Effect of Lactobacillus and Bifidobacterium on the inhibition of Clostridium difficile in mouse infection model

Abstract

Clostridium difficile is a major cause antibiotic-associated diarrhea and colitis in patients with broad-spectrum antibiotic therapy. A disruption of the gut microbiota by using antibiotics results in colonization with C. difficile and release of toxins that cause leaky gut and the production inflammatory cytokines. We identified six specific strains of Lactobacillus or Bifidobacterium are able to reduce leaky gut and inflammation caused by C. difficile in vitro. In this study, we aim to investigate the effect of these strains either alone or in combination on the inhibition of C. difficile infection in a C57BL/6 mouse model. The administration of L. rhamnosus L34 (1x10⁶ cells) for 4 days at the day of clindamycin injection to the day before sacrifice (D-1 to D2) reduced mortality, body weight change, diarrhea, gut leakage and pathology of mice and also suppressed the production of tissue and systemic inflammatory cytokines including MIP-2, KC, IL-1β and TNF-α. The administration of 1x10⁸ cells of L. casei L39, L. casei B13, L. casei B106, B. bifidum NB42 or B. pseudocatenulatum NB48 alone reduced mortality, body weight change and diarrhea in mice. L. casei L39, L. casei B13 and L. casei 106 administration also reduced the production of some tissue and systemic inflammatory cytokines. The effect of Bifidobacterium spp. on cytokine production was not determined yet. Only Lacto cocktail (L. rhamnosus L34 and L. casei L39) attenuated the disease severity whereas Bifido cocktail (B. bifidum NB42 or B. pseudocatenulatum NB48) or Lacto-Bifido cocktail (L. rhamnosus L34, L. casei L39, B. bifidum NB42, B. pseudocatenulatum NB48) did not. These strains are promising probiotics for C. difficile infection.