Healthier Old Individuals Have a More Diverse Gut Microbiome

Researchers here comment on recent discoveries regarding age-related changes in the gut microbiome. In recent years, evidence has amassed for microbes in the gut to have a meaningful influence over the pace of aging, perhaps even in the same ballpark as that of regular moderate exercise. In the same way that healthier older people tend to be fitter, healthier older people also tend to have more diverse gut microbe populations. How much of this is cause versus the consequence of other factors, such as changes in diet or loss of immune function that occur in old age, remains a topic for debate. There is, however, more than enough evidence from animal studies to suggest that reverting gut microbes to a more youthful distribution is beneficial - though the size of the effect on lifespan is likely to be much smaller in our species, as is usually the case for interventions of this nature.

The human gut harbors trillions of bacteria (known as the gut microbiota), which play important roles in health and diseases. Several recent studies have characterized the human gut microbiome in the elderly. Gut microbial diversity generally decreases when people age, which is likely due to changes in physiology, diet, medication, and lifestyles. Decreased diversity, considered an indicator of an unhealthy microbiome, has been linked to different chronic conditions such as obesity and type 2 diabetes. In addition to decreased diversity, the changes of the gut microbiome composition to an imbalanced state, i.e. dysbiosis, also correlates with frailty, inflammation, and neurodegenerative disorders.

Given the fact that most of the elderly experience gut associated comorbidities, it is extremely challenging to define a healthy gut microbiome in this population. Changes in the gut environment such as inflammation, leaky gut, production of reactive oxygen species and application of medications can all affect the gut microbiome. In that regard, centenarians have been used as a model of healthy aging because of their capability to delay or avoid chronic diseases. Therefore, the gut microbiome in this cohort might be used to define a healthy gut microbiome. The genetics, and recently epigenetics, of the centenarians have been extensively investigated, but relatively little is known about their gut microbiotas until now.

Researchers examined the gut microbiome of a cohort of healthy, long-living Chinese individuals including nonagenarians (90-99 years old) and centenarians (older than 100). They found that this cohort of long-living people possesses a more diverse gut microbiota than younger adults, contradictory to conventional views. They also found that a group of bacteria, members of which are known short-chain fatty acid (SCFA) producers such as Clostridium cluster XIVa, are enriched in the long-living Chinese. To verify their discovery, they analyzed an independent Italian data set. Consistently, the long-living Italians also had more diverse gut microbiotas than the younger group. When they combined the Italian and the Chinese data sets, they found that although the gut microbiota structures are significantly different, probably due to the differences in diet, genetics, and environment, 11 of the top 50 bacterial features that differentiate the long-living individuals from the younger group were shared.

These studies clearly revealed that more diverse and balanced gut microbiotas are present in healthy, long-living people, whereas disturbed gut microbiotas with dysbiosis are observed in the elderly who suffer from different comorbidities. We thus hypothesize that modulation of the gut microbiome to maintain a healthy gut microbiome will promote healthy aging. One rationale behind this hypothesis is inflammaging, i.e. increased chronic, low-grade inflammation in the elderly, which is associated with different chronic diseases. SCFAs are important in maintaining gut homeostasis. SCFAs provide the primary energy for colon epithelial cells and possess anti-inflammation properties. The enrichment of these SCFA producers in long-living individuals suggests that these bacteria might reduce inflammation and its resulting damage in this cohort, which likely contributed to their healthy aging.



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