Feces of Centenarians

Interestingly, there were similarities in the microbiomes of Chinese and Italian centenarians, suggesting that there may be certain universal characteristics of a longevity-promoting microbiome. For example, centenarians have up to 15-fold higher levels of butyrate producers.

In a study of several dozen 105- to 109-year-olds, increased levels of bacteria such as bifidobacteria and Akkermansia were found, which are associated with health. In vaginally delivered and breastfed infants, bifidobacteria make up up to 90 percent of the gut bacteria, but this share can drop to under 5 percent in adults, and even lower in older people and those with chronic inflammatory bowel disease. But centenarians have a higher proportion of beneficial bacteria in the gut.

Bifidobacteria are often used as probiotics, but their postbiotics may have anti-aging effects. Bifidobacterium is one of the many bacteria that secrete “exopolysaccharides”—a scientific-sounding term for slime. This is what dental plaque consists of, the biofilm that bacteria form on our teeth. Exopolysaccharides produced by a bifidobacterial strain from the feces of centenarians showed anti-aging effects in mice by reducing the accumulation of age pigments in the brain and increasing the antioxidant capacity of the blood and liver.

Akkermansia muciniphila is named after the late Dutch microbiologist Antoon Akkermans; the second part comes from Latin and Greek and means “mucus lover.” This bacterial species is the dominant colonizer of the protective mucus layer in the intestine, which is secreted by the intestinal mucosa. Unfortunately, this mucus layer becomes thinner and thinner with age, a problem that is further exacerbated by a low-fiber diet. When we eat a low-fiber diet, we starve our microbial self. And then the depleted bacteria of our gut flora have to compete for scarce resources and draw on the mucus barrier as an alternative energy source, for example, which weakens our defenses. In mice that received human microbiomes with a high-fiber diet versus one without fiber, the erosion of the mucus barrier by gluttonous bacteria can be switched on and off from day to day. This can even be demonstrated in a Petri dish. Researchers created layers of human intestinal cells and showed that dripped-on fiber (from green bananas and broccoli) in customary dietary doses “significantly reduced” the number of E. coli bacteria that penetrated the mucus barrier. In addition to high-fiber foods, A. muciniphila directly helps restore the protective layer by stimulating mucus secretion.

A. muciniphila is a likely candidate for a biomarker indicating healthy aging, because it is abundant in centenarians and particularly scarce in frail older people. In a comparative study, the microbiomes of people between 70 and 90 were examined who aged “healthily” versus “unhealthily,” defined by whether they had cancer, diabetes, heart, lung, or brain diseases. Akkermansia, the bacterial species most strongly correlated with healthier aging, was found three times as often in stool samples from the healthily aging cohort as in those from the participants who did not age healthily. In centenarians, a decline in A. muciniphila is a microbiome change that occurs about seven months before death, even though there are seemingly no changes in physical condition, food intake, or appetite at that time. To demonstrate its causal role in aging, the researchers showed that administered A. muciniphila significantly extended lifespan in mice with accelerated aging.

Cause, Effect, or Confounder?

In studies of centenarians’ feces, a high-fiber diet is repeatedly recommended, one of the most commonly stated general recommendations for living extremely long and staying healthy. An alternative is a fecal transplant from pooled stool of centenarians. Both approaches assume that fiber-rich stool and a long life are cause and effect, but it remains highly controversial whether age-related changes in the microbiome are a cause, a consequence, or a confounder.

Aging is accompanied by dysbiosis, an unhealthy disruption of the balance of the gut flora, characterized by the loss of fiber-eating bacterial species. Rather than believing that a changing microbiome contributes to the aging process, it is easier to imagine that aging contributes to a changing microbiome. Age-related loss of taste and smell and of teeth can lead to eating less fiber-rich food and more salted, sweetened, easier-to-chew processed foods. The decline in the amount and variety of whole plant foods—the only natural source of abundant fiber—can bring about dysbiosis that leads to disability and early death. Or the lower food quality directly leads to increased susceptibility to disease, and the dysbiosis is merely an incidental side effect of the unhealthy diet.

However, aging can also be associated with dysbiosis independently of diet. Although the number of antibiotic prescriptions for children and adults through middle age has decreased in recent years, it shot up in older people. Even non-antibiotic medications can disrupt the microbiome. A study in which more than 1000 FDA-approved drugs were brought together with 40 representative gut bacterial strains found that 24 percent of drugs on the market inhibited the growth of at least one bacterial strain. Reduced physical activity can also contribute to intestinal sluggishness and stalled digestion, leaving the gut bacteria with no choice but to break down proteins and produce putrefaction after their favorite prebiotics are used up. In many nursing homes, residents receive a low-fiber diet that can contribute to the “decimation” of a healthy microbiome. Although researchers interpreted the connection between dysbiosis and frailty as meaning that poor diet leads to poor gut flora, which in turn makes people sick, the arrows of causality can point in any direction. Perhaps it is even a chicken-and-egg cycle. With so many related factors, you can imagine how difficult it is to analyze the causal chain of events.

These questions keep coming up in microbiome research. For example, centenarians’ microbiomes not only digest fiber better. They also break down industrial environmental toxins better, such as petrochemicals, food preservatives like benzoates, and naphthalene, which is used in petroleum refining, as well as haloalkanes, which are widely used as flame retardants, refrigerants, propellants, and solvents. None of these detoxification pathways were found in the microbiomes of the Hadza, one of the last hunter-gatherer tribes in Africa. Did better detoxification in centenarians’ guts (compared to younger people) contribute to their longevity, or did their longevity contribute to their better detoxification (given their age-related longer exposure to and accumulation of chemicals)?

The microbiomes of 100- to 110-year-olds can metabolize plant fats better than animal fats, but perhaps that is only because they eat a more plant-based diet. The centenarians in Bama County, the region with particularly long-lived people, whose microbiomes were found to have such an enormous share of fiber-eating bacteria, ate over 70 percent more fiber compared to the 80- to 99-year-olds in the same region (38 grams versus only 22 grams per 2000 calories). The only way to find out whether their long life with a healthy diet merely led to a better microbiome, or whether their better microbiome concretely contributed to them living longer, is to study it.