Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians

Yuko Sato, Koji Atarashi, Damian R. Plichta, Yasumichi Arai, Satoshi Sasajima, Sean M. Kearney, Wataru Suda, Kozue Takeshita, Takahiro Sasaki, Shoki Okamoto, Ashwin N. Skelly, Yuki Okamura, Hera Vlamakis, Youxian Li, Takeshi Tanoue, Hajime Takei, Hiroshi Nittono, Seiko Narushima, Junichiro Irie, Hiroshi ItohKyoji Moriya, Yuki Sugiura, Makoto Suematsu, Nobuko Moritoki, Shinsuke Shibata, Dan R. Littman, Michael A. Fischbach, Yoshifumi Uwamino, Takashi Inoue, Akira Honda, Masahira Hattori, Tsuyoshi Murai, Ramnik J. Xavier, Nobuyoshi Hirose, Kenya Honda

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Centenarians display decreased susceptibility to ageing-associated illness, chronic inflammation, and infectious disease1–3. Here we show that centenarians have a distinct gut microbiome enriched in microbes capable of generating unique secondary bile acids (BAs), including iso-, 3-oxo-, allo-, 3-oxoallo-, and isoallo-lithocholic acid (LCA). Among these BAs, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from a centenarian’s faecal microbiota, we identified Odoribacteraceae strains as effective producers of isoalloLCA both in vitro and in vivo. Furthermore, we found that the enzymes 5α-reductase (5AR) and 3β-hydroxysteroid dehydrogenase (3βHSDH) were responsible for isoalloLCA production. IsoalloLCA exerted potent antimicrobial effects against gram-positive (but not gram-negative) multidrug-resistant pathogens, including Clostridioides difficile and Enterococcus faecium. These findings suggest that specific bile acid metabolism may be involved in reducing the risk of pathobiont infection, thereby potentially contributing to the maintenance of intestinal homeostasis.

Original languageEnglish
JournalNature
DOIs
Publication statusAccepted/In press - 2021

ASJC Scopus subject areas

  • General

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