Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review

AIM: To study the clinical efficacy and safety of Fecal microbiota transplantation (FMT). We systematically reviewed FMT used as clinical therapy. METHODS: We searched MEDLINE, EMBASE, the Cochrane Library and Conference proceedings from inception to July, 2013. Treatment effect of FMT was calculated as the percentage of patients who achieved clinical improvement per patient category, on an intention-to-treat basis. RESULTS: We included 45 studies; 34 on Clostridium difficile-infection (CDI), 7 on inflammatory bowel disease, 1 on metabolic syndrome, 1 on constipation, 1 on pouchitis and 1 on irritable bowel syndrome (IBS). In CDI 90% resolution of diarrhea in 33 case series (n = 867) was reported, and 94% resolution of diarrhea after repeated FMT in a randomized controlled trial (RCT) (n = 16). In ulcerative colitis (UC) remission rates of 0% to 68% were found (n = 106). In Crohn's disease (CD) (n = 6), no benefit was observed. In IBS, 70% improvement of symptoms was found (n = 13). 100% Reversal of symptoms was observed in constipation (n = 3). In pouchitis, none of the patients (n = 8) achieved remission. One RCT showed significant improvement of insulin sensitivity in metabolic syndrome (n = 10). Serious adverse events were rare. CONCLUSION: FMT is highly effective in CDI, and holds promise in UC. As for CD, chronic constipation, pouchitis and IBS data are too limited to draw conclusions. FMT increases insulin sensitivity in metabolic syndrom

The mucosa-associated microbiota of PSC patients is characterized by low diversity and low abundance of uncultured Clostridiales II

BACKGROUND: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease that is strongly associated with a particular phenotype of inflammatory bowel disease (IBD) with right-sided colonic involvement. In IBD, several studies demonstrated significant aberrancies in the intestinal microbiota in comparison with healthy controls. We aimed to explore the link between IBD and PSC by studying the intestinal mucosa-adherent microbiota in PSC and ulcerative colitis (UC) patients and noninflammatory controls. METHODS: We included 12 PSC patients, 11 UC patients, and nine noninflammatory controls. The microbiota composition was determined in ileocecal biopsies from each patient by 16S rRNA-based analyses using the human intestinal tract chip. RESULTS: Profiling of the mucosa-adherent microbiota of PSC patients, UC patients, and noninflammatory controls revealed that these groups did not cluster separately based on microbiota composition. At the genus-like level, the relative abundance of uncultured Clostridiales II was significantly lower (almost 2-fold) in PSC (0.26 ± 0.10%) compared with UC (0.41 ± 0.29%) and controls (0.49 ± 0.25%) (p = 0.02). Diversity and richness in the microbiota composition differed across the groups and were significantly lower in PSC patients compared with noninflammatory controls (p = 0.04 and p = 0.02, respectively). No significant differences were found in evenness. CONCLUSIONS: Reduced amounts of uncultured Clostridiales II in PSC biopsies in comparison with UC and healthy controls can be considered a signature of a compromised gut, as we have recently observed that this group of as yet uncultured Firmicutes correlates significantly with health

Findings from a Randomized Controlled Trial of Fecal Transplantation for Patients with Ulcerative Colitis

BACKGROUND: & Aims: Several case series have reported the effects of fecal microbiota transplantation (FMT) for ulcerative colitis (UC). We assessed the efficacy and safety of FMT for patients with UC in a double-blind randomized trial. METHODS: Patients with mild to moderately active UC (n=50) were assigned to groups that underwent FMT with feces from healthy donors or were given autologous fecal microbiota (control); each was administered via naso-duodenal tube at the start of the study and 3 weeks later. The study was performed at the Academic Medical Center in Amsterdam from June 2011 through May 2014. The composite primary endpoint was clinical remission (simple clinical colitis activity index scores =2) combined with =1 point decrease in the Mayo endoscopic score at week 12. Secondary endpoints were safety and microbiota composition by phylogenetic microarray in fecal samples. RESULTS: Thirty-seven patients completed the primary endpoint assessment. In the intention-to-treat analysis, 7/23 patients who received fecal transplants from healthy donors (30.4%) and 5/25 controls (20.0%) achieved the primary endpoint (P=.51). In the per protocol analysis, 7/17 patients who received fecal transplants from healthy donors (41.2%) and 5/20 controls (25.0%) achieved the primary endpoint (P=.29). Serious adverse events occurred in 4 patients (2 in the FMT group) but these were not considered to be related to the FMT. At 12 weeks the microbiota of responders in the FMT group was similar to that of their healthy donors; remission was associated with proportions of Clostridium clusters IV and XIVa. CONCLUSIONS: In this phase 2 trial, there was no statistically significant difference in clinical and endoscopic remission between patients with UC who received fecal transplants from healthy donors and those who received their own fecal microbiota, which may be due to limited numbers. However, the microbiota of responders had distinct features from that of nonresponders, warranting further study. ClinicalTrials.gov no: NCT0165003

Findings from a Randomized Controlled Trial of Fecal Transplantation for Patients with Ulcerative Colitis

BACKGROUND: & Aims: Several case series have reported the effects of fecal microbiota transplantation (FMT) for ulcerative colitis (UC). We assessed the efficacy and safety of FMT for patients with UC in a double-blind randomized trial. METHODS: Patients with mild to moderately active UC (n=50) were assigned to groups that underwent FMT with feces from healthy donors or were given autologous fecal microbiota (control); each was administered via naso-duodenal tube at the start of the study and 3 weeks later. The study was performed at the Academic Medical Center in Amsterdam from June 2011 through May 2014. The composite primary endpoint was clinical remission (simple clinical colitis activity index scores =2) combined with =1 point decrease in the Mayo endoscopic score at week 12. Secondary endpoints were safety and microbiota composition by phylogenetic microarray in fecal samples. RESULTS: Thirty-seven patients completed the primary endpoint assessment. In the intention-to-treat analysis, 7/23 patients who received fecal transplants from healthy donors (30.4%) and 5/25 controls (20.0%) achieved the primary endpoint (P=.51). In the per protocol analysis, 7/17 patients who received fecal transplants from healthy donors (41.2%) and 5/20 controls (25.0%) achieved the primary endpoint (P=.29). Serious adverse events occurred in 4 patients (2 in the FMT group) but these were not considered to be related to the FMT. At 12 weeks the microbiota of responders in the FMT group was similar to that of their healthy donors; remission was associated with proportions of Clostridium clusters IV and XIVa. CONCLUSIONS: In this phase 2 trial, there was no statistically significant difference in clinical and endoscopic remission between patients with UC who received fecal transplants from healthy donors and those who received their own fecal microbiota, which may be due to limited numbers. However, the microbiota of responders had distinct features from that of nonresponders, warranting further study. ClinicalTrials.gov no: NCT0165003

Research Review: Williams syndrome: A critical review of the cognitive, behavioral, and neuroanatomical phenotype

This review critically examines the research findings which characterize the cognitive, behavioral, and neuroanatomical features of Williams syndrome (WS). This article analyzes 178 published studies in the WS literature covering the following areas: 1) General intelligence, 2) Language skills, 3) Visuospatial and face processing skills, 4) Behavior patterns and hypersociability, 5) Musical abilities, and 6) Brain structure and function. We identify methodological issues relating to small sample size, use and type of control groups, and multiple measures of task performance. Previously described 'peaks' within the cognitive profile are closely examined to assess their veracity. This review highlights the need for methodologically sound studies that utilize multiple comparison groups, developmental trajectories, and longitudinal analyses to examine the WS phenotype, as well as those that link brain structure and function to the cognitive and behavioral phenotype of WS individual