@article{671828ff50584bba8a5ed9eb97115979,
title = "Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians",
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.",
author = "Yuko Sato and Koji Atarashi and Plichta, {Damian R.} and Yasumichi Arai and Satoshi Sasajima and Kearney, {Sean M.} and Wataru Suda and Kozue Takeshita and Takahiro Sasaki and Shoki Okamoto and Skelly, {Ashwin N.} and Yuki Okamura and Hera Vlamakis and Youxian Li and Takeshi Tanoue and Hajime Takei and Hiroshi Nittono and Seiko Narushima and Junichiro Irie and Hiroshi Itoh and Kyoji Moriya and Yuki Sugiura and Makoto Suematsu and Nobuko Moritoki and Shinsuke Shibata and Littman, {Dan R.} and Fischbach, {Michael A.} and Yoshifumi Uwamino and Takashi Inoue and Akira Honda and Masahira Hattori and Tsuyoshi Murai and Xavier, {Ramnik J.} and Nobuyoshi Hirose and Kenya Honda",
note = "Funding Information: Acknowledgements We thank L. Besse for project management and making data available through the SRA and the Broad Institute Genomics Platform and Microbial {\textquoteright}Omics Core for sample processing and sequencing data generation; A. Minowa, M. Asakawa, K. Sugita and members of the JSR-Keio University Medical and Chemical Innovation Center for their technical support; N. Hasegawa, K. Fukunaga, T. Kanai, K. Masaki, S. Azekawa, K. Sasahara, S. Hosomi, M. Shimura and Y. Abe for their assistance in collecting clinical samples; S. Atsushi and members of the Honda laboratory for their suggestions during the course of this studies. K.H. was funded through AMED LEAP under grant number JP20gm0010003, Grant-in-Aid for Specially Promoted Research from JSPS (no. 20H05627), Public/Private R&D Investment Strategic Expansion Program (PRISM) from Cabinet Office of the Government of Japan, the Naito Foundation and the Takeda Science Foundation. The centenarian study was funded by the Japan Ministry of Agriculture, Forestry and Fisheries (M.S.) and Keio Global Research Institute (Y.A. and N.H.). The older-participant recruitment study was funded by a Grant-in-Aid for Scientific Research (no. 18H03055) from the Japan Society for the Promotion of Science and JST Research Complex Program (JP15667051). D.R.P. and R.J.X. were funded by the Center for the Study of Inflammatory Bowel Disease (DK043351), Center for Microbiome informatics and Therapeutics (CMIT) and AT009708. Y. Sato. was supported by the Terumo Life Science Foundation. Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2021",
month = nov,
day = "18",
doi = "10.1038/s41586-021-03832-5",
language = "English",
volume = "599",
pages = "458--464",
journal = "Nature Cell Biology",
issn = "1465-7392",
publisher = "Nature Publishing Group",
number = "7885",
}