P1204 Oral Streptococcus mutans isolates aggravated colitis in mice

Abstract

Abstract Background The incidence of inflammatory bowel disease (IBD) is increasing year by year and the mechanism is unclear. A great number of studies have shown that the gut microbiota composition of IBD patients has changed and the diversity of gut microbiota decreases. The abundance of firmicutes decreases, and the abundance of Proteobacteria increases, which eventually leads to the immune disorders and intestinal inflammation. The mouth is the "gateway" of the digestive tract, which has various microbiota. The entry of extraneous microbiota from the mouth into the intestines play an important role in influencing the composition of the gut microbiota. The continuous disorder of the oral microenvironment (such as periodontitis and dental caries) are also closely related to intestinal inflammation. Methods A series of in vivo and in vitro experiments were conducted to investigate the effect and mechanism of S. mutans on colitis mice. Results S.mutans strain UA159 which is closely related to dental caries significantly aggravated colitis in DSS induced mice, as shown by body weight loss, shorter colon length, and increased inflammatory histological scores (Fig1A). UA159 up-regulated intestinal pro-inflammatory cytokines and inhibited the expression of barrier molecules in DSS mice (Fig1B). The proportion of adaptive immune cells (Th1, Th17) was up-regulated in intestinal lamina propria of UA159-administered mice (Fig1C-D).The fecal microbiota composition of UA159 mice was different from control group. The pro-inflammatory effects of UA159 on DSS mice disappeared when antibiotics were used to eliminate the intestinal microbiota. It is suggested that S.mutans may play a proinflammatory role by influencing the intestinal microbiota of mice (Fig1E). We followed 55 IBD patients for more than 1 year and found that IBD patients with poor control had a higher proportion of S.mutans in saliva (Fig1F). S.mutans strains were isolated from IBD saliva samples and were found to cluster in different branches in the phylogenetic tree (Fig1G). S.mutans isolates have different pro-inflammatory effects on colitis mice and intestinal epithelial cells (Fig1H-I). Subsequent experiments are under way to further explore the mechanism leading to the differences of the pro-inflammatory effects. Conclusion Our study were the first to find that oral S.mutans has aggravated intestinal inflammation. S.mutans UA159 aggravated colitis in mice through damaging intestinal mucosal barrier function, enhancing immune response and disrupting intestinal microbiota (Fig1J). The difference in pro-inflammatory effect of S.mutans derived from different IBD patients saliva may be related to the individual clinical outcome.