not-yet-known not-yet-known not-yet-known unknown Background: We have previously described that 87,6 % of children with juvenile colorectal polyp (JCP) from La Plata Children’s Hospital are sensitized to food allergens. Tissues of JCP are characterized by type 2 inflammation and the abundant presence of active sites of IgE synthesis. Objective: The aim of this work was to study a potential link between polyps and gut microbiota dysbiosis. Methods : We characterized bacterial populations in feces of food allergen-sensitized children with JCP, feces from healthy children and those associated with JCP tissues. Microbial diversity and composition were evaluated using next generation sequencing of the amplified 16S rRNA gene V3-V4 hypervariable region. Results: The principal component analysis applied to β-diversity discriminated well among sample groups. The taxonomic characterization of the bacterial communities in stool samples from food-sensitized children showed a reduced abundance of Bacteroidetes (Bacteroides) and, at the genera and species levels, an increased number of Mediterraneibacter faecis, Prevotella copri, Catenibacterium , and Prevotella hominis , Sutterella wadsworthensis and Phascolarctobacterium A succinatutens compared to feces of healthy children. We found that the microbiome associated with the polyp tissues was enriched in inflammation- and colorectal cancer associated bacteria, including Fusobacterium, Escherichia and Corynebacterium, with elevated levels of Escherichia fergussoni , Akkermansia muciniphila and Enterocloster . Conclusion: Our study highlights differences in bacterial diversity between food sensitized and healthy children’s feces, and that associated with the polyps. This is the first comprehensive description of JCP microbiota in food sensitized patients and may reveal mechanisms of allergic inflammation and polyp formation, underscoring the importance of monitoring for potential malignant lesions.

Background: Manifestations of food allergies vary among patients, being the most common gastrointestinal, skin and respiratory symptoms. This study aimed to identify and characterize polyp Th2 cells as a critical component of the allergic reaction. We previously characterized colorectal polyps in patients sensitized to food allergens as inflammatory, with a Type 2-dominated stroma, with elevated IL-13, IL-4 and locally synthesized IgE. Methods: We isolated milk-specific T cells from tissue and blood of food-sensitized patients (n=10) and obtained cell lines and cell clones. Proliferation, specificity, cytokine secretion, gut homing markers and TCR nature were analyzed after antigen recall; CCL25 was assessed in polyps and surrounding tissue. Results: Lamina propria and peripheral T cells responded similarly to cow´s milk proteins, showing similar cell proliferation index and Th2 cytokine release in vitro. All CD4 + T cells expressed the membrane T αβ receptor and secreted higher IL-13 amounts than unstimulated cells, whereas IFN-γ secretion remained unchanged. Remarkably, the gut homing chemokine receptor CCR9 was augmented in cow’s milk-specific peripheral and lamina propria T cells, and CCL25 was found to be expressed in the inflammatory polyp tissue and not in the adjacent mucosa. Conclusion: We isolated and characterized cow´s milk-specific lamina propria CD4 + TCRαβ + Th2 cells from colonic inflammatory polyps. The CCR9 expression on polyp cells and the increased production of tissue CCL25 might facilitate T cells’ recruitment, which are key players in the allergic reaction to promote local IgE synthesis. Our findings may be critical to proposing rational and novel T cell-targeted immunotherapies.