scholarly journals Development of A Rational Framework For Understanding The Efficacy of Fecal Microbiota Transplantation In Calf Diarrhea Prevention

2021 ◽  
Author(s):  
Jahidul Islam ◽  
Masae Tanimizu ◽  
Yu Shimizu ◽  
Yoshiaki Goto ◽  
Natsuki Ohtani ◽  
...  
Keyword(s):  
Management Practices ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Donor Selection ◽  
Procrustes Analysis ◽  
Dihydroxyacetone Phosphate ◽  
Rrna Gene ◽  
Strong Positive Correlation ◽  
Learning Approaches ◽  
Potential Biomarker

Abstract Background: Establishing fecal microbiota transplantation (FMT) to prevent multifactorial diarrhea in calves is challenging because of differences in farm management practices, the lack of optimal donors, and recipient selection. In this study, the underlying factors of successful and unsuccessful FMT trials are elucidated, and the potential markers for predicting successful FMT are identified using fetal metagenomics via 16S rRNA gene sequencing, fecal metabolomics via CE-TOFMS, and machine-learning approaches. Results: 20 FMT trials, in which feces from healthy donors were intrarectally transferred into recipient diarrheal calves, were conducted with a success rate of 70%. Selenomonas was identified as a microorganism genus that showed significant donor–recipient compatibility in successful trials. A strong positive correlation between the microbiome and metabolome data, which is a prerequisite factor for FMT success, was confirmed by Procrustes analysis in successful trials (r = 0.7439, P = 0.0001). Additionally, weighted correlation network analysis confirmed the positively or negatively correlated pairs of bacterial taxa (family Veillonellaceae) and metabolomic features (i.e., amino acids and short chain fatty acids) responsible for FMT success. Further analysis aimed at establishing criteria for donor selection identified the genus Sporobacter as a potential biomarker in successful donor selection. Low levels of metabolites, such as glycerol 3-phosphate, dihydroxyacetone phosphate, and isoamylamine, in the donor or recipients prior to FMT are predicted to facilitate FMT. Conclusions: Overall, we provide the first substantial evidence of the factors related to FMT success or failure; these findings could improve the design of future microbial therapeutics for preventing diarrhea in calves.

scholarly journals Lyophilized Fecal Microbiota Transplantation Capsules for Recurrent Clostridium difficile Infection

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S381-S381
Author(s):  
Hebert Dupont ◽  
Zhi-Dong Jiang ◽  
Ashley Alexander ◽  
Nadim Ajami ◽  
Joseph F Petrosino ◽  
...  
Keyword(s):  
Oral Delivery ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Gene Profiling ◽  
Intestinal Microbiome ◽  
Published Data ◽  
Rrna Gene ◽  
Second Phase ◽  
Microbiome Diversity

Abstract Background Fecal microbiota (FM) transplantation (FMT) is a highly effective treatment of recurrent C. difficile infection (rCDI). We have published data showing efficacy of fresh, frozen and lyophilized donor microbiota administered by colonoscopy. Most groups are moving toward use of frozen product given by enema and in evaluating encapsulated product for oral delivery. Methods This was a prospective, randomized study of subjects with rCDI (≥ 3 episodes) treated with encapsulated lyophilized FM 100 g given once or 100 g given on two successive days (total 200 g) vs. frozen FM product 100 g given by single retention enema, between March 2015 and February 2017. The clinical outcome was absence of CDI during the 60 days after FMT. The subjects were followed for 6 months for safety. In a subset recipients, microbiome composition by 16S rRNA gene profiling were analyzed on stools obtained pre- and day 2, 7, 14, 30, 60 and 90 days after FMT. Results A total of 54 subjects were enrolled (37/54; 69% female) with a median age of 71 years (range: 20–97). In the first 14 subjects treated, cure rates for oral capsules 100 g FM was 5/8 (63%) vs. 6/6 (100%) for those receiving 100 g frozen FM by enema (P = 0.209). In the second phase of the study cure rate for oral capsules 200 g FM was 17/18 (91%) vs. 20/21 (94%) for the subjects treated by enema by 100 g of frozen product (P = 0.782). No side effects were felt to be related to the procedure or the FMT products were recorded during 6 months follow-up. Two subjects died during follow-up between 3 and 6 months after study due to underlying medical conditions felt to be unrelated to FMT. Microbiota analysis were performed on 40 subjects of which 19/40 (48%) had received capsules. Figure showed that restoration of the intestinal microbiome diversity and Taxa began apparent by 2 days after FMT in both groups and resembled the donor product by 2 weeks with stabilization of the microbiota diversity and Taxa persisting for the 90 days of observation. Conclusion Administration of encapsulated, lyophilized FM resulted in durable restoration of intestinal microbiome diversity comparable to results seen with frozen product given by enema. Disclosures All authors: No reported disclosures.

scholarly journals An Immunologic Compatibility Testing Was Not Useful for Donor Selection in Fecal Microbiota Transplantation for Ulcerative Colitis

2021 ◽  
Vol 12 ◽  
Author(s):  
Manuel Ponce-Alonso ◽  
Carlota García-Hoz ◽  
Ana Halperin ◽  
Javier Nuño ◽  
Pilar Nicolás ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Clinical Success ◽  
Immunological Response ◽  
Organ Donor ◽  
Fecal Microbiota ◽  
Mucosal Immune Response ◽  
Donor Selection ◽  
Selection For

Fecal microbiota transplantation (FMT) is an effective procedure against Clostridioides difficile infection (CDI), with promising but still suboptimal performance in other diseases, such as ulcerative colitis (UC). The recipient’s mucosal immune response against the donor’s microbiota could be relevant factor in the effectiveness of FMT. Our aim was to design and validate an individualized immune-based test to optimize the fecal donor selection for FMT. First, we performed an in vitro validation of the test by co-culturing lymphocytes obtained from the small intestine mucosa of organ donor cadavers (n=7) and microbe-associated molecular patterns (MAMPs) obtained from the feces of 19 healthy donors. The inflammatory response was determined by interleukin supernatant quantification using the Cytometric Bead Array kit (B&D). We then conducted a clinical pilot study with 4 patients with UC using immunocompetent cells extracted from rectal biopsies and MAMPs from 3 donor candidates. We employed the test results to guide donor selection for FMT, which was performed by colonoscopy followed by 4 booster instillations by enema in the following month. The microbiome engraftment was assessed by 16S rDNA massive sequencing in feces, and the patients were clinically followed-up for 16 weeks. The results demonstrated that IL-6, IL-8, and IL-1ß were the most variable markers, although we observed a general tolerance to the microbial insults. Clinical and colonoscopy remission of the patients with UC was not achieved after 16 weeks, although FMT provoked enrichment of the Bacteroidota phylum and Prevotella genus, with a decrease in the Actinobacteriota phylum and Agathobacter genus. The most relevant result was the lack of Akkermansia engraftment in UC. In summary, the clinical success of FMT in patients with UC appears not to be influenced by donor selection based on the explored recipient’s local immunological response to FMT, suggesting that this approach would not be valid for FMT fecal donor optimization in such patients.

scholarly journals Fecal microbiota transplantation: donor selection criteria, storage and preparation of biomaterials (review of current recommendations)

2021 ◽  
Vol 93 (2) ◽  
pp. 215-221
Author(s):  
A. A. Iakupova ◽  
S. R. Abdulkhakov ◽  
A. G. Safin ◽  
I. M. Alieva ◽  
Ju. V. Oslopova ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Selection Criteria ◽  
Fecal Microbiota Transplantation ◽  
Treatment Method ◽  
Fecal Microbiota ◽  
Donor Selection ◽  
Fecal Material ◽  
Processing And Storage ◽  
And Storage ◽  
Existing Data

Fecal microbiota transplantation is a treatment method based on the introduction of donated fecal material to the recipient in order to restore the damaged composition of the intestinal microbiota. This review summarizes existing data on indications for fecal microbiota transplantation, recommendations for donor selection, processing and storage of donor biomaterial.

scholarly journals Fecal filtrate transplantation protects against necrotizing enterocolitis

2021 ◽  
Author(s):  
Anders Brunse ◽  
Ling Deng ◽  
Xiaoyu Pan ◽  
Yan Hui ◽  
Josué L. Castro-Mejía ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Necrotizing Enterocolitis ◽  
Fecal Microbiota Transplantation ◽  
Gastrointestinal Disorder ◽  
Preventive Therapy ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Ileal Mucosa ◽  
Relevant Animal Model ◽  
Life Threatening

AbstractNecrotizing enterocolitis (NEC) is a life-threatening gastrointestinal disorder afflicting preterm infants, which is currently unpreventable. Fecal microbiota transplantation (FMT) is a promising preventive therapy, but the transfer of pathogenic microbes or toxic compounds raise concern. Removal of bacteria from donor feces by micropore filtering may reduce this risk of bacterial infection, while residual bacteriophages could maintain the NEC-preventive effects. We aimed to assess preclinical efficacy and safety of fecal filtrate transplantation (FFT). Using fecal material from healthy suckling piglets, we compared rectal FMT administration (FMT, n = 16) with cognate FFT by either rectal (FFTr, n = 14) or oro-gastric administration (FFTo, n = 13) and saline (CON, n = 16) in preterm, cesarean-delivered piglets as models for preterm infants. We assessed gut pathology and analyzed mucosal and luminal bacterial and viral composition using 16S rRNA gene amplicon and meta-virome sequencing. Finally, we used isolated ileal mucosa, coupled with RNA-Seq, to gauge the host response to the different treatments. Oro-gastric FFT completely prevented NEC, which was confirmed by microscopy, whereas FMT did not perform better than control. Oro-gastric FFT increased viral diversity and reduced Proteobacteria relative abundance in the ileal mucosa relative to control. An induction of mucosal immunity was observed in response to FMT but not FFT. As preterm infants are extremely vulnerable to infections, rational NEC-preventive strategies need incontestable safety profiles. We show in a clinically relevant animal model that FFT, as opposed to FMT, efficiently prevents NEC without any recognizable side effects.

25 DONOR SELECTION OF FECAL MICROBIOTA TRANSPLANTATION IS IMPORTANT TO LONG-TERM MAINTENANCE OF ULCERATIVE COLITIS

2020 ◽  
Vol 158 (3) ◽  
pp. S59
Author(s):  
Koki Okahara ◽  
Dai Ishikawa ◽  
Kei Nomura ◽  
Shoko Ito ◽  
Keiichi Haga ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Donor Selection ◽  
Term Maintenance ◽  
Selection Of

P078 DONOR SELECTION INFLUENCES THERAPEUTIC EFFECTS OF FECAL MICROBIOTA TRANSPLANTATION FOR ULCERATIVE COLITIS

2020 ◽  
Vol 158 (3) ◽  
pp. S58-S59
Author(s):  
Keiichi Haga ◽  
Dai Ishikawa ◽  
Koki Okahara ◽  
Kei Nomura ◽  
Shoko Ito ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Donor Selection ◽  
Therapeutic Effects

scholarly journals Challenges in fecal donor selection and screening for fecal microbiota transplantation: A review

Gut Microbes ◽  
2017 ◽  
Vol 8 (3) ◽  
pp. 225-237 ◽  
Author(s):  
Michael H. Woodworth ◽  
Cynthia Carpentieri ◽  
Kaitlin L. Sitchenko ◽  
Colleen S. Kraft
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Donor Selection

scholarly journals Gut microbiota determines the social behavior of mice and induces metabolic and inflammatory changes in their adipose tissue

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Oryan Agranyoni ◽  
Sapir Meninger-Mordechay ◽  
Atara Uzan ◽  
Oren Ziv ◽  
Mali Salmon-Divon ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Social Behavior ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Critical Role ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
The Social ◽  
Inflammatory Profile

AbstractThe link between the gut microbiota and social behavior has been demonstrated, however the translational impact of a certain microbiota composition on stable behavioral patterns is yet to be elucidated. Here we employed an established social behavior mouse model of dominance (Dom) or submissiveness (Sub). A comprehensive 16S rRNA gene sequence analysis of Dom and Sub mice revealed a significantly different gut microbiota composition that clearly distinguishes between the two behavioral modes. Sub mice gut microbiota is significantly less diverse than that of Dom mice, and their taxa composition uniquely comprised the genera Mycoplasma and Anaeroplasma of the Tenericutes phylum, in addition to the Rikenellaceae and Clostridiaceae families. Conversely, the gut microbiota of Dom mice includes the genus Prevotella of the Bacteriodetes phylum, significantly less abundant in Sub mice. In addition, Sub mice show lower body weight from the age of 2 weeks and throughout their life span, accompanied with lower epididymis white adipose tissue (eWAT) mass and smaller adipocytes together with substantially elevated expression of inflammation and metabolic-related eWAT adipokines. Finally, fecal microbiota transplantation into germ-free mice show that Sub-transplanted mice acquired Sub microbiota and adopted their behavioral and physiological features, including depressive-like and anti-social behaviors alongside reduced eWAT mass, smaller adipocytes, and a Sub-like eWAT adipokine profile. Our findings demonstrate the critical role of the gut microbiome in determining dominance vs. submissiveness and suggest an association between gut microbiota, the eWAT metabolic and inflammatory profile, and the social behavior mode.

scholarly journals Applying fecal microbiota transplantation (FMT) to treat recurrent Clostridium difficile infections (rCDI) in children

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4663 ◽  
Author(s):  
Shaaz Fareed ◽  
Neha Sarode ◽  
Frank J. Stewart ◽  
Aneeq Malik ◽  
Elham Laghaie ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Adverse Effects ◽  
Gut Microbiome ◽  
Pediatric Patients ◽  
Fecal Microbiota Transplantation ◽  
Diversity Index ◽  
Microbial Community Composition ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Significant Difference

Background Fecal Microbiota Transplantation (FMT) is an innovative means of treating recurrent Clostridium difficile infection (rCDI), through restoration of gut floral balance. However, there is a lack of data concerning the efficacy of FMT and its impact on the gut microbiome among pediatric patients. This study analyzes clinical outcomes and microbial community composition among 15 pediatric patients treated for rCDI via FMT. Methods This is a prospective, observational, pilot study of 15 children ≤18 years, who presented for rCDI and who met inclusion criteria for FMT at a pediatric hospital and pediatric gastroenterology clinic. Past medical history and demographics were recorded at enrollment and subsequent follow-up. Specimens of the donors’ and the patients’ pre-FMT and post-FMT fecal specimen were collected and used to assess microbiome composition via 16S rRNA gene sequencing. Results FMT successfully prevented rCDI episodes for minimum of 3 months post-FMT in all patients, with no major adverse effects. Three patients reported continued GI bleeding; however, all three also had underlying Inflammatory Bowel Disease (IBD). Our analyses confirm a significant difference between pre-and post-FMT gut microbiome profiles (Shannon diversity index), whereas no significant difference was observed between post-FMT and donor microbiome profiles. At the phyla level, post-FMT profiles showed significantly increased levels of Bacteroidetes and significantly decreased levels of Proteobacteria. Subjects with underlying IBD showed no difference in their pre-and post-FMT profiles. Conclusion The low rate of recurrence or re-infection by C. difficile, coupled with minimal adverse effects post-FMT, suggests that FMT is a viable therapeutic means to treat pediatric rCDI. Post-FMT microbiomes are different from pre-FMT microbiomes, and similar to those of healthy donors, suggesting successful establishment of a healthier microbiome.

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