総説・解説等

The human intestinal microbiota has profound effects on human physiology, including the development and maintenance of the host immune and metabolic systems. Under physiological conditions, the intestinal microbiota maintains a symbiotic relationship with the host. Abnormalities in the host-microbe relationship, however, have been implicated in multiple disorders such as inflammatory bowel diseases (IBDs), metabolic syndrome, and autoimmune diseases. There is a close correlation between dietary factors and the microbial composition in the gut. Long-term dietary habits influence the composition of the gut microbial community and consequently alter microbial metabolic activity. The diet-microbiota axis plays a vital role in the regulation of the host immune system, at least partly through altering microbial metabolism. In this review, we will describe the current findings regarding how dietary factors and microbial metabolites regulate the host immune system.

The intestinal microbiota has been implicated in a wide range of diseases, including inflammatory bowel disease, obesity and cancer. Food ingredients are considered a major determinant of gut microbial composition, as exemplified by high-fat diet-induced dysbiosis that can affect host physiology. Accumulating studies show that microbial metabolites are key regulators of the intestinal epithelial barrier and gut immunity. In particular, shortchain fatty acids produced by bacterial fermentation of indigestible polysaccharides have profound impacts on host physiology beyond the gut. In this review, we describe the influences of the diet-microbiota-metabolite axis on host physiology, and especially on the immune and metabolic systems.

Commensal microbiota colonizing the digestive tract is a symbiotic partner of its host, as it plays a critical role in nutrient metabolism as well as the development and maturation of the host immune system. Although it is clear that regulation of the host-commensal relationship is crucial to mammalian health, the underlying mechanisms regulating gut homeostasis are yet to be elucidated. Epigenetic modifications, including DNA methylation and histone methylation/acetylation, alter the structure of chromatin to regulate the transcriptional program of eukaryotic cells. At the whole genome level, these modifications possibly play a key role in regulating the mutually beneficial relationship between the host and the gut microbiota. In this review, we describe how the commensal microbiota and its metabolic by-products modify the epigenome of host cells, and in turn, change their development and functional behavior.