Gut Short‐Chain Fatty Acids and Fasting Blood Glucose in Rural Chinese Middle‐Aged and Elderly Populations: Role of Gut Fermentation Phenotype

AIMS: Gut short-chain fatty acids (SCFAs) show inconsistent associations with glucose metabolism, suggesting that their metabolic significance depends on the underlying gut fermentation context. Gut fermentation phenotype was categorized according to the molar proportion of butyrate, reflecting distinct substrate-related fermentation contexts that may contribute to heterogeneity in the associations between gut SCFAs and glycaemic regulation. This study investigates whether gut fermentation phenotypes modify the relationship between faecal SCFAs and fasting glucose in 249 middle-aged and older adults from rural Shaanxi, China. MATERIALS AND METHODS: Participants are classified into carbohydrate and non-carbohydrate fermentation phenotypes according to the molar proportion of butyrate (cutoff: 14.5%). Interaction analyses and stratified multivariable linear regression models were used to assess effect modification. RESULTS: Interaction analyses reveal a significant modifying effect of fermentation phenotype on the association between butyrate and fasting glucose (β = -3.411, p < 0.001). Stratified analyses further demonstrate a positive association between butyrate and fasting glucose in the carbohydrate fermentation phenotype (β = 2.000, p < 0.001), whereas a negative but non-significant association is observed in the non-carbohydrate fermentation phenotype (β = -1.035, p = 0.124). The two phenotypes exhibit distinct microbial diversity, community composition and predicted functional profiles. Hyperglycaemia within the carbohydrate fermentation phenotype is characterized by depletion of commensal-associated taxa and enrichment of fermentation-related microorganisms. CONCLUSIONS: These findings suggest that fermentation phenotype represents an important determinant of the metabolic implications of SCFAs and provides a framework for interpreting heterogeneous associations between SCFAs and glucose metabolism.