Unraveling the Gut-Liver-Brain Axis: Microbiome, Inflammation, and Emerging Therapeutic Approaches

The gut-liver-brain axis (GLB axis) plays a crucial role in maintaining metabolic, immune, and neurological homeostasis. The gut microbiota influences systemic health through its metabolites, including short-chain fatty acids (SCFAs), bile acids (BAs), and tryptophan (Trp) derivatives, which regulate immune function, lipid metabolism, and neurotransmitter balance. Dysbiosis is an imbalance in gut microbiota that has been implicated in metabolic dysfuntion associated fatty liver disease (MAFLD), alcohol-associated liver disease (AALD), and neuroinflammatory conditions such as schizophrenia. Increased gut permeability allows microbial byproducts like lipopolysaccharides (LPSs) to enter the liver and brain, activating inflammatory pathways that contribute to disease progression. Moreover, hepatic dysfunction can lead to neuroinflammation and cognitive impairments. Understanding the interplay between microbial metabolites and host physiology provides insight into novel therapeutic interventions. Strategies such as probiotics, prebiotics, synbiotics, fecal microbiota transfer (FMT), and postbiotics offer potential treatments to restore gut eubiosis and mitigate disease severity. This review highlights the mechanistic role of the GLB axis in health and disease, emphasizing microbiome-targeted therapies as a promising avenue for managing metabolic and neuropsychiatric disorders. Trial Registration: ClinicalTrials.gov identifier: NCT04823676, NCT02496390, NCT06024681, NCT02721264.