Young Microbiomes in Very Old People

Research published today in Nature Aging has illustrated how the gut microbiomes of the longest-lived people are more likely to have bacterial populations associated with youth.

A known difference

This is far from the first study showing a connection between a healthy, youthful microbiome and enhanced longevity. In most people, the gut microbiome gradually transitions towards harmful bacterial populations that are linked to age-related diseases [1]. Significant previous work has been done in characterizing these differences, creating classifications based on microbial patterns (enterotypes) [2].

This study builds upon that previous work by carefully measuring and analyzing the enterotypes of centenarians in comparison to younger people, focusing on the variations and compositions of multiple bacterial species.

Robust sampling shows a late-life reversal

While this study was demographically limited in that it was confined to a community of people in Guangxi, China, the sample size was relatively large: 297 people older than 100, 301 people between 90 and 99, 386 people between 66 and 85, 277 people between 45 and 65, and 314 people btween 20 and 44 were the cohorts in this study. There was also a longitudinal analysis of 45 of the centenarians conducted 18 months after the original study.

Examining the various bacterial populations, the researchers found that it was most informative to classify the enterotypes into four groups according to the bacteria that drove them the most: Bacteroides, Escherichia-Shigella, Prevotella, and Blautia. No single one of these enterotypes had a majority among any of the age groups. Instead, Bacteroides had a roughly 44% plurality among the two younger groups, while Escherichia-Shigella had a plurality of 36.5% among the third-oldest group and 42.2% among the second-oldest group. However, this trend was reversed among the oldest age group, which had 29.6% of its members in the Bacteroides enterotype (which was far less common in the previous two) and 38.0% in the Escherichia-Shigella group.

By itself, the presence of the Bacteroides enterotype did not seem to be connected to health status in centenarians, although there did appear to be a connection in the third-oldest group; people in that group with more serious health problems were less likely to have Bacteroides enterotypes. While most centenarians are female (77.1% in this study), the researchers did not find any sex-based differences in microbiomial sampling, and differences in BMI did not explain the changes with aging.

Looking for specific taxonomic groups

The connection between gut bacteria and health became much more apparent when the researchers took a closer look at the various classifications of bacteria involved. Four bacterial groups that are associated with pathology, namely Klebsiella, Streptococcus, Enterobacter, and Rhodococcus, were found to be more likely to occur in the third-oldest group. Meanwhile, probiotic bacterial groups associated with better health, particularly B. stercoris, B. thetaiotaomicron, B. uniformis, and B. ovatus [3], were more likely to be enriched in both younger people and centenarians. Other groups associated with anti-inflammatory activities were found to be enriched in the same way.

A broad diversity of beneficial gut microbiota was found to be important in maintaining stability. The longitudinal portion of this study found that centenarians with greater species diversity were less likely to have changes to their gut microbiomes over the intervening 18 months. Centenarians also had specific biomarkers; 29 biochemical features were found to characterize a stool sample as being more likely to come from a centenarian.

Conclusion

The broad diversity of enterotypes among the differently aged populations, and the connection between enterotypes and health in the third-oldest group, implies that maintaining gut microbiome health is associated with living long enough to become a centenarian. It is not likely that people begin with enterotypes associated with youth, change in their old age, and then change back towards more youthful enterotypes as they grow even older. Rather, it is far more logical that many of the centenarians in this study never lost their youthful enterotypes to begin with; their dietary habits and other personal characteristics kept their gut microbiomes youthful. The researchers concur with this assessment:

In our study, no significant changes in Bacteroidetes abundance were observed for long-lived participants regardless of health status. This result further supports the hypothesis that centenarians maintained their gut Bacteroidetes composition.

To directly prove this association would require a large cohort that is monitored over decades, determining one’s likelihood of living to old age with a certain enterotype. However, the relationship between gut health and overall health is well-known, and this study adds to the body of evidence suggesting that gut microbiota significantly impact aging.

Literature

[1] Claesson, M. J., Jeffery, I. B., Conde, S., Power, S. E., O’connor, E. M., Cusack, S., … & O’toole, P. W. (2012). Gut microbiota composition correlates with diet and health in the elderly. Nature, 488(7410), 178-184.

[2] Costea, P. I., Hildebrand, F., Arumugam, M., Bäckhed, F., Blaser, M. J., Bushman, F. D., … & Bork, P. (2018). Enterotypes in the landscape of gut microbial community composition. Nature microbiology, 3(1), 8-16.

[3] Brown, E. M., Ke, X., Hitchcock, D., Jeanfavre, S., Avila-Pacheco, J., Nakata, T., … & Xavier, R. J. (2019). Bacteroides-derived sphingolipids are critical for maintaining intestinal homeostasis and symbiosis. Cell host & microbe, 25(5), 668-680.