Gut-brain axis and brain health: modulating neuroinflammation, cognitive decline, and neurodegeneration

The microbiota-gut-brain axis is a pivotal medium of crosstalk between the central nervous system (CNS) and the gastrointestinal tract. It is an intricate network of synergistic molecular pathways that exert their effects far beyond their local vicinity and even affect the systemic functioning of the body. The current review explores the involvement of the gut-brain axis (GBA) in the functioning of the nervous system, with a special emphasis on the neurodegeneration, cognitive decline, and neuroinflammation that occur in Alzheimer's disease (AD) and Parkinson's disease (PD). Gut-derived microbial metabolites play an important role in facilitating this interaction. We also highlighted the complex interaction between gut-derived metabolites and CNS processes, demonstrating how microbial dysbiosis might result in clinical disorders. Short-chain fatty acids have neuroprotective properties, whereas branched-chain amino acids, trimethylamine-N-oxide (TMAO), and tryptophan derivatives such as indole have negative effects at high concentrations. Furthermore, we cover pharmaceutical and nonpharmacological approaches for restoring the gut microbial balance and promoting neurological health. We further expanded on nutritional therapies and lifestyle changes, such as the Mediterranean diet and exercise. Next, we focused on food-controlling habits such as caloric restriction and intermittent fasting. Moreover, interventional techniques such as prebiotics, probiotics, and pharmacological medications have also been utilized to modify the GBA. Historical microbiome research from early discoveries to recent studies linking gut health to cognitive and emotional well-being has increased our understanding of the GBA.