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Fecal Changes Following Introduction of Milk in Infants With Outgrowing Non-IgE Cow's Milk Protein Allergy Are
Lucía Guadamuro1, Maria Diaz1, Santiago Jiménez2,3
1Department of Microbiology and Biochemistry of Dairy Products, Instituto de Productos Lácteos de Asturias (IPLA)-Consejo Superior de Investigaciones Científicas (CSIC), Villaviciosa, Spain.
Insights
Infants with cow's milk protein allergy (CMPA) showed gut microbiota shifts and reduced protein metabolites after milk introduction. Probiotic use influenced these changes, suggesting a role in gut homeostasis for CMPA recovery.
Area of Science:
- Pediatric Gastroenterology
- Immunology
- Microbiome Research
Background:
- Cow's milk protein allergy (CMPA) is a common infant allergy, often non-IgE mediated, presenting with digestive issues.
- Gut microbiota composition in early life is linked to food allergy development and tolerance.
- Probiotic interventions are explored for their potential impact on infant gut health and allergy management.
Purpose of the Study:
- To investigate changes in gut microbiota, metabolic, and cytokine profiles in infants with non-IgE mediated CMPA.
- To analyze these changes following a standardized oral cow's milk challenge and subsequent dietary dairy introduction.
- To compare outcomes between infants receiving a probiotic (Lactobacillus rhamnosus GG) and those who did not.
Main Methods:
- Twelve infants (1-2 years) with CMPA underwent a standardized oral cow's milk challenge.
- Fecal samples were collected pre-challenge, 1 week, and 1 month post-challenge for 16S rRNA gene sequencing, qPCR for lactobacilli, metabolite analysis, and cytokine profiling.
- Infants were on hypoallergenic formulas, with some receiving Lactobacillus rhamnosus GG supplementation.
Main Results:
- Lactic acid bacteria significantly increased in infants who outgrew CMPA post-milk introduction.
- Protein fermentation metabolites (branched-chain fatty acids, p-cresol) decreased.
- Pro-inflammatory cytokines (TNF-α, IFN-γ) increased post-challenge, with distinct microbial, metabolic, and cytokine profiles observed between probiotic and non-probiotic groups.
Conclusions:
- Introduction of intact milk proteins alters the infant gut environment, impacting immune mediators, microbiota, and metabolites.
- Probiotic consumption (Lactobacillus rhamnosus GG) during CMPA may aid gut homeostasis by modulating these profiles.
- These findings highlight the interplay between diet, microbiome, and immune responses in CMPA tolerance development.
Abstract:
Cow's milk protein allergy (CMPA) is the most common allergy in the first year of life. Non-IgE mediated CMPA is characterized by digestive symptoms and tolerance development before the age of three. Gut microbiota composition in early life has been associated with food allergy. The ingestion of different foods/nutrients may mark different shifts in the microbial colonization of the infant intestine as well as the consumption of probiotics. Aim: To analyze changes in microbiota composition and metabolic and cytokine profiles in fecal samples from infants with non-IgE mediated CMPA after successful milk challenges, tolerance acquisition, and increasing dairy introduction in their diet. Methods: Twelve children with CMPA, aged between 1 and 2 years old, were recruited for the study. Participants were initially consuming hypoallergenic hydrolyzed formulas (four of them supplemented with the probiotic Lactobacillus rhamnosus GG), before being exposed to a standardized oral challenge (SOC) with cow's milk. Fecal samples were collected before, 1 week, and 1 month after performing the SOC. Changes in gut microbiota were determined by high-throughput amplicon sequencing of the 16S rRNA gene. Levels of lactobacilli were also determined by quantitative PCR (qPCR). Microbial metabolites were analyzed by chromatographic methods and fecal cytokines related to the Th1/Th2 balance were determined by immunoassay. Results: Lactic acid bacteria significantly increased in infants who outgrew non-IgE CMPA, after the introduction of milk. Microbial metabolites derived from the fermentation of proteins, such as branched chain fatty acids, and p-cresol, diminished. After the SOC, some cytokines related to inflammation (TNF-α, IFN-γ) increased. Accompanying the introduction of an unrestricted diet, we found significant differences in fecal microbial composition, metabolites, and cytokines between infants who did not consume the probiotic L. rhamnosus GG and those that did. Conclusions: These findings indicate that the introduction of intact milk proteins is followed by modifications in the infant gut environment through changes in immune mediators, microbiota, and its metabolic end-products. Consumption of probiotics during CMPA may contribute to gut homeostasis by fine-tuning these profiles.