• Elevated bacterial composition uniqueness predicts better health and survival in older age
  • Specific age-related patterns of gut bacteria are linked to higher levels of blood metabolic byproducts like indoles that may contribute to healthy aging

The types of microorganisms inhabiting the gut – the microbiome – change as people approach their later years. Whether these changes reflect and possibly contribute to declining health is unclear. Figuring out what features differentiate healthy, aged guts from others remains crucial to determine how gut composition relates to age-related health problems.

Price and colleagues from the Institute for Systems Biology in Seattle, Washington, published a study in Nature Metabolism that identified gut microbiome compositional uniqueness as a factor determining healthy aging. Their study analyzed the health trajectories of over 9,000 individuals aged 18 to 101 years and indicated the late-life microbial drift toward a unique composition is absent in less healthy individuals. Core gut bacterial species found in most humans like Bacteroides were depleted in healthy, aged individuals, but retaining high levels of this species in older age with low microbiome uniqueness predicts significantly reduced survival. The study also pointed to changes in blood metabolic byproducts (metabolites) with higher gut bacterial uniqueness levels, which may provide clues as to how gut bacteria changes during aging affect longevity.

“We propose that gut microbiomes of healthy individuals continue to develop along a distinct trajectory,” stated Price and colleagues in their publication. “This trajectory originates in adulthood, is accompanied by a rise in specific plasma microbial metabolites, reflects a healthy aging phenotype and is predictive of extended survival in the latest decades of human life.”

With Age, Individual Gut Microbiomes Become More Dissimilar

Price and colleagues performed analyses of gut bacteria diversity and found gut composition begins to drift toward a unique composition beginning between the ages of 40 and 50 years. Gut bacteria composition uniqueness reflects how dissimilar one person’s gut bacteria are in comparison to other people. In their analyses, the team of researchers found the uniqueness of gut bacteria increased with each decade of life.

(Wilmanski et al., 2021 | Nature Metabolism) Gut microbiome uniqueness increases in older age. The boxplot shows a gut microbiome uniqueness measure called the Bray-Curtis dissimilarity metric increases across the adult lifespan.

Blood Metabolic Byproduct Content Reflects Microbiome Uniqueness

Since the group’s research previously showed that microbiome composition influenced blood metabolite levels, Price and colleagues looked at how gut microbiome uniqueness reflects metabolite composition. By looking at blood metabolites, they found that the drift toward a more unique microbiome composition with age is characterized by a shift in gut bacteria metabolism.

“Interestingly, this uniqueness pattern appears to start in mid-life – 40-50 years old – and is associated with a clear blood metabolomic signature, suggesting that these microbiome changes may not simply be diagnostic of healthy aging, but that they may also contribute directly to health as we age,” said one of the lead scientists of the study, Dr. Tomasz Wilmanski, in a press release. For example, higher levels of indoles, which have been shown to reduce gut inflammation, were found in healthy aging older adults. Interestingly, long-term gut inflammation has been proposed to be a major contributing factor to age-related disease progression. Higher levels of blood metabolites like indoles resulting from unique gut bacterial composition metabolism may partially explain how a unique microbiome composition contributes to healthy aging.

Microbiome Uniqueness Predicts a Longer Lifespan

To pin down the long-term health implications of increased gut microbiome uniqueness with age, Price and colleagues analyzed the microbiomes from older men over the age of 78 years. They found greater microbiome uniqueness in healthy, older men whereas microbiome uniqueness was lower for individuals with worse health. The researchers also found that for individuals over the age of 85 years, the risk of death decreased with more unique gut microbiomes. Aged individuals with higher levels of the core gut bacteria species Bacteroides had a higher chance of death, also, meaning that increased microbiome uniqueness and loss of Bacteroides bacterial composition can predict healthy aging and reduced risk of death.

(Wilmanski et al., 2021 | Nature Metabolism) Survival during aging increases substantially with loss of the core bacterial microbiome species Bacteroides and increased microbiome uniqueness. Healthy, aged individuals lose Bacteroides bacterial species microbiome abundance with passing years (A, left). The rest of the cohort not classified as healthy did not lose Bacteroides abundance with age (A, right). Over the course of a four-year follow-up, individuals with low Bacteroides survived more than high Bacteroides individuals (B), and those with greater gut bacteria uniqueness lived longer (C).

“We show two distinct aging trajectories: 1) a decline in core microbes and an accompanying rise in uniqueness in healthier individuals, consistent with prior results in community-dwelling centenarians, and 2) the maintenance of core microbes in less healthy individuals,” said Price and colleagues in a press release.

Using These Findings to Develop Lifespan-Extending Techniques

As our understanding of the aging gut and microbiome expands, the need for monitoring and modifying them to promote healthy aging and longevity will, too. Findings from this study may result in the development of new techniques to examine and modify the microbiome, which could have substantial implications for the world’s aging population.