ICMI 2015

T.71 Human feces-derived Fusicatenibacter saccharivorans reduced in IBD patients induces IL-10 to suppress murine model of colitis

Thursday, July 16, 2015
Grand Hall and Gallery, Ground Floor & 1st Floor (Maritim Hotel)
Takanori Kanai , Keio University School of Medicine, Tokyo, Japan
Kozue Takeshita , Keio University School of Medicine, Tokyo, Japan
Tadakazu Hisamatsu , Keio University, Tokyo, Japan
Makoto Naganuma , Keio University School of Medicine, Tokyo, Japan
Shinta Mizuno , Keio University School of Medicine, Tokyo, Japan
Koji Nomoto , Yakult Central Institute, Tokyo, Japan
Experimental and clinical findings indicate association between inflammatory bowel disease (IBD) and intestinal microbiota, and Honda’s group demonstrated that Clostridium (C.) species, clusters IV and XIVa, induce IL-10-producing regulatory T cells, and protect the development of colitis in mice. Furthermore, we previously demonstrated that a single strain of C. butyricum induces IL-10-producing regulatory macrophages via PAMP-TLRs pathway, resulting in the suppression of colitis (Cell Host Microbe 2013). In this study, we analyzed the bacterial composition of human fecal samples from patients with ulcerative colitis (UC), Crohn’s disease (CD), and healthy subjects. First, we confirmed that the number of the total fecal bacteria in active UC was less than quiescent UC. The alteration of bacterial number was not observed in CD. Furthermore, we found that the prevalence of Fusicatenibacter saccharivorans (FS), which belong to C. cluster XIVa, was strikingly lower in active UC than quiescent UC. Administration of FS derived from human healthy subject suppressed the development of acute DSS-colitis in mice. To explore the mechanism, we stimulated colitic lamina propria mononuclear cells (LPMC) from murine IBD models with heat-killed FS. LPMC incubated with FS produced higher amounts of IL-10 compared to those stimulated with Enterococcus faecalis (EF), which was used as a control of gram-positive bacteria. FS also induced IL-10 production from human LPMC isolated from UC patients. The results suggest human-derived FS suppress intestinal inflammation, probably through IL-10 induction, and would be a future strategy of IBD bacteriotherapy to colonize in the intestine of IBD patients.