scholarly journals Stool preparation under anaerobic conditions contributes to retention of obligate anaerobes: potential improvement for fecal microbiota transplantation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hirotaka Shimizu ◽  
Katsuhiro Arai ◽  
Takashi Asahara ◽  
Takuya Takahashi ◽  
Hirokazu Tsuji ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Controlled Trial ◽  
Quantitative Polymerase Chain Reaction ◽  
Fecal Microbiota ◽  
23S Rrna ◽  
Facultative Anaerobes ◽  
Before And After ◽  
Viable Bacteria ◽  
Potential Improvement

Abstract Background Fecal microbiota transplantation (FMT) in patients with ulcerative colitis has shown variable efficacy depending on the protocol used. A previous randomized controlled trial reported that anaerobic preparation of donor stool contributes to improved efficacy. Despite the suggestion that viable obligate anaerobes would be decreased through aerobic handling, there have been only a limited number of reports on how these aerobic or anaerobic procedures affect the composition of viable microbiota in the fecal slurries used for FMT. Methods We adopted 16S and 23S rRNA-targeted reverse transcription-quantitative polymerase chain reaction to quantify viable bacteria in fecal slurries. This study utilized specific primers designed to detect obligate anaerobes (including Clostridium coccoides group, C. leptum subgroup, Bacteroides fragilis group, Bifidobacterium, Atopobium cluster, and Prevotella) and facultative anaerobes (including total lactobacilli, Enterobacteriaceae, Enterococcus, Streptococcus, and Staphylococcus). We then calculated the ratio change (RC) between before and after mixing, and compared the resulting values between anaerobic-prep and aerobic-prep in samples fixed immediately after blending (RCAn0 vs. RCAe0) and in samples maintained (under anaerobic or aerobic conditions) for 1 h after blending (RCAn1 vs. RCAe1). Results For most obligate anaerobes, the median RC tended to be less than 1, indicating that the number of obligate anaerobes was decreased by the blending procedure. However, in samples maintained for 1 h after blending, anaerobic-prep counteracted the decrease otherwise seen for the C. coccoides group and B. fragilis groups (P < 0.01 for both). The C. leptum subgroup also tended to show higher RC by anaerobic-prep than by aerobic-prep, although this effect was not statistically significant. Among facultative anaerobes, Enterobacteriaceae, Enterococcus, and Staphylococcus showed median RC values of more than 1, indicating that these organisms survived and even grew after mixing. Moreover, oxygen exposure had no significant influence on the survival of the facultative anaerobes. Conclusions The conditions under which the blending procedure was performed affected the proportion of live anaerobes in fecal slurries. The obligate anaerobes tended to be decreased by blending processes, but anaerobic-prep significantly mitigated this effect. Anaerobic-prep may improve the efficacy of FMT by permitting the efficient transfer of obligate anaerobes to patients with ulcerative colitis.

scholarly journals Long-Term Efficacy of Low-Intensity Single Donor Fecal Microbiota Transplantation in Ulcerative Colitis and Outcome-Specific Gut Bacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Rongrong Ren ◽  
Xuefeng Gao ◽  
Yichao Shi ◽  
Jianfeng Li ◽  
Lihua Peng ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Bacteroides Fragilis ◽  
Fecal Microbiota ◽  
Low Intensity ◽  
Single Donor ◽  
Before And After

Aims: To assess the long-term efficacy and safety of single-donor, low-intensity fecal microbiota transplantation (FMT) in treating ulcerative colitis (UC), and to identify the outcome-specific gut bacteria.Design: Thirty-one patients with active UC (Mayo scores ≥ 3) were recruited, and all received FMT twice, at the start of the study and 2∼3 months later, respectively, with a single donor and a long-term follow-up. The fecal microbiome profile was accessed via 16S rRNA sequencing before and after FMT.Results: After the first FMT, 22.58% (7/31) of patients achieved clinical remission and endoscopy remission, with the clinical response rate of 67.74% (21/31), which increased to 55% (11/20) and 80% (16/20), respectively, after the second FMT. No serious adverse events occurred in all patients. During 4 years of follow-up, the mean remission period of patients was 26.5 ± 19.98 m; the relapse rate in the 12 remission patients was 33.33% within 1 year, and 58.3% within 4 years. At baseline, UC patients showed an enrichment in some proinflammatory microorganisms compared to the donor, such as Bacteroides fragilis, Clostridium difficile, and Ruminococcus gnavus, and showed reduced amounts of short-chain fatty acid (SCFA) producing bacteria especially Faecalibacterium prausnitzii. FMT induced taxonomic compositional changes in the recipient gut microbiota, resulting in a donor-like state. Given this specific donor, UC recipients with different outcomes showed distinct gut microbial features before and after FMT. In prior to FMT, relapse was characterized by higher abundances of Bacteroides fragilis and Lachnospiraceae incertae sedis, together with lower abundances of Bacteroides massiliensis, Roseburia, and Ruminococcus; Prevotella copri was more abundant in the non-responders (NR); and the patients with sustained remission (SR) had a higher abundance of Bifidobacterium breve. After FMT, the NR patients had a lower level of Bifidobacterium compared to those with relapse (Rel) and SR, while a higher level of Bacteroides spp. was observed in the Rel group.Conclusion: Low-intensity single donor FMT could induce long remission in active UC. The gut microbiota composition in UC patients at baseline may be predictive of therapeutic response to FMT.

scholarly journals 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

2020 ◽  
Author(s):  
Caroline Trang-Poisson ◽  
Elise Kerdreux ◽  
Alexandra Poinas ◽  
Lucie Planche ◽  
Harry Sokol ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Medical Condition ◽  
Controlled Trial ◽  
Intestinal Flora ◽  
Fecal Microbiota ◽  
Ileal Reservoir ◽  
Double Blind ◽  
Multiresistant Bacteria ◽  
Anal Anastomosis

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, currently there is 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, WHO 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: The trial, published on May 14, 2018, is registered at ClinicalTrials.Gov under registration number NCT03524352: https://clinicaltrials.gov/ct2/show/NCT03524352?term=NCT03524352&rank=1

scholarly journals Selecting donors for faecal microbiota transplantation in ulcerative colitis

2020 ◽  
Author(s):  
Marcel A. de Leeuw ◽  
Manuel X. Duval
Keyword(s):  
Ulcerative Colitis ◽  
Selection Criteria ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Data Sets ◽  
Indeterminate Colitis ◽  
Facultative Anaerobes ◽  
Inflammatory Bowel ◽  
Microbiome Data ◽  
Synthetic Microbial Communities

BackgroundInflammatory bowel disease (IBD) is a set of conditions characterized by non-infectious chronic inflammation of the gastrointestinal tract. These primarily include Crohn’s disease (CD), ulcerative colitis (UC) and indeterminate colitis. Fecal microbiota transplantation (FMT) has proven to be an effective treatment for some patients with active UC. There is currently no procedure allowing to predict the patients’ response and to select the most adequate donor(s).AimInvestigate microbiome characteristics in association with responder/non-responder status and develop selection criteria for donor samples to be used for UC FMT.MethodsAvailable UC longitudinal FMT microbiome data sets were in part combined and reanalyzed, with focus on species level changes in the microbiota, using state-of-the-art 16S analysis routines.ResultsWe predicted antibiotic resistance to be higher in non-responders (p=0.0064). Microbiomes of UC FMT responder donors have higher phylogenetic diversity (p=0.0026) and a higher proportion of facultative anaerobes (p=3.3E-5) as compared to non-responder donors. We predicted succinate and histamine to be increased in non-responder donors and non-responders, respectively. Sialic acid catabolism was also predicted to be increased in non-responder donors. Tryptamine and indole-3-acetaldehyde were predicted to be increased in responder donors.ConclusionsOur findings contribute to the establishment of selection criteria for UC FMT donor samples and composition guidelines for future synthetic microbial communities. Our results suggest that oxidative stress resistant facultative anaerobes are important for the establishment of an anaerobic environment and a successful UC FMT therapy. Several metabolites can be tested for additional optimization or prioritization of stool bank samples for UC FMT. Our results question the usefulness of antibiotics based preparation of the gut, prior to FMT.

scholarly journals 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

2020 ◽  
Author(s):  
Caroline Trang-Poisson ◽  
Elise Kerdreux ◽  
Alexandra Poinas ◽  
Lucie Planche ◽  
Harry Sokol ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Fecal Microbiota Transplantation ◽  
Medical Condition ◽  
Controlled Trial ◽  
Intestinal Flora ◽  
Fecal Microbiota ◽  
Ileal Reservoir ◽  
Double Blind ◽  
Multiresistant Bacteria ◽  
Anal Anastomosis

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, currently there is 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, WHO 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: The trial, published on May 14, 2018, is registered at ClinicalTrials.Gov under registration number NCT03524352: https://clinicaltrials.gov/ct2/show/NCT03524352term=NCT03524352&rank=1

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