Pouch Inflammation Is Associated With a Decrease in Specific Bacterial Taxa

Reshef, Lea; Kovacs, Amir; Ofer, Amos; Yahav, Lior; Maharshak, Nitsan; Keren, Nirit; Konikoff, Fred M.; Tulchinsky, Hagit; Gophna, Uri; Dotan, Iris

doi:10.1053/j.gastro.2015.05.041

Cited by 81 publications

(60 citation statements)

References 44 publications

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“…39 In our cohort, abundance of Enterobacteriaceae was often found in a flare state. While Fusobacteriaceae has been reported as correlating with increased disease severity in patients with pouchitis, 40 subjects in our cohort had minimal presence of this family and no correlation to disease state. An increase in Pasteurellaceae (predominately Haemophilus parainfleunzae) in mucosal biopsy specimens is correlated with disease activity in Crohn’s disease.…”

Section: Discussioncontrasting

confidence: 68%

Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohnʼs Disease

Vaughn

Vatanen

Allegretti

et al. 2016

Inflammatory Bowel Diseases

182

169

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Background The microbiota in the lumen of patients with Crohn’s disease (CD) is characterized by reduced diversity, particularly Firmicutes and Bacteroidetes. It is unknown whether the introduction of the intestinal microbiota from healthy individuals could correct this dysbiosis and reverse mucosal inflammation. We investigated the response to fecal microbial transplantation (FMT) from healthy individuals to subjects with active CD Methods We performed a prospective open-label study (uncontrolled) of FMT from healthy donors to subjects with active CD. A single FMT was performed via colonoscopy. Recipients’ microbial diversity, mucosal T-cell phenotypes and clinical and inflammatory parameters were measured over 12 weeks, and safety over 26 weeks. Results Nineteen subjects were treated with FMT and completed the study follow-up. Fifty-eight percent (11/19) demonstrated a clinical response (HBI decrease > 3) following FMT. Fifteen subjects had sufficient pre/post fecal samples for analysis. A significant increase in microbial diversity occurred after FMT (p=0.02). This was greater in clinical responders than non-responders. Patients who experienced a clinical response demonstrated a significant shift in fecal microbial composition towards their donor’s profile as assessed by the Bray-Curtis index at 4 weeks (p=0.003). An increase in regulatory T-cells (CD4+CD25+CD127lo) was also noted in recipients’ lamina propria following FMT. No serious adverse events were noted over the 26-week study period. Conclusion In this open label study, FMT led to an expansion in microbial bacterial diversity in patients with active CD. FMT was overall safe, although the clinical response was variable. Determining donor microbial factors that influence clinical response is needed prior to randomized clinical trials of FMT in CD. ClinicalTrials ID # NCT01847170

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Section: Discussioncontrasting

confidence: 68%

Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohnʼs Disease

Vaughn

Vatanen

Allegretti

et al. 2016

Inflammatory Bowel Diseases

182

169

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“…S2); however, beta microbial diversity during the follow-up period was high, suggestive of erratic compositional swings. Interestingly, a large abundance of Fusobacteraceae was seen during the first month during the UDCA treatment, a microbial family previously reported to be associated with inflammatory pouchitis [29]. Later time points were notable for decreased abundance of Fusobacteraceae and an increase in Lachnospiraceae family members, a pattern associated with less pouch inflammation [29].…”

Section: Resultsmentioning

confidence: 96%

“…Indeed, we were able to achieve fecal concentrations of UDCA at least 10-fold higher than were found sufficient to inhibit taurocholate-induced germination of C. difficile spores in vitro , despite the day-to-day variability that is characteristic of fecal spot measurements. Fecal microbial composition retained the general imprint of antibiotic treatments, such as expansion of Enterobacteraceae , after initiation of UDCA [29], making it highly unlikely that some spontaneous microbiota recovery contributed to C. difficile suppression. UDCA treatment was associated with a decrease in abundance of Fusobacteraceae and an increase in Lachnospiraceae families over time, a pattern seen with less pouch inflammation [29].…”

Section: Discussionmentioning

confidence: 99%

“…Fecal microbial composition retained the general imprint of antibiotic treatments, such as expansion of Enterobacteraceae , after initiation of UDCA [29], making it highly unlikely that some spontaneous microbiota recovery contributed to C. difficile suppression. UDCA treatment was associated with a decrease in abundance of Fusobacteraceae and an increase in Lachnospiraceae families over time, a pattern seen with less pouch inflammation [29]. In fact, endoscopic examination did confirm resolution of pouchitis.…”

Section: Discussionmentioning

confidence: 99%

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Ursodeoxycholic Acid Inhibits Clostridium difficile Spore Germination and Vegetative Growth, and Prevents the Recurrence of Ileal Pouchitis Associated With the Infection

Weingarden

Chen

Zhang

et al. 2016

Journal of Clinical Gastroenterology

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Goals Test whether ursodeoxycholic acid is inhibitory to Clostridium difficile and can be used in the treatment of C. difficile associated ileal pouchitis. Background Restoration of secondary bile metabolism may be the key mechanism for fecal microbiota transplantation (FMT) in treating recurrent C. difficile infections (RCDI). Therefore, it is possible that exogenous administration of inhibitory bile acids may be used directly as non-antibiotic therapeutics for this indication. The need for such a treatment alternative is especially great in patients with refractory C. difficile associated pouchitis, where the efficacy of FMT may be limited. Study We measured the ability of ursodeoxycholic acid (UDCA) to suppress germination and vegetative growth of 11 clinical isolate strains of C. difficile from patients treated with FMT for RCDI. In addition, we used oral UDCA to treat a patient with RCDI pouchitis that proved refractory to multiple antibiotic treatments and FMT. Results UDCA was found inhibitory to germination and vegetative growth of all C. difficile strains tested. Fecal concentrations of UDCA from the patient with RCDI pouchitis exceeded levels necessary to inhibit germination and growth of C. difficile in vitro. The patient has remained infection-free for over ten months following initiation of UDCA. Conclusions UDCA can be considered as a therapeutic option in patients with C. difficile associated pouchitis. Further studies need to be done to define the optimal dose and duration of such treatment. In addition, bile acid derivatives inhibitory to C. difficile that are able to achieve high intracolonic concentrations may be developed as therapeutics for RCDI colitis.

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“…At first, it might appear that ‘too much' microbiota is responsible for triggering IBD; but in fact, IBD is characterized by a shift in the composition of gastrointestinal microbiota. Patients with CD, ulcerative colitis (UC), and pouchitis display a reduced diversity of microbiota compared to healthy subjects [55]. The IBD metagenome contains 25% fewer genes than the healthy gut with metaproteomic studies showing a parallel decrease in proteins and functional pathways.…”

Section: Antibiotics - Friend or Foe In The Pathogenesis And Course Omentioning

confidence: 99%

Effects of Antibiotics on Gut Microbiota

Lange

Buerger²,

Stallmach³

et al. 2016

Dig Dis

451

311

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The gut microbiota influences essential human functions including digestion, energy metabolism, and inflammation by modulating multiple endocrine, neural, and immune pathways of the host. Its composition and complexity varies markedly across individuals and across different sites of the gut, but provides a certain level of resilience against external perturbation. Short-term antibiotic treatment is able to shift the gut microbiota to long-term alternative dysbiotic states, which may promote the development and aggravation of disease. Common features of post-antibiotic dysbiosis include a loss of taxonomic and functional diversity combined with reduced colonization resistance against invading pathogens, which harbors the danger of antimicrobial resistance. This review summarizes the antibiotic-related changes of the gut microbiota and potential consequences in health and disease.

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Pouch Inflammation Is Associated With a Decrease in Specific Bacterial Taxa

Cited by 81 publications

References 44 publications

Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohnʼs Disease

Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohnʼs Disease

Ursodeoxycholic Acid Inhibits Clostridium difficile Spore Germination and Vegetative Growth, and Prevents the Recurrence of Ileal Pouchitis Associated With the Infection

Effects of Antibiotics on Gut Microbiota

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