SEATTLE, February 18, 2021 / PRNewswire / – The gut microbiome is an integral part of the body, but its role in human aging is unclear. ISB researchers and their co-workers have identified different signatures in the gut microbiome that are associated with either healthy or unhealthy aging patterns, which in turn predict survival in a population of older people. The work is published February 18 in the journal Nature Metabolism. (After publication, the article can be found here.)
The research team analyzed gut microbiome, phenotypic and clinical data from over 9,000 people between the ages of 18 and 101 years in three independent cohorts. In particular, the team focused on longitudinal data from a cohort of over 900 shared elderly people (78-98 years of age) that they could use to track health and survival outcomes.
The data showed that gut microbiomes became increasingly unique (that is, increasingly different from others) with age from mid-to-late adulthood, reflecting a steady decline in the frequency of core bacterial genera (e.g., Bacteroides) shared between people.
It is noteworthy that in healthy aging, the microbiomes became increasingly unique to each individual, while the metabolic functions that the microbiomes performed shared characteristics. This signature of gut uniqueness was strongly correlated with several microbially derived metabolites in blood plasma, including one – tryptophan-derived indole – previously shown to extend the lifespan of mice. Blood levels of another metabolite – phenylacetylglutamine – showed the strongest association with uniqueness, and previous work has shown that this metabolite is indeed greatly elevated in centenarians’ blood.
“This signature of uniqueness can predict patient survival in the last few decades of life,” said ISB research scientist Dr. Tomasz Wilmanskiwho led the study. Healthy individuals around the age of 80 showed a sustained microbial drift towards a unique compositional state, but this drift was absent in less healthy individuals.
“Interestingly, this uniqueness pattern appears to begin in mid-life – 40-50 years old – and is associated with a distinct metabolomic signature of the blood, suggesting that these microbiome changes are not only a diagnosis of healthy aging, but also contribute to it can go straight to health as we get older, “said Wilmanski. For example, indoles are known to reduce inflammation in the bowel and chronic inflammation is believed to be a major driver of the progression of age-related morbidities.
“Previous results in microbiome aging research appear to be inconsistent. Some reports show a decline in nucleus genus in hundred-year-old populations, while others show relative stability of the microbiome until the onset of age-related health decline,” said microbiome specialist Dr. . Sean Gibbons, corresponding author of the paper. “Our work, which is the first to include a detailed analysis of health and survival, can resolve these inconsistencies. In particular, we show two different aging trajectories: 1) a decrease in core microbes and an associated increase in uniqueness in healthier individuals, consistent with previous results centenarians living in the community; and 2) nuclear microbial maintenance in less healthy individuals. “
This analysis underscores the fact that the adult gut microbiome evolves in healthy individuals with advanced age but not in unhealthy individuals, and that microbiome compositions associated with health in early to middle adulthood may not be compatible with health in late adulthood are.
“This is exciting work that we believe will have significant clinical implications for monitoring and modifying gut microbiome health throughout a person’s lifetime,” said ISB Professor Dr. Nathan Price, corresponding author of the paper.
This research project was carried out by ISB and staff at Oregon Health and Science University. University of California San Diego, University of Pittsburgh, University of California Davis, Lifestyle Medicine Institute and University of Washington. It was supported in part by a Catalyst Award for Healthy Longevity from the National Academy of Medicine and the Longevity Consortium of the National Institute on Aging.
About ISB
The Institute for Systems Biology (ISB) is a collaborative and interdisciplinary non-profit biomedical research organization based in Seattle. We focus on some of the most pressing human health issues including aging, brain health, cancer, COVID-19, sepsis, and many infectious diseases. Our science is translational and we are committed to in-depth scientific research that leads to real clinical impact. ISB is a subsidiary of providence, one of the largest not-for-profit healthcare systems in The United States. Follow us online at www.isbscience.org as well as on Facebook and Twitter.
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