Gut microbiome and aging: Physiological and mechanistic insights

Abstract

The development of human gut microbiota begins as soon as the neonate leaves the protective environment of the uterus (or maybe in-utero) and is exposed to innumerable microorganisms from the mother as well as the surrounding environment. Concurrently, the host responses to these microbes during early life manifest during the development of an otherwise hitherto immature immune system. The human gut microbiome, which comprises an extremely diverse and complex community of microorganisms inhabiting the intestinal tract, keeps on fluctuating during different stages of life. While these deviations are largely natural, inevitable and benign, recent studies show that unsolicited perturbations in gut microbiota configuration could have strong impact on several features of host health and disease. Our microbiota undergoes the most prominent deviations during infancy and old age and, interestingly, our immune health is also in its weakest and most unstable state during these two critical stages of life, indicating that our microbiota and health develop and age hand-in-hand. However, the mechanisms underlying these interactions are only now beginning to be revealed. The present review summarizes the evidences related to the age-associated changes in intestinal microbiota and vice-versa, mechanisms involved in this bi-directional relationship, and the prospective for development of microbiota-based interventions such as probiotics for healthy aging.

Lactobacillus and Bifidobacterium Improves Physiological Function and Cognitive Ability in Aged Mice by the Regulation of Gut Microbiota

“…The change of microbial composition is always accompanied with significant functional alteration . Although Lactobacillus and Bifidobacterium treatment affected different aspects of functions in gut microbiota, the anti‐aging effects of both probiotics were similar in our study, suggesting different probiotic strains may act through different mechanisms and pathways.…”

“…Various theories have been proposed for the cause of aging, suggesting that different and complicated mechanisms underlie the process of aging . Studies have found that oxidative stress, DNA damage, and inflammation play pivotal roles in age‐associated decline of physiological, genomic, metabolic, and immunological functions . Therefore, anti‐aging therapy and agents targeting these theories are developed, which have dramatically improved human life expectancy .…”

“…Probiotics, which restore and/or maintain the homeostasis of gut microbial ecosystem, can be particularly crucial during old age, and thereby could be used as preventive and/or therapeutic strategy for promoting longevity. Increasing evidences have supported the benefits of probiotics in elderly people, which mainly include protecting against pathogens, regulating immune response, enhancing barrier functions, preventing gastrointestinal disease, attenuating inflammation, and oxidative stress .…”

Microbial Metabolites and Intestinal Stem Cells Tune Intestinal Homeostasis

“…[ 16,165 ] In line with this, alterations in the intestinal epithelial physiology, as well as gut microbiota composition and metabolite production, accompany the aging process. [ 166,167 ] Accumulating evidence suggests the aged intestinal epithelium—instead of being hypo‐proliferative as suggested by instinct—contains more proliferating cells and has a higher proliferation rate. [ 168–171 ] Concomitantly, there is also an increase in apoptosis in the stem cell population, [ 170,171 ] and a retarded response to fasting or irradiation‐induced damage.…”

“…[ 174,175 ] Multiple factors contribute to these age associated changes in gut microbiota and its metabolic repertoire, including changes in lifestyle, dietary habits, lack of mobility, compromised immunity, and reduced intestinal functionality. [ 167 ] Rampelli et al., for example, found that microbial genes for tryptophan metabolism, involved in the production of indole derivatives or other tryptophan metabolites, are enriched in aged groups compared to young controls. [ 18 ] Apart from microbial pathways, the main host mechanism for tryptophan metabolism is the kynurenine pathway that degrades tryptophan to kynurenine via the enzyme indoleamine 2,3‐dioxygenase (IDO).…”