Centenarian Microbiomes: Lessons on Gut Health, IBS, and Longevity

Background

People who live to 100 or beyond, also known as centenarians, fascinate researchers and clinicians as examples of health and longevity. Not only have these individuals surpassed expected lifespan by a considerable margin, but they often live healthy lifestyles and exhibit traits that are indicative of mental, social, and emotional well-being. Centenarians maintain a high quality of life, can live independently, and remain cognitively sharp beyond many of their peers  [1].  Biological age assessments among centenarians suggests their cells and biological systems are considerably younger biologically than they are chronologically [2], yet investigators continue to study this group globally to learn more about what primary contributors influence their longevity success.

Interestingly, recent research findings indicate many centenarians’ gut microbiomes resemble those of much younger individuals [3]. This discovery has sparked interest in the gut microbiome as a potential contributor to healthy aging and resilience against age-related diseases [4,5,6]. Some evidence points to microbiome diversity as an important factor. A 2022 study, for example, found that older individuals had more diverse gut microbiomes than younger ones [7]. This could possibly be linked to early-life environmental exposures, such as growing up on farms without sewer systems, resulting in later-life resilience. Studying the gut microbiomes of centenarians may give us clues about aging biology, the gut microbiome, and microbiome dysbiosis-associated health conditions, like irritable bowel syndrome (IBS). These findings encourage us to ask: what can the guts of centenarians teach us about aging well?

The Gut Microbiome and Aging

The gut microbiome is the ecosystem of microbes, including bacteria, archaea, fungi, and viruses, that live within your digestive tract. These trillions of microorganisms play a vital role in your digestive and overall health, including breaking down food, modulating metabolism, producing vitamins, regulating the immune system, producing hormones, and even promoting mental health and brain wellness [8].

This pluripotent network of living organisms is also highly sensitive and directly reflects an individual’s lifestyle, diet, and environment. It is easily modified alongside changes in these factors, which can have both positive and negative consequences, depending on what lifestyle changes occur. For example, increased consumption of dietary fiber can support the growth of beneficial bacteria, which then ferment fiber into short-chain fatty acids (SCFAs) such as butyrate, acetate, and propionate. These are compounds known to have anti-inflammatory effects while strengthening the gut barrier [9]. Conversely, high-fat, low-fiber diets may promote harmful, pro-inflammatory species [10]. 

Microbiome dysbiosis occurs when the microorganism community is imbalanced, which may include a loss of beneficial bacteria, an increase in harmful microbes, or even a loss of diversity. Antibiotics, stress, diet, or infection can all lead to this, and microbiome dysbiosis can cause digestive issues, but also inflammation, a weakened immune system, metabolic disorders such as obesity or type 2 diabetes, and mental conditions like depression or anxiety. Emerging evidence also links dysbiosis with neurodegenerative diseases such as Parkinson’s and Alzheimer’s [11]. 

The gut microbiome typically changes throughout the course of aging, with infant microbiomes rapidly diversifying and adapting to the environment in the first three years of life, then becoming more stable through early and middle adulthood. Once individuals reach late adulthood, microbiome diversity tends to decrease, and potentially be weakened by pathogens or pro-inflammatory bacteria, which may lead to dysbiosis and attributed health consequences. Dysbiosis can be either transient, which is reversible and arises from short-term disruptions such as antibiotic use, acute illness, or dietary changes, or chronic. Chronic dysbiosis involves long-term imbalances in microbial communities that contribute to persistent low-grade inflammation, impaired nutrient processing, and a weakened immune response. Over time, these disruptions may accelerate biological aging and increase vulnerability to age-related diseases such as metabolic disorders or neurodegeneration.

However, we’re learning that not all aging microbiomes follow the same path. Some older adults, including centenarians, maintain highly diverse and resilient microbial communities, which may contribute to their health and longevity [4]. 

Breakthrough Research: Centenarian Microbiome Profiles

A breakthrough study out of Barcelona, published as a preprint in February 2025, details the genetic and microbiome profile of Maria Branyas Morera, an American–Spanish supercentenarian who lived to 117 years and 168 days [12]. Supercentenarians are individuals who live beyond 110 years and are a rarity in the human population — in 2024, the number of centenarians worldwide was approximately 772,000 [13]. They represent a unique biological model for studying extreme longevity, particularly because many maintain cognitive function and a relatively high quality of life until the very end of life.

Through microscopic and molecular investigation, the research team painted a complete picture of age and health using blood, saliva, urine, and stool samples, comparing these findings with healthy, non-centenarian control populations. Microbial diversity was assessed through 16S rRNA gene sequencing, measuring both alpha diversity (richness and evenness within the gut microbiome) and beta diversity (differences in microbial composition compared to controls)  [12]. Distinctiveness was further evaluated by identifying taxa that were either enriched or depleted relative to both age-matched and younger populations.

Findings of note included her biological age, calculated using the estimated DNA methylation age of three tissues across six different calibrated epigenetic clocks (biological timekeepers that estimate physiological age). Her biological age—ranging from 83.89 to 107.90 years—was significantly younger than her chronological age. This suggests that not only did Maria live long, but she may have biologically aged more slowly.

Maria’s microbiome composition was also striking, particularly when compared to a control population of individuals aged 61 to 91 years [12]. Her microbiome exhibited a higher overall within-sample diversity, as well as a clearly distinctive microbial profile compared to controls. Higher microbial diversity is widely associated with greater resilience to disease, improved metabolic health, and reduced systemic inflammation — all hallmarks of healthy aging.

She also had elevated levels of Bifidobacterium compared with controls, a highly beneficial bacterial genus typically declining with age. Bifidobacterium species produce short-chain fatty acids (SCFAs), particularly acetate, which help maintain the integrity of the intestinal barrier and reduce pro-inflammatory cytokine production [9,14]. These mechanisms help limit systemic low-grade inflammation, a key driver of age-related disease.

Taking a Bifidobacterium probiotic is an increasingly popular intervention to slow age-related disorders. These probiotics are now being studied for their effects on age-related cognitive decline, metabolic diseases, and even frailty, with several clinical trials underway globally [15]. Early clinical findings suggest that certain Bifidobacterium strains may improve cognitive function in older adults, with benefits observed in memory, orientation, and even slower brain atrophy progression in those with mild cognitive impairment  [16,17].

Additionally, her microbiome had lower levels of Clostridium than the younger control sample, another common microbiome bacterium associated with inflammatory, aging-associated diseases. Certain strains within the Clostridium genus can produce toxins that damage intestinal cells and increase gut permeability (“leaky gut”), allowing inflammatory molecules to enter circulation. This can trigger chronic immune activation and contribute to low-grade inflammation and neuroinflammation, both linked to neurodegenerative risk [18]. 

Together, these findings highlight the opposing roles these genera can play in modulating inflammation and the microbiome composition associated with healthy aging. Bifidobacterium acts as a protective, anti-inflammatory agent supporting gut and systemic health, while certain Clostridium strains promote inflammation and barrier dysfunction that may accelerate aging-related pathology.

A profile of her dietary behavior over the past 20 years revealed that she consumed three yogurts per day and followed a Mediterranean diet, both of which may have contributed to her unique microbiome profile. The Mediterranean diet and yogurt are rich in prebiotics, probiotics, fiber, and polyphenols—elements shown to nourish beneficial bacteria [19].

Centenarians Around the Globe

A comparative study, which looked at the gut microbiota of centenarians around the globe alongside that of individuals aged 25-45, demonstrated that centenarians have distinct microbes, and the study team was able to identify specific markers related to healthy aging [20].

First, these researchers identified a population in India with a high centenarian prevalence, as well as a comparison population of younger individuals in a region with low centenarian prevalence. They found that the centenarian gut microbiome composition was different from that of the younger sample, despite regional similarities. These differences included both taxonomic diversity and the presence of unique microbial strains, suggesting that long life may be associated with a particular microbial ecosystem.

To validate these results and potentially identify microbiotic biomarkers of healthy aging across populations, the researchers then conducted a meta-analysis with the findings of other global studies in Italy, Japan, and China (125 centenarians) [20]. 

They found that, despite nationality, the centenarians had a higher level of biodiversity than the younger adults. This consistent finding across geographically and culturally diverse cohorts indicates that a diverse gut microbiome may be a universal hallmark of longevity, regardless of diet, lifestyle, or genetic background.

Furthermore, similar potential signatures of healthy aging across the populations were associated with specific microbiome inhabitants, including Akkermansia, Alistipes, and Ruminococcaceae D16. These specific genera have been independently associated with beneficial effects, including enhanced gut barrier integrity, anti-inflammatory activity, and improved metabolic function [21,22,23]. For example, Akkermansia muciniphila is known to degrade mucin in the gut, stimulating mucus layer renewal and promoting tight junction protein expression, all of which enhance gut barrier integrity [21]. Alistipes species have been reported to generate anti-inflammatory metabolites, and members of Ruminococcaceae are key butyrate producers, which strengthens intestinal barrier junctions [22,23].

These findings may reflect an omnipresent series of changes in the microbiome associated with extreme aging that may potentially protect individuals throughout aging via anti-inflammatory or advantageous metabolic pathways, such as lipid metabolism [24]. As such, these microbial signatures could one day serve as predictive tools or therapeutic targets to promote healthier aging and reduce age-related disease risk through microbiome-centered interventions.

Microbial Biomarkers of Healthy Aging

The findings across these two studies have interesting implications for longevity, healthy aging, and gut health. Certain microbial taxa, which are consistently present across individuals over the age of 100, may reflect a microbial signature of aging, independent of genetics or geography. This suggests that the gut microbiome may not just be a byproduct of aging but an active participant in the aging process.

Alongside these taxa, future work is warranted looking at microbial metabolites (or the small molecules produced by these microbes), to further investigate their role in maintaining the gut barrier, controlling inflammation, and potentially even neuroprotection. 

Metabolites such as short-chain fatty acids (e.g., butyrate) and bile acids have already been implicated in host–microbiome communication and are likely candidates for mediating the observed benefits [25]. Butyrate, in particular, acts as a histone deacetylase (HDAC) inhibitor, influencing gene expression in ways that reduce inflammation, and serves as a primary energy source for colonocytes, which help to maintain the epithelial barrier integrity of the intestinal tract and prevent the migration of pathogens or toxins into the body [26]. Understanding how these compounds interact with host physiology could open new therapeutic avenues for preventing age-related diseases such as cognitive decline, frailty, or chronic inflammatory conditions.

In addition to specific biomarkers, the overall presence of high microbial diversity in these populations may reflect other mechanisms of healthy aging, like resilience to dietary changes and stress, as well as the role of lifestyle in gut health. Greater microbial diversity is generally associated with a more robust and adaptable microbiome, which may help centenarians resist disturbances such as infection, medication, or dietary shifts.

Dysbiosis and IBS

Let’s connect these findings back to common gut concerns we experience in day-to-day life. A diverse, flourishing gut microbiome is essential for healthy aging, though in younger, Western and industrial populations, we see a growing rate of gut dysbiosis and associated health concerns, such as irritable bowel syndrome (IBS). This increasing dysbiosis stands in stark contrast to the microbiomes of long-lived populations, where high microbial diversity and the presence of anti-inflammatory taxa appear to support longevity and gut integrity. 

Irritable bowel syndrome is a disorder of gut-brain interaction, where individuals experience abdominal pain and changes in bowel habits. There is a 10-15% prevalence of IBS in the United States, and the condition widely impacts individuals across the ages of 20-65 [27]. The rate of IBS is growing worldwide, particularly alongside industrialization processes [28]. 

IBS patients’ microbiome profiles differ from those of healthy controls, showing lower levels of overall diversity, lower levels of healthy bacteria, and distinct microbes [29]. IBS patients also have lower levels of Bifidobacterium, the healthy genus attributed to anti-inflammation, though lowers with age [30]. These IBS microbial profiles lead to visceral hypersensitivity and low-grade inflammation in IBS patients. 

The gut-brain axis is central to IBS symptoms, meaning the discomfort and bowel changes are not “all in the patient’s head.” Dysbiosis can alter gut signaling, neurotransmitter levels, and inflammation, which together influence pain perception and bowel function [31]. Modulating the microbiome through diet, probiotics, prebiotics, synbiotics, or even fecal microbiota transplantation has shown some promise in reducing IBS symptoms, although responses vary between individuals [32,33,34].

Interventional studies in humans have tested specific diets, such as the low FODMAP diet, and supplementation with Bifidobacterium or multi-strain probiotics, showing improvements in abdominal pain, bloating, and bowel habits [35]. Exercise has also been linked to modest improvements in gut microbial diversity and IBS symptoms [36]. While these approaches can help manage symptoms, a full “cure” is not guaranteed, as IBS involves complex gut-brain interactions.

In this way, IBS may represent a modern microbial signature of chronic inflammation and disrupted gut-brain signaling, conditions also implicated in age-related diseases. Our Western lifestyles reduce microbial richness, which may possibly contribute to both IBS and accelerated aging, particularly in the context of reduced helpful bacteria like Bifidobacterium. 

The Future of Microbiome & Longevity Interventions 

These studies provide vital first line evidence that there are distinct gut-microbiome profiles related to healthy aging. From overall diversity to increased quantities of certain taxa shown to have health benefits, despite geographic or genetic origin, centenarians are demonstrating consistent microbiome trends. These findings underscore the importance of the gut microbiome not just as a byproduct of aging, but as an active participant in the aging process, potentially mediating inflammation, immune function, and even neuroprotection.

Let’s look at how this research could shape future gut-health supplements. For example, microbiota modulation during mid-life, in both IBS and healthy patients, can expand beyond Bifidobacterium, a recognized and widely adopted microbiotic longevity intervention, and can use specific pre- and pro- biotic blends inspired by centenarian microbiome profiles and lifestyles. Rather than viewing interventions as one-size-fits-all, tailoring strategies to age-specific microbial vulnerabilities, like restoring butyrate producers, may offer targeted ways to preserve both gut and cognitive health.

Future research may also look into fecal microbiota transplant (FMT) from healthy aging donors. Preclinical models offer a promising precedent for future research. In mice, FMT from young donors significantly improved cognitive function, reduced systemic and neuroinflammation, and even reversed aging-related declines in locomotor and exploration behaviors [37]. Early pilot studies in humans should evaluate the cognitive, inflammatory, and gut-symptom outcomes, providing further evidence for certain taxa and longevity. 

Longitudinal studies tracking gut composition across the life course, especially in relation to modifiable lifestyle factors like diet, physical activity, and antibiotic exposure, will also be essential. One foundational example worth building upon is the Pioneer 100 Wellness Project. This study monitored the microbiomes, metabolomics, and clinical markers of 101 individuals and identified associations between gut microbial states and health biomarkers. This work revealed that people can transition between different microbial profiles depending on health and lifestyle changes [38]. 

Given the overlap in microbial depletion seen in both IBS and aging populations, including reductions in beneficial genera like Bifidobacterium, addressing gut dysbiosis in IBS patients may offer dual benefits: symptom relief and decelerated aging. 

Implications for Your Gut Health and Longevity 

Ultimately, by decoding the microbial hallmarks of healthy aging, we open new possibilities for preventive medicine, leveraging gut ecology not only to treat disease, but also to extend healthspan. Research into the centenarian microbiome provides intriguing clues about how gut health may support healthy ageing. While there is no single “ideal” microbiome to strive for, centenarians often share features such as higher microbial diversity and greater abundance of short-chain fatty acid (SCFA) producers, resulting in a more resilient and stable microbe composition. This correlation suggests that aiming for diversity and stability may be more meaningful than targeting a specific set of microbes.

For individuals wondering about their own microbiome composition, like whether it is diverse, there are commercial tests available. The current options on the market provide broad profiles of the microbiome makeup, so they are not yet capable of diagnosing health issues or predicting longevity. 

Regardless of test results, lifestyle factors known to promote microbial diversity, including diets rich in fiber, regular physical activity, and limited unnecessary antibiotic use, remain the strongest evidence-based strategies for supporting gut health. Dietary patterns like the Mediterranean diet, which emphasize whole grains, legumes, vegetables, fruits, nuts, and healthy fats, have consistently been linked to a richer and more stable gut microbiota compared to Western dietary patterns [39].^, Conversely, diets high in processed foods, saturated fats, and added sugars are associated with reduced diversity and inflammation-linked taxa [40].

As for supplementation, the evidence is still emerging. Some probiotic strains show promise for improving digestion or reducing inflammation, like Bifidobacterium longum BB68S, but most studies involve short-term outcomes, not aging or longevity [41]. At this stage, the most reliable strategy is to support microbial health through lifestyle, such as consuming a well-rounded diet, full of diverse fruits and vegetables, probiotic-rich foods, and healthy fats, limiting alcohol consumption, or increasing exercise. For the future, it is worth keeping an eye on research-backed discoveries regarding fecal microbiota transplantation or next-generation probiotics.

Conclusion

The study of centenarians offers a powerful reminder that longevity is not simply a matter of years lived, but of resilience sustained across systems — including the gut. Evidence that centenarians maintain diverse, balanced microbiomes suggests that microbial health may actively support healthier aging by modulating inflammation, strengthening the gut barrier, and influencing cognitive and metabolic outcomes. These findings point toward a future where cultivating microbial diversity is recognized not only as a digestive health goal but also as a cornerstone of preventive longevity strategies.

While the science is still evolving, the message is clear: lifestyle choices that nourish the gut — from fiber-rich diets and probiotic foods to regular movement and mindful antibiotic use — remain the most reliable path to microbial vitality. As research progresses, microbiome-inspired therapies may expand our toolkit for promoting both gut health and lifespan, but the centenarians’ example underscores that everyday practices already carry meaningful power to support healthspan.