Anti-Inflammatory Properties of Ripe and Unripe Papaya Pectin in a Neonatal Human Stem Cell-Derived Ileum Model

Pectin, a dietary fiber found in fruits and vegetables, has recognized anti-inflammatory properties. While papaya is rich in pectin, the impact of different ripening stages on its anti-inflammatory effects within the human neonatal gastrointestinal tract remains unexplored. Ripe and unripe papaya contain structurally distinct pectins, potentially leading to differing anti-inflammatory effects. Herein, ripe and unripe papaya pectins were tested in an in vitro model of human neonatal intestinal mucosa, in the presence or absence of commensal Escherichia coli (E. coli) as a surrogate for early intestinal colonizers. Papaya pectin enhanced cell viability regardless of ripening stage or the presence of E. coli. Both pectins reduced the IL-6 production in cultures exposed to E. coli, but only unripe pectin decreased IL-8 levels. Additionally, treatment with either pectin downregulated genes related to tight junctions and innate immune signaling (e.g., claudin-3, catenin-1, catenin-3, SUGT1, TRAF6, and NLRP3) in the presence of E. coli. Dimensionality reduction analyses further suggest that pectin induced distinct transcriptional profiles depending on the presence of bacteria. These results demonstrate that papaya pectin modulates epithelial barrier in a manner dependent on ripening stage and microbial context, providing novel insights into its functional and stage-specific anti-inflammatory activity.