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

47 Citations (Scopus)

Abstract

Centenarians have a decreased susceptibility to ageing-associated illnesses, chronic inflammation and infectious diseases1–3. Here we show that centenarians have a distinct gut microbiome that is enriched in microorganisms that are capable of generating unique secondary bile acids, including various isoforms of lithocholic acid (LCA): iso-, 3-oxo-, allo-, 3-oxoallo- and isoallolithocholic acid. Among these bile acids, the biosynthetic pathway for isoalloLCA had not been described previously. By screening 68 bacterial isolates from the faecal microbiota of a centenarian, 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 (3β-HSDH) were responsible for the production of isoalloLCA. 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 the metabolism of specific bile acids may be involved in reducing the risk of infection with pathobionts, thereby potentially contributing to the maintenance of intestinal homeostasis.

Original languageEnglish
Pages (from-to)458-464
Number of pages7
JournalNature
Volume599
Issue number7885
DOIs
Publication statusPublished - 2021 Nov 18

ASJC Scopus subject areas

  • General

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