Associations Between Gut Microbiota Abundance, Dietary Purine Intake, and Fecal Short-Chain Fatty Acids Across the Clinical Spectrum of Hyperuricemia: A Cross-Sectional Study in Mexican Adults

Background: Hyperuricemia and gout are closely associated with alterations in gut microbiota function. Short-chain fatty acids (SCFAs) produced by intestinal microorganisms may modulate immune responses and inflammation relevant to gout pathophysiology. This study evaluated fecal SCFA concentrations, their associations with dietary purine intake, and the relationship between Akkermansia spp. and Prevotella spp. abundance and fecal SCFA profiles across the clinical spectrum of hyperuricemia. Methods: This cross-sectional study included 380 Mexican adults: normouricemic controls (n = 141), individuals with asymptomatic hyperuricemia (AH; n = 98), and patients with gout (n = 141). Fecal SCFAs were quantified by GC-FID and bacterial abundance by qPCR. Dietary intake was assessed by semi-quantitative food frequency questionnaire and classified by purine content. Between-group differences were evaluated by the Kruskal–Wallis test (Benjamini–Hochberg correction); multivariable linear regression adjusted for age, sex, and BMI was used to assess associations, including a pre-specified dietary purine intake per clinical group interaction term. Results: Fecal acetate and propionate were significantly higher in gout patients than controls, whereas AH individuals had significantly higher butyrate. Moderate-purine food intake showed opposing associations with fecal acetate in controls (β = +3.61, p = 0.019) and gout patients (β = −4.59, p = 0.036), with a significant interaction (p = 0.004). Exploratory analyses revealed a positive association between Prevotella spp. abundance and fecal acetate exclusively in the gout group (β = 0.085, p = 0.020). Conclusion: These findings suggest distinct fecal SCFA profiles across stages of urate-related disease, with a disease-specific gut metabolic response to dietary purine intake potentially contributing to the inflammatory environment of established gout. Longitudinal studies with whole-microbiome profiling are needed to establish causality.