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.

This study investigates whether fecal microbiota transplantation (FMT) can alleviate gut microbiota dysbiosis induced by a high-fat diet (HFD) through modulation of fatty acid metabolism, competition for nutrients, production of short-chain fatty acids (SCFAs), and restoration of mucus layer integrity. To elucidate the mechanisms by which FMT regulates colonic microbial function and host metabolic responses, 80 male Bal b/c mice were randomly assigned to four experimental groups (n = 20 per group): Normal Diet Group (NDG), High-Fat Diet Group (HDG), Restrictive Diet Group (RDG), and HDG recipients of NDG-derived fecal microbiota (FMT group). The intervention lasted for 12 weeks, during which body weight was monitored biweekly. At the end of the experiment, tissue and fecal samples were collected to assess digestive enzyme activities, intestinal histomorphology, gene expression related to gut barrier function, and gut microbiota composition via 16S rRNA gene sequencing. Results showed that mice in the HDG exhibited significantly higher final body weight and greater weight gain compared to those in the NDG and RDG (p < 0.05). Notably, FMT treatment markedly attenuated HFD-induced weight gain (p < 0.05), reducing it to levels comparable with the NDG (p > 0.05). While HFD significantly elevated the activities of α-amylase and trypsin (p < 0.05), FMT supplementation effectively suppressed these enzymatic activities (p < 0.05). Moreover, FMT ameliorated HFD-induced intestinal architectural damage, as evidenced by significant increases in villus height and the villus height-to-crypt depth ratio (V/C) (p < 0.05). At the molecular level, FMT significantly downregulated the expression of pro-inflammatory cytokines (IL-1β, IL-1α, TNF-α) and upregulated key tight junction proteins (Occludin, Claudin-1, ZO-1) and mucin-2 (MUC2) relative to the HDG (p < 0.05). 16S rRNA analysis demonstrated that FMT substantially increased the abundance of beneficial genera such as Lactobacillus and Bifidobacterium while reducing opportunistic pathogens including Romboutsia (p < 0.05). Furthermore, alpha diversity indices (Chao1 and ACE) were significantly higher in the FMT group than in all other groups (p < 0.05), indicating enhanced microbial richness and community stability. Functional prediction using PICRUSt2 revealed that FMT-enriched metabolic pathways (particularly those associated with SCFA production) and enhanced gut barrier-related functions. Collectively, this study deepens our understanding of host–microbe interactions under HFD-induced metabolic stress and provides mechanistic insights into how FMT restores gut homeostasis, highlighting its potential as a therapeutic strategy for diet-induced dysbiosis and associated metabolic disorders.

Intensive yak fattening in cold alpine regions requires essential long-term high-concentration feeding, which disrupts rumen microbial homeostasis and causes inefficient digestion of nutrients. Lactobacillus may have probiotic potential for ruminants, yet its regulation of rumen function is poorly understood under high-energy diets. During a 120-day feeding experiment, 120 male Pamir yaks were allocated to four dietary treatments, with LEG and LLG serving as the primary comparison for evaluating 0.02% Lactobacillus supplementation to explore the regulatory effects of Lactobacillus supplementation on the rumen microbiota and host metabolism of yaks during a fattening process based on a concentrate feed diet via phenotypic data (body wight and nutrient digestibility) and multi-omics analyses (rumen microbial sequencing and rumen epithelial transcriptome) in a concentrate-based rearing yak model. The results showed that Lactobacillus intervention reduced OTU (Operational Taxonomic Unit) richness during the early fattening period and subsequently promoted microbial recovery through colonization resistance, which significantly enhanced microbial diversity (p < 0.05), and restructured the microbial community structure toward efficient energy utilization under high-concentrate feeding by reducing Prevotellaceae and Ruminococcaceae abundance, increasing the Bacillota/Bacteroidota ratio (p < 0.05). Concurrently, Lactobacillus enhanced the apparent digestibility of dry matter, crude protein, and fibrous components (p < 0.05). According to the transcriptomic analysis, there was an activation of signaling pathways related to IL-18 and TNF, and up-regulation of immune-and metabolism-related genes, in addition to strengthening the rumen mucosal barrier function. Multi-omics integration supported that dietary supplementation of Lactobacillus can optimize rumen fermentation, enhance nutrient digestion, and strengthen immune defense in Pamir yaks fed high-concentrate in cold seasons. These modifications demonstrate the positive effects of the Lactobacillus supplementation strategy on yak rumen health without interfering with the high-energy intensive rearing pattern. The present research presents a scientific basis for the use of targeted probiotic strategies to improve the rumen health and efficiency of alpine yak production systems.