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Background: Food protein‐induced allergic proctocolitis (FPIAP) is the leading cause of rectal bleeding in infants. Tolerance is presumed to develop until the first year of age, although natural history studies are scarce, making the determination of the ideal duration for any intervention, challenging. Intestinal microbiota (IM) is crucial in food allergy development; however, data for FPIAP remain limited. This study aimed to assess FPIAP remission after 3 months of milk avoidance and its correlation with IM longitudinal changes. Methods: A prospective observational study of infants aged ≤6 months with a diagnosis of FPIAP. After 3 months of management according to a clinical algorithm, infants were subjected to a milk challenge using either a cow (CM) or a goat (GM) milk formula in a random order. Stool samples were collected longitudinally for microbiome analysis. Results: Out of 61 infants, 57 were challenged (29 with CM, 28 with GM). Of these, 55 (96.5%) achieved tolerance, with no difference in tolerance rates between CM (28/29) and GM (27/28). The average age of tolerance development was 6.3 months. Enterobacteriaceae clusters (Klebsiella‐ and Shigella‐dominated) were most often represented in samples from symptomatic infants. In contrast, Bacteroides and Bifidobacteria clusters emerged later, in apparently healthy infants. Conclusion: A 3‐month intervention was sufficient for almost all infants to achieve tolerance. GM was tolerated equally well to CM. Symptomatic FPIAP is associated with immature enterotypes, while disease remission coincides with microbiome changes in time. [ABSTRACT FROM AUTHOR]