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新型胆汁酸生物合成途径在百岁老人的微生物组中富集
2021-07-31 23:34

日本庆应义塾大学Kenya Honda、美国哈佛医学院Ramnik J. Xavier等研究人员合作发现,新型胆汁酸生物合成途径在百岁老人的微生物组中富集。相关论文于2021年7月29日在线发表于国际学术期刊《自然》。

研究人员表明,百岁老人有一个独特的肠道微生物群,富含能够产生独特的次级胆汁酸(BA)的微生物,包括 iso-, 3-oxo-, allo-, 3-oxoallo-, and isoallo-石胆酸(LCA)。在这些BA中,isoalloLCA的生物合成途径以前未被描述。通过筛选一位百岁老人粪便微生物群中的68种细菌分离物,研究人员发现Odoribacteraceae菌株在体外和体内都是isoalloLCA的有效生产者。

此外,研究人员发现5α-还原酶(5AR)和3β-羟类固醇脱氢酶(3βHSDH)负责生产isoalloLCA。isoalloLCA对革兰氏阳性(而非革兰氏阴性)多重耐药病原体,包括艰难梭菌和粪肠球菌,发挥了强大的抗菌作用。这些发现表明,特定的胆汁酸代谢可能参与减少病原体感染的风险,从而可能有助于维持肠道的平衡。

据了解,百岁老人对与年龄有关的疾病、慢性炎症和传染病的易感性降低。

附:英文原文

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

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

Issue&Volume: 2021-07-29

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.

DOI: 10.1038/s41586-021-03832-5

Source: https://www.nature.com/articles/s41586-021-03832-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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