at 6 hours (group IV). At 24 h post-CLP, ileal tissues were harvested for histological and immunohistochemical analyses while endotoxin, IL-6 and IL-10 levels in systemic circulation were determined. In a second experiment the same groups were observed for seven days for mortality, with daily administration of hydrocortisone (group III) and FMT (group IV) in surviving rats.

RESULTS: HC administration and FMT significantly reduced mortality of septic rats by 50%. These interventions totally reversed intestinal mucosal atrophy by increasing villous density and mucosal thickness (μm, mean ± SD: Group I: 620 ± 35, Group II: 411 ± 52, Group III: 622 ± 19, Group IV:617 ± 44). HC and FMT reduced the apoptotic body count in intestinal crypts whereas increased the mitotic/apoptotic index. Activated caspase-3 expression in intestinal crypts was significantly reduced by HC or FMT (activated caspase-3 (+) enterocytes/10 crypts, mean ± SD: Group I: 1,6 ± 0,5, Group II: 5,8 ± 2,4, Group III: 3,6 ± 0,9, Group IV:2,3 ± 0,6). Both treatments increased Paneth cell count and decreased intraepithelial CD3(+) T lymphocytes and inflammatory infiltration of lamina propria to control levels. In the sham group almost the total of intestinal epithelial cells expressed occludin (92 ± 8%) and claudin-1 (98 ± 4%) and CLP reduced this expression to 34 ± 12% for occludin and 35 ± 7% for claudin-1. Administration of HC significantly increased occludin (51 ± 17%) and claudin-1 (77 ± 9%) expression. FMT exerted also a significant restoring effect in TJ by increasing occludin (56 ± 15%) and claudin-1 (84 ± 7%) expression. The beneficial effects of these treatments on gut barrier function led to significant reduction of systemic endotoxemia (EU/ml, mean ± SD: Group I: 0,93 ± 0,36, Group II: 2,14 ± 1,74, Group III: 1,48 ± 0,53, Group IV: 1,61 ± 0,58,), while FMT additionally decreased IL-6 and IL-10 levels.

CONCLUSION: Fecal microbiota transplantation and stress dose hydrocortisone administration in septic rats induce a multifactorial improvement of the gut mechanical and immunological barriers, preventing endotoxemia and leading to improved survival.}, } @article {pmid32495834, year = {2020}, author = {Rasmussen, TS and Koefoed, AK and Jakobsen, RR and Deng, L and Castro-Mejía, JL and Brunse, A and Neve, H and Vogensen, FK and Nielsen, DS}, title = {Bacteriophage-mediated manipulation of the gut microbiome - promises and presents limitations.}, journal = {FEMS microbiology reviews}, volume = {44}, number = {4}, pages = {507-521}, doi = {10.1093/femsre/fuaa020}, pmid = {32495834}, issn = {1574-6976}, abstract = {Gut microbiome (GM) composition and function are linked to human health and disease, and routes for manipulating the GM have become an area of intense research. Due to its high treatment efficacy, the use of fecal microbiota transplantation (FMT) is generally accepted as a promising experimental treatment for patients suffering from GM imbalances (dysbiosis), e.g. caused by recurrent Clostridioides difficile infections (rCDI). Mounting evidence suggests that bacteriophages (phages) play a key role in successful FMT treatment by restoring the dysbiotic bacterial GM. As a refinement to FMT, removing the bacterial component of donor feces by sterile filtration, also referred to as fecal virome transplantation (FVT), decreases the risk of invasive infections caused by bacteria. However, eukaryotic viruses and prophage-encoded virulence factors remain a safety issue. Recent in vivo studies show how cascading effects are initiated when phage communities are transferred to the gut by e.g. FVT, which leads to changes in the GM composition, host metabolome, and improve host health such as alleviating symptoms of obesity and type-2-diabetes (T2D). In this review, we discuss the promises and limitations of FVT along with the perspectives of using FVT to treat various diseases associated with GM dysbiosis.}, } @article {pmid32495743, year = {2020}, author = {Chinna Meyyappan, A and Milev, R}, title = {The Safety, Efficacy, and Tolerability of Microbial Ecosystem Therapeutic-2 in People With Major Depression and/or Generalized Anxiety Disorder: Protocol for a Phase 1, Open-Label Study.}, journal = {JMIR research protocols}, volume = {9}, number = {6}, pages = {e17223}, pmid = {32495743}, issn = {1929-0748}, abstract = {BACKGROUND: The bidirectional signaling between the gut microbiota and the brain, known as the gut-brain axis, is being heavily explored in current neuropsychiatric research. Analyses of the human gut microbiota have shown considerable individual variability in bacterial content, which is hypothesized to influence brain function, and potentially mood and anxiety symptoms, through gut-brain axis communication. Preclinical and clinical research examining these effects suggests that fecal microbiota transplant (FMT) may aid in improving the severity of depression and anxiety symptoms by recolonizing the gastrointestinal (GI) tract with healthy bacteria. The microbial ecosystem therapeutic (ie, microbial ecosystem therapeutic-2 [MET-2]) used in this study is an alternative treatment to FMT, which comprises 40 different strains of gut bacteria from a healthy donor.

OBJECTIVE: The primary objective of this study is to assess subjective changes in mood and anxiety symptoms before, during, and after administration of MET-2. The secondary objectives of this study are to assess the changes in metabolic functioning and the level of repopulation of healthy gut bacteria, the safety and tolerability of MET-2, and the effects of early stress on biomarkers of depression/anxiety and the response to treatment.

METHODS: Adults experiencing depressive or anxiety symptoms will be recruited from the Kingston area. These participants will orally consume an encapsulated MET-2 once daily-containing 40 strains of purified and laboratory-grown bacteria from a single healthy donor-for 8 weeks, followed by a 2-week treatment-free follow-up period. Participants will undergo a series of clinical assessments measuring mood, anxiety, and GI symptoms using validated clinical scales and questionnaires. Molecular data will be collected from blood and fecal samples to assess metabolic changes, neurotransmitter levels, inflammatory markers, and the level of engraftment of the fecal samples that may predict outcomes in depression or anxiety.

RESULTS: Given the association between the gut bacteria and the risk factors of depression, we expect to observe an improvement in the severity of depressive and anxiety symptoms following treatment, and we expect that this improvement is mediated by the recolonization of the GI tract with healthy bacteria. The recruitment for this study has been completed, and the data obtained are currently being analyzed.

CONCLUSIONS: This is the first time MET-2 is being tested in psychiatric indications, specifically depression and anxiety. As such, this may be the first study to show the potential effects of microbial therapy in alleviating psychiatric symptoms as well as its safety and tolerability.

DERR1-10.2196/17223.}, } @article {pmid32493442, year = {2020}, author = {Trang-Poisson, C and Kerdreux, E and Poinas, A and Planche, L and Sokol, H and Bemer, P and Cabanas, K and Hivernaud, E and Biron, L and Flet, L and Montassier, E and Le Garcasson, G and Chiffoleau, A and Jobert, A and Lepelletier, D and Caillon, J and Le Pape, P and Imbert, BM and Bourreille, A}, title = {Impact of fecal microbiota transplantation on chronic recurrent pouchitis in ulcerative colitis with ileo-anal anastomosis: study protocol for a prospective, multicenter, double-blind, randomized, controlled trial.}, journal = {Trials}, volume = {21}, number = {1}, pages = {455}, pmid = {32493442}, issn = {1745-6215}, support = {16-267//Ministère des Affaires Sociales, de la Santé et des Droits des Femmes/ ; }, abstract = {BACKGROUND: Almost 15% of patients with ulcerative colitis (UC) will require a proctocolectomy with ileal pouch-anal anastomosis (IPAA) as a result of fulminant colitis, dysplasia, cancer, or medical refractory diseases. Around 50% will experience pouchitis, an idiopathic inflammatory condition involving the ileal reservoir, responsible for digestive symptoms, deterioration in quality of life, and disability. Though the majority of initial cases of pouchitis are easily managed with a short course of antibiotics, in about 10% of cases, inflammation of the pouch becomes chronic with very few treatments available. Previous studies have suggested that manipulating the composition of intestinal flora through antibiotics, probiotics, and prebiotics achieved significant results for treating acute episodes of UC-associated pouchitis. However, there is currently no established effective treatment for chronic antibiotic-dependent pouchitis. Fecal microbiota transplantation (FMT) is a novel therapy involving the transfer of normal intestinal flora from a healthy donor to a patient with a medical condition potentially caused by the disrupted homeostasis of intestinal microbiota or dysbiosis.

METHODS: Our project aims to compare the delay of relapse of chronic recurrent pouchitis after FMT versus sham transplantation. Forty-two patients with active recurrent pouchitis after having undergone an IPAA for UC will be enrolled at 12 French centers. The patients who respond to antibiotherapy will be randomized at a ratio of 1:1 to receive either FMT or sham transplantation.

DISCUSSION: On April 30, 2014, the World Health Organization published an alarming report on antibiotic resistance. Finding an alternative medical treatment to antibiotics in order to prevent relapses of pouchitis is therefore becoming increasingly important given the risk posed by multiresistant bacteria. Moreover, if the results of this study are conclusive, FMT, which is less expensive than biologics, could become a routine treatment in the future.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT03524352. Registered on 14 May 2018.}, } @article {pmid32492490, year = {2020}, author = {Gulati, M and Singh, SK and Corrie, L and Kaur, IP and Chandwani, L}, title = {Delivery routes for faecal microbiota transplants: Available, anticipated and aspired.}, journal = {Pharmacological research}, volume = {159}, number = {}, pages = {104954}, doi = {10.1016/j.phrs.2020.104954}, pmid = {32492490}, issn = {1096-1186}, abstract = {Fecal microbiota transplant (FMT) has seen a historic emergence in last decade with its sojourn recently entering into a chequered path, due to a few reports of infection and subsequent mortality. Though FMT has been extensively reported, there is no comprehensive report on the delivery routes available for this non-pharmacological treatment option. Safety, efficacy and cost of FMT not only depend on the quality of contents but also on the delivery route employed. A number of delivery routes are in use for conducting FMT, which include upper gastrointestinal routes (UGI) i.e. nasogastric/nasojejunal tube, endoscopy, oral capsules and lower gastrointestinal routes (LGI) like retention enema, sigmoidoscopy or colonoscopy. Capsules, both conventional as well as colon targeted have been the most commonly used formulations. Surprisingly, the success rates with conventional gastric delivery capsules and colon targeted capsules were found to be quite similar indicating the sufficiency of the inoculum size to withstand the microbial loss in the gastric milieu. Patient compliance, cost effectiveness, comfort of administration, level of invasiveness, patient's hospital admission, risk of aspiration and infections, multiplicity of administration required, recurrence rate are the main factors that seem to influence the choice for route of administration of physicians. The best route for FMT has not been established yet. Extensive studies are required to understand the interplay of route adopted, type of donor, physical nature of sample (fresh or frozen), patient compliance and cost effectiveness to design an approach for the risk free, convenient and cost-effective administration route for FMT.}, } @article {pmid32487252, year = {2020}, author = {Adelman, MW and Woodworth, MH and Langelier, C and Busch, LM and Kempker, JA and Kraft, CS and Martin, GS}, title = {The gut microbiome's role in the development, maintenance, and outcomes of sepsis.}, journal = {Critical care (London, England)}, volume = {24}, number = {1}, pages = {278}, pmid = {32487252}, issn = {1466-609X}, support = {K23 AI144036/AI/NIAID NIH HHS/United States ; K23AI144036//National Institute of Allergy and Infectious Diseases/International ; K08 HS-025240//Agency for Healthcare Research and Quality (US)/International ; UL1 TR-002378/TR/NCATS NIH HHS/United States ; K23HL138461-01A1/HL/NHLBI NIH HHS/United States ; }, mesh = {Fecal Microbiota Transplantation/methods/*standards ; Gastrointestinal Microbiome/*immunology/physiology ; Humans ; Probiotics/therapeutic use ; Sepsis/complications/*physiopathology/*therapy ; }, abstract = {The gut microbiome regulates a number of homeostatic mechanisms in the healthy host including immune function and gut barrier protection. Loss of normal gut microbial structure and function has been associated with diseases as diverse as Clostridioides difficile infection, asthma, and epilepsy. Recent evidence has also demonstrated a link between the gut microbiome and sepsis. In this review, we focus on three key areas of the interaction between the gut microbiome and sepsis. First, prior to sepsis onset, gut microbiome alteration increases sepsis susceptibility through several mechanisms, including (a) allowing for expansion of pathogenic intestinal bacteria, (b) priming the immune system for a robust pro-inflammatory response, and (c) decreasing production of beneficial microbial products such as short-chain fatty acids. Second, once sepsis is established, gut microbiome disruption worsens and increases susceptibility to end-organ dysfunction. Third, there is limited evidence that microbiome-based therapeutics, including probiotics and selective digestive decontamination, may decrease sepsis risk and improve sepsis outcomes in select patient populations, but concerns about safety have limited uptake. Case reports of a different microbiome-based therapy, fecal microbiota transplantation, have shown correlation with gut microbial structure restoration and decreased inflammatory response, but these results require further validation. While much of the evidence linking the gut microbiome and sepsis has been established in pre-clinical studies, clinical evidence is lacking in many areas. To address this, we outline a potential research agenda for further investigating the interaction between the gut microbiome and sepsis.}, } @article {pmid32486476, year = {2020}, author = {Okahara, K and Ishikawa, D and Nomura, K and Ito, S and Haga, K and Takahashi, M and Shibuya, T and Osada, T and Nagahara, A}, title = {Matching between Donors and Ulcerative Colitis Patients Is Important for Long-Term Maintenance after Fecal Microbiota Transplantation.}, journal = {Journal of clinical medicine}, volume = {9}, number = {6}, pages = {}, pmid = {32486476}, issn = {2077-0383}, support = {JP16K09328//Japan Society for the Promotion of Science/ ; }, abstract = {We previously demonstrated that fresh fecal microbiota transplantation (FMT) following triple antibiotic therapy (amoxicillin, fosfomycin, metronidazole (AFM); A-FMT) resulted in effective colonization of Bacteroidetes species, leading to short-term clinical response in ulcerative colitis (UC). Its long-term efficacy and criteria for donor selection are unknown. Here, we analyzed the long-term efficacy of A-FMT compared to AFM monotherapy (mono-AFM). AFM was administered to patients with mild to severe UC for 2 weeks until 2 days before fresh FMT. Clinical response and efficacy maintenance were defined by the decrease and no exacerbation in clinical activity index. The population for intention-to-treat analysis comprised 92 patients (A-FMT, n = 55; mono-AFM, n = 37). Clinical response was observed at 4 weeks post-treatment (A-FMT, 56.3%; mono-AFM, 48.6%). Maintenance rate of responders at 24 months post-treatment was significantly higher with A-FMT than mono-AFM (p = 0.034). Significant differences in maintenance rate according to the age difference between donors and patients were observed. Additionally, sibling FMT had a significantly higher maintenance rate than parent-child FMT. Microbial analysis of patients who achieved long-term maintenance showed that some exhibited similarity to their donors, particularly Bacteroidetes species. Thus, A-FMT exhibited long-term efficacy. Therefore, matching between donors and UC patients may be helpful in effectively planning the FMT regimen.}, } @article {pmid32485282, year = {2020}, author = {Wang, MX and Lin, L and Chen, YD and Zhong, YP and Lin, YX and Li, P and Tian, X and Han, B and Xie, ZY and Liao, QF}, title = {Evodiamine has therapeutic efficacy in ulcerative colitis by increasing Lactobacillus acidophilus levels and acetate production.}, journal = {Pharmacological research}, volume = {159}, number = {}, pages = {104978}, doi = {10.1016/j.phrs.2020.104978}, pmid = {32485282}, issn = {1096-1186}, abstract = {Emerging evidence implicates gut microbiota have an important role in ulcerative colitis (UC). Previous study indicated that Evodiamine (EVO) can alleviate colitis through downregulating inflammatory pathways. However, specific relationship between EVO-treated colitis relief and regulation of gut microbiota is still unclear. Here, our goal was to determine the potential role of gut microbiota in the relief of UC by EVO. By using pathology-related indicators, 16S rRNA sequencing and metabolomics profiling, we assessed the pharmacological effect of EVO on dextran sulfate sodium (DSS)-induced colitis rats as well as on the change of gut microbiota and metabolism. Fecal derived from EVO-treated rats was transplanted into colitis rats to verify the effect of EVO on gut microbiota, and 'driver bacteria' was found and validated by 16S rRNA sequencing, metagenome and qRT-PCR. The effect of Lactobacillus acidophilus (L. acidophilus) was investigated by vivo experiment, microbiota analysis, Short-chain fatty acids (SCFAs) quantification and colon transcriptomics. EVO reduced the susceptibility to DSS-induced destruction of epithelial integrity and severe inflammatory response, and regulated the gut microbiota and metabolites. Fecal Microbiota Transplantation (FMT) alleviated DSS-induced colitis, increased the abundance of L. acidophilus and the level of acetate. Furthermore, gavaged with L. acidophilus reduced pro-inflammatory cytokines, promoted the increase of goblet cells and the secretion of antimicrobial peptides, regulated the ratio of Firmicutes/Bacteroidetes and increased the level of acetate. Our results indicated that EVO mitigation of DSS-induced colitis is associated with increased in L. acidophilus and protective acetate production, which may be a promising strategy for treating UC.}, } @article {pmid32483373, year = {2020}, author = {Burberry, A and Wells, MF and Limone, F and Couto, A and Smith, KS and Keaney, J and Gillet, G and van Gastel, N and Wang, JY and Pietilainen, O and Qian, M and Eggan, P and Cantrell, C and Mok, J and Kadiu, I and Scadden, DT and Eggan, K}, title = {C9orf72 suppresses systemic and neural inflammation induced by gut bacteria.}, journal = {Nature}, volume = {582}, number = {7810}, pages = {89-94}, pmid = {32483373}, issn = {1476-4687}, support = {R01 NS089742/NS/NINDS NIH HHS/United States ; 5R01NS089742/NH/NIH HHS/United States ; K99 MH119327/MH/NIMH NIH HHS/United States ; K99 AG057808/AG/NIA NIH HHS/United States ; 1K99MH119327-01/NH/NIH HHS/United States ; 5K99AG057808-02/NH/NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/genetics/pathology ; Animals ; Anti-Bacterial Agents/pharmacology ; Autoimmunity/drug effects/genetics/immunology ; C9orf72 Protein/*genetics ; Cell Movement/drug effects ; Cytokines/immunology ; Fecal Microbiota Transplantation ; Female ; Frontotemporal Dementia/genetics/pathology ; Gastrointestinal Microbiome/drug effects/immunology/*physiology ; Gliosis/genetics/*microbiology/*pathology/prevention & control ; Inflammation/*genetics/*microbiology/pathology/prevention & control ; Loss of Function Mutation/genetics ; Male ; Mice ; Microglia/immunology/microbiology/pathology ; Spinal Cord/immunology/microbiology/*pathology ; Survival Rate ; }, abstract = {A hexanucleotide-repeat expansion in C9ORF72 is the most common genetic variant that contributes to amyotrophic lateral sclerosis and frontotemporal dementia1,2. The C9ORF72 mutation acts through gain- and loss-of-function mechanisms to induce pathways that are implicated in neural degeneration3-9. The expansion is transcribed into a long repetitive RNA, which negatively sequesters RNA-binding proteins5 before its non-canonical translation into neural-toxic dipeptide proteins3,4. The failure of RNA polymerase to read through the mutation also reduces the abundance of the endogenous C9ORF72 gene product, which functions in endolysosomal pathways and suppresses systemic and neural inflammation6-9. Notably, the effects of the repeat expansion act with incomplete penetrance in families with a high prevalence of amyotrophic lateral sclerosis or frontotemporal dementia, indicating that either genetic or environmental factors modify the risk of disease for each individual. Identifying disease modifiers is of considerable translational interest, as it could suggest strategies to diminish the risk of developing amyotrophic lateral sclerosis or frontotemporal dementia, or to slow progression. Here we report that an environment with reduced abundance of immune-stimulating bacteria10,11 protects C9orf72-mutant mice from premature mortality and significantly ameliorates their underlying systemic inflammation and autoimmunity. Consistent with C9orf72 functioning to prevent microbiota from inducing a pathological inflammatory response, we found that reducing the microbial burden in mutant mice with broad spectrum antibiotics-as well as transplanting gut microflora from a protective environment-attenuated inflammatory phenotypes, even after their onset. Our studies provide further evidence that the microbial composition of our gut has an important role in brain health and can interact in surprising ways with well-known genetic risk factors for disorders of the nervous system.}, } @article {pmid32474336, year = {2020}, author = {Lin, H and Wang, Q and Yuan, M and Liu, L and Chen, Z and Zhao, Y and Das, R and Duan, Y and Xu, X and Xue, Y and Luo, Y and Mao, D}, title = {The prolonged disruption of a single-course amoxicillin on mice gut microbiota and resistome, and recovery by inulin, Bifidobacterium longum and fecal microbiota transplantation.}, journal = {Environmental pollution (Barking, Essex : 1987)}, volume = {265}, number = {Pt A}, pages = {114651}, doi = {10.1016/j.envpol.2020.114651}, pmid = {32474336}, issn = {1873-6424}, mesh = {Amoxicillin ; Animals ; *Bifidobacterium longum ; Fecal Microbiota Transplantation ; Feces ; *Gastrointestinal Microbiome ; Humans ; Inulin ; Mice ; RNA, Ribosomal, 16S ; }, abstract = {The usages of antibiotics in treating the pathogenic infections could alter the gut microbiome and associated resistome, causing long term adverse impact on human health. In this study, mice were treated with human-simulated regimen 25.0 mg kg-1 of amoxicillin for seven days, and their gut microbiota and resistome were characterized using the 16S rRNA amplicons sequencing and the high-throughput qPCR, respectively. Meanwhile, the flora restorations after individual applications of inulin, Bifidobacterium longum (B. longum), and fecal microbiota transplantation (FMT) were analyzed for up to 35 days. The results revealed the prolonged negative impact of single course AMX exposure on mice gut microbiota and resistome. To be specific, pathobionts of Klebsiella and Escherichia-Shigella were significantly enriched, while prebiotics of Bifidobacterium and Lactobacillus were dramatically depleted. Furthermore, β-lactam resistance genes and efflux resistance genes were obviously enriched after amoxicillin exposure. Compared to B. longum, FMT and inulin were demonstrated to preferably restore the gut microbiota via reconstituting microbial community and stimulating specific prebiotic respectively. Such variation of microbiome caused their distinct alleviations on resistome alteration. Inulin earned the greatest elimination on AMX induced ARG abundance and diversity enrichment. FMT and B. longum caused remove of particular ARGs such as ndm-1, blaPER. Network analysis revealed that most of the ARGs were prone to be harbored by Firmicutes and Proteobacteria. In general, gut resistome shift was partly associated with the changing bacterial community structures and transposase and integron. Taken together, these results demonstrated the profound disruption of gut microbiota and resistome after single-course amoxicillin treatment and different restoration by inulin, B. longum and FMT.}, } @article {pmid32468608, year = {2020}, author = {Kragsnaes, MS and Nilsson, AC and Kjeldsen, J and Holt, HM and Rasmussen, KF and Georgsen, J and Ellingsen, T and Holm, DK}, title = {How do I establish a stool bank for fecal microbiota transplantation within the blood- and tissue transplant service?.}, journal = {Transfusion}, volume = {60}, number = {6}, pages = {1135-1141}, doi = {10.1111/trf.15816}, pmid = {32468608}, issn = {1537-2995}, support = {//Odense University Hospital/ ; }, abstract = {Worldwide, there is a rising demand for thoroughly screened, high-quality fecal microbiota transplantation (FMT) products that can be obtained at a reasonable cost. In the light of this evolving therapeutic area of the intestinal microbiota, both private and public stool banks have emerged. However, some of the larger difficulties when establishing stool banks are caused by the absence of or international disagreement on regulation and legislative formalities. In this context, the establishment of a stool bank within a nonprofit blood and tissue transplant service has several advantages. Especially, this setting can ensure that every step of the donation process, laboratory handling, and donor-traceability is in agreement with the current expert guidelines and meets the requirements of the European Union's regulative directives on human cells and tissues. Although safety and documentation are the top priority of the stool bank setup presented here, cost-effectiveness of the production is possible due to a high donor screening success rate and the knowhow, infrastructure, facilities, personnel, and laboratory- and quality-management systems that were already in place. Overall, our experience is that a centralized, nonprofit, blood and tissue transplant service is an ideal and safe facility to run a stool bank of high quality FMT products that are based on stool donations from volunteer, unpaid, healthy, blood donors.}, } @article {pmid32466801, year = {2020}, author = {Jian, X and Zhu, Y and Ouyang, J and Wang, Y and Lei, Q and Xia, J and Guan, Y and Zhang, J and Guo, J and He, Y and Wang, J and Li, J and Lin, J and Su, M and Li, G and Wu, M and Qiu, L and Xiang, J and Xie, L and Jia, W and Zhou, W}, title = {Alterations of gut microbiome accelerate multiple myeloma progression by increasing the relative abundances of nitrogen-recycling bacteria.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {74}, pmid = {32466801}, issn = {2049-2618}, support = {31900102//National Natural Science Foundation of China/International ; 81570205, 81630007//National Natural Science Foundation of China/International ; 81800209//National Natural Science Foundation of China/International ; 2019M652792//China Postdoctoral Science Foundation/International ; ZLXD2017004//Strategic Priority Research Program of Central South University/International ; }, abstract = {BACKGROUND: Gut microbiome alterations are closely related to human health and linked to a variety of diseases. Although great efforts have been made to understand the risk factors for multiple myeloma (MM), little is known about the role of the gut microbiome and alterations of its metabolic functions in the development of MM.

RESULTS: Here, in a cohort of newly diagnosed patients with MM and healthy controls (HCs), significant differences in metagenomic composition were discovered, for the first time, with higher bacterial diversity in MM. Specifically, nitrogen-recycling bacteria such as Klebsiella and Streptococcus were significantly enriched in MM. Also, the bacteria enriched in MM were significantly correlated with the host metabolome, suggesting strong metabolic interactions between microbes and the host. In addition, the MM-enriched bacteria likely result from the regulation of urea nitrogen accumulated during MM progression. Furthermore, by performing fecal microbiota transplantation (FMT) into 5TGM1 mice, we proposed a mechanistic explanation for the interaction between MM-enriched bacteria and MM progression via recycling urea nitrogen. Further experiments validated that Klebsiella pneumoniae promoted MM progression via de novo synthesis of glutamine in mice and that the mice fed with glutamine-deficient diet exhibited slower MM progression.

CONCLUSIONS: Overall, our findings unveil a novel function of the altered gut microbiome in accelerating the malignant progression of MM and open new avenues for novel treatment strategies via manipulation of the intestinal microbiota of MM patients. Video abstract.}, } @article {pmid32466620, year = {2020}, author = {Nance, CL and Deniskin, R and Diaz, VC and Paul, M and Anvari, S and Anagnostou, A}, title = {The Role of the Microbiome in Food Allergy: A Review.}, journal = {Children (Basel, Switzerland)}, volume = {7}, number = {6}, pages = {}, pmid = {32466620}, issn = {2227-9067}, abstract = {Food allergies are common and estimated to affect 8% of children and 11% of adults in the United States. They pose a significant burden-physical, economic and social-to those affected. There is currently no available cure for food allergies. Emerging evidence suggests that the microbiome contributes to the development and manifestations of atopic disease. According to the hygiene hypothesis, children growing up with older siblings have a lower incidence of allergic disease compared with children from smaller families, due to their early exposure to microbes in the home. Research has also demonstrated that certain environmental exposures, such as a farming environment, during early life are associated with a diverse bacterial experience and reduced risk of allergic sensitization. Dysregulation in the homeostatic interaction between the host and the microbiome or gut dysbiosis appears to precede the development of food allergy, and the timing of such dysbiosis is critical. The microbiome affects food tolerance via the secretion of microbial metabolites (e.g., short chain fatty acids) and the expression of microbial cellular components. Understanding the biology of the microbiome and how it interacts with the host to maintain gut homeostasis is helpful in developing smarter therapeutic approaches. There are ongoing trials evaluating the benefits of probiotics and prebiotics, for the prevention and treatment of atopic diseases to correct the dysbiosis. However, the routine use of probiotics as an intervention for preventing allergic disease is not currently recommended. A new approach in microbial intervention is to attempt a more general modification of the gut microbiome, such as with fecal microbiota transplantation. Developing targeted bacterial therapies for food allergy may be promising for both the treatment and prevention of food allergy. Similarly, fecal microbiota transplantation is being explored as a potentially beneficial interventional approach. Overall, targeted bacterial therapies for food allergy may be promising for both the treatment and prevention of food allergy.}, } @article {pmid32460890, year = {2020}, author = {Li, M and Li, C and Wu, X and Chen, T and Ren, L and Xu, B and Cao, J}, title = {Microbiota-driven interleukin-17 production provides immune protection against invasive candidiasis.}, journal = {Critical care (London, England)}, volume = {24}, number = {1}, pages = {268}, pmid = {32460890}, issn = {1466-609X}, support = {81722001//National Natural Science Foundation of China/International ; 81572038//National Natural Science Foundation of China/International ; }, mesh = {Animals ; Candidiasis/drug therapy/*immunology ; Fecal Microbiota Transplantation/methods ; Humans ; Interleukin-17/*pharmacology/therapeutic use ; Mice ; Mice, Inbred C57BL ; Microbiota/drug effects/*physiology ; }, abstract = {BACKGROUND: The intestinal microbiota plays a crucial role in human health, which could affect host immunity and the susceptibility to infectious diseases. However, the role of intestinal microbiota in the immunopathology of invasive candidiasis remains unknown.

METHODS: In this work, an antibiotic cocktail was used to eliminate the intestinal microbiota of conventional-housed (CNV) C57/BL6 mice, and then both antibiotic-treated (ABX) mice and CNV mice were intravenously infected with Candida albicans to investigate their differential responses to infection. Furthermore, fecal microbiota transplantation (FMT) was applied to ABX mice in order to assess its effects on host immunity against invasive candidiasis after restoring the intestinal microbiota, and 16S ribosomal RNA gene sequencing was conducted on fecal samples from both uninfected ABX and CNV group of mice to analyze their microbiomes.

RESULTS: We found that ABX mice displayed significantly increased weight loss, mortality, and organ damage during invasive candidiasis when compared with CNV mice, which could be alleviated by FMT. In addition, the level of IL-17A in ABX mice was significantly lower than that in the CNV group during invasive candidiasis. Treatment with recombinant IL-17A could improve the survival of ABX mice during invasive candidiasis. Besides, the microbial diversity of ABX mice was significantly reduced, and the intestinal microbiota structure of ABX mice was significantly deviated from the CNV mice.

CONCLUSIONS: Our data revealed that intestinal microbiota plays a protective role in invasive candidiasis by enhancing IL-17A production in our model system.}, } @article {pmid32457246, year = {2020}, author = {Abhyankar, MM and Ma, JZ and Scully, KW and Nafziger, AJ and Frisbee, AL and Saleh, MM and Madden, GR and Hays, AR and Poulter, M and Petri, WA}, title = {Immune Profiling To Predict Outcome of Clostridioides difficile Infection.}, journal = {mBio}, volume = {11}, number = {3}, pages = {}, pmid = {32457246}, issn = {2150-7511}, support = {T32 AI007496/AI/NIAID NIH HHS/United States ; R01 AI124214/AI/NIAID NIH HHS/United States ; }, abstract = {There is a pressing need for biomarker-based models to predict mortality from and recurrence of Clostridioides difficile infection (CDI). Risk stratification would enable targeted interventions such as fecal microbiota transplant, antitoxin antibodies, and colectomy for those at highest risk. Because severity of CDI is associated with the immune response, we immune profiled patients at the time of diagnosis. The levels of 17 cytokines in plasma were measured in 341 CDI inpatients. The primary outcome of interest was 90-day mortality. Increased tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand 5 (CCL-5), suppression of tumorigenicity 2 receptor (sST-2), IL-8, and IL-15 predicted mortality by univariate analysis. After adjusting for demographics and clinical characteristics, the mortality risk (as indicated by the hazard ratio [HR]) was higher for patients in the top 25th percentile for TNF-α (HR = 8.35, P = 0.005) and IL-8 (HR = 4.45, P = 0.01) and lower for CCL-5 (HR = 0.18, P ≤ 0.008). A logistic regression risk prediction model was developed and had an area under the receiver operating characteristic curve (AUC) of 0.91 for 90-day mortality and 0.77 for 90-day recurrence. While limited by being single site and retrospective, our work resulted in a model with a substantially greater predictive ability than white blood cell count. In conclusion, immune profiling demonstrated differences between patients in their response to CDI, offering the promise for precision medicine individualized treatment.IMPORTANCEClostridioides difficile infection is the most common health care-associated infection in the United States with more than 20% patients experiencing symptomatic recurrence. The complex nature of host-bacterium interactions makes it difficult to predict the course of the disease based solely on clinical parameters. In the present study, we built a robust prediction model using representative plasma biomarkers and clinical parameters for 90-day all-cause mortality. Risk prediction based on immune biomarkers and clinical variables may contribute to treatment selection for patients as well as provide insight into the role of immune system in C. difficile pathogenesis.}, } @article {pmid32453670, year = {2020}, author = {Kaźmierczak-Siedlecka, K and Daca, A and Fic, M and van de Wetering, T and Folwarski, M and Makarewicz, W}, title = {Therapeutic methods of gut microbiota modification in colorectal cancer management - fecal microbiota transplantation, prebiotics, probiotics, and synbiotics.}, journal = {Gut microbes}, volume = {11}, number = {6}, pages = {1518-1530}, pmid = {32453670}, issn = {1949-0984}, abstract = {The link between gut microbiota and the development of colorectal cancer has been investigated. An imbalance in the gut microbiota promotes the progress of colorectal carcinogenesis via multiple mechanisms, including inflammation, activation of carcinogens, and tumorigenic pathways as well as damaging host DNA. Several therapeutic methods are available with which to alter the composition and the activity of gut microbiota, such as administration of prebiotics, probiotics, and synbiotics; these can confer various benefits for colorectal cancer patients. Nowadays, fecal microbiota transplantation is the most modern way of modulating the gut microbiota. Even though data regarding fecal microbiota transplantation in colorectal cancer patients are still rather limited, it has been approved as a clinical method of treatment-recurrent Clostridium difficile infection, which may also occur in these patients. The major benefits of fecal microbiota transplantation include modulation of immunotherapy efficacy, amelioration of bile acid metabolism, and restoration of intestinal microbial diversity. Nonetheless, more studies are needed to assess the long-term effects of fecal microbiota transplantation. In this review, the impact of gut microbiota on the efficiency of anti-cancer therapy and colorectal cancer patients' overall survival is also discussed.}, } @article {pmid32448639, year = {2020}, author = {Castro Rocha, FA and Duarte-Monteiro, AM and Henrique da Mota, LM and Matias Dinelly Pinto, AC and Fonseca, JE}, title = {Microbes, helminths, and rheumatic diseases.}, journal = {Best practice & research. Clinical rheumatology}, volume = {34}, number = {4}, pages = {101528}, pmid = {32448639}, issn = {1532-1770}, abstract = {There has been a progressive interest on modifications of the human defense system following insults occurring in the interface between our body and the external environment, as they may provoke or worsen disease states. Studies suggest that billions of germs, which compose the gut microbiota influence one's innate and adaptive immune responses at the intestinal level, but these microorganisms may also impact rheumatic diseases. The microbiota of the skin, respiratory, and urinary tracts may also be relevant in rheumatology. Evidence indicates that changes in the gut microbiome alter the pathogenesis of immune-mediated diseases such as rheumatoid arthritis and ankylosing spondylitis but also of other disorders like atherosclerosis and osteoarthritis. Therapeutic strategies to modify the microbiota, including probiotics and fecal microbiota transplantation, have been received with skepticism, which, in turn, has drawn attention back to previously developed interventions such as antibiotics. Helminths adapted to humans over the evolution process, but their role in disease modulation, particularly immune-mediated diseases, remains to be understood. The present review focuses on data concerning modifications of the immune system induced by interactions with microbes and pluricellular organisms, namely helminths, and their impact on rheumatic diseases. Practical aspects, including specific microbiota-targeted therapies, are also discussed.}, } @article {pmid32445528, year = {2020}, author = {Ostojic, SM}, title = {Letter: balancing gut hydrogen as a proxy for bacteriotherapy benefits in irritable bowel syndrome.}, journal = {Alimentary pharmacology & therapeutics}, volume = {51}, number = {12}, pages = {1451-1452}, doi = {10.1111/apt.15782}, pmid = {32445528}, issn = {1365-2036}, mesh = {*Clostridium Infections ; Fecal Microbiota Transplantation ; *Gastrointestinal Microbiome ; Humans ; Hydrogen ; *Irritable Bowel Syndrome ; }, } @article {pmid32443576, year = {2020}, author = {Kløve, S and Genger, C and Mousavi, S and Weschka, D and Bereswill, S and Heimesaat, MM}, title = {Toll-Like Receptor-4 Dependent Intestinal and Systemic Sequelae Following Peroral Campylobacter coli Infection of IL10 Deficient Mice Harboring a Human Gut Microbiota.}, journal = {Pathogens (Basel, Switzerland)}, volume = {9}, number = {5}, pages = {}, pmid = {32443576}, issn = {2076-0817}, support = {ZIM; ZF4117904 AJ8//Bundesministerium für Forschung und Technologie/ ; Zoonoses research consortium PAC-Campylobacter, IP7/ 01KI1725D//Bundesministerium für Bildung, Wissenschaft und Forschung/ ; }, abstract = {Zoonotic Campylobacter, including C. jejuni and C. coli, are among the most prevalent agents of food-borne enteritis worldwide. The immunopathological sequelae of campylobacteriosis are caused by Toll-like Receptor-4 (TLR4)-dependent host immune responses, induced by bacterial lipooligosaccharide (LOS). In order to investigate C. coli-host interactions, including the roles of the human gut microbiota and TLR4, upon infection, we applied a clinical acute campylobacteriosis model, and subjected secondary abiotic, TLR4-deficient IL10-/- mice and IL10-/- controls to fecal microbiota transplantation derived from human donors by gavage, before peroral C. coli challenge. Until day 21 post-infection, C. coli could stably colonize the gastrointestinal tract of human microbiota-associated (hma) mice of either genotype. TLR4-deficient IL10-/- mice, however, displayed less severe clinical signs of infection, that were accompanied by less distinct apoptotic epithelial cell and innate as well as adaptive immune cell responses in the colon, as compared to IL10-/- counterparts. Furthermore, C. coli infected IL10-/-, as opposed to TLR4-deficient IL10-/-, mice displayed increased pro-inflammatory cytokine concentrations in intestinal and, strikingly, systemic compartments. We conclude that pathogenic LOS might play an important role in inducing TLR4-dependent host immune responses upon C. coli infection, which needs to be further addressed in more detail.}, } @article {pmid32440192, year = {2020}, author = {Elsalem, L and Jum'ah, AA and Alfaqih, MA and Aloudat, O}, title = {The Bacterial Microbiota of Gastrointestinal Cancers: Role in Cancer Pathogenesis and Therapeutic Perspectives.}, journal = {Clinical and experimental gastroenterology}, volume = {13}, number = {}, pages = {151-185}, pmid = {32440192}, issn = {1178-7023}, abstract = {The microbiota has an essential role in the pathogenesis of many gastrointestinal diseases including cancer. This effect is mediated through different mechanisms such as damaging DNA, activation of oncogenic pathways, production of carcinogenic metabolites, stimulation of chronic inflammation, and inhibition of antitumor immunity. Recently, the concept of "pharmacomicrobiomics" has emerged as a new field concerned with exploring the interplay between drugs and microbes. Mounting evidence indicates that the microbiota and their metabolites have a major impact on the pharmacodynamics and therapeutic responses toward anticancer drugs including conventional chemotherapy and molecular-targeted therapeutics. In addition, microbiota appears as an attractive target for cancer prevention and treatment. In this review, we discuss the role of bacterial microbiota in the pathogenesis of different cancer types affecting the gastrointestinal tract system. We also scrutinize the evidence regarding the role of microbiota in anticancer drug responses. Further, we discuss the use of probiotics, fecal microbiota transplantation, and antibiotics, either alone or in combination with anticancer drugs for prevention and treatment of gastrointestinal tract cancers.}, } @article {pmid32437393, year = {2020}, author = {Fretheim, H and Chung, BK and Didriksen, H and Bækkevold, ES and Midtvedt, Ø and Brunborg, C and Holm, K and Valeur, J and Tennøe, AH and Garen, T and Midtvedt, T and Trøseid, M and Zarè, H and Lund, MB and Hov, JR and Lundin, KEA and Molberg, Ø and Hoffmann-Vold, AM}, title = {Fecal microbiota transplantation in systemic sclerosis: A double-blind, placebo-controlled randomized pilot trial.}, journal = {PloS one}, volume = {15}, number = {5}, pages = {e0232739}, pmid = {32437393}, issn = {1932-6203}, mesh = {Bacteria ; Double-Blind Method ; Fatty Acids/metabolism ; Fecal Incontinence/etiology ; *Fecal Microbiota Transplantation/adverse effects ; Feces/chemistry ; Female ; Humans ; Immunoglobulin A/metabolism ; Immunoglobulin M/metabolism ; Leukocyte L1 Antigen Complex/metabolism ; Male ; Middle Aged ; Pilot Projects ; Placebos ; Scleroderma, Systemic/*microbiology/*therapy ; Treatment Outcome ; }, abstract = {OBJECTIVES: Systemic sclerosis (SSc) is an auto-immune, multi organ disease marked by severe gastrointestinal (GI) involvement and gut dysbiosis. Here, we aimed to determine the safety and efficacy of fecal microbiota transplantation (FMT) using commercially-available anaerobic cultivated human intestinal microbiota (ACHIM) in SSc.

METHODS: Ten patients with SSc were randomized to ACHIM (n = 5) or placebo (n = 5) in a double-blind, placebo-controlled 16-week pilot. All patients had mild to severe upper and lower GI symptoms including diarrhea, distention/bloating and/or fecal incontinence at baseline. Gastroduodenoscopy transfer of ACHIM or placebo was performed at weeks 0 and 2. Primary endpoints were safety and clinical efficacy on GI symptoms assessed at weeks 4 and 16. Secondary endpoints included changes in relative abundance of total, immunoglobulin (Ig) A- and IgM-coated fecal bacteria measured by 16s rRNA sequencing.

RESULTS: ACHIM side effects were mild and transient. Two placebo controls experienced procedure-related serious adverse events; one developed laryngospasms at week 0 gastroduodenoscopy necessitating study exclusion whilst one encountered duodenal perforation during gastroduodenoscopy at the last study visit (week 16). Decreased bloating, diarrhea and/or fecal incontinence was observed in four of five patients in the FMT group (week 4 or/and 16) and in two of four in the placebo group (week 4 or 16). Relative abundance, richness and diversity of total and IgA-coated and IgM-coated bacteria fluctuated more after FMT, than after placebo.

CONCLUSIONS: FMT of commercially-available ACHIM is associated with gastroduodenoscopy complications but reduces lower GI symptoms by possibly altering the gut microbiota in patients with SSc.}, } @article {pmid32434586, year = {2020}, author = {Xiao, HW and Cui, M and Li, Y and Dong, JL and Zhang, SQ and Zhu, CC and Jiang, M and Zhu, T and Wang, B and Wang, HC and Fan, SJ}, title = {Gut microbiota-derived indole 3-propionic acid protects against radiation toxicity via retaining acyl-CoA-binding protein.}, journal = {Microbiome}, volume = {8}, number = {1}, pages = {69}, pmid = {32434586}, issn = {2049-2618}, support = {R01 AT005076/AT/NCCIH NIH HHS/United States ; R01 GM063075/GM/NIGMS NIH HHS/United States ; P30 CA196521/CA/NCI NIH HHS/United States ; OCM-094//Centers for Medicare and Medicaid Services/International ; }, abstract = {BACKGROUND: We have proved fecal microbiota transplantation (FMT) is an efficacious remedy to mitigate acute radiation syndrome (ARS); however, the mechanisms remain incompletely characterized. Here, we aimed to tease apart the gut microbiota-produced metabolites, underpin the therapeutic effects of FMT to radiation injuries, and elucidate the underlying molecular mechanisms.

RESULTS: FMT elevated the level of microbial-derived indole 3-propionic acid (IPA) in fecal pellets from irradiated mice. IPA replenishment via oral route attenuated hematopoietic system and gastrointestinal (GI) tract injuries intertwined with radiation exposure without precipitating tumor growth in male and female mice. Specifically, IPA-treated mice represented a lower system inflammatory level, recuperative hematogenic organs, catabatic myelosuppression, improved GI function, and epithelial integrity following irradiation. 16S rRNA gene sequencing and subsequent analyses showed that irradiated mice harbored a disordered enteric bacterial pattern, which was preserved after IPA administration. Notably, iTRAQ analysis presented that IPA replenishment retained radiation-reprogrammed protein expression profile in the small intestine. Importantly, shRNA interference and hydrodynamic-based gene delivery assays further validated that pr