Lactate alleviates intestinal barrier injury in weaned piglets via activation of the Wnt/β-catenin pathway and promotion of intestinal epithelial cell proliferationOA
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 6021-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.
Mingyu Wang;Yifan Chen;Jiaojiao Chen;Aimin Wu;Daiwen Chen;Bing Yu;Jun He;Jie Yu;Xiangbing Mao;Zhiqing Huang;Yuheng Luo;Junqiu Luo;Ping Zheng
Institute of Animal Nutrition,Sichuan Agricultural University,Key Laboratory of Animal Disease-Resistance Nutrition,Ministry of Education,and Key Laboratory of Animal Disease-Resistant Nutrition,Sichuan Province,Chengdu 611130,People’s Republic of ChinaCollege of Animal Science and Technology,Hebei Agricultural University,Hebei 071000,People’s Republic of ChinaInstitute of Animal Nutrition,Sichuan Agricultural University,Key Laboratory of Animal Disease-Resistance Nutrition,Ministry of Education,and Key Laboratory of Animal Disease-Resistant Nutrition,Sichuan Province,Chengdu 611130,People’s Republic of ChinaInstitute of Animal Nutrition,Sichuan Agricultural University,Key Laboratory of Animal Disease-Resistance Nutrition,Ministry of Education,and Key Laboratory of Animal Disease-Resistant Nutrition,Sichuan Province,Chengdu 611130,People’s Republic of ChinaInstitute of Animal Nutrition,Sichuan Agricultural University,Key Laboratory of Animal Disease-Resistance Nutrition,Ministry of Education,and Key Laboratory of Animal Disease-Resistant Nutrition,Sichuan Province,Chengdu 611130,People’s Republic of ChinaInstitute of Animal Nutrition,Sichuan Agricultural University,Key Laboratory of Animal Disease-Resistance Nutrition,Ministry of Education,and Key Laboratory of Animal Disease-Resistant Nutrition,Sichuan Province,Chengdu 611130,People’s Republic of ChinaInstitute of Animal Nutrition,Sichuan Agricultural University,Key Laboratory of Animal Disease-Resistance Nutrition,Ministry of Education,and Key Laboratory of Animal Disease-Resistant Nutrition,Sichuan Province,Chengdu 611130,People’s Republic of ChinaInstitute of Animal Nutrition,Sichuan Agricultural University,Key Laboratory of Animal Disease-Resistance Nutrition,Ministry of Education,and Key Laboratory of Animal Disease-Resistant Nutrition,Sichuan Province,Chengdu 611130,People’s Republic of ChinaInstitute of Animal Nutrition,Sichuan Agricultural University,Key Laboratory of Animal Disease-Resistance Nutrition,Ministry of Education,and Key Laboratory of Animal Disease-Resistant Nutrition,Sichuan Province,Chengdu 611130,People’s Republic of ChinaInstitute of Animal Nutrition,Sichuan Agricultural University,Key Laboratory of Animal Disease-Resistance Nutrition,Ministry of Education,and Key Laboratory of Animal Disease-Resistant Nutrition,Sichuan Province,Chengdu 611130,People’s Republic of ChinaInstitute of Animal Nutrition,Sichuan Agricultural University,Key Laboratory of Animal Disease-Resistance Nutrition,Ministry of Education,and Key Laboratory of Animal Disease-Resistant Nutrition,Sichuan Province,Chengdu 611130,People’s Republic of ChinaInstitute of Animal Nutrition,Sichuan Agricultural University,Key Laboratory of Animal Disease-Resistance Nutrition,Ministry of Education,and Key Laboratory of Animal Disease-Resistant Nutrition,Sichuan Province,Chengdu 611130,People’s Republic of ChinaInstitute of Animal Nutrition,Sichuan Agricultural University,Key Laboratory of Animal Disease-Resistance Nutrition,Ministry of Education,and Key Laboratory of Animal Disease-Resistant Nutrition,Sichuan Province,Chengdu 611130,People’s Republic of China
农业科技
ApoptosisIntestinal inflammationLactateLgr5PigletsProliferationWnt/β-catenin pathway
《Journal of Animal Science and Biotechnology》 2026 (1)
P.443-456,14
funded by the Sichuan Science and Technology Program(2021ZDZX0009)the earmarked fund from the National Natural Science Foundation of China(31972577)。
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