It is well known that some intestinal bacteria, such as Escherichia coli, can produce a remarkable amount of molecular hydrogen (H-2). Although the antioxidant effects of H-2 are well documented, the present study examined whether H-2 released from intestinally colonized bacteria could affect Concanavalin A (ConA)-induced mouse hepatitis. Systemic antibiotics significantly decreased the level of H-2 in both liver and intestines along with suppression of intestinal bacteria. As determined by the levels of AST, ALT, TNF-alpha and IFN-gamma in serum, suppression of intestinal bacterial flora by antibiotics increased the severity of ConA-induced hepatitis, while reconstitution of intestinal flora with H-2-producing E. coli, but not H-2-deficient mutant E. coli, down-regulated the ConA-induced liver inflammation. Furthermore, in vitro production of both TNF-alpha and IFN-gamma by ConA-stimulated spleen lymphocytes was significantly inhibited by the introduction of H-2. These results indicate that H-2 released from intestinal bacteria can suppress inflammation induced in liver by ConA. (C) 2009 Elsevier Inc. All rights reserved.