Introduction: Enterotoxigenic Escherichia coli (ETEC) is the main diarrhea-causing pathogen in children and young animals and has become a global health concern. Berberine is a type of “medicine and food homology” and has a long history of use in China, particularly in treating gastrointestinal disorders and bacterial diarrhea.Methods: In this study, we explored the effects of berberine on growth performance, intestinal inflammation, oxidative damage, and intestinal microbiota in a weaned piglet model of ETEC infection. Twenty-four piglets were randomly divided into four groups—a control group (fed a basal diet [BD] and infused with saline), a BD+ETEC group (fed a basal diet and infused with ETEC), a LB+ETEC group (fed a basal diet with 0.05% berberine and infused with ETEC infection), and a HB+ETEC group (fed a basal diet with 0.1% berberine and infused with ETEC).Results: Berberine significantly improved the final body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI) (P<0.05) of piglets, and effectively decreased the incidence of diarrhea among the animals (P<0.05). Additionally, berberine significantly downregulated the expression levels of the genes encoding TNF-α, IL-1β, IL-6, IL-8, TLR4, MyD88, NF-κB, IKKα, and IKKβ in the small intestine of piglets (P<0.05). ETEC infection significantly upregulated the expression of genes coding for Nrf2, CAT, SOD1, GPX1, GST, NQO1, HO-1, GCLC, and GCLM in the small intestine of the animals (P<0.05). Berberine significantly upregulated 12 functional COG categories and 7 KEGG signaling pathways. A correlation analysis showed that berberine significantly increased the relative abundance of beneficial bacteria (Gemmiger, Pediococcus, Levilactobacillus, Clostridium, Lactiplantibacillus, Weissella, Enterococcus, Blautia, and Butyricicoccus) and decreased that of pathogenic bacteria (Prevotella, Streptococcus, Parabacteroides, Flavonifractor, Alloprevotella) known to be closely related to intestinal inflammation and oxidative stress in piglets. In conclusion, ETEC infection disrupted the intestinal microbiota in weaned piglets, upregulating the TLR4/MyD88/NF-κB and Nrf2 signaling pathways, and consequently leading to intestinal inflammation and oxidative stress-induced damage.Discussion: Our data indicated that berberine can optimize intestinal microbiota balance and modulate the TLR4/MyD88/NF-κB and Nrf2 signaling pathways, thus helping to alleviate intestinal inflammation and oxidative damage caused by ETEC infection in weaned piglets.

Introduction: Enterotoxic Escherichia coli (ETEC) is the main pathogen that causes diarrhea, especially in young children. This disease can lead to substantial morbidity and mortality and is a major global health concern. Managing ETEC infections is challenging owing to the increasing prevalence of antibiotic resistance. Berberine, categorized as a substance with similarities in “medicine and food,” has been used in China for hundreds of years to treat gastrointestinal disorders and bacteria-induced diarrhea. This study investigated the preventive effect of dietary berberine on the intestinal mucosal barrier induced by ETEC and the microbial community within the intestines of weaned piglets.Methods: Twenty-four piglets were randomly divided into four groups. Piglets were administered either a standard diet or a standard diet supplemented with berberine at concentrations of 0.05 and 0.1%. and orally administered ETEC or saline.Results: Dietary supplementation with berberine reduced diamine oxidase, d-lactate, and endotoxin levels in piglets infected with ETEC (P < 0.05). Berberine increased jejunal villus height, villus/crypt ratio, mucosal thickness (P < 0.05), and goblet cell numbers in the villi and crypts (P < 0.05). Furthermore, berberine increased the optical density of mucin 2 and the mucin 2, P-glycoprotein, and CYP3A4 mRNA expression levels (P < 0.05). Berberine increased the expressions of zonula occludins-1 (ZO-1), zonula occludins-2 (ZO-2), Claudin-1, Occludin, and E-cadherin in the ileum (P < 0.05). Moreover, berberine increased the expression of BCL2, reduced intestinal epithelial cell apoptosis (P < 0.05) and decreased the expression of BAX and BAK in the duodenum and jejunum, as well as that of CASP3 and CASP9 in the duodenum and ileum (P < 0.05). Berberine decreased the expression of IL-1β, IL-6, IL-8, TNF-α, and IFN-γ (P < 0.05) and elevated total volatile fatty acids, acetic acid, propionic acid, valeric acid, and isovaleric acid concentrations (P < 0.05). Notably, berberine enhanced the abundance of beneficial bacteria including Enterococcus, Holdemanella, Weissella, Pediococcus, Muribaculum, Colidextribacter, Agathobacter, Roseburia, Clostridium, Fusicatenibacter, and Bifidobacterium. Simultaneously, the relative abundance of harmful and pathogenic bacteria, such as Prevotella, Paraprevotella, Corynebacterium, Catenisphaera, Streptococcus, Enterobacter, and Collinsella, decreased (P < 0.05).Discussion: Berberine alleviated ETEC-induced intestinal mucosal barrier damage in weaned piglets models. This is associated with enhancement of the physical, chemical, and immune barrier functions of piglets by enhancing intestinal microbiota homeostasis.

Traditional Chinese medicine (TCM) has long been demonstrated to exert a therapeutic effect on various diseases and has been used as a substitute for antibiotics in pig production. However, few studies have investigated the relationship between the intestinal microbiota and apparent nutrient digestibility when weaned piglet diets are supplemented with TCM. One hundred and sixty-two 25-day-old weaning piglets were housed in an environmentally controlled nursery facility and fed a basal diet (control group, n = 54) or a TCM complex (Fructus mume 1%, Scutellaria baicalensis Georgi 3%) (TCM group, n = 54), or a fermented diet with a complex of these two TCMs (F-TCM group, n = 54). Compared with the control group, in the TCM and F-TCM groups, the average daily gain (ADG) increased (p < 0.05), the F:G ratio and diarrhea rate decreased (p < 0.05), and the apparent digestibility of dry matter (DM) and ether extract (EE) of weaned piglets increased (p < 0.05). Bacteroidetes and Firmicutes were the predominant phyla, representing approximately 95% of all sequences. The abundance of four genera and 10 OTUs (belonging to Ruminococcaceae_UCG-014, Lachnoclostridium, Prevotellaceae_NK3B31 group, Prevotella_1) were negatively correlated with apparent EE digestibility (p < 0.05). The results suggest that weaned piglets fed with antibiotic-free diets supplemented with Fructus mume and Scutellaria baicalensis Georgi gained more weight and were healthier. When added to the diet, the complex of these two TCMs may have a direct impact on apparent EE digestibility by modifying the gut microbial composition, which favors the health of weaned piglets.

Sustained dysfunction of the intestinal barrier caused by early weaning is a major factor that induces postweaning diarrhea in weaned piglets. In both healthy and diseased states, the intestinal barrier is regulated by goblet cells. Alterations in the characteristics of goblet cells are linked to intestinal barrier dysfunction and inflammatory conditions during pathogenic infections. In this review, we summarize the current understanding of the mechanisms of the unfolded protein response (UPR) and anterior gradient 2 (AGR2) in maintaining intestinal barrier function and how modifications to these systems affect mucus barrier characteristics and goblet cell dysregulation. We highlight a novel mechanism underlying the UPR-AGR2 pathway, which affects goblet cell differentiation and maturation and the synthesis and secretion of mucin by regulating epidermal growth factor receptor and mucin 2. This study provides a theoretical basis and new insights into the regulation of intestinal health in weaned piglets.

Deoxynivalenol (DON) is a prevalent foodborne contaminant present in crops, posing significant risks to food safety and public health worldwide. Mitochondria, as the primary target of DON, play a crucial role in DON-mediated gastrointestinal toxicity. Taurine, a multifunctional nutrient, has been reported to exert antioxidant and anti-inflammatory effects by modulating mitochondrial function. However, whether taurine could alleviate intestinal injury by restoring mitochondrial function under DON exposure remains unclear. To address this knowledge gap, this study systematically investigated the potential protective effects of taurine on DON-induced intestinal damage in a piglet model. Twenty-four piglets were randomly assigned to four groups for 24 days: BD group (basal diet), DON group (3 mg/kg DON-contaminated diet), DON+LT group (DON diet with 0.3 % taurine), and DON+HT group (DON diet with 0.6 % taurine). Serum samples were collected for biochemical analysis, while jejunal tissues were examined for histology, barrier function, oxidative stress, inflammation, apoptosis, mitochondrial function, as well as related gene and protein expression. The results revealed that taurine effectively restored jejunal morphology disrupted by DON, as evidenced by increases in villus height/width and the villus height to crypt depth ratio. It preserved intestinal barrier integrity, reflected by reductions in diamine oxidase and D-lactate levels, alongside increased expression of genes and proteins related to intestinal mucus and mechanical barrier function. Furthermore, taurine mitigated intestinal oxidative stress by reducing reactive oxygen species, 8-hydroxydeoxyguanosine, and malondialdehyde levels, while enhancing antioxidant defenses. It also alleviated inflammation by suppressing pro-inflammatory cytokines and attenuated intestinal epithelial apoptosis through mitochondrial caspase-dependent and apoptosis-inducing factor-mediated pathways. Intriguingly, taurine improved the damaged mitochondrial structure and functionality within the intestinal epithelium irritated by DON. This improvement included enhanced respiratory chain complex activity, increased ATP levels, and mtDNA copy number. Additionally, taurine regulated gene expression related to mitochondrial respiration, fusion, fission, and autophagy. Simultaneously, taurine reversed the DON-induced inhibition of the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α)-nuclear respiratory factor 1/2 (NRF1/2) axis, a critical pathway regulating mitochondrial biogenesis, respiratory function, and oxidative stress responses. Correlation analysis revealed significant associations between the PGC1α-NRF1/2 axis and mitochondrial function, as well as correlations with intestinal health parameters, including barrier function, redox status, inflammation, and apoptosis. In summary, this study provides the first evidence that dietary taurine supplementation effectively alleviates intestinal injury in DON-challenged piglets through mitochondrial restoration, which is strongly associated with the reactivation of the PGC1α-NRF1/2 axis. Our findings highlight the potential of mitochondrial-targeted therapies to mitigate gastrointestinal toxicity caused by the foodborne contaminant DON in both humans and animals.

This study aimed to investigate the microbial structure and function in the rectum of weaned piglets with berberine supplementation. Twelve healthy 21-day-old Duorc × (Landrace × Large White) weaned piglets (similar body weight) were evenly divided into control and berberine groups and were fed a basal diet supplemented with 0 and 0.1% berberine, respectively. After 21 days, metagenomic sequencing analysis was performed to detect microbial composition and function in the rectum of weaned piglets. Results showed that there were 10,597,721,931–14,059,392,900 base pairs (bp) and 10,186,558,171–15,859,563,342 bp of clean data in the control and berberine groups, respectively. The Q20s of the control and berberine groups were 97.15 to 97.7% and 96.26 to 97.68%, respectively. The microorganisms in the berberine group had lower (p < 0.05) Chao1, alternating conditional expectation, Shannon, and Simpson indices at the species levels than those in the control group. Analysis of similarity showed that there were significant differences (p < 0.01) between the control and berberine groups at the genus and species levels of the gut microorganisms. Dietary berberine significantly increased (p < 0.05) the abundance of Subdoligranulum variabile, but decreased (p < 0.05) the abundance of Prevotella copri compared with the control group. Carbohydrate-active enzymes analysis revealed that the levels of polysaccharide lyases and carbohydrate esterases were lower (p < 0.05) in the berberine group than that in the control group. Linear discriminant analysis effect size analysis showed that berberine supplementation could induce various significant Kyoto Encyclopedia of Genes and Genomes pathways, including carbohydrate metabolism, environmental information processing, and microbial metabolism in diverse environments. In conclusion, our findings suggest that berberine could improve the composition, abundance, structure, and function of gut microbiome in the weaned piglets, potentially providing a suitable approach for the application of berberine in human and animal health.