Gut Microbiome Modulation by Diet and Lifestyle in Kidney Stone Disease and Autism Spectrum Disorder: Emerging Mechanisms and Translational Prospects

Abstract

Background: The gut microbiome occupies a central position in mediating the physiological consequences of diet, lifestyle, and physical activity. While this interplay is broadly recognized, its mechanistic consequences in two clinically underserved conditions—urolithiasis (kidney stone disease) and autism spectrum disorder (ASD)—remain poorly explained. Both conditions share convergent pathophysiology rooted in metabolic dysregulation, impaired epithelial barrier function, immune dysregulation, and altered microbial metabolite profiles, all of which are modifiable through dietary and behavioral interventions. Methods: This minireview synthesizes current evidence from clinical, epidemiological, and mechanistic studies to evaluate the bidirectional relationship between gut microbial ecology and disease pathogenesis in urolithiasis and ASD, with emphasis on dietary compounds, fermented foods, probiotics, and lifestyle behaviors as modulatory pedals. Results: In urolithiasis, evidence implicates reduced abundance of oxalate-degrading taxa (notably Oxalobacter formigenes), dysbiotic short-chain fatty acid (SCFA) profiles, and urinary microbiome perturbations in stone formation and recurrence. In ASD, microbial alterations in gastrointestinal-symptomatic individuals converge on reduced butyrate-producing taxa, elevated pro-inflammatory species, and altered serotonin and gamma-aminobutyric acid (GABA) biosynthetic pathways. Conclusion: Dietary interventions—particularly high-fiber regimens, polyphenol-rich foods, fermented products, and targeted probiotic formulations—show mechanistic plausibility for microbiome restoration in both conditions. However, clinical translation is constrained by methodological heterogeneity, confounding lifestyle variables, and a paucity of longitudinal, mechanistically anchored trials. We outline a research agenda prioritizing standardized multi-omics, paired gut–urine sampling protocols, and rigorously controlled dietary interventions to bridge this gap.