Fecal short-chain fatty acids in infants with cow's milk protein allergy ‒ A systematic review

Introduction: gut microbiota dysbiosis is closely associated with the development of allergic diseases. Short-chain fatty acids (SCFAs), as microbial metabolites, regulate immune responses and may represent a therapeutic target. Cow's milk protein allergy (CMPA) is one of the most common food allergies in infancy, making SCFAs a potential biomarker and modulator in this context. Objective: to synthesize current evidence on fecal SCFA concentrations in infants diagnosed with CMPA. Methods: a systematic search was conducted in MEDLINE/PubMed and LILACS for studies published from July 2011 to October 2025, following PRISMA 2020 guidelines. Inclusion criteria required studies to report fecal SCFA concentrations in infants with CMPA and include a control group. Exclusion criteria were animal models, reviews, studies without relevant measurements, or publications not in English or Spanish. Methodological quality was assessed using the Quality Assessment Tool for Observational and Cross-sectional Cohort Studies, and reporting quality was verified through the STROBE checklist. Results: six studies fulfilled the criteria. Findings were heterogeneous: two studies reported higher SCFA levels in CMPA infants compared with controls, while three studies showed lower levels. One study did not provide specific values. Several investigations observed associations between SCFA concentrations and distinct bacterial taxa, suggesting interplay between microbial composition and metabolite production. Conclusions: evidence remains inconsistent regarding SCFA alterations in infants with CMPA. Further standardized, robustly designed studies are required to determine whether fecal SCFAs can serve as reliable indicators or mediators in CMPA pathophysiology.