P090 Prevotella copri promotes colitis in mice by reducing expression of ATF4 and disturbing the gut microbiota

Abstract Background Colitis is a disease that carries a significant global disease burden, with a growing prevalence. Studies in humans and mice have explored the role of the intestinal microbiota that contribute to inflammatory bowel disease (IBD). Prevotella copri is a common human gut microbe that has been linked to inflammatory disorders. Methods C57BL/6 mice were divided into four groups: normal control group, P. copri group, DSS model group, DSS model+ P. copri group. Mice were gavaged with P. copri or PBS for 14 consecutive days, starting from the first day. Experimental colitis was induced by 2% DSS treatment from day 8. Mouse colon tissues were analyzed by quantitative real-time polymerase chain reaction, immunoblots, immunohistochemistry, and transcriptome. Serum and intestinal epithelial cell (IEC) amino acids were measured by high-performance liquid chromatography-tandem mass spectrometry. The analysis of the microbiome was done through the 16S ribosomal DNA sequencing. Results In the present study, our experiment confirmed that P. copri was significantly associated with the exacerbation of DSS-induced colitis by reducing expression of ATF4 and altering the gut microbiota composition. Leucine concentration of serum and IEC were increased in P. copri-gavaged mice, which clearly suppresses ATF4 expression. The dysbiosis of the intestinal microbiota and impaired α-defensin production by Paneth cells are also the leading causes of why P. copri-gavaged mice are more susceptible to DSS-induced colitis. Conclusion Taken together, the results proposed that P. copri aggravated the severity of colitis in the mice with DSS-induced colitis. This was done by reducing the expression of ATF4 and disturbing the gut microbiota. Thus, targeting P. copri may be an effective strategy in the treatment of IBD.