Animal and human data make a compelling case for differences in the gut microbiome between individuals to contribute to variations in the pace of aging. There is an even better case for age-related changes in the relative proportions of microbial species making up the gut microbiome to accelerate degenerative aging, via loss of beneficial metabolite production and increased chronic inflammation, among other mechanisms. Most directly, fecal microbiota transplantation from young donors to old individuals produces a lasting rejuvenation of the gut microbiome that in turn improves health and extends life.
Straightforward analysis of human epidemiological data can only produce correlations between measures of health and outcomes such as mortality and disease risk. Mendelian randomization is a way to add known genetic influences on health into the mix in order to generate some support for causation from the epidemiological data. In today’s open access paper, researchers apply this strategy to the correlations between gut microbiome composition and longevity in sizable human study populations. The evidence suggests that gut microbiome differences do influence long-term health and life expectancy, as one might expect from the more direct intervention studies in animals.
Mendelian randomization analyses support causal relationships between gut microbiome and longevity
The gut microbiome plays a significant role in longevity, and dysbiosis is indeed one of the hallmarks of aging. However, the causal relationship between gut microbiota and human longevity or aging remains elusive. Our study assessed the causal relationships between gut microbiome and longevity using Mendelian Randomization (MR). Summary statistics for the gut microbiome were obtained from four genome-wide association study (GWAS) meta-analysis of the MiBioGen consortium (N = 18,340), Dutch Microbiome Project (N = 7738), German individuals (N = 8956), and Finland individuals (N = 5959). Summary statistics for Longevity were obtained from five GWAS meta-analysis, including Human healthspan (N = 300,447), Longevity (N = 36,745), Lifespans (N = 1,012,240), Parental longevity (N = 389,166), and Frailty (one of the primary aging-linked physiological hallmarks, N = 175,226).
Our findings reveal several noteworthy associations, including a negative correlation between Bacteroides massiliensis and longevity, whereas the genus Subdoligranulum and Alistipes, as well as species Alistipes senegalensis and Alistipes shahii, exhibited positive associations with specific longevity traits. Moreover, the microbial pathway of coenzyme A biosynthesis I, pyruvate fermentation to acetate and lactate II, and pentose phosphate pathway exhibited positive associations with two or more traits linked to longevity. Conversely, the TCA cycle VIII (helicobacter) pathway consistently demonstrated a negative correlation with lifespan and parental longevity. Our findings of this MR study indicated many significant associations between gut microbiome and longevity. These microbial taxa and pathways may potentially play a protective role in promoting longevity or have a suppressive effect on lifespan.
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