Bacteroides thetaiotaomicron ameliorates colon inflammation in preclinical models of Crohn's disease

Abstract

Background Alterations in the gut microbiota are strongly associated with the development of inflammatory bowel disease (IBD), particularly with Crohn's disease, which is characterized by reduced abundance of commensal anaerobic bacteria including members of the Bacteroides genus. Our aim was to investigate the protective effects of Bacteroides thetaiotaomicron, an abundant member of this genus, in different rodent models of IBD. Methods We assessed the effect of B. thetaiotaomicron administration on primary readouts of colitis (weight loss, histopathology, and immune parameters) in dextran sodium sulphate (DSS) and interleukin-10 knockout (IL10KO) models of IBD. Efficacy of a freeze-dried bacterial formulation and a purified recombinant protein of B. thetaiotaomicron was also investigated. Results B. thetaiotaomicron showed protective effects in both DSS and IL10KO rodent models, as demonstrated by significant amelioration of weight loss, colon shortening, histopathological damage and immune activation. This efficacy was not exclusive to actively growing bacterial preparations but was retained by freeze-dried cells of B. thetaiotaomicron. A pirin-like protein (PLP) of B. thetaiotaomicron, identified by microarray analysis during coculture of the bacterial strain with Caco-2 cells, reduced pro-inflammatory NF-ΰ B signalling in these intestinal epithelial cells. Recombinant PLP partially recapitulated the effect of the whole strain in a rat DSS model. Conclusions B. thetaiotaomicron displays strong efficacy in preclinical models of IBD and protects against weight loss, histopathological changes in the colon and inflammatory markers. These data indicate that the live strain or its products may be a novel alternative to current treatment options for Crohn's disease.