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Gut microbe metabolism implicated in longevity — Japan study of centenarians

In people over the age of 100, an enrichment in a distinct set of gut microbes that can generate unique bile acids might contribute to longevity by inhibiting the growth of gut pathogens, according to a study in Nature.

The study, which compares the gut microbes of centenarians, elderly individuals and younger people in Japan, raises the possibility of manipulating the bile acid pool for health benefits.

The community of microbes in our gut has a role in our health, and changes as we age. Centenarians are less susceptible to age-related chronic diseases and infection than are elderly individuals below the age of 100. It is thought that the composition of the gut microbiota in centenarians may be associated with extreme longevity, but the mechanisms have been unclear.

To probe the potential link between microbiota composition and longevity, Kenya Honda and colleagues studied three groups of Japanese people: 160 centenarians (aged over 100), 112 elderly individuals (aged 85–89) and 47 younger individuals (aged 21–55 years old). They found that, compared with elderly and young individuals, centenarians are enriched in gut microbes that are capable of generating unique secondary bile acids through novel biosynthetic pathways. The authors identify a range of bacteria responsible for producing these bile acids, and map the pathway that leads to the production of isoallo-lithocholic acid (isoalloLCA). IsoalloLCA is shown to have antimicrobial effects against a range of gut pathogens.

Experiments in mice suggest that isoalloLCA can inhibit the growth of Clostridium difficile — a bacterium that can cause severe diarrhoea, especially in people who are being treated with antibiotics.

The authors suggest that it may be possible to exploit the bile-acid-metabolising capabilities of bacterial strains identified in this study to manipulate the bile acid pool for health benefits. However, they add that further studies are needed to validate the association between bile acids and longevity.

Study details

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 Itoh, Kyoji 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

Published in Nature, 29 July 2021

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.

 

Full Nature article – Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians (Restricted access)

 

See more from MedicalBrief archives:

 

Healthy gut is a biomarker for healthy ageing

 

Off-the-shelf probiotics 'are almost useless'

 

Abnormal stroke-related brain blood vessels linked to gut bacteria

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