Gut Microbiome

The human gut microbiota is an intricate ecosystem within the gastrointestinal tract that plays a pivotal role in health and disease. ^[1] The composition and activity of the gut microbiota codevelop with the host from birth and are subject to a complex interplay that depends on the host genome, nutrition and lifestyle. ^[2] Beyond its role in inflammatory disease, this microbial community has a beneficial role during normal homeostasis, modulating the host immune system and influencing host development, physiology and metabolism. ^[3]

The gut microbiota is involved in the regulation of multiple host metabolic pathways, giving rise to interactive host-microbiota metabolic, signaling and immune-inflammatory axes that physiologically connect the gut, liver, muscle and brain. ^[2] Short-chain fatty acids are produced by the gut microbiota during the fermentation of partially and non-digestible polysaccharides, and act through two major signaling mechanisms, inhibition of histone deacetylases and activation of G-protein-coupled receptors. ^[4] Short-chain fatty acids have anti-inflammatory, antitumorigenic and antimicrobial effects and alter gut integrity, highlighting their role as a major player in the maintenance of gut and immune homeostasis. ^[4] Compositional perturbations of the gut microbiota, termed dysbiosis, are associated with a wide range of diseases, whereas an intact microbiota contributes to host homeostasis. ^[5] The gut microbiome communicates with the brain through microbiota-derived signaling molecules, immune mediators and gut hormones as well as vagal and spinal afferent neurons. ^[6]

The gut microbiota undergoes extensive changes across the lifespan, and the gut microbiota of older people differs from that of younger adults, with changes occurring gradually with time rather than at a single chronological threshold. ^[7] Across the lifespan and especially in old age, a diverse microbiome that includes organisms suspected to produce anti-inflammatory metabolites such as short-chain fatty acids has been reported to be associated with healthy aging. ^[8] Age-related microbial dysbiosis is involved in reshaping immune responses during aging, manifesting as immunosenescence and inflammaging that accompany many age-associated enteric and extraenteric diseases. ^[9] The gut microbiota has a central role in both metaflammation and inflammaging owing to its ability to release inflammatory products and crosstalk with other organs and systems. ^[10] Gut microbiota can contribute to healthy longevity by enhancing intestinal barrier integrity, providing protection from inflammaging, ameliorating nutrient-sensing pathways, optimizing

The gut microbiota can be regulated, suggesting a potential target for aging interventions through gut-microbiota-targeted anti-aging strategies. ^[9] Prebiotics, non-digestible food ingredients that selectively stimulate the growth or activity of beneficial microorganisms, modulate the gut microbiota partly by promoting the production of short-chain fatty acids. ^[1] A direct causal relationship between dysbiosis and inflammatory bowel disease has not been definitively established in humans, and evidence suggests chronic inflammation in turn shapes the gut microbiota and contributes to dysbiosis. ^[12] A deeper understanding of the host-microbiota axes is a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota to combat disease and improve health. ^[2]