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Longevity of centenarians is reflected by the gut microbiome with youth-associated signatures

Centenarians display youth-associated features in gut #microbiome such as over-representation of #Bacteroides-dominated enterotype, increase in species evenness, enrichment of potentially beneficial Bacteroidetes, depletion of potential pathobionts.



Abstract

Centenarians are an excellent model to study the relationship between the gut microbiome and longevity. To characterize the gut microbiome signatures of aging, we conducted a cross-sectional investigation of 1,575 individuals (20–117 years) from Guangxi province of China, including 297 centenarians (n = 45 with longitudinal sampling). Compared to their old adult counterparts, centenarians displayed youth-associated features in the gut microbiome characterized by an over-representation of a Bacteroides-dominated enterotype, increase in species evenness, enrichment of potentially beneficial Bacteroidetes and depletion of potential pathobionts. Health status stratification in older individuals did not alter the directional trends for these signature comparisons but revealed more apparent associations in less healthy individuals. Importantly, longitudinal analysis of centenarians across a 1.5-year period indicated that the youth-associated gut microbial signatures were enhanced with regard to increased evenness, reduction in interindividual variation and stability of Bacteroides, and that centenarians with low microbial evenness were prone to large microbiome instability during aging. These results together highlight a youth-related aging pattern of the gut microbiome for long-lived individuals.

Main

Longevity is a complex trait in which genetic, epigenetic and environmental determinants interact to extend the human lifespan to reach 100 years or beyond1. However, the concept of aging contains a paradox, which was well illustrated by Jonathan Swift: “Everyone wants to live forever, but no one wants to grow old”. Regarding the factors contributing to human health, increasing evidence has indicated that the human gut microbiome, defined by both host genetics and environmental factors, has a critical role in human metabolism, immune response and the etiology of many chronic diseases2,3. Thus, increasing attention has been recently paid to the gut microbiome’s contributions to human health, diseases and aging4,5,6. As people become older, their microbiome exhibits altered diversity compared with that of younger counterparts, with fewer beneficial microorganisms and more opportunistic pathogens7,8,9. In addition, increasing evidence suggests that the aging patterns of the gut microbiome are associated with health status10,11,12. In this regard, centenarians, who have successfully survived and evaded various chronic diseases, represent an excellent model of longevity and aging13. Investigating aging patterns of the gut microbiome in centenarians can enable a better understanding of the mechanisms underlying longevity. A number of cross-sectional studies suggested that the microbiota composition of centenarians is important in healthy aging. Examples include the work of Biagi et al., which identified a reduction in the core microbiota composition and enrichment of health-associated bacteria, including Akkermansia, Bifidobacterium and Christensenella, in the centenarian group8. Furthermore, trajectory cohort studies of individuals spanning different age groups and demographic locations showed that as people age, gut microbiome diversity declines and potential pathobionts increase; studies also suggested the existence of the gut microbiome and functional signatures that are associated with longevity14,15,16,17,18,19. Although these studies established a link between the gut microbiome and longevity, they suffered from either limited cohort sizes or the absence of a sufficiently long trajectory or longitudinal setting. Hence, further studies with more detailed comparisons, larger sample sizes, longer trajectory controls and even longitudinal settings are necessary to identify the microbiome signatures and aging patterns in centenarians, which can elucidate the relationship between the gut microbiome and longevity. In addition, gut microbiome signatures and dynamics have been further defined in several age populations by recent technological advancements in microbiome studies, such as machine learning, microbial fingerprinting and enterotype stratification20,21,22. It is important to apply these new methods to further characterize the gut microbiome of centenarians. We present a cross-sectional study with a large cohort (n = 1,575 participants), including 297 centenarians and four other age groups (20–117 years). Furthermore, we integrated a longitudinal study of 45 centenarians for 1.5 years to investigate microbial alterations. Our findings revealed that centenarians have unique enterotypes relative to their old adult counterparts, which combine signatures in young and old adult individuals and exhibit prominent features that show high similarity to young adults in terms of youth-associated microbial hallmarks (for example, high evenness, abundant Bacteroidetes and low level of potential pathobionts). Our longitudinal analysis results indicate that during the aging of the centenarians, these features continued to develop and were enhanced or conserved. In summary, our study supports the idea that longevity is associated with the gut microbiome via certain youth-associated signatures. Read more at: https://www.nature.com/articles/s43587-023-00389-y




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