ORIGINAL RESEARCH article
Front. Immunol.
Sec. Nutritional Immunology
Diagnostic and Metabolic Insights into Secondary Lactose Intolerance in Infants via Fecal Lactose Quantification and Gut Microbiome Profiling
Provisionally accepted
- 1State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products and Institute of Agro-product Safety and Nutrition; Zhejiang Academy of Agricultural Sciences, Hangzhou, China
- 2Zhejiang Academy of Agricultural Sciences, Hangzhou, China
- 3Children's Hospital of Soochow University, Suzhou, China
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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: SLI infants exhibited significantly higher residual fecal lactose and lactate levels accompanied by reduced fecal short-chain fatty acid (SCFA) availability, consistent with incomplete lactose digestion and altered microbial fermentation. Microbiota profiling revealed marked depletion of Bacteroidetes and certain Firmicutes (e.g. Ruminococcaceae, Erysipelotrichaceae, Peptostreptococcaceae, Megasphaera), along with reduced glycolysis pathways. In vitro 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.
Keywords: 16S rRNA, Gut Microbiota, In vitro fermentation, lactose glycolysis, SCFAs, Secondary lactose intolerance
Received: 24 Sep 2025; Accepted: 20 Jan 2026.
Copyright: © 2026 Kuang, Zhang, Bian, Wang, Li, WU and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Qingbin WU
Jinjun Li
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