In vivo protective role of gut commensal bacteria on epithelial barrier function, disease severity and clinical signs in an DSS-induced acute colitis mouse model

Ulcerative Colitis (UC) is a severe inflammatory bowel disease (IBD) characterized by multifactorial complex disorders during onset and progression. Symptomatic short term treatment options include corticosteroids, immune-suppressive agents, monoclonal antibodies and the amino-salicylate mesalazin. Serious side effects and drug resistance urgently require development of alternative therapeutic options. Here we use a DSS-induced acute colitis mouse model to study beneficial effects of three commensal gut bacterial species which are found in reduced numbers in UC patient guts. Administration of Faecalibacterium prausnitzii, Bacteroides faecis and Roseburia intestinalis into diseased mice alone and in combination reduced Disease Activity Index (DAI) scores, inhibited colon shortening, strengthened the colonic epithelial barrier, positively modulated tight junction protein expression, reduced crypt disruption, goblet cell loss, submucosal edema, modulated cytokine secretion and epithelial damage caused by DSS administration. Further immune modulation occurred via inhibition of loss of CD4+CD25+Treg cells in the spleen. No adverse effects of commensal bacterial treatment on general gut microbial composition was noted in our study. Moreover, commensal bacterial therapy of DSS-induced ulcerative mice performed equally well compared to the standard contemporary mesalazine treatment regime. In summary, such a commensal bacterial treatment cocktail should seriously be considered in future studies as novel therapeutic option.