Go With Your Gut: Study Finds Unique Microbiomes Predict Lifespan in Older Adults

Within the intricate folds of the five-foot-long tube in our guts known as the large intestine lives upwards of 100 trillion bacteria. Hosting approximately 4,000 different species, our large intestine, also known as the colon, is prime real estate for microbes, both good and bad. Referred to as the gut microbiome, this collection of bacteria that resides in our intestinal tracts can be imagined as a lush rainforest — just as a rainforest requires a diversity of plants and animals to flourish and remain in balance, our microbiome also needs a wide variety of bacterial species to thrive. 

Once thought to solely play a role in digesting food and synthesizing certain vitamins, research over the past two decades has exploded with new insights into how these microbes affect human health. From autoimmune disorders to Alzheimer’s disease to aging, there is no organ or system in the body that is not affected by the ecosystem of these minuscule organisms that we carry with us. In a recent study published in Nature Metabolism, a Seattle-based team from the biomedical research organization ISB focused on just one aspect of the microbiome: its role in aging and longevity — and how developing a unique array of gut microbes extends lifespans and contributes to better health in older adults. 

The Changing Landscapes of Aging Microbiomes

The quantity and diversity of bacteria in our microbiomes can vary widely from person to person. Starting at birth, each microbiome begins its unique journey, being altered along the way by dietary and lifestyle habits, environmental conditions, age, and medications. It can even change based on which people — or animals — you share your home with. 

Despite these person-to-person differences, each individual microbiome tends to stay relatively stable in terms of the species it houses for most of its life. However, upon reaching mid-to-late adulthood, the microbes in our guts start to shift. Rather than most of the species being made up of Bacteroides — one of the “core bacteria” that humans have in common — healthy older adults will begin to have more unique bacterial signatures that diverge from the core species. And this uniqueness is important — the guts of semi-supercentenarians (people who live to be 105 years old) show much higher levels of bacterial diversity. 

Conversely, a lack of this microbial uniqueness with age has been associated with increased frailty and physiological decline in older adults.  Although we now know much more about the microbiome than years past, it’s still relatively unknown when these age-related changes to the microbiome start to occur and what impact it has — until now, with this research authored by Wilmanski and colleagues.

Uniquely Linking Lifespan and Gut Bacteria 

In this study, the research team looked at the microbiome profiles of over 9,000 adults from three different cohorts, ranging in age from 18 to 101 years. As previous research has been limited by much smaller sample sizes, this study provides microbiome- and longevity-related data from the largest group of older adults to date. After analyzing microbial and clinical markers, the researchers found that healthy older adults will start to see a shift in their microbiome between age 40 and 50, with the biggest change being a reduction in Bacteroides and an increase in more unique bacterial species. However, it doesn’t stop at age 50 — the microbiome will continue to become more diverse with each passing decade in a healthy adult. 

This microbial uniqueness also translated to better health, as older adults with more diverse microbiomes had lower LDL (“bad”) cholesterol and triglycerides with higher vitamin D levels. Conversely, older adults who were less healthy, which was measured by walking speed, mobility scores, and medication use, did not see this microbial shift and had correspondingly worse clinical markers. 

Notably, this depletion of Bacteroides with an increase in more unique bacterial species correlated with increased lifespan. In a smaller sample of community-dwelling older adults (i.e., not living in a nursing home or hospital), the research team found that low microbial uniqueness was significantly linked to an increased risk of dying from any cause, with an even stronger association found in those over age 85. However, this microbial uniqueness and its associated longevity boost only applied to healthy individuals. Older adults who were deemed ‘unhealthy’ had less diverse microbial makeups and no increase in lifespan, suggesting that a unique microbiome not only reflects a longer life, but also contributes to it. 

From Microbes to Metabolism

In addition to supporting longer lives, unique microbial signatures were also linked to increased levels of several metabolites, or small compounds that are byproducts of metabolism. Two of these metabolites, indole and phenylacetylglutamine, were found to be significantly associated with better health outcomes. Metabolism of the amino acid tryptophan creates the byproduct indole, which has been linked to increased lifespan in animal studies, reduced inflammation, and improved immune and physical function in older adults. Similarly, the metabolite phenylacetylglutamine, derived from the amino acid phenylalanine, showed the strongest link with microbial uniqueness in this study. This has been corroborated with previous research that found higher phenylacetylglutamine levels in the blood of centenarians.

Until now, the limited research on microbial shifts with age has been small and inconsistent in terms of which bacterial species grow or decline in older adults. Based on the larger scope of this study, Dr. Sean Gibbons, a corresponding author of this study, summarizes, “Our work, which is the first to incorporate a detailed analysis of health and survival, may resolve these inconsistencies. Specifically, 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.”

You Are What Your Microbes Eat

In this study, the ISB research team provides evidence for the importance of maintaining healthy and unique microbiomes with age. Although microbial uniqueness beginning in our 40s and 50s is key for long lifespans and healthspans, creating a diverse microbiome is possible at any age. This could have potentially wide-reaching implications for older adults’ health and longevity, with Wilmanski and colleagues concluding, “As our understanding of the aging microbiome increases, monitoring and identifying modifiable features that may promote healthy aging and longevity will have important clinical implications for the world’s growing older population.” 

With this research comes an increased understanding of how the human microbiome changes with age — and how those changes affect health and longevity. To join the ranks of supercentenarians living to 110 and beyond, don’t forget to pay attention to the trillions of microorganisms we host in our guts. After all, it’s not just “you are what you eat,” but rather, “you are what your microbes eat.” 

References: 

Collino S, Montoliu I, Martin FP, et al. Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism. PLoS One. 2013;8(3):e56564. doi:10.1371/journal.pone.0056564

Sender R, Fuchs S, Milo R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol. 2016;14(8):e1002533. Published 2016 Aug 19. doi:10.1371/journal.pbio.1002533

Sonowal R, Swimm A, Sahoo A, et al. Indoles from commensal bacteria extend healthspan. Proc Natl Acad Sci U S A. 2017;114(36): E7506-E7515. doi:10.1073/pnas.1706464114

Wilmanski T, Diener C, Rappaport N, et al. Gut microbiome pattern reflects healthy aging and predicts survival in humans. Nat Metab. 2021;3(2):274-286. doi:10.1038/s42255-021-00348-0