The gut-liver-nervous system axis in neuroregeneration and neurodegeneration: Mechanistic pathways, therapeutical modulation, and translational relevance

Abstract

The gut microbiota is increasingly recognized as an important regulator of systemic metabolism, immune activity, and nervous system function. Interactions among the intestine, liver, immune system, and nervous system may therefore represent a biologically interconnected network with relevance to neurodegeneration, neuroregeneration, and other chronic disorders. The aim of this review was to summarize current evidence supporting the gut-liver-nerve axis and to evaluate its potential relevance to neuroinflammation, neurodegeneration, peripheral nerve regeneration, intervertebral disc degeneration, metabolic liver disease, and emerging therapeutic strategies. A narrative literature review was conducted using PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar, covering publications available up to May 2026. Studies addressing the gut-liver-nervous system axis, gut microbiota, microbial metabolites, bile acid signaling, intestinal barrier dysfunction, neuroinflammation, neurodegeneration, peripheral nerve regeneration, intervertebral disc degeneration, and metabolic liver disease were identified and qualitatively synthesized. A total of 35 publications were included in the final qualitative synthesis. Available evidence indicates that microbial metabolites, including short-chain fatty acids, tryptophan-derived metabolites, and bile acid derivatives, participate in immune, metabolic, and neural signaling. Dysbiosis and impaired intestinal barrier function may contribute to systemic inflammation and altered gut-liver communication. Emerging evidence also supports an association between gut microbiota and intervertebral disc degeneration. Prebiotics, probiotics, synbiotics, fecal microbiota transplantation, postbiotics, microbial metabolites, and bile acid-directed approaches represent potential therapeutic strategies, although neurological applications remain predominantly investigational. The gut-liver-nervous system axis represents a promising biological and therapeutic framework, but definitive clinical evidence for neuroregenerative efficacy remains limited. Further mechanistic and controlled translational studies are required to establish causality and therapeutic applicability.