JY-039

Necrotizing enterocolitis (NEC) is a serious condition in premature infants, driven by dysbiosis-induced inflammation and barrier damage. This study screened probiotics for efficient 2'-fucosyllactose (2'-FL) utilization and intestinal repair potential. Lactiplantibacillus plantarum JY039 (L. plantarum JY039, JY039) was selected from 25 strains (p < 0.05) based on 2'-FL metabolism, intestinal adhesion, and Lgr5 induction in TNF-α-damaged organoids. JY039 showed versatile carbon metabolism and sensitivity to 11 antibiotics, indicating its clinical safety. In TNF-α-injured organoids, it elevated intestinal stem cell (ISC) markers (Olfm4 and Ascl2, 4-fold) and proliferation markers (c-Myc, Ki67, and cyclins, 3-fold), with EdU intensity increasing 4-fold versus NEC models. In NEC rats, JY039 (10⁹ CFU/mL) reduced pathology scores and permeability, restored tight junctions, modulated cytokines (TNF-α, IL-6, myeloperoxidase decreased; and IL-10 increased, p < 0.05), activated ISC regeneration, and enriched Lactococcus and Akkermansia. JY039 effectively maintained epithelial regeneration and improved the microbial imbalance, representing a safe NEC candidate. It also offers guidance for producing a functional infant formula.