Gut microbiota-derived metabolites contribute negatively to hindgut barrier function development at the early weaning goat model  

作　　者：Ke Zhang Yangbin Xu Yuxin Yang Mengmeng Guo Ting Zhang Bo Zong Shuhong Huang Langda Suo Baohua Ma Xiaolong Wang Yujiang Wu Daniel Brugger Yulin Chen 

机构地区：[1]Key Laboratory of Animal Genetics,Breeding and Reproduction of Shaanxi Province,College of Animal Science and Technology,Northwest A&F University,Yangling,712100,China [2]College of Veterinary Medicine,Northwest A&F University,Yangling,712100,China [3]Institute of Animal Sciences,Tibet Academy of Agricultural and Animal Husbandry Sciences,Lhasa,850009,China [4]Institute of Animal Nutrition and Dietetics,Vetsuisse-Faculty,University of Zurich,8057,Zurich,Switzerland

出　　处：《Animal Nutrition》2022年第3期111-123,共13页动物营养（英文版）

基　　金：Qinghai Province Key R&D and Transformation Plan(2020-NK-127);Tibet Science and Technology Department's"13th Five-Year Plan"Major Agriculture Project(XZ201901NA02);the Key Technology R&D Program of Xinjiang Groups(2020AB016);Science and Technology Program of Tibet(XZ202001YD0017C);Agriculture Research System of China(CARS-39-12).

摘　　要：Early weaning induces intestinal injury,leading to a series of long-term symptoms such as inflammation,malabsorption and diarrhea.In this study,we hypothesized that microbes and theirmetabolitesmodulate the host's inflammatory response to early weaning stress in a goatmodel.A total of 18 female Tibetan goat kids(n?9)wereweaned fromtheirmothers at 28 d(D28)and 60 d(D60)postpartum.D60 and D28 groupswere fed the same solid diet ad libitum fromweaning to 75 d of age.The colonic epithelium was subject to RNAsequencing,the caecal digesta metabolomics were assessed by liquid chromatographyetandem mass spectrometry(LC-MS/MS),and the caecal microbiota composition was analysed by 16S ribosomal RNA gene sequencing.We foundthatearlyweaningsubstantially increased the colonic pro-apoptotic gene expressionof B-cell lymphoma associated X(Bax),caspase-9,and caspase-3,and decreased the expression of zonula occludens-1(ZO-1)and claudin-1(P<0.01).In addition,a significant Bacteroides acidifaciens enrichmentwas observed in the hindgut of early-weaned goats(P<0.01),which negatively correlated with lysophosphatidylcholine products.Similarly,the chemokine signaling,IL-17 signaling,and peroxisome proliferatorsactivated receptor(PPAR)signaling pathways were upregulated in the colonic mucosa of the early-weaned goats.By applying caecal microbiota transplantation from goats to defaunated C57/6J mice,we confirmed that caecalmicrobiota of D28 goat kids increased the relative abundance of B.acidifaciens and significantly upregulated the genes of Bax,G proteinecoupled receptor(GPR)109A,GPR 43,fatty acid binding protein 6,nuclear receptor subfamily 1 group H member 3,angiotensin converting enzyme 2,and IL-6 expression(P<0.05),and decreased ZO-1,and claudin-1 protein expression in the mice jejunum and colon(P<0.001).These results proposed that the hindgut microbiota andmetabolites mediate the barrier functionweakening duringearlyweaning,and the relative abundance of B.acidifacienswas negatively correlatedwiththe hindgut barrier gene expression.Th

关 键 词：Hindgut microbiome RUMINANT DYSBIOSIS Inflammation Colon 

分 类 号：S827[农业科学—畜牧学]