Fig.4.

Schematic illustration of putative pathway(s) by which aging-related alterations in gut microbiome and entero-neuro-endocrine system may affect brain health via deteriorated gut-brain communication signaling. In healthy adult host, the balanced gut microbiome configuration and intestinal barrier integrity help in maintaining balanced arrays of microbes, microbial by-products (e.g. short-chain fatty acids; SCFAs) and other entities such as neurotransmitters across the gut wall thereby maintaining a balanced enteric-immune and -inflammatory system through controlled proliferation of dendritic cells and macrophages which eventually helps in keeping the gut-brain communication and the functioning of central nervous system (CNS) under control. In old age, the altered gut microbiota diversity and weakened gut barrier integrity may perturb the microbial and biochemical environment across the intestinal epithelial cell lining via abnormal levels of SCFAs, lipopolysaccharide (LPS), secretory Immunoglobulin A (sIgA), histamins, serotonin (5-hydroxytryptamine; 5-HT), etc. thereby instigating an abnormal (hyper) inflammatory responses eventually affecting (disturbing) the gut-brain communication [84, 90, 93, 103, 104, 109, 112, 124, 158].