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Individualized Reconstitution of Human Milk Microbiota: A Feasible Approach in Real-World Settings

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GUT MICROBIOTA IN INFANTS WITH COW MILK ALLERGY: A SYSTEMATIC REVIEW OF CONTROLLED STUDIES

Marcela Duarte de Sillos¹, Juliana Satomi de Souza Matsuo², Mauro Batista de Morais³

¹Universidade Federal de São Paulo (UNIFESP), Departamento de Pediatria da Escola Paulista de Medicina (EPM), Médica Assistente da Disciplina de Gastroenterologia Pediátrica, São Paulo, SP, Brasil.

Arquivos De Gastroenterologia

|August 19, 2026

Abstract

Background:

Alterations in the gut microbiota may be involved in the pathophysiology of cow milk allergy (CMA). However, whether gut microbiota abnormalities contribute to the diagnostic confirmation of CMA through specific microbiome signatures is still unknown.

Objective:

To conduct a systematic review of the literature on the gut microbiota of infants with CMA.

Methods:

This systematic review included studies on the gut microbiota of infants aged <2 years with CMA at diagnosis and at follow-up after different interventions to control clinical manifestations and compared them with that of healthy controls. The PubMed database was used for literature search. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol was applied. This review was registered on the PROSPERO platform (CRD42024574354).

Results:

A total of 1,096 articles were identified. After applying inclusion and exclusion criteria, 18 studies were selected for the systematic review. Clinical manifestations included infants with immunoglobulin E (IgE)-mediated CMA (n=7), those with non-IgE-mediated CMA (n=10), or both (n=1). An oral challenge test for CMA diagnosis was mentioned in 11 studies, and in seven of them, a double-blind placebo-controlled challenge test was used. Most studies (n=13) used 16S rRNA gene sequencing to investigate the intestinal microbiota, and only three studies used shotgun metagenomic analysis. There was significant heterogeneity in the expression of results on microbiota characteristics. Alpha diversity was similar in the control group in most studies. A low abundance of Bifidobacteria was observed in some studies (n=5).

Conclusion:

The results of this systematic review did not identify a typical microbiota pattern in infants with CMA. Studies including infants before elimination diet and with a diagnosis confirmed by an oral challenge test, and studies including one group of infants of the same age on exclusive breastfeeding and another group of infants of the same age on formula feeding as a control group are needed. Therefore, currently available data do not allow CMA diagnosis through a microbiota signature.

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