Fecal microbiota transplantation for the maintenance of remission in patients with ulcerative colitis: A randomized controlled trial.

BACKGROUND: Fecal microbial transplantation (FMT) is a promising new method for treating active ulcerative colitis (UC), but knowledge regarding FMT for quiescent UC is scarce. AIM: To investigate FMT for the maintenance of remission in UC patients. METHODS: Forty-eight UC patients were randomized to receive a single-dose FMT or autologous transplant via colonoscopy. The primary endpoint was set to the maintenance of remission, a fecal calprotectin level below 200 µg/g, and a clinical Mayo score below three throughout the 12-mo follow-up. As secondary endpoints, we recorded the patient's quality of life, fecal calprotectin, blood chemistry, and endoscopic findings at 12 mo. RESULTS: The main endpoint was achieved by 13 out of 24 (54%) patients in the FMT group and by 10 out of 24 (41%) patients in the placebo group (log-rank test, P = 0.660). Four months after FMT, the quality-of-life scores decreased in the FMT group compared to the placebo group (P = 0.017). In addition, the disease-specific quality of life measure was higher in the placebo group than in the FMT group at the same time point (P = 0.003). There were no differences in blood chemistry, fecal calprotectin, or endoscopic findings among the study groups at 12 mo. The adverse events were infrequent, mild, and distributed equally between the groups. CONCLUSION: There were no differences in the number of relapses between the study groups at the 12-mo follow-up. Thus, our results do not support the use of a single-dose FMT for the maintenance of remission in UC.

Colonic Gene Expression and Fecal Microbiota in Diarrhea-predominant Irritable Bowel Syndrome: Increased Toll-like Receptor 4 but Minimal Inflammation and no Response to Mesalazine.

BACKGROUND/AIMS: Diarrhea-predominant irritable bowel syndrome (IBS-D) has been previously associated with evidence of immune activation and altered microbiota. Our aim is to assess the effect of the anti-inflammatory agent, mesalazine, on inflammatory gene expression and microbiota composition in IBS-D. METHODS: We studied a subset of patients (n = 43) from a previously published 12-week radomized placebo-controlled trial of mesalazine. Mucosal biopsies were assessed by immunohistochemistry and reverse transcription-polymerase chain reaction for a range of markers of inflammation, altered permeability, and sensory receptors including Toll-like receptors (TLRs) at randomization after treatment. All biopsy data were compared to 21 healthy controls. Patient's stool microbiota composition was analysed through 16S ribosomal RNA sequencing. RESULTS: We found no evidence of increased immune activation compared to healthy controls. However, we did find increased expression of receptors in both sensory pathways and innate immune response including TLR4. Higher TLR4 expression was associated with greater urgency. TLR4 expression correlated strongly with the expression of the receptors bradykinin receptor B2, chemerin chemokine-like receptor 1, and transient receptor potential cation channel, subfamily A, member 1 as well as TLR4's downstream adaptor myeloid differentiation factor 88. Mesalazine had minimal effect on either gene expression or microbiota composition. CONCLUSIONS: Biopsies from a well-characterized IBS-D cohort showed no substantial inflammation. Mesalazine has little effect on gene expression and its previous reported effect on fecal microbiota associated with much greater inflammation found in inflammatory bowel diseases is likely secondary to reduced inflammation. Increased expression of TLR4 and correlated receptors in IBS may mediate a general increase in sensitivity to external stimuli, particularly those that signal via the TLR system.

Colonic Mucosal Microbiota and Association of Bacterial Taxa with the Expression of Host Antimicrobial Peptides in Pediatric Ulcerative Colitis.

Inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), are chronic debilitating disorders of unknown etiology. Over 200 genetic risk loci are associated with IBD, highlighting a key role for immunological and epithelial barrier functions. Environmental factors account for the growing incidence of IBD, and microbiota are considered as an important contributor. Microbiota dysbiosis can lead to a loss of tolerogenic immune effects and initiate or exacerbate inflammation. We aimed to study colonic mucosal microbiota and the expression of selected host genes in pediatric UC. We used high-throughput 16S rDNA sequencing to profile microbiota in colonic biopsies of pediatric UC patients (n = 26) and non-IBD controls (n = 27). The expression of 13 genes, including five for antimicrobial peptides, in parallel biopsies was assessed with qRT-PCR. The composition of microbiota between UC and non-IBD differed significantly (PCoA, p = 0.001). UC children had a decrease in Bacteroidetes and an increase in several family-level taxa including Peptostreptococcaceae and Enterobacteriaceae, which correlated negatively with the expression of antimicrobial peptides REG3G and DEFB1, respectively. Enterobacteriaceae correlated positively with the expression siderophore binding protein LCN2 and Betaproteobacteria negatively with DEFB4A expression. The results indicate that reciprocal interaction of epithelial microbiota and defense mechanisms play a role in UC.

Randomised clinical trial: faecal microbiota transplantation versus autologous placebo administered via colonoscopy in irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS) has been associated with microbial dysbiosis. AIM: To investigate the efficacy of faecal microbiota transplantation (FMT) in the treatment of IBS. METHODS: Forty-nine IBS patients were randomised to receive autologous or allogenic FMT via colonoscopy. The primary endpoint was a sustained, minimum of 50-point, reduction in the IBS Symptom Severity Score. The secondary outcomes were levels of anxiety and depression, changes in quality of life, gut microbiota and faecal water content as assessed with validated questionnaires, intestinal microbiota composition and stool dry weight. RESULTS: The primary endpoint was not achieved in either group. However, there was a transient reduction in the mean IBS Symptom Severity Score in the FMT group at 12 weeks after treatment as compared to baseline (P = 0.01). The groups did not differ in the number of patients achieving clinical response at 12 weeks. In the FMT-treated patients, microbial composition had changed to resemble that of the donor and the stool water content decreased significantly compared to baseline. The depression score decreased in patients with a reduction in IBS symptoms after FMT, but not in those placebo-treated patients who experienced a reduction in IBS symptoms. CONCLUSIONS: FMT provided only a transient relief of symptoms, although it induced a sustained alteration in the microbiota of IBS patients. Therefore, FMT delivered by a single infusion via colonoscopy cannot be recommended as a treatment for IBS in clinical practice. ClinicalTrials.Org, Trial registration number: NCT03561519.

Effects of bowel cleansing on the intestinal microbiota.

OBJECTIVE: An adequate bowel cleansing is essential for a successful colonoscopy. Although purgative consumption is safe for the patient, there is little consensus on how the intestinal microbiota is affected by the procedure, especially regarding the potential long-term consequences. DESIGN: 23 healthy subjects were randomised into two study groups consuming a bowel preparation (Moviprep), either in two separate doses of 1 L or as a single 2-L dose. Participants donated faecal samples at the baseline, after bowel cleansing, 14 and 28 days after the treatment. The intestinal microbiota composition was determined with phylogenetic microarray as well as quantitative PCR analysis and correlated with the previously quantified faecal serine proteases. RESULTS: The lavage introduced an instant and substantial change to the intestinal microbiota. The total microbial load was decreased by 31-fold and 22% of the participants lost the subject-specificity of their microbiota. While the bacterial levels and community composition were essentially restored within 14 days, the rate of recovery was dose dependent: consumption of the purgative in a single dose had a more severe effect on the microbiota composition than that of a double dose, and notably increased the levels of Proteobacteria, Fusobacteria and bacteria related to Dorea formicigenerans. The abundance of the latter also correlated with the amount of faecal serine proteases that were increased after purging. CONCLUSIONS: Our results suggest that the bowel cleansing using two separate dosages introduces fewer alterations to the intestinal microbiota than a single dose and hence may be preferred in clinical practice.