P679 The keystone bacterium Christensenella minuta improves colitis in in vivo preclinical Inflammatory Bowel Disease models

Abstract

Abstract Background There is increasing evidence that microbiome-based therapies can correct dysbiosis and reduce inflammation associated with Inflammatory Bowel Diseases (IBD). In particular, the human commensal family of Christensenellaceae bacteria has been reported as missing in several cohorts of Crohn’s disease patients, indicating that it may have a role in maintaining microbial symbiosis in this population. To assess its potential for IBD management, we used the reference type species Christensenella minuta DSM 22607 to examine its anti-inflammatory properties. Methods We first performed two distinct independent preclinical colitis models: i) a moderate DNBS-induced colitis model in mice and ii) a severe TNBS-induced colitis model in rats. To decipher the mechanisms of action of C. minuta underlying the observed effects, we determined its ability to produce short chain fatty acids (SCFA) at different growth phases and we assessed its capacity to modulate the inflammatory response of human colonic cells. Results Our results showed that in both rodent models, C. minuta prevented intestinal damages by decreasing macroscopic scores, reduced colonic inflammation by limiting neutrophils infiltration in the colon and stimulated mucosal healing. We also confirmed that C. minuta is a high acetate and moderate butyrate producer. Finally, we showed that C. minuta displayed potent anti-inflammatory properties by decreasing the secretion of the pro-inflammatory cytokine IL-8 through NF-kB inhibition in HT-29 cells. Conclusion Together, these results revealed for the first time the strong anti-inflammatory properties of C. minuta and confirm its high potential as an innovative microbiome-based biotherapy for IBD.