The Gut Microbiome of Centenarians

The state of the gut microbiome is arguably as influential on health as exercise. Various microbial species present in the gut produce beneficial metabolites, such as butyrate, or harmful metabolites, such as isoamylamine, or can provoke chronic inflammation in a variety of ways. An individual can have a better or worse microbiome, assessing these and other functional contributions to health. With age, the balance of populations shifts towards fewer benefits and greater harm, unfortunately.

Since the composition of the microbiome can be assessed accurately and cheaply via 16S rRNA sequencing, understanding of the gut microbiome is advancing rapidly. There is no one optimal gut microbiome, but some species are more helpful than others. Looking at human populations, researchers are beginning to see patterns emerge from the study of the gut microbiome in healthier and more long-lived people. Today's open access paper is an example of this sort of work, in which the microbiomes of centenarians are assessed and compared with the broader population.

This is all interesting, but a short-cut to improving the aged gut microbiome does exist, in advance on understanding all of the desired component species, proportions, and effects on health. That is to conduct a fecal microbiota transplant from a young donor into an older recipient, using screened stool samples from a service such as Human Microbes. In animal studies, lasting rejuvenation of the gut microbiome, along with improved health and extended life span, can be achieved in this way. Robust human data has yet to be obtained, despite the use of fecal microbiota transplantation as a treatment for severe dysbiosis, but that is just a matter of time.

Gut microbiota as an antioxidant system in centenarians associated with high antioxidant activities of gut-resident Lactobacillus

Clinical studies have also shown that the diversity and composition of the gut microbiota is non-linear with age. In centenarians, the abundances of Roseburia and Escherichia were significantly higher than in non-centenarians, while Lactobacillus, Faecalibacterium, Parabacteroides, Butyricimonas, Coprococcus, Megamonas, Mitsuokella, Sutterella, and Akkermansia were significantly lower in centenarians than in non-centenarians. The age-related trajectories of the human gut microbiome are characterized by a loss of genes for short-chain fatty acid production and an overall decrease in glycolytic potential, while proteolytic functions are more abundant than in the gut metagenome of young adults.

A study using metagenomic sequencing to identify compositional and functional differences in the gut microbiota associated with age groups in Sardinia, Italy. The data showed that the gut microbiota of Sardinian centenarians was mainly characterized by depletion of Faecalibacterium prausnitzii and Eubacterium rectale, while enriched Methanobrevibacter smithii and Bifidobacterium adolescentis compared with young and old. Functional analysis showed that centenarians had higher metabolic capacity, especially glycolysis and fermentation of short-chain fatty acids (SCFAs), and lower genes encoding carbohydrate-degrading enzymes, including fiber and galactose.

Studies have shown that centenarians have a unique gut microbiome rich in microorganisms capable of producing unique secondary bile acids, including various isomers of lithocholic acid (LCA). These findings suggest that the metabolism of specific bile acids may be involved in reducing the risk of pathogenic infection and thus may contribute to the maintenance of intestinal homeostasis. Although we believe that longevity appears to be achieved by maintaining gut microbiota homeostasis, whether changes in gut microbiota are a consequence or a cause of aging, and the exact relationship between gut microbiota and aging remains to be further explored.

In this study, we combined metagenomic sequencing and large-scale in vitro culture to reveal the unique gut microbial structure of the world's longevity town - Jiaoling, China, centenarians, and people of different ages. Functional strains were isolated and screened in vitro, and the possible relationship between gut microbes and longevity was explored and validated in vivo, revealing associations of the gut microbiota with age and a number of clinical and metabolic parameters.

We uncovered age-specific gut microbiota characteristics, including a core set of seven microbial taxa enriched in centenarians and the gut microbiota of centenarians exhibited higher xenobiotics biodegradation and metabolism, oxidoreductase. We revealed age-related gut microbial characteristics in all populations, including increased alpha diversity and increased levels of abundances of the health-related bacteria such as Akkermansia, Lactobacillus, and short-chain fatty acid (SCFA) producers, and targeted screening an age-related gut-resident Lactobacillus with independent intellectual property rights, which metabolites and itself have good antioxidant effects.

Comments

I was wondering if Aubrey de Grey and the LEV Foundation were considering fecal microbiota transplantation as part of their big combination study.

any thoughts?

Posted by: Gregory Schulte at January 9th, 2023 5:40 PM

Intuitively it would seem that some kind of supplements or foods or something should be able to achieve the same end more safely? I mean obviously they've done the research and I haven't. Intuitively young BLOOD makes sense to transfuse ... but young microbes in the gut ... I can't immediately get my head around it. So once they get in there they colonize and spread and your entire gut is rejuvenated?

Posted by: Hoeberian at January 9th, 2023 5:51 PM
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