Multi-strain probiotic administration decreases necrotizing enterocolitis severity and alters the epigenetic profile in mice.

Abstract

Background: Probiotic administration may decrease the incidence of necrotizing enterocolitis (NEC) through mechanisms that are largely unknown. We investigated the effects of probiotics on intestinal epigenetics and assessed their effects on intestinal inflammation and motility using both ileum-predominant and combined ileo-colitis mouse NEC models.

Methods: C57BL/6 J mice were gavage-fed a multi-strain probiotic from postnatal days 3-11, consisting of B. infantis, B. lactis, and S. thermophilus. From p8, mice were exposed to ileo-colitis NEC involving formula containing NEC bacteria and 0.5% DSS. DNA methylation was measured using the Infinium Methylation Assay. Gastrointestinal motility was assessed by 70 Kd FITC-dextran transit time. Probiotic colonization was measured in probiotic-fed mice by qPCR.

Results: Probiotic administration caused significant changes in the small intestine's epigenetic signature, a reduction in NEC severity, and improved intestinal motility. The effects of probiotics were more pronounced in the ileo-colitis NEC model.

Conclusions: These findings shed light on the role of probiotics in two clinically relevant models of NEC, add additional insights into their underlying mechanism of action, and reveal unanticipated epigenetic modifications to the intestinal mucosa after their use.

Impact: These findings shed light on the role of multi-strain probiotics in two clinically relevant animal models of NEC, and add additional insights into their underlying mechanism of action This study provides a new, clinically relevant model for the study of NEC including administration of 0.5% DSS, to include ileal dominant and ileo-colonic dominant phenotypes of the disease. These results reveal that clinically relevant strains of probiotic bacteria can exert epigenetic effects on the small intestine in mice, and can attenuate the epigenetic changes induced by NEC.