Epidemiologic and genetic evidence linking peripheral neuropathy to gut dysbiosis: a systematic review

Abstract

Peripheral neuropathy affects a substantial proportion of the global population and remains incompletely explained by established risk factors. Preclinical studies suggest that gut dysbiosis can modulate neuroimmune pathways and neuropathic phenotypes. However, synthesis of human clinical evidence remains limited. Following PRISMA guidelines, a systematic review was conducted across PubMed and the Cochrane Library to identify human observational/interventional studies evaluating gut dysbiosis in relation to peripheral neuropathic outcomes. Seven eligible clinical studies were identified. Directional concordance of evidence was assessed using a binomial sign test. An albatross plot was constructed to visualize standardized evidence strength and approximate effect size across heterogeneous designs. Mendelian randomization (MR) studies were evaluated as orthogonal evidence of causality. All seven clinical studies demonstrated positive associations between gut dysbiosis and neuropathic symptomatology, yielding a low probability of directional concordance due to chance alone (0.78%). Albatross plot visualization indicated that most studies clustered near the δ = 0.3 effect size contour, suggesting broadly consistent, moderate effects across the literature despite methodological heterogeneity among studies. There were conserved microbial shifts identified across disparate patient groups, including the enrichment of pro-inflammatory genera and depletion of short-chain fatty acid-producing taxa. Six MR studies orthogonally supported positive causal relationships between gut dysbiosis and neuropathic risk across large genetically characterized cohorts. Convergent epidemiologic and genetic evidence supports the feasibility of a biological signal and possible reproducible association between gut dysbiosis and peripheral neuropathy across diverse clinical contexts. These findings strengthen the plausibility that microbial perturbations may contribute to neuropathic vulnerability and highlight the gut microbiome as a potentially modifiable upstream determinant of peripheral nerve health.