马斌,王磊,陈小伟,沙玉柱,陈倩玲,杨文鑫,黄薇,刘秀

• 1:甘肃农业大学动物科学技术学院
• 2:张掖市家畜繁育改良工作站
• 3:甘肃农业大学动物医学院

摘要(Abstract)：

为探究不同海拔的藏绵羊瘤胃微生物代谢物及血清代谢组特征，本研究以分布在海拔高度为2 500 m(LA)、3 500 m(MA)和4 500 m(HA)的3.5岁、健康状况良好的藏绵羊母羊各6只为研究对象，通过非靶向代谢组学技术（LC-MS/MS）对其瘤胃液和血清进行代谢组测定分析。结果表明，3个海拔的藏绵羊群体中共鉴定出1 394个瘤胃微生物代谢物，其中果糖赖氨酸含量3 500 m组显著高于其他两个海拔组（P<0.05）,L-犬尿氨酸含量随海拔升高显著减少（P<0.05）。通过KEGG功能注释分析发现，3 500 m与4 500 m组藏绵羊瘤胃微生物的差异代谢物主要富集在氨基酸、脂质和碳水化合物代谢途径中，其中3 500 m组的差异代谢物上调，主要富集在维生素B6代谢通路，4 500 m组的差异代谢物富集在嘧啶代谢通路。在不同海拔藏绵羊血清中共鉴定出3 582个代谢物，3 500 m和4 500 m组藏绵羊的差异代谢物主要富集在氨基酸代谢、脂质代谢和细胞色素P450介导的外源性物质代谢等通路中。另外，在瘤胃液和血清中鉴定到274个共有代谢物，这些共有代谢物主要富集在代谢相关通路中。综上所述，不同海拔藏绵羊的瘤胃微生物代谢物和血清代谢物在脂质代谢、能量代谢和免疫代谢相关的通路中富集，可能参与了藏绵羊对高原环境变化的适应性调节。

关键词(KeyWords)： 藏绵羊;瘤胃;微生物代谢物;血清代谢物;海拔

Abstract:

Keywords:

基金项目(Foundation): 甘肃省技术创新引导计划（24CXNG008）

作者(Author): 马斌,王磊,陈小伟,沙玉柱,陈倩玲,杨文鑫,黄薇,刘秀

参考文献(References)：

• [1] WEN Y,LI S,ZHAO F,et al. Changes in the mitochondrial dynamics and functions together with the mRNA/miRNA network in the heart tissue contribute to hypoxia adaptation in Tibetan sheep[J]. Animals(Basel),2022,12(5):583.
• [2] JING X,WANG W,DEGEN A,et al. Tibetan sheep have a high capacity to absorb and to regulate metabolism of SCFA in the rumen epithelium to adapt to low energy intake[J]. Br J Nutr,2020,123(7):721-736.
• [3] HACKMANN T J,SPAIN J N. Invited review:ruminant ecology and evolution:perspectives useful to ruminant livestock research and production[J]. J Dairy Sci,2010,93(4):1320-1334.
• [4] LIN L,XIE F,SUN D,et al. Ruminal microbiome-host crosstalk stimulates the development of the ruminal epithelium in a lamb model[J]. Microbiome,2019,7(1):83.
• [5] REY M,ENJALBERT F,COMBES S,et al. Establishment of ruminal bacterial community in dairy calves from birth to weaning is sequential[J]. J Appl Microbiol,2014,116(2):245-257.
• [6] CECONI I,RUIZ-MORENO M J,DILORENZO N,et al. Effect of urea inclusion in diets containing corn dried distillers grains on feedlot cattle performance,carcass characteristics,ruminal fermentation,total tract digestibility,and purine derivatives-to-creatinine index[J]. J Anim Sci,2015,93(1):357-369.
• [7] JIANG S Z,YANG Z B,YANG W R,et al. Diets of differentially processed wheat alter ruminal fermentation parameters and microbial populations in beef cattle[J]. J Anim Sci,2015,93(11):5378-5385.
• [8] ZHANG Z,XU D,WANG L,et al. Convergent evolution of rumen microbiomes in high-altitude mammals[J]. Curr Biol,2016,26(14):1873-1879.
• [9] HESS M,SCZYRBA A,EGAN R,et al. Metagenomic discovery of biomass-degrading genes and genomes from cow rumen[J]. Science,2011,331(6016):463-467.
• [10] MUEGGE B D,KUCZYNSKI J,KNIGHTS D,et al. Diet drives convergence in gut microbiome functions across mammalian phylogeny and within humans[J]. Science,2011,332(6032):970-974.
• [11] ZENG B,ZHANG S,XU H,et al. Gut microbiota of Tibetans and Tibetan pigs varies between high and low altitude environments[J].Microbiol Res,2020,235:126447.
• [12] SHA Y,REN Y,ZHAO S,et al. Response of ruminal microbiotahost gene interaction to high-altitude environments in Tibetan sheep[J]. Int J Mol Sci,2022,23(20):12430.
• [13] HUA C,TIAN J,TIAN P,et al. Feeding a high concentration diet induces unhealthy alterations in the composition and metabolism of ruminal microbiota and host response in a goat model[J]. Front Microbiol,2017,8:138.
• [14] TIAN H,WANG W,ZHENG N,et al. Identification of diagnostic biomarkers and metabolic pathway shifts of heat-stressed lactating dairy cows[J]. J Proteomics,2015,125:17-28.
• [15] XUE M Y,SUN H Z,WU X H,et al. Multi-omics reveals that the rumen microbiome and its metabolome together with the host metabolome contribute to individualized dairy cow performance[J]. Microbiome,2020,8(1):64.
• [16] MALMUTHUGE N,LIANG G,GUAN L L. Regulation of rumen development in neonatal ruminants through microbial metagenomes and host transcriptomes[J]. Genome Biol,2019,20(1):172.
• [17] MAO S Y,HUO W J,ZHU W Y. Microbiome-metabolome analysis reveals unhealthy alterations in the composition and metabolism of ruminal microbiota with increasing dietary grain in a goat model[J]. Environ Microbiol,2016,18(2):525-541.
• [18] YANG S,SADILEK M,LIDSTROM M E. Streamlined pentafluorophenylpropyl column liquid chromatography-tandem quadrupole mass spectrometry and global(13)C-labeled internal standards improve performance for quantitative metabolomics in bacteria[J]. J Chromatogr A,2010,1217(47):7401-7410.
• [19] DUNN W B,BROADHURST D,BEGLEY P,et al. Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry[J].Nature Protocols,2011,6(7):1060-1083.
• [20] WANT E J,WILSON I D,GIKA H,et al. Global metabolic profiling procedures for urine using UPLC-MS[J]. Nature Protocols,2010,5(6):1005-1018.
• [21] LIU X,SHA Y,LV W,et al. Multi-omics reveals that the rumen transcriptome,microbiome,and its metabolome co-regulate cold season adaptability of Tibetan sheep[J]. Frontiers in Microbiology,2022,13:859601.
• [22] KANEHISA M,GOTO S. KEGG:kyoto encyclopedia of genes and genomes[J]. Nucleic Acids Res,2000,28(1):27-30.
• [23] BUI T P,RITARI J,BOEREN S,et al. Production of butyrate from lysine and the Amadori product fructoselysine by a human gut commensal[J]. Nat Commun,2015,6:10062.
• [24] LANE M A,BALDWIN R T,JESSE B W. Developmental changes in ketogenic enzyme gene expression during sheep rumen development[J]. J Anim Sci,2002,80(6):1538-1544.
• [25] SAKAKIBARA K,FENG G G,LI J,et al. Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltagedependent K+channels[J]. J Pharmacol Sci,2015,129(1):31-37.
• [26] BROSNAN J T,BROSNAN M E. Glutamate:a truly functional amino acid[J]. Amino Acids,2013,45(3):413-418.
• [27] ALARCON P,HIDALGO A I,MANOSALVA C,et al. Metabolic disturbances in synovial fluid are involved in the onset of synovitis in heifers with acute ruminal acidosis[J]. Sci Rep,2019,9(1):5452.
• [28] LIU C,WU H,LIU S,et al. Dynamic alterations in yak rumen bacteria community and metabolome characteristics in response to feed type[J]. Front Microbiol,2019,10:1116.
• [29] MARIZ L,AMARAL P M,VALADARES F S,et al. Dietary protein reduction on microbial protein,amino acid digestibility,and body retention in beef cattle:2. Amino acid intestinal absorption and their efficiency for whole-body deposition[J]. J Anim Sci,2018,96(2):670-683.
• [30] CONTE G,DIMAURO C,DAGHIO M,et al. Exploring the relationship between bacterial genera and lipid metabolism in bovine rumen[J].Animal,2022,16(5):100520.
• [31] JENKINS T C. Lipid metabolism in the rumen[J]. J Dairy Sci,1993,76(12):3851-3863.
• [32] PETERSON C T,RODIONOV D A,OSTERMAN A L,et al. B vitamins and their role in immune regulation and cancer[J]. Nutrients,2020,12(11):3380.
• [33] STACH K,STACH W,AUGOFF K. Vitamin B6in health and disease[J]. Nutrients,2021,13(9):3229.
• [34] CARTER N S,YATES P,ARENDT C S,et al. Purine and pyrimidine metabolism in Leishmania[J]. Adv Exp Med Biol,2008,625:141-154.
• [35] TIWARI K,DUBEY V K. Fresh insights into the pyrimidine metabolism in the trypanosomatids[J]. Parasit Vectors,2018,11(1):87.
• [36] LIU J,HONG S,YANG J,et al. Targeting purine metabolism in ovarian cancer[J]. J Ovarian Res,2022,15(1):93.
• [37] ZHAO K,CHEN Y H,PENNER G B,et al. Transcriptome analysis of ruminal epithelia revealed potential regulatory mechanisms involved in host adaptation to gradual high fermentable dietary transition in beef cattle[J]. BMC Genomics,2017,18(1):976.
• [38] WANG B,WU L,CHEN J,et al. Metabolism pathways of arachidonic acids:mechanisms and potential therapeutic targets[J]. Signal Transduct Target Ther,2021,6(1):94.
• [39] COELHO A I,BERRY G T,RUBIO-GOZALBO M E. Galactose metabolism and health[J]. Curr Opin Clin Nutr Metab Care,2015,18(4):422-427.
• [40] KIM M K,NA J R,LEE T H,et al. Solirubrobacter soli sp. nov.,isolated from soil of a ginseng field[J]. Int J Syst Evol Microbiol,2007,57(Pt7):1453-1455.
• [41] WOO C Y,KIM J. Lysobacter terrestris sp. nov.,isolated from soil[J]. Int J Syst Evol Microbiol,2022,72(1). DOI:10.1099/ijsem.0.005204.
• [42] BOOTH W T,DAVIS R R,DEORA R,et al. Structural mechanism for regulation of DNA binding of Bps R,a Bordetella regulator of biofilm formation,by 6-hydroxynicotinic acid[J]. PLoS One,2019,14(11):e223387.
• [43] CHEN Y Y,LEE M H,HSU C C,et al. Methyl cinnamate inhibits adipocyte differentiation via activation of the CaMKK2-AMPK pathway in 3T3-L1 preadipocytes[J]. J Agric Food Chem,2012,60(4):955-963.
• [44] SRINIVASAN S,TORRES A G,RIBAS D P L. Inosine in biology and disease[J]. Genes(Basel),2021,12(4):600.
• [45] HOTTI H,RISCHER H. The killer of socrates:coniine and related alkaloids in the plant kingdom[J]. Molecules,2017,22(11):1962.
• [46] SHEN B,YANG Z,HAN S,et al. Bta-miR-124a affects lipid metabolism by regulating PECR gene[J]. Biomed Res Int,2019,2019:2596914.
• [47] SHRODE R L,CADY N,JENSEN S N,et al. Isoflavone consumption reduces inflammation through modulation of phenylalanine and lipid metabolism[J]. Metabolomics,2022,18(11):84.