Longitudinal Follow‐Up of Gut and Salivary Microbiota in Children With Food Protein‐Induced Enterocolitis Syndrome

BACKGROUND: Gut microbiota and their metabolites play a key role in digestive dysimmunity and tolerance breakdown, leading to pathologies such as food protein-induced enterocolitis syndrome (FPIES). This study aimed to compare both the gut and salivary microbiota over time between the allergic and tolerant patients and the matched controls. METHODS: Faecal and salivary samples were collected longitudinally from FPIES allergic patients on an elimination diet, and after their natural tolerance acquisition, and from matched controls (1:1 ratio). 16S rRNA gene sequencing and biostatistical analyses (ALDEx2, ANCOM-BC, DESeq2, LEfSe, and MaAsLIN2) were used to compare microbiota composition between groups. The measurement of faecal short-chain fatty acids (SCFAs) using gas chromatography evaluated the gut microbiota functions. RESULTS: Thirty-eight allergic patients were included (median age: 1.3 years), and 22 became tolerant over time. Allergic patients exhibited lower gut and salivary alpha-diversities, and several different genera (12 in stools, including less Ruminococcus, and 2 in saliva), and higher relative abundance of acetate than the controls. With tolerance acquisition, faecal alpha-diversities partially increased, whereas SCFAs normalised. Ultimately, there were more differences in faecal and salivary microbiota in allergic patients versus after tolerance acquisition (i.e., more Blautia, Ruminococcus, Faecalibacterium, Prevotella-9, and less Escherichia-Shigella in tolerant patients) than between the controls over time. CONCLUSION: The faecal and salivary dysbiosis observed in allergic patients with FPIES partially resolved after tolerance acquisition. Understanding the underlying mechanisms of dysbiosis is crucial to prevent and help manage FPIES. A prolonged follow-up could determine whether dysbiosis resolution may be complete, and whether this early infancy dysbiosis has long-term consequences on health.