Limosilactobacillus reuteri DS0384 promotes intestinal epithelial maturation via the postbiotic effect in human intestinal organoids and infant mice

Abstract

Little is known about the modulatory capacity of the microbiota in early intestinal development. We examined various intestinal models that respond to gut microbial metabolites based on human pluripotent stem cell-derived human intestinal organoids (hIOs): physiologically relevant in vitro fetal-like intestine, intestinal stem cell, and intestinal disease models. We found that a newly isolated Limosilactobacillus reuteri strain DS0384 accelerated maturation of the fetal intestine using 3D hIO with immature fetal characteristics. Comparative metabolomic profiling analysis revealed that the secreted metabolite N-carbamyl glutamic acid (NCG) is involved in the beneficial effect of DS0384 cell-free supernatants on the intestinal maturation of hIOs. Experiments in an intestinal stem cell spheroid model and hIO-based intestinal inflamed model revealed that the cell-free supernatant from DS0384 comprising NCG promoted intestinal stem cell proliferation and was important for intestinal protection against cytokine-induced intestinal epithelial injury. The probiotic properties of DS0384 were also evaluated, including acid and bile tolerance and ability to adhere to human intestinal cells. Seven-day oral administration of DS0384 and cell-free supernatant promoted the intestinal development of newborn mice. Moreover, NCG exerted a protective effect on experimental colitis in mice. These results suggest that DS0384 is a useful agent for probiotic applications and therapeutic treatment for disorders of early gut development and for preventing intestinal barrier dysfunction.

Optimizing postbiotic production through solid-state fermentation with Bacillus amyloliquefaciens J and Lactiplantibacillus plantarum SN4 enhances antibacterial, antioxidant, and anti-inflammatory activities

“…In this study, we detected that the postbiotics enhance intestinal epithelial wound healing after a mechanical injury such as a cell scratch in IPEC-J2 cells. It was also reported by Lee et al ( 2022 ) that the postbiotics of L. reuteri DS0384, prepared with liquid fermentation, promoted intestinal stem cell proliferation and protected intestinal epithelial cells from cytokine-induced injury. These findings indicated that postbiotics played a crucial role in health and nutrition.…”

Preconception maternal gut dysbiosis affects enteric nervous system development and disease susceptibility in offspring

“…Among these bacteria, L. reuteri stands out due to its ability to produce various bene cial metabolites vital for bodily functions and its profound impact on the microbial community structure 32,33 . Previously studies have shown that L. reuteri can effectively enhance gut and central nervous system development in offspring whose mothers were exposed to high-fat diet, LPS, or antibiotic 34,35 . In our multi-omics analysis, L. reuteri emerged as a key species contributing to ENS development.…”

Lactobacillus acidophilus FCQHC4L1 strengthens the intestinal mucus barrier and inhibits endoplasmic reticulum stress

“…Intestinal mucus acts as a barrier to protect the intestinal epithelial cells from harmful substances and is crucial for maintaining good health [1]. A growing body of evidence confirms that LAB promote intestinal mucin secretion and strengthen the intestinal mucus barrier [13][14][38][39] . Herein, we found that L. acidophilus FCQHC4L1 strengthened the intestinal mucus barrier.…”