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Lactiplantibacillus plantarum JY039 Ameliorates Necrotizing Enterocolitis via Intestinal Stem Cell Regeneration

Jinfeng Guo1, Ying Zhao1, Kaiqi Gao1

  • 1Key Lab of Dairy Science, Ministry of Education, College of Food Science, Northeast Agricultural University, Harbin, Heilongjiang Province 150030, China.

Journal of Agricultural and Food Chemistry
|December 22, 2025
PubMed

Insights

Lactiplantibacillus plantarum JY039 effectively repairs intestinal barrier damage in necrotizing enterocolitis (NEC) models. This probiotic candidate promotes stem cell regeneration and restores gut microbiota balance, offering a safe therapeutic option for premature infants.

Area of Science:

  • Microbiology
  • Gastroenterology
  • Neonatology

Background:

  • Necrotizing enterocolitis (NEC) is a critical condition in premature infants, characterized by gut dysbiosis, inflammation, and barrier dysfunction.
  • Probiotics are explored for NEC prevention and treatment, but require specific functional traits like nutrient utilization and barrier repair capabilities.

Purpose of the Study:

  • To screen and identify probiotic strains with efficient 2'-fucosyllactose (2'-FL) metabolism and intestinal repair potential for NEC.
  • To evaluate the efficacy and safety of the selected probiotic, *Lactiplantibacillus plantarum* JY039 (JY039), in preclinical NEC models.

Main Methods:

  • Screening of 25 probiotic strains for 2'-FL utilization, intestinal adhesion, and Lgr5 induction in TNF-α-damaged organoids.
  • Assessment of JY039's carbon metabolism, antibiotic sensitivity, and effects on intestinal stem cell (ISC) markers and proliferation in vitro.
  • Evaluation of JY039's therapeutic effects in a rat model of NEC, including pathology scoring, permeability assessment, tight junction restoration, cytokine modulation, and microbial analysis.

Main Results:

  • *Lactiplantibacillus plantarum* JY039 was selected for its superior 2'-FL metabolism and Lgr5 induction.
  • JY039 demonstrated safety with versatile carbon metabolism and sensitivity to 11 antibiotics.
  • In vitro, JY039 significantly upregulated ISC markers (Olfm4, Ascl2) and proliferation markers (c-Myc, Ki67, cyclins).
  • In NEC rats, JY039 reduced pathology and permeability, restored tight junctions, modulated inflammatory cytokines (decreased TNF-α, IL-6; increased IL-10), activated ISC regeneration, and improved gut microbiota composition.
  • JY039 effectively maintained epithelial regeneration and corrected microbial imbalance.

Conclusions:

  • *Lactiplantibacillus plantarum* JY039 is a promising, safe probiotic candidate for managing necrotizing enterocolitis in premature infants.
  • JY039 demonstrates significant potential in promoting intestinal barrier repair and restoring gut homeostasis.
  • The findings provide a basis for developing functional infant formulas and therapeutic strategies targeting NEC.

Keywords:
2′-fucosyllactoseLactiplantibacillus plantarumintestinal organoidsintestinal stem cellsnecrotizing enterocolitis

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