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
Sheep were domesticated in the Fertile Crescent and then spread globally,where they have been encountering various environmental conditions.The Tibetan sheep has adapted to high altitudes on the Qinghai-Tibet Plateau ...Sheep were domesticated in the Fertile Crescent and then spread globally,where they have been encountering various environmental conditions.The Tibetan sheep has adapted to high altitudes on the Qinghai-Tibet Plateau over the past 3000 years.To explore genomic variants associated with high-altitude adaptation in Tibetan sheep,we analyzed Illumina short-reads of 994 whole genomes representing∼60 sheep breeds/populations at varied altitudes,PacBio High fidelity(HiFi)reads of 13 breeds,and 96 transcriptomes from 12 sheep organs.Association testing between the inhabited altitudes and 34,298,967 variants was conducted to investigate the genetic architecture of altitude adaptation.Highly accurate HiFi reads were used to complement the current ovine reference assembly at the most significantly associatedβ-globin locus and to validate the presence of two haplotypes A and B among 13 sheep breeds.The haplotype A carried two homologous gene clusters:(1)HBE1,HBE2,HBB-like,and HBBC,and(2)HBE1-like,HBE2-like,HBB-like,and HBB;while the haplotype B lacked the first cluster.The high-altitude sheep showed highly frequent or nearly fixed haplotype A,while the low-altitude sheep dominated by haplotype B.We further demonstrated that sheep with haplotype A had an increased hemoglobin–O_(2)affinity compared with those carrying haplotype B.Another highly associated genomic region contained the EGLN1 gene which showed varied expression between high-altitude and low-altitude sheep.Our results provide evidence that the rapid adaptive evolution of advantageous alleles play an important role in facilitating the environmental adaptation of Tibetan sheep.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supported by the Tibetan R&D Program,China(Grant No.XZ202101ZD0001N)the China Agriculture Research System(Grant No.CARS-39)the National Natural Science Foundation of China(Grant Nos.31900313,32161143010,and 31972526).
文摘Sheep were domesticated in the Fertile Crescent and then spread globally,where they have been encountering various environmental conditions.The Tibetan sheep has adapted to high altitudes on the Qinghai-Tibet Plateau over the past 3000 years.To explore genomic variants associated with high-altitude adaptation in Tibetan sheep,we analyzed Illumina short-reads of 994 whole genomes representing∼60 sheep breeds/populations at varied altitudes,PacBio High fidelity(HiFi)reads of 13 breeds,and 96 transcriptomes from 12 sheep organs.Association testing between the inhabited altitudes and 34,298,967 variants was conducted to investigate the genetic architecture of altitude adaptation.Highly accurate HiFi reads were used to complement the current ovine reference assembly at the most significantly associatedβ-globin locus and to validate the presence of two haplotypes A and B among 13 sheep breeds.The haplotype A carried two homologous gene clusters:(1)HBE1,HBE2,HBB-like,and HBBC,and(2)HBE1-like,HBE2-like,HBB-like,and HBB;while the haplotype B lacked the first cluster.The high-altitude sheep showed highly frequent or nearly fixed haplotype A,while the low-altitude sheep dominated by haplotype B.We further demonstrated that sheep with haplotype A had an increased hemoglobin–O_(2)affinity compared with those carrying haplotype B.Another highly associated genomic region contained the EGLN1 gene which showed varied expression between high-altitude and low-altitude sheep.Our results provide evidence that the rapid adaptive evolution of advantageous alleles play an important role in facilitating the environmental adaptation of Tibetan sheep.
