2020年12月2日
Identification of unique bile acid-metabolizing bacteria from the microbiome of centenarians
- DOI
- 10.21203/rs.3.rs-115113/v1
- 出版者・発行元
- Research Square Platform LLC
<title>Abstract</title>
Centenarians, or individuals who have lived more than a century, represent the ultimate model of successful longevity associated with decreased susceptibility to ageing-associated illness and chronic inflammation. The gut microbiota is considered to be a critical determinant of human health and longevity. Here we show that centenarians (average 107 yo) have a distinct gut microbiome enriched in microbes capable of generating unique secondary bile acids, including iso-, 3-oxo-, and isoallo-lithocholic acid (LCA), as compared to elderly (85-89 yo) and young (21-55 yo) controls. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from a centenarian’s faecal microbiota, we identified <italic>Parabacteroides merdae</italic> and <italic>Odoribacteraceae</italic> strains as effective producers of isoalloLCA. Furthermore, we generated and tested mutant strains of <italic>P. merdae</italic> to show that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3βHSDH) were responsible for isoalloLCA production. This secondary bile acid derivative exerted the most potent antimicrobial effects among the tested bile acid compounds against gram-positive (but not gram-negative) multidrug-resistant pathogens, including <italic>Clostridioides difficile</italic> and vancomycin-resistant <italic>Enterococcus faecium</italic>. These findings suggest that specific bile acid metabolism may be involved in reducing the risk of pathobiont infection, thereby potentially contributing to longevity.
Centenarians, or individuals who have lived more than a century, represent the ultimate model of successful longevity associated with decreased susceptibility to ageing-associated illness and chronic inflammation. The gut microbiota is considered to be a critical determinant of human health and longevity. Here we show that centenarians (average 107 yo) have a distinct gut microbiome enriched in microbes capable of generating unique secondary bile acids, including iso-, 3-oxo-, and isoallo-lithocholic acid (LCA), as compared to elderly (85-89 yo) and young (21-55 yo) controls. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from a centenarian’s faecal microbiota, we identified <italic>Parabacteroides merdae</italic> and <italic>Odoribacteraceae</italic> strains as effective producers of isoalloLCA. Furthermore, we generated and tested mutant strains of <italic>P. merdae</italic> to show that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3βHSDH) were responsible for isoalloLCA production. This secondary bile acid derivative exerted the most potent antimicrobial effects among the tested bile acid compounds against gram-positive (but not gram-negative) multidrug-resistant pathogens, including <italic>Clostridioides difficile</italic> and vancomycin-resistant <italic>Enterococcus faecium</italic>. These findings suggest that specific bile acid metabolism may be involved in reducing the risk of pathobiont infection, thereby potentially contributing to longevity.
- リンク情報
- ID情報
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- DOI : 10.21203/rs.3.rs-115113/v1