Interactional Effects of Food Macronutrients with Gut Microbiome: Implications for Host Health and Risk.

Macronutrients in the diet (e.g., carbohydrates, proteins, and lipids) that are rarely absorbed in the small intestine can typically traverse to the colon where they are metabolized by the gut microbiota to produce a spectrum of beneficial or detrimental metabolites. These gut-microbiota-dependent small-molecule metabolites are subsequently absorbed by the intestinal mucosa to participate in various physiological responses. Notably, succinate as a star dicarboxylic acid metabolite stemming from microbial fermentation of nondigestible carbohydrates regulates blood glucose homeostasis by promoting intestinal gluconeogenesis while inhibiting hepatic gluconeogenesis. Furthermore, protein- or tryptophan-derived indole metabolites have emerged as a promising target for modulating neuropathic diseases. Fascinatingly, the linkage between gut microbiota and lncRNA introduces a novel promising dimension for modulating lipid absorption, metabolism, and storage. Ongoing advancements in elucidating the interplay between macronutrients, gut microbiota, and host health may facilitate the development of gut microbiota-directed clinical precision nutrition strategies through intake of tailored macronutrients.