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[4Ferm-01-KL]Gut microbial dietary component metabolism useful for health maintenance

○Jun Ogawa1, Michiki Takeuchi1, Akinori Ando1, Ryotaro Hara1, Shigenobu Kishino1 (1. Div. Appl. Life Sci., Grad. Sch. Agric., Kyoto University (Japan))
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Keywords:

glucosinolate,polyphenol,urolithin,quercetin,fatty acid

The accumulation of knowledge about gut microbiota and gut metabolites obtained by the latest multi-omics research is leading novel health promoting technologies, coupled with cohort studies that reveal the relationship between health status and the gut environment. As to the metabolic aspects, we analyzed the metabolism of dietary components, such as food-derived molecules such as phytochemicals and fatty acids by intestinal bacteria. Furthermore, the enzyme systems and genes involved, and the evaluation of physiological functions of derived metabolites were carried out. Novel enzyme systems were found in gut microbial metabolisms of plant-derived bioactive compounds such as glucosinolates, polyphenols, and flavonoids. Cruciferous vegetables are rich sources of glucosinolates. Glucosinolates are degraded into isothiocyanates, which are potent anticarcinogens, by human gut bacteria. A quantitative comparative proteomic analysis of glucosinolate-metabolizing lactic acid bacteria revealed the involvement of the phosphotransferase system in the substrate phosphorylation and a hydrolase in the hydrolysis of phosphorylated substrate. The same quantitative comparative proteomic approach also revealed the involvement of a novel ellagic acid lactonase and urolithin-dehydroxylating enzymes, regioselective dehydroxylases, consisting of molybdopterin-containing protein and iron-sulfur cluster-containing protein. Flavone reductase (FLR) from gut microorganisms has been reported to convert quercetin in the presence of NADH-specific FMN oxidoreductase, but the product has not been identified. We identified the quercetin-converted product by FLR as taxifolin. Dietary fatty acid metabolism by gut microbiota generating hydroxy, oxo, enone, and conjugated fatty acids were discovered. The enzymes involved in those metabolisms, i.e., hydratase, dehydrogenase, isomerase, ene-reductase, were investigated and applied for cascade reactions to produce fatty acid metabolites. The existence of these gut microbial metabolites in host tissues were confirmed by newly established lipidomics technology and their physiological activities were revealed and found to promote the health of the host, being promising functional foods and pharmaceuticals. The newly found enzyme systems were useful to produce bioactive metabolites of dietary components. Based on the scientific findings on these novel metabolisms and the enzyme systems involved, new concepts of postbiotics (gut microbial food component metabolites) as novel health promoting tools and precision nutrition applying the gene information of novel enzyme systems were proposed.

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