The Gut Microbiome Changes Over the Course of Aging

This short open access review is a good introduction to what is known of the changes to the microbial population of the gut that take place over the course of aging. Collectively, the activity of gut microbes is influential on health, arguably to a similar degree as exercise, though far less well quantified at this time. Altering the distribution of bacterial populations in older animals, to better resemble what is observed in young animals, leads to benefits to health, for example. Some of the specific mechanisms by which beneficial gut microbes improve health are being uncovered, such as the secretion of propionate, a compound now being developed as a dietary supplement. Much more remains to be established, of course; this is a part of the broader field still in its comparative infancy.

Dwelling at the interface between host epithelia and the external environment, commensal microbes actively modulate development, nutrient absorption, and disease onset in the host. Host metabolism is significantly modulated by commensal microbes, and the gut microbial composition significantly affects blood metabolite composition. Just as the composition of the microbiota varies within and between tissues, microbial consortia do also vary through time within individual tissues. Although individual gut microbiota are largely unstable in the first years of life, they become more stable during adulthood and undergo dramatic changes in richness and composition upon onset of disease and frailty. The onset of specific diseases, such as cancer, obesity, diabetes, or inflammatory bowel disease, is associated with specific microbial signatures.

Studies in humans and laboratory model organisms, such as flies, fish, and mice, have additionally shown that the composition of the gut microbiota dramatically changes during aging and is associated with host health and life span. In mice, e.g., lipopolysaccharide (LPS) from gut microbiota can accelerate age-dependent inflammation ("inflammaging"), and mice lacking Toll-Like receptor 4 (TLR4), which is the LPS receptor, are protected from age-dependent inflammation, showing that a microbial-specific substrate induces aging-specific phenotypes. Inflammaging can be further exacerbated in germ-free mice by gut microbiota transfers from aged donor mice, showing a direct causal relation between age-specific microbial communities and host aging.

Using deep learning to analyze human microbiome data helped build a human microbiome aging clock, which predicts host age with an accuracy of about four years. While during adulthood microbial composition contributes to cellular and tissue homeostasis, age-dependent changes in the microbial composition may contribute to increasing frailty and disease onset in later life. The causes leading to the changes in microbiota composition and function during host aging are still poorly understood and possibly include direct or indirect microbial selection by the host and microbe-microbe interactions, as well as microbial evolution.



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