[Gut microbiota, host defense and immunity: analysis with integrative omics approach].
Complex host-gut microbiota interaction is involved in the formation of a unique ecosystem in our body, the "gut ecosystem". In order to understand the complex gut ecosystem, we propose integrated multi-omics approach, where multiple layers of unbiased cyclopedic analyses such as genomics, transcriptomics and metabolomics are combined. Applying this approach, we have revealed the mechanism that gut microbiota-derived acetate, a short-chain fatty acid, protects mice from enterohemorrhagic Escherichia coli O157-infectious death. We have also shown that butyrate produced by gut microbiota such as order Clostridiales promotes differentiation of regulatory T cells from naïve T cells in colonic lamina propria, through epigenetic modification. Epigenetic modification by butyrate also acts on colonic macrophages to confer anti-inflammatory phenotype by rendering them hyporesponsive to Toll-like receptor signaling. Short-chain fatty acids also signal via their G protein-coupled receptors. For example, it has been suggested that gut microbiota-derived short-chain fatty acids absorbed in the blood play a role in regulation of systemic inflammation by inducing apoptosis of neutrophils as well as chemotaxis of regulatory T cells.
RIKEN Center for Integrative Medical Sciences.
Hiroshi
H
Ohno
D000085:Acetates; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002087:Butyrates / Q000378:metabolism; D004927:Escherichia coli Infections / Q000276:immunology; D019453:Escherichia coli O157 / Q000276:immunology; D005232:Fatty Acids, Volatile / Q000276:immunology / Q000502:physiology; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D007422:Intestines / Q000276:immunology* / Q000382:microbiology*; D055432:Metabolomics; D051379:Mice; D064307:Microbiota / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D043562:Receptors, G-Protein-Coupled / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology
D000085:Acetates; D002087:Butyrates; D005232:Fatty Acids, Volatile; D043562:Receptors, G-Protein-Coupled; D051193:Toll-Like Receptors