Diagnostic and metabolic insights into secondary lactose intolerance in infants via fecal lactose quantification and gut microbiome profiling

Background: Secondary Lactose intolerance (SLI) is common among infants in China, primarily resulting from secondary lactase deficiency due to mucosal damage. Current diagnostic methods are limited by poor sensitivity and specificity. Objective: To investigate gut microbial composition and metabolic dysfunction in infants with SLI and to explore the potential utility of residual fecal lactose as a non-invasive indicator related to SLI. Results: fermentation assays demonstrated a consistent reduction in total acid, acetate, and propionate production across multiple media, while lactate and gas production were significantly elevated in SLI samples under lactose, FOS, GOS, and starch-enriched conditions. Butyrate synthesis was partially preserved under protein-rich or minimal carbon media, indicating selective resilience of butyrogenic pathways. Microbial β-diversity analysis confirmed structural dysbiosis, with increased abundance of gas-associated taxa, including Clostridium. Conclusion: Residual fecal lactose, when interpreted alongside microbial and metabolic profiles, may serve as a non-invasive indicator associated with secondary lactose intolerance in infants. These findings delineate microbiota-metabolism features consistent with SLI pathophysiology and provide a conceptual framework for future validation studies and the development of nutritional or probiotic interventions.