Longitudinal Study of the Intestinal, Cutaneous and Salivary Microbiota in Children With Food-induced Enterocolitis Syndrome (SEIPA)

1.1 Current state of knowledge Food Protein- Induced Enterocolitis Syndrome (FPIES) is a food allergy with a prevalence of 0.34% and an incidence of 15.4 children per 100,000 per year. It is a non-IgE-mediated allergy, manifested by vomiting 1 to 4 hours after ingestion of the suspect food (major criteria), without any skin or respiratory manifestations. According to the last definition (JACI 2017), at least 3 minor criteria should be required associated with vomiting among the following: a second similar episode of vomiting after ingestion of the same food, the appearance of repeated vomiting 1 to 4 hours after ingestion of another food, lethargy, pronounced pallor, the need for emergency treatment or intravenous rehydration after ingestion of a suspect food, the onset of diarrhea within 24 hours, hypotension, or hypothermia at the time of reaction. The most frequently responsible foods for PFIES are cow's milk, cereals, soy and fish. The triggers depend on the country, probably in relation to eating habits. The median tolerant age is later than in the other forms of non-IgE-mediated allergy, namely between the age of 3 to 5 years and it is later for solid foods than liquid foods. The average age of acquiring tolerance for cow's milk varies in the literature, around 8-10 months in Korea, around 1 year in Israel, around 5 years in the United States, but much later (14 years) if specific IgE occurs during follow-up. There is no data in France on the curing age of SEIPA in cow's milk.

A first reintroduction of the responsible food is proposed at the age of 12-18 months if the diagnosis was made during the first months of life, and if specific IgE are negative according to the latest recommendations. Failure of the oral food challenge (OFC), a new OFC is proposed every 6 months until healing.

When the specific IgE are positive, it is then an atypical FPIES, and the methods of reintroduction of the food will depend on the evolution of IgE.

The link between microbiota and development of allergic diseases is now well known. The intestinal microbiota varies in terms of diversity and bacterial distribution in patients with food allergies compared to non-allergic patients. The microbiota plays an early role in the development of the immune system, and therefore in the development or prevention of food allergies involving the pro-inflammatory and pro-allergic Th17 pathway.

The intestinal microbiota is evaluated by bacterial diversity using RNA16 sequencing, in particular alpha-diversity (specific to a sample), and beta-diversity (comparison between several samples), bacterial richness, and by the determination of bacterial metabolites such as short-chain fatty acids, such as butyrates, the measurement of fecal calprotectin, IgA, and cytokines excreted in stool (eg β-defensin, TNF-α, cationic protein of eosinophils : ECP) .