BackgroundStudies of colonoscopic fecal microbiota transplant (FMT) in patients with recurrent CDI, indicate that this is a very effective treatment for preventing further relapses. In order to provide this service at Stony Brook University Hospital, we initiated an open-label prospective study of single colonoscopic FMT among patients with ≥ 2 recurrences of CDI, with the intention of monitoring microbial composition in the recipient before and after FMT, as compared with their respective donor. We also initiated a concurrent open label prospective trial of single colonoscopic FMT of patients with ulcerative colitis (UC) not responsive to therapy, after obtaining an IND permit (IND 15642). To characterize how FMT alters the fecal microbiota in patients with recurrent Clostridia difficile infections (CDI) and/or UC, we report the results of a pilot microbiome analysis of 11 recipients with a history of 2 or more recurrences of C. difficile infections without inflammatory bowel disease (CDI-only), 3 UC recipients with recurrent C. difficile infections (CDI + UC), and 5 UC recipients without a history of C. difficile infections (UC-only).MethodV3V4 Illumina 16S ribosomal RNA (rRNA) gene sequencing was performed on the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient fecal samples along with those collected from the healthy donors. Fitted linear mixed models were used to examine the effects of Group (CDI-only, CDI + UC, UC-only), timing of FMT (Donor, pre-FMT, 1-week post-FMT, 3-months post-FMT) and first order Group*FMT interactions on the diversity and composition of fecal microbiota. Pairwise comparisons were then carried out on the recipient vs. donor and between the pre-FMT, 1-week post-FMT, and 3-months post-FMT recipient samples within each group.ResultsSignificant effects of FMT on overall microbiota composition (e.g., beta diversity) were observed for the CDI-only and CDI + UC groups. Marked decreases in the relative abundances of the strictly anaerobic Bacteroidetes phylum, and two Firmicutes sub-phyla associated with butyrate production (Ruminococcaceae and Lachnospiraceae) were observed between the CDI-only and CDI + UC recipient groups. There were corresponding increases in the microaerophilic Proteobacteria phylum and the Firmicutes/Bacilli group in the CDI-only and CDI + UC recipient groups. At a more granular level, significant effects of FMT were observed for 81 genus-level operational taxonomic units (OTUs) in at least one of the three recipient groups (p<0.00016 with Bonferroni correction). Pairwise comparisons of the estimated pre-FMT recipient/donor relative abundance ratios identified 6 Gammaproteobacteria OTUs, including the Escherichia-Shigella genus, and 2 Fusobacteria OTUs with significantly increased relative abundance in the pre-FMT samples of all three recipient groups (FDR < 0.05), however the magnitude of the fold change was much larger in the CDI-only and CDI + UC recipients than in the UC-only recipients. Depletion of butyrate producing OTUs, such as Faecalibacterium, in the...

Background The co-occurrence of autoimmune diseases is well recognized. Though studies have suggested that eosinophilic esophagitis (EoE) is more common in patients with inflammatory bowel diseases (IBD), whether co-occurrence of EoE modifies natural history of IBD is unknown. Methods This was a retrospective case-control study at a referral center. Cases consisted of patients with IBD and EoE, with both diseases diagnosed using established criteria. Controls comprised patients with IBD without concomitant EoE. Two controls were selected per case and were matched for duration of IBD. Relevant covariates regarding disease presentation and natural history were extracted from the medical record and compared between the 2 groups. Results A total of 95 IBD-EoE cases and 190 IBD controls were included in our study. The IBD-EoE group was diagnosed with IBD at a younger age than those with IBD alone (22.3 years vs 29.0 years; P &lt; 0.001) and were more likely to be male (80.0% vs 45.8%; P &lt; 0.001). There were no differences in medical or surgical therapy for IBD between the 2 groups. Among those with IBD-EoE, patients for whom IBD was diagnosed first presented more commonly with dysphagia (50.8% vs 26.9%; P = 0.04) and endoscopically had evidence of esophageal rings (50.0% vs 23.1%; P = 0.02) when compared with those where EoE was diagnosed first. Conclusion Patients with concurrent IBD-EoE are diagnosed at a younger age and more likely to be males but have similar natural history as those without EoE. There were differences in EoE phenotype based on whether the EoE or IBD was diagnosed first.

No abstract

of an opportunistic infection following treatment of high dose steroids. Patient 4 had multi-organ failure prior to start of treatment with vedolizumab and died. Patients 5 and 6 have no symptoms of serious GvHD after 2 and 3 doses of vedolizumab. Four out of 6 patients could be discharged from hospital. Immunophenotyping of peripheral blood revealed initial high levels of CD25 + Treg cells in 4 out of 6 evaluable patients and the values showed a decline into normal range after start of therapy and with signs of clinical effect. Conclusions: This case series suggests that targeting integrin a4b7 is feasible, safe and gives clinical responses in steroid refractory intestinal GvHD. The mechanism of action is not known, but may be due to the inhibition of alloreactive T-cells homing to the intestinal mucosa. The mechanism behind the Treg patterns is unclear. One might speculate that the initially high levels of Tregs are part of the physiologic reaction to the alloreactive inflammation in the intestinal mucosa.