Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucid...Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucidate the effects of milk replacer(MR)feeding on growth,lipid metabolism,colonic epithelial gene expression,colonic microbiota composition and systemic metabolism in goat kids compared to breast milk(BM)feeding,addressing a critical knowledge gap in early life nutrition.Methods Ten female goat kids were divided into 2 groups:those fed breast milk(BM group)and those fed a milk replacer(MR group).Over a period of 28 d,body weight was monitored and blood and tissue samples were collected for biochemical,transcriptomic and metabolomic analyses.Profiling of the colonial microbiota was performed using 16S rRNA gene sequencing.Intestinal microbiota transplantation(IMT)experiments in gnotobiotic mice were per-formed to validate causality.Results MR-fed pups exhibited reduced daily body-weight gain due to impaired lipid metabolism as evidenced by lower serum and liver total cholesterol(TC)and non-esterified fatty acid(NEFA)concentrations.Transcriptomic analysis of the colonic epithelium revealed upregulated genes involved in negative regulation of lipid metabolism,concomitant with microbiota shifts characterized by a decrease in Firmicutes and an increase in Actinobacteria.Specifically,genera such as Bifidobacterium and Prevotella were enriched in the MR group,while Clostridium and Fae-calibacterium were depleted.Metabolomics analyses confirmed alterations in bile acid and fatty acid metabolic path-ways.IMT experiments in mice recapitulated the metabolic phenotype observed in MR-fed goats,confirming the role of the microbiota in modulating host lipid metabolism.Conclusions Milk replacer feeding in goat kids disrupts lipid metabolism and gut microbiota dynamics,result-ing in reduced growth rates and metabolic alterations.These findings highlight the importance of early nutritional intervention on metabolic programming and suggest that modulation of the gut microbiota may be a target for improving growth and metabolic health in ruminants.This study contributes to the understanding of nutritional management strategies in livestock and their impact on animal health and productivity.展开更多
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...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.This studydemonstrateshowweaningstress canaffectkeyhostemicrobe interaction regulators in the hindgut,in a lysophosphatidylcholine dependent and independent manner.Furthermore,based on our mice data,these results are transferable to other mammal species.展开更多
基金financially supported by National Natural Science Foundation of China (32160801)China Agriculture Research System (CARS-39-12)+1 种基金Young Talent Fund of Association for Science and Technology in Shaanxi, China (2023-6-2-1)“Double-chain” project on livestock breeding (2022GDTSLD-46)
文摘Background Dysregulation of lipid metabolism and its consequences on growth performance in young ruminants have attracted attention,especially in the context of alternative feeding strategies.This study aims to elucidate the effects of milk replacer(MR)feeding on growth,lipid metabolism,colonic epithelial gene expression,colonic microbiota composition and systemic metabolism in goat kids compared to breast milk(BM)feeding,addressing a critical knowledge gap in early life nutrition.Methods Ten female goat kids were divided into 2 groups:those fed breast milk(BM group)and those fed a milk replacer(MR group).Over a period of 28 d,body weight was monitored and blood and tissue samples were collected for biochemical,transcriptomic and metabolomic analyses.Profiling of the colonial microbiota was performed using 16S rRNA gene sequencing.Intestinal microbiota transplantation(IMT)experiments in gnotobiotic mice were per-formed to validate causality.Results MR-fed pups exhibited reduced daily body-weight gain due to impaired lipid metabolism as evidenced by lower serum and liver total cholesterol(TC)and non-esterified fatty acid(NEFA)concentrations.Transcriptomic analysis of the colonic epithelium revealed upregulated genes involved in negative regulation of lipid metabolism,concomitant with microbiota shifts characterized by a decrease in Firmicutes and an increase in Actinobacteria.Specifically,genera such as Bifidobacterium and Prevotella were enriched in the MR group,while Clostridium and Fae-calibacterium were depleted.Metabolomics analyses confirmed alterations in bile acid and fatty acid metabolic path-ways.IMT experiments in mice recapitulated the metabolic phenotype observed in MR-fed goats,confirming the role of the microbiota in modulating host lipid metabolism.Conclusions Milk replacer feeding in goat kids disrupts lipid metabolism and gut microbiota dynamics,result-ing in reduced growth rates and metabolic alterations.These findings highlight the importance of early nutritional intervention on metabolic programming and suggest that modulation of the gut microbiota may be a target for improving growth and metabolic health in ruminants.This study contributes to the understanding of nutritional management strategies in livestock and their impact on animal health and productivity.
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)+2 种基金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).
文摘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.This studydemonstrateshowweaningstress canaffectkeyhostemicrobe interaction regulators in the hindgut,in a lysophosphatidylcholine dependent and independent manner.Furthermore,based on our mice data,these results are transferable to other mammal species.
