# Lactobacillus Re-Engineers Gut Microbiota to Overcome E. coli Colonization Resistance in Mice

## TL;DR

Lactobacillus helps mice overcome E. coli infection by restoring gut health and strengthening the intestinal barrier.

## Contribution

This study reveals how Lactobacillus modulates gut microbiota and host defenses to counter E. coli colonization.

## Key findings

- Lactobacillus supplementation restored body mass, intestinal structure, and microbial functions during E. coli infection.
- Lactobacillus enhanced mucosal barrier integrity by upregulating tight junction proteins and mucin biosynthesis.
- Microbiome analysis showed increased beneficial bacteria and improved metabolic pathways with Lactobacillus treatment.

## Abstract

Lactobacillus is recognized as one of the most pivotal beneficial microbiota residing in the gastrointestinal ecosystems of animals, exhibiting multifaceted health-promoting effects. These biological advantages encompass regulating gut microbiota composition, stimulating intestinal motility, maintaining microecological homeostasis, mitigating inflammatory cascades, and improving gastrointestinal functional capacity. Our experimental evidence revealed that concurrent administration of Lactobacillus during E. coli colonization promoted the restoration of core physiological parameters, including body mass equilibrium, digestive enzymatic activity, intestinal histoarchitecture, and microbial metabolic functions. This therapeutic strategy consequently elevated endogenous probiotic populations while suppressing pathogen-induced inflammatory signaling pathways. Furthermore, microbiome analysis demonstrated that Lactobacillus supplementation significantly increased beneficial symbiont populations through enhancing nutritional metabolic networks (particularly amino acid transport and energy conversion pathways) and environmental signal transduction systems (p < 0.05), while simultaneously advancing mucosal layer maturation. Crucially, we established that Lactobacillus intervention ameliorated E. coli-induced enteric dysfunction and reinforced intestinal barrier integrity through microbiota-mediated modulation of epithelial tight junction complexes and mucin biosynthesis mechanisms (Occludin, Claudin-1, ZO-1, MUC1, and MUC2; p < 0.05).

The intestinal health and functionality of animals play pivotal roles in nutrient digestion and absorption, as well as in maintaining defense against pathogenic invasions. These biological processes are modulated by various determinants, including husbandry conditions, dietary composition, and gut microbial ecology. The excessive use of anthropogenic antibiotics may disrupt intestinal microbiota composition, potentially leading to dysbiosis that directly compromises host homeostasis. While Lactobacillus species are recognized for their immunomodulatory properties, their precise mechanisms in regulating host anti-inflammatory gene expression and influencing mucosal layer maturation, particularly regarding E. coli colonization resistance, require further elucidation. To investigate the regulatory mechanisms of Lactobacillus in relation to intestinal architecture and function during E. coli infection, we established a colonic infection model using Bal b/c mice, conducting systematic analyses of intestinal morphology, inflammatory mediator profiles, and microbial community dynamics. Our results demonstrate that Lactobacillus supplementation (Pediococcus acidilactici) effectively mitigated E. coli O78-induced enteritis, with co-administration during infection facilitating the restoration of physiological parameters, including body mass, intestinal histoarchitecture, and microbial metabolic functions. Microbiome profiling revealed that the Lactobacillus intervention significantly elevated Lactococcus abundance while reducing Weissella populations (p < 0.05), concurrently enhancing metabolic pathways related to nutrient assimilation and environmental signal processing (including translation mechanisms, ribosomal biogenesis, amino acid transport metabolism, and energy transduction systems; p < 0.05). Mechanistically, Lactobacillus administration attenuated E. coli-induced intestinal pathology through multiple pathways: downregulating pro-inflammatory cytokine expression (IL-1β, IL-1α, and TNF-α), upregulating epithelial junctional complexes (Occludin, Claudin-1, and ZO-1), and stimulating mucin biosynthesis (MUC1 and MUC2; p < 0.05). These modifications collectively enhanced mucosal barrier integrity and promoted epithelial maturation. This investigation advances our comprehension of microbiota–host crosstalk during enteropathogenic infections under probiotic intervention, offering valuable insights for developing novel nutritional strategies and microbial management protocols in animal husbandry.