Lactate alleviates intestinal barrier injury in weaned piglets via activation of the Wnt/β-catenin pathway and promotion of intestinal epithelial cell proliferation
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Background
Inflammatory bowel disease causes intestinal structural damage, impairs gut function, hinders animal growth and development, and reduces farming efficiency. Previous studies demonstrated that lactate alleviates dextran sulfate sodium (DSS)-induced inflammation and mitigates weight loss by enhancing intestinal barrier functions. However, the mechanisms underlying lactate-mediated protection of the intestinal epithelial barrier remain unclear. This study aimed to explore the protective effect of lactate on intestinal barrier damage in colitis piglets and the possible underlying mechanisms through in vivo and in vitro experiments.
Methods
A total of 60 21-day-old weaned female piglets were randomly assigned into three groups based on weight: the control group (basal diet with physiological saline gavage), the DSS group (basal diet with 5% DSS gavage), and the DSS + LA group (2% lactate diet with 5% DSS gavage). There were 10 replicates per treatment, with 2 piglets per replicate. Jejunal morphology was assessed via hematoxylin and eosin staining, while Western blotting quantified the protein levels of proliferation markers, including cluster of differentiation 24 (CD24), cyclin D1, and wingless/integrated (Wnt)/β-catenin signaling components. In vitro, 0.08% DSS and 2–32 mmol/L sodium lactate-treated intestinal porcine epithelial cell line-J2 (IPEC-J2) cells ( n = 4) were assessed for viability (Cell Counting Kit-8 assay), apoptosis (flow cytometry), and proliferation parameters, including cell cycle analysis and Leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5 + ) stem cell quantification.
Results
In vivo, DSS administration induced jejunal villus shortening ( P < 0.05), downregulated protein levels of CD24, cyclin D1, casein kinase 1 (CK1), and dishevelled-2 (DVL2) ( P < 0.05). In vitro, DSS promoted apoptosis, inhibited proliferation, diminished the Lgr5 + cell populations ( P < 0.05), and reduced S-phase cell proportions ( P < 0.05). Conversely, lactate supplementation ameliorated DSS-induced villus atrophy ( P < 0.05), restored CD24, cyclin D1, CK1, and DVL2 protein levels ( P < 0.05). Furthermore, in vitro, sodium lactate attenuated DSS-induced apoptosis ( P < 0.05), enhanced IPEC-J2 proliferation ( P < 0.05), expanded Lgr5 + cells ( P < 0.05), and increased S-phase progression ( P < 0.05).
Conclusions
In summary, lactate ameliorated intestinal barrier damage in DSS-induced colitis by activating the Wnt/β-catenin pathway and restoring the balance between epithelial cell proliferation and apoptosis. This study provides novel mechanistic evidence supporting lactate’s therapeutic potential for IBD management.
