February 1, 2024

Lithocholic acid (LCA) is enriched in the microbiome of centenarians

The centenarian’s riddle explores the keys to longevity. 

Many scientists estimate longevity is based 20% on genetics, with 80% determined by your lifestyle choices and environment, but for some centenarians answer to the mystery might lie in the gut[1].

The rise in longevity during the past two or three centuries is arguably the greatest collective human achievement and has contributed to the increased prevalence of older individuals in the population. The group of individuals aged 80 and over is growing faster than other segments of the population, and within this group the number of centenarians has risen exponentially worldwide[2].

Fragmentary evidence suggests that early levels of human life expectancy were around 25 years. In 1900 the mean life span in the most advantaged countries had already risen to around 50 years. Recently, in 2021 an American tycoon launched Blueprint, a project with the aim of monitoring and reversing his biological age, more specifically, a protocol or a science experiment to explore the future of being human[3]. Although chronological age correlates with various age-related diseases and conditions, the question is are aging clocks malleable in humans?

Several authors believethat limits exist, based on demographic evidence[4].

Scientific data suggests that maintenance of cognitive capacity and good health at very old age may be associated with cellular mechanisms related to oxidative stress and DNA metabolism[5].

What is the role of bile acids in the gut microbiome?

Recent research on centenarians shows that they have a particular gut microbiome enriched in microorganisms capable of generating unique secondary bile acids: the lithocholic acid (LCA)[6]

Lithocholic acid (LCA) is a bile acid produced by intestinal flora used to assess cholestasis and it acts as a detergent to solubilize fats for absorption and is itself absorbed. The gut microbiota synthesizes hundreds of molecules, many of which influence host physiology[7].

Prof. Sato from the Department of Microbiology and Immunology of Tokyo, and his equip discovered the centenarian’s gut microbiome synthesizes hundreds of molecules, among the most abundant metabolites are the secondary bile acids deoxycholic acid (DCA) and lithocholic acid (LCA).

What we know about LCA activity is:

  • it inhibits Clostridium difficile growth,
  • it can modulate the gut-liver axis, including the regulation of gut microbiota, intestinal barrier.

Sato et al. discover centenarians’ gut microbiome contains certain taxa, including the bile acid metabolizer Clostridium scindens. This one is a member of the gut microbiota and can dehydroxylating bile acids.

Bile acids, gut microbiota, and the host have close and complex interactions, which play a central role in modulating host immune and metabolic homeostasis.

More broadly, LCA acid and its derivatives are a major component of the recirculating pool of bile acids.

Bile Acid functions in gut microbiome interactions and longevity

Primary BAs play critical roles in:

  • cholesterol metabolism,
  • lipid digestion,
  • host-microbe interaction.

Gut dysbiosis alters the production of secondary BAs, and leads to colonic inflammation, balancing nutrient intake with high fiber and low saturated fat intake is critical for maintaining a healthy gut microbiome.

These findings suggest that lithocholic acid greatly extends yeast longevity, it is involved in reducing the risk of infection and inflammation, for example, it has shown to accumulate in the serum of long living human and play a role in improving liver and pancreatic function[8].

Longevity appears to be achieved by genetics, environment, and lifestyle. Maintaining gut microbiota homeostasis, appear to be one of the secrets to “don’t die”.

[1] Rimal B, Patterson AD. Role of bile acids and gut bacteria in healthy ageing of centenarians. Nature. 2021 Nov;599(7885):380-381.

[2] Teixeira L, Araújo L, Jopp D, Ribeiro O. Centenarians in Europe. Maturitas. 2017 Oct;104:90-95.

[3] https://blueprint.bryanjohnson.co

[4] Between Zeus and the Salmon: The Biodemography of Longevity. National Research Council (US) Committee on Population; Wachter KW, Finch CE, editors. Washington (DC): National Academies Press (US); 1997.

[5] Sanchez-Roman I, Ferrando B, Holst CM, Mengel-From J, Rasmussen SH, Thinggaard M, Bohr VA, Christensen K, Stevnsner T. Molecular markers of DNA repair and brain metabolism correlate with cognition in centenarians. Geroscience. 2022 Feb;44(1):103-125.

[6] Sato Y, Atarashi K, Plichta DR, Arai Y, Sasajima S, Kearney SM, Suda W, Takeshita K, Sasaki T, Okamoto S, Skelly AN, Okamura Y, Vlamakis H, Li Y, Tanoue T, Takei H, Nittono H, Narushima S, Irie J, Itoh H, Moriya K, Sugiura Y, Suematsu M, Moritoki N, Shibata S, Littman DR, Fischbach MA, Uwamino Y, Inoue T, Honda A, Hattori M, Murai T, Xavier RJ, Hirose N, Honda K. Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians. Nature. 2021 Nov;599(7885):458-464.

[7] Funabashi M, Grove TL, Wang M, Varma Y, McFadden ME, Brown LC, Guo C, Higginbottom S, Almo SC, Fischbach MA. A metabolic pathway for bile acid dehydroxylation by the gut microbiome. Nature. 2020 Jun;582(7813):566-570.

[8] Zeng H, Umar S, Rust B, Lazarova D, Bordonaro M. Secondary Bile Acids and Short Chain Fatty Acids in the Colon: A Focus on Colonic Microbiome, Cell Proliferation, Inflammation, and Cancer. Int J Mol Sci. 2019 Mar 11;20(5):1214.