Gut microbiota-derived metabolites and their importance in neurological disorders

Abstract

Microbial-derived metabolites are the intermediate or end products of bacterial digestion. They are one of the most important molecules for the gut to connect with the brain. Depending on the levels of specific metabolites produced in the host, it can exert beneficial or detrimental effects on the brain and have been linked to several neurodegenerative and neuropsychiatric disorders. However, the underlying mechanisms remain largely unexplored. Insight into these mechanisms could reveal new pathways or targets, resulting in novel treatment approaches targeting neurodegenerative diseases. We have reviewed selected metabolites, including short-chain fatty acids, aromatic amino acids, trimethylamine-N-oxide, urolithin A, anthocyanins, equols, imidazole, and propionate to highlight their mechanism of action, underlying role in maintaining intestinal homeostasis and regulating neuro-immunoendocrine function. Further discussed on how altered metabolite levels can influence the gut–brain axis could lead to new prevention strategies or novel treatment approaches to neural disorders.

Dietary (Poly)phenols and Cognitive Decline: A Systematic Review and Meta‐Analysis of Observational Studies

“…[ 75 ] For instance, metabolites generated by the gut microbiota, including short‐chain fatty acids, aromatic amino acids, trimethylamine‐ N ‐oxide, urolithin A, equol, imidazole, and propionate are known to maintain intestinal homeostasis and regulate neuro‐immunoendocrine function. [ 76 ] Moreover, compounds such as anthocyanins are transformed by the gut microbiota into metabolites (including, but not limited to, gallic acid, vanillic acid, protocatechuic acid, 4‐hydroxybenzoic acid, and syringic acid) that are absorbed in human body and ultimately help regulating the gut‐brain axis. [ 77 ] Other metabolites from flavonols, such as 3,4‐dihydroxyphenylacetic acid, 3,4‐dihydroxybenzoic acid, 4‐hydroxybenzoic acid, 3‐hydroxybenzoic acid, propionic acid, and other small molecules are also associated with a better gut microbiota profile.…”

Radioprotective potential of probiotics against gastrointestinal and neuronal toxicity: a preclinical study

“…Moreover, enteric glial cells, which are crucial for maintaining neural networks and regulating gut homeostasis, are developed in mice by the regulation of their gut bacteria [34,45,46]. Though the exact mechanism behind the probiotics-induced recovery of neuronal damage is unknown, this process may be facilitated by the involvement of secretion of inflammatory molecules [36] from the supplemented microbial species, and hence, probiotics containing microbial species secreting beneficial metabolites [47] might prove to be a suitable formulation to combat neurodamage.…”

The Role of Intestinal Microbiota and Diet as Modulating Factors in the Course of Alzheimer’s and Parkinson’s Diseases

“…The major products of bacterial fermentation of indigestible polysaccharides and fibers are SCFAs such as acetate, propionate, and butyrate. SCFAs have been demonstrated to regulate the BBB, modify neuroplasticity, modulate microglia development, regulate neurotransmission, and promote the synthesis of serotonin [ 39 ]. Furthermore, SCFAs can influence neuroinflammation through regulating the synthesis and migration of immune cells, including neutrophils, T cells, and inflammatory cytokines [ 40 ].…”