Gut microbial short-chain fatty acids in host defense and immune regulation

Abstract

Our guts are inhabited by an enormous number of commensal bacteria, commonly referred to as the gut microbiota. Complex host-gut microbiota interactions are involved in the formation of the unique “gut ecosystem”. This ecosystem is thought to play a variety of roles in host physiology and pathology, including the modification and shaping of the host immune system. We have proposed an integrated omics approach for a comprehensive understanding of the gut ecosystem, where different levels of cyclopedic analyses, such as (meta)transcriptome and metabolome, are combined with the metagenome. Using this approach, we have discovered the mechanism by which the gut microbiota-derived short-chain fatty acid acetate protects mice from enterohemorrhagic Escherichia coli O157-infectious death. We have also shown that butyrate produced by the gut microbiota promotes differentiation of peripherally derived regulatory T cells in colonic lamina propria through epigenetic modification. In this minireview, I will discuss recent advances in our understanding of the role of gut microbial short-chain fatty acids in host defense and immune regulation, focusing mainly on results from our laboratory. Rec.2/9/2015, ACC.2/23/2015, pp114-121 Correspondence should be addressed to: Hiroshi Ohno, M.D., Ph.D., Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences (IMS), 1-7-22 Suehiro, Tsurumi, Yokohama 230-0045, Japan. Phone: +81-45-503-7031, Fax: +81-45-503-7068, E-mail: hiroshi.ohno@riken.jp