胃肠道菌群与黏膜免疫在围产期奶牛健康中的作用

doi:10.11843/j.issn.0366-6964.2023.07.009

摘要/Abstract

摘要： 胃肠道菌群的变化在动物健康和疾病中扮演重要角色，越来越多的研究证据将机体的免疫系统与胃肠道菌群联系了起来。其主要机制可能是菌群紊乱导致菌群-免疫互作失调，营养代谢与能量调控失衡，免疫系统受损，最后诱发疾病。围产期奶牛面临维持机体正常生理代谢的严峻挑战，奶牛在围产期容易感染多种疾病，给牧场带来了严重的经济损失。最近的研究表明，围产期奶牛瘤胃菌群紊乱是导致生产性疾病发生的重要诱因，胃肠道菌群与宿主黏膜免疫系统之间的互作在维持胃肠道动态平衡和抑制炎症中起着关键作用。本文综述了围产期奶牛胃肠道菌群变化特征及胃肠道黏膜免疫系统组成，并讨论了菌群与黏膜免疫互作机制在维持奶牛健康中发挥的重要作用，最后介绍了菌群紊乱与免疫失衡介导的奶牛生产性疾病，旨在为探索围产期奶牛饲养管理及疾病防控提供新思路。

关键词: 围产期奶牛, 胃肠道菌群, 黏膜免疫, 菌群失调

Abstract: The changes of gastrointestinal flora play an important role in animal health and disease, and more and more research evidence has linked the immune system with gastrointestinal flora. The main mechanism may be that the disturbance of flora leads to the imbalance of flora-immune interaction, the imbalance of nutritional metabolism and energy regulation, the damage of immune system, and finally induces disease. Perinatal dairy cows face the severe challenge of maintaining normal physiological metabolism. Dairy cows are easy to be infected with a variety of diseases during the perinatal period, which brings serious economic losses to the pasture. Recent studies have shown that the disturbance of rumen flora in perinatal dairy cows is an important cause of productive diseases, and the dynamic interaction between gastrointestinal flora and host mucosal immune system plays a key role in maintaining gastrointestinal dynamic balance and inhibiting inflammation. In this paper, the changes of gastrointestinal microflora and the composition of gastrointestinal mucosal immune system in perinatal dairy cows were reviewed, and the important role of the interaction mechanism of microflora and mucosal immunity in maintaining the health of dairy cows was discussed. Finally, the productive diseases of dairy cows mediated by flora disorder and immune imbalance were introduced in order to provide new ideas for perinatal cow feeding and management and disease prevention and control.

Key words: perinatal dairy cows, gastrointestinal microbiota, mucosal immunity, dysbacteriosis

中图分类号:

S857.2

赵婉莉, 曹棋棋, 杨悦, 邓昭举, 徐闯. 胃肠道菌群与黏膜免疫在围产期奶牛健康中的作用[J]. 畜牧兽医学报, 2023, 54(7): 2751-2760.

ZHAO Wanli, CAO Qiqi, YANG Yue, DENG Zhaoju, XU Chuang. The Interaction between Gastrointestinal Microbiota and Mucosal Immunity in Health of Perinatal Dairy Cows[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(7): 2751-2760.

参考文献 85

[1]	FILIPE J, INGLESI A, AMADORI M, et al. Preliminary evidence of endotoxin tolerance in dairy cows during the transition period[J]. Genes (Basel), 2021, 12(11):1801.
[2]	PITTA D W, KUMAR S, VECCHIARELLI B, et al. Temporal dynamics in the ruminal microbiome of dairy cows during the transition period[J]. J Anim Sci, 2014, 92(9):4014-4022.
[3]	SHI N, LI N, DUAN X W, et al. Interaction between the gut microbiome and mucosal immune system[J]. Mil Med Res, 2017, 4:14.
[4]	KAMADA N, SEO S U, CHEN G Y, et al. Role of the gut microbiota in immunity and inflammatory disease[J]. Nat Rev Immunol, 2013, 13(5):321-335.
[5]	REYNOLDS C K, DVRST B, LUPOLI B, et al. Visceral tissue mass and rumen volume in dairy cows during the transition from late gestation to early lactation[J]. J Dairy Sci, 2004, 87(4):961-971.
[6]	FAUBLADIER C, JULLIAND V, DANEL J, et al. Bacterial carbohydrate-degrading capacity in foal faeces:changes from birth to pre-weaning and the impact of maternal supplementation with fermented feed products[J]. Br J Nutr, 2013, 110(6):1040-1052.
[7]	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.
[8]	FOUTS D E, SZPAKOWSKI S, PURUSHE J, et al. Next generation sequencing to define prokaryotic and fungal diversity in the bovine rumen[J]. PLoS One, 2012, 7(11):e48289.
[9]	ROMAGNOLI E M, KMIT M C P, CHIARAMONTE J B, et al. Ecological aspects on rumen microbiome[M]//DE AZEVEDO J L, QUECINE M C. Diversity and Benefits of Microorganisms from the Tropics. Cham:Springer, 2017:367-389.
[10]	MCCANN J C, WILEY L M, FORBES T D, et al. Relationship between the rumen microbiome and residual feed intake-efficiency of Brahman bulls stocked on bermudagrass pastures[J]. PLoS One, 2014, 9(3):e91864.
[11]	杨艳, 瞿明仁, 欧阳克蕙, 等. 反刍动物瘤胃微生物区系研究进展[J]. 江西农业学报, 2020, 32(10):110-115.YANG Y, QU M R, OUYANG K H, et al. Research progress in rumen microflora of ruminants[J]. Acta Agriculturae Jiangxi, 2020, 32(10):110-115. (in Chinese)
[12]	ZHU Z G, KRISTENSEN L, DIFFORD G F, et al. Changes in rumen bacterial and archaeal communities over the transition period in primiparous Holstein dairy cows[J]. J Dairy Sci, 2018, 101(11):9847-9862.
[13]	ZHU Z G, NOEL S J, DIFFORD G F, et al. Community structure of the metabolically active rumen bacterial and archaeal communities of dairy cows over the transition period[J]. PLoS One, 2017, 12(11):e0187858.
[14]	LIMA F S, OIKONOMOU G, LIMA S F, et al. Prepartum and postpartum rumen fluid microbiomes:characterization and correlation with production traits in dairy cows[J]. Appl Environ Microbiol, 2015, 81(4):1327-1337.
[15]	DIEHO K, VAN DEN BOGERT B, HENDERSON G, et al. Changes in rumen microbiota composition and in situ degradation kinetics during the dry period and early lactation as affected by rate of increase of concentrate allowance[J]. J Dairy Sci, 2017, 100(4):2695-2710.
[16]	DERAKHSHANI H, TUN H M, CARDOSO F C, et al. Linking peripartal dynamics of ruminal microbiota to dietary changes and production parameters[J]. Front Microbiol, 2017, 7:2143.
[17]	JASIRWAN C O M, MURADI A, HASAN I, et al. Correlation of gut Firmicutes/Bacteroidetes ratio with fibrosis and steatosis stratified by body mass index in patients with non-alcoholic fatty liver disease[J]. Biosci Microbiota Food Health, 2021, 40(1):50-58.
[18]	DING G Z, CHANG Y, ZHAO L P, et al. Effect of Saccharomyces cerevisiae on alfalfa nutrient degradation characteristics and rumen microbial populations of steers fed diets with different concentrate-to-forage ratios[J]. J Anim Sci Biotechnol, 2014, 5(1):24.
[19]	项开合, 胡晓宇, 李爽, 等. 奶牛围产期瘤胃菌群变化及影响因素研究进展[J]. 动物医学进展, 2022, 43(8):93-97.XIANG K H, HU X Y, LI S, et al. Progress on changes of rumen microbiota and its influencing factors in dairy cows during perinatal period[J]. Progress in Veterinary Medicine, 2022, 43(8):93-97. (in Chinese)
[20]	SANSONETTI P J. War and peace at mucosal surfaces[J]. Nat Rev Immunol, 2004, 4(12):953-964.
[21]	PELASEYED T, BERGSTRÖM J H, GUSTAFSSON J K, et al. The mucus and mucins of the goblet cells and enterocytes provide the first defense line of the gastrointestinal tract and interact with the immune system[J]. Immunol Rev, 2014, 260(1):8-20.
[22]	ENSS M L, GROSSE-SIESTRUP H, SCHMIDT-WITTIG U, et al. Changes in colonic mucins of germfree rats in response to the introduction of a "normal" rat microbial flora. Rat colonic mucin[J]. J Exp Anim Sci, 1992, 35(3):110-119.
[23]	NOWACKI M R. Cell proliferation in colonic crypts of germ-free and conventional mice——preliminary report[J]. Folia Histochem Cytobiol, 1993, 31(2):77-81.
[24]	ZASLOFF M. Antimicrobial peptides in health and disease[J]. N Engl J Med, 2002, 347(15):1199-1200.
[25]	SPERANDIO B, FISCHER N, SANSONETTI P J. Mucosal physical and chemical innate barriers:Lessons from microbial evasion strategies[J]. Semin Immunol, 2015, 27(2):111-118.
[26]	NAKAJIMA A, VOGELZANG A, MARUYA M, et al. IgA regulates the composition and metabolic function of gut microbiota by promoting symbiosis between bacteria[J]. J Exp Med, 2018, 215(8):2019-2034.
[27]	MACPHERSON A J, HUNZIKER L, MCCOY K, et al. IgA responses in the intestinal mucosa against pathogenic and non-pathogenic microorganisms[J]. Microbes Infect, 2001, 3(12):1021-1035.
[28]	VAN DER WAAIJ L A, LIMBURG P C, MESANDER G, et al. In vivo IgA coating of anaerobic bacteria in human faeces[J]. Gut, 1996, 38(3):348-354.
[29]	TSURUTA T, INOUE R, TSUKAHARA T, et al. Commensal bacteria coated by secretory immunoglobulin A and immunoglobulin G in the gastrointestinal tract of pigs and calves[J]. Anim Sci J, 2012, 83(12):799-804.
[30]	CUNNINGHAM-RUNDLES C. Physiology of IgA and IgA deficiency[J]. J Clin Immunol, 2001, 21(5):303-309.
[31]	SHROFF K E, MESLIN K, CEBRA J J. Commensal enteric bacteria engender a self-limiting humoral mucosal immune response while permanently colonizing the gut[J]. Infect Immun, 1995, 63(10):3904-3913.
[32]	KUHN K A, PEDRAZA I, DEMORUELLE M K. Mucosal immune responses to microbiota in the development of autoimmune disease[J]. Rheum Dis Clin North Am, 2014, 40(4):711-725.
[33]	RAJASEKARAN S A, BEYENBACH K W, RAJASEKARAN A K. Interactions of tight junctions with membrane channels and transporters[J]. Biochim Biophys Acta Biomembr, 2008, 1778(3):757-769.
[34]	MIYAUCHI E, O'CALLAGHAN J, BUTTÓ L F, et al. Mechanism of protection of transepithelial barrier function by Lactobacillus salivarius:strain dependence and attenuation by bacteriocin production[J]. Am J Physiol Gastrointest Liver Physiol, 2012, 303(9):G1029-G1041.
[35]	SULTANA R, MCBAIN A J, O'NEILL C A. Strain-dependent augmentation of tight-junction barrier function in human primary epidermal keratinocytes by Lactobacillus and Bifidobacterium lysates[J]. Appl Environ Microbiol, 2013, 79(16):4887-4894.
[36]	ARAUJO G, YUNTA C, TERRÉ M, et al. Intestinal permeability and incidence of diarrhea in newborn calves[J]. J Dairy Sci, 2015, 98(10):7309-7317.
[37]	KURASHIMA Y, KIYONO H. Mucosal ecological network of epithelium and immune cells for gut homeostasis and tissue healing[J]. Annu Rev Immunol, 2017, 35:119-147.
[38]	RESCIGNO M, URBANO M, VALZASINA B, et al. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria[J]. Nat Immunol, 2001, 2(4):361-367.
[39]	BELKAID Y, HAND T W. Role of the microbiota in immunity and inflammation[J]. Cell, 2014, 157(1):121-141.
[40]	TROY E B, KASPER D L. Beneficial effects of Bacteroides fragilis polysaccharides on the immune system[J]. Front Biosci (Landmark Ed), 2010, 15(1):25-34.
[41]	KIM D, YOO S A, KIM W U. Gut microbiota in autoimmunity:potential for clinical applications[J]. Arch Pharm Res, 2016, 39(11):1565-1576.
[42]	ZHAN K, GONG X X, CHEN Y Y, et al. Short-chain fatty acids regulate the immune responses via G protein-coupled receptor 41 in bovine rumen epithelial cells[J]. Front Immunol, 2019, 10:2042.
[43]	WANG J J, WEI Z K, ZHANG X, et al. Butyrate protects against disruption of the blood-milk barrier and moderates inflammatory responses in a model of mastitis induced by lipopolysaccharide[J]. Br J Pharmacol, 2017, 174(21):3811-3822.
[44]	BELKAID Y. Regulatory T cells and infection:a dangerous necessity[J]. Nat Rev Immunol, 2007, 7(11):875-888.
[45]	MALMUTHUGE N, LI M J, GOONEWARDENE L A, et al. Effect of calf starter feeding on gut microbial diversity and expression of genes involved in host immune responses and tight junctions in dairy calves during weaning transition[J]. J Dairy Sci, 2013, 96(5):3189-3200.
[46]	MALMUTHUGE N, LI M J, FRIES P, et al. Regional and age dependent changes in gene expression of Toll-like receptors and key antimicrobial defence molecules throughout the gastrointestinal tract of dairy calves[J]. Vet Immunol Immunopathol, 2012, 146(1):18-26.
[47]	RAKOFF-NAHOUM S, PAGLINO J, ESLAMI-VARZANEH F, et al. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis[J]. Cell, 2004, 118(2):229-241.
[48]	LIANG G X, MALMUTHUGE N, BAO H, et al. Transcriptome analysis reveals regional and temporal differences in mucosal immune system development in the small intestine of neonatal calves[J]. BMC Genomics, 2016, 17(1):602.
[49]	SMITS H H, ENGERING A, VAN DER KLEIJ D, et al. Selective probiotic bacteria induce IL-10-producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin[J]. J Allergy Clin Immunol, 2005, 115(6):1260-1267.
[50]	MALMUTHUGE N, GRIEBEL P J, GUAN L L. The gut microbiome and its potential role in the development and function of newborn calf gastrointestinal tract[J]. Front Vet Sci, 2015, 2:36.
[51]	OKUMURA R, TAKEDA K. Roles of intestinal epithelial cells in the maintenance of gut homeostasis[J]. Exp Mol Med, 2017, 49(5):e338.
[52]	GEBREYESUS G, DIFFORD G F, BUITENHUIS B, et al. Predictive ability of host genetics and rumen microbiome for subclinical ketosis[J]. J Dairy Sci, 2020, 103(5):4557-4569.
[53]	KHAFIPOUR E, LI S, TUN H M, et al. Effects of grain feeding on microbiota in the digestive tract of cattle[J]. Anim Front, 2016, 6(2):13-19.
[54]	MASLOWSKI K M, VIEIRA A T, NG A, et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43[J]. Nature, 2009, 461(7268):1282-1286.
[55]	FERNANDO S C, PURVIS II H T, NAJAR F Z, et al. Rumen microbial population dynamics during adaptation to a high-grain diet[J]. Appl Environ Microbiol, 2010, 76(22):7482-7490.
[56]	MCCANN J C, LUAN S Y, CARDOSO F C, et al. Induction of subacute ruminal acidosis affects the ruminal microbiome and epithelium[J]. Front Microbiol, 2016, 7:701, doi:10. 3389/fmicb. 2016. 00701.
[57]	KLEEN J L, HOOIJER G A, REHAGE J, et al. Subacute ruminal acidosis (SARA):a review[J]. J Vet Med A Physiol Pathol Clin Med, 2003, 50(8):406-414.
[58]	MOREIRA A P B, TEXEIRA T F S, FERREIRA A B, et al. Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia[J]. Br J Nutr, 2012, 108(5):801-809.
[59]	KRAUSE K M, OETZEL G R. Inducing subacute ruminal acidosis in lactating dairy cows[J]. J Dairy Sci, 2005, 88(10):3633-3639.
[60]	PLAIZIER J C, KRAUSE D O, GOZHO G N, et al. Subacute ruminal acidosis in dairy cows:the physiological causes, incidence and consequences[J]. Vet J, 2008, 176(1):21-31.
[61]	WANG X X, LI X B, ZHAO C X, et al. Correlation between composition of the bacterial community and concentration of volatile fatty acids in the rumen during the transition period and ketosis in dairy cows[J]. Appl Environ Microbiol, 2012, 78(7):2386-2392.
[62]	REYNOLDS C K, HUNTINGTON G B, TYRRELL H F, et al. Net metabolism of volatile fatty acids, D-β-hydroxybutyrate, nonesterified fatty acids, and blood gasses by portal-drained viscera and liver of lactating Holstein cows[J]. J Dairy Sci, 1988, 71(9):2395-2405.
[63]	NISBET D J, MARTIN S A. Effect of a Saccharomyces cerevisiae culture on lactate utilization by the ruminal bacterium Selenomonas ruminantium[J]. J Anim Sci, 1991, 69(11):4628-4633.
[64]	MA C, ZHAO J, XI X, et al. Bovine mastitis may be associated with the deprivation of gut Lactobacillus[J]. Benef Microbes, 2016, 7(1):95-102.
[65]	CHOPYK D M, GRAKOUI A. Contribution of the intestinal microbiome and gut barrier to hepatic disorders[J]. Gastroenterology, 2020, 159(3):849-863.
[66]	WANG Y, NAN X M, ZHAO Y G, et al. Rumen microbiome structure and metabolites activity in dairy cows with clinical and subclinical mastitis[J]. J Anim Sci Biotechnol, 2021, 12(1):36.
[67]	HU X Y, LI S, MU R Y, et al. The rumen microbiota contributes to the development of mastitis in dairy cows[J]. Microbiol Spectr, 2022, 10(1):e0251221.
[68]	ZHANG K, CHANG G J, XU T L, et al. Lipopolysaccharide derived from the digestive tract activates inflammatory gene expression and inhibits casein synthesis in the mammary glands of lactating dairy cows[J]. Oncotarget, 2016, 7(9):9652-9665.
[69]	汪悦, 南雪梅, 蒋林树, 等. 奶牛胃肠道菌群与奶牛乳房炎关联性及其对乳房炎调控潜力的研究进展[J]. 畜牧兽医学报, 2021, 52(8):2083-2092.WANG Y, NAN X M, JIANG L S, et al. Research progress on the correlation between gastrointestinal microbiota and bovine mastitis in dairy cows and its regulatory potential for mastitis[J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(8):2083-2092. (in Chinese)
[70]	JEON S J, LIMA F S, VIEIRA-NETO A, et al. Shift of uterine microbiota associated with antibiotic treatment and cure of metritis in dairy cows[J]. Vet Microbiol, 2018, 214:132-139.
[71]	HU X Y, GUO J, ZHAO C J, et al. The gut microbiota contributes to the development of Staphylococcus aureus-induced mastitis in mice[J]. ISME J, 2020, 14(7):1897-1910.
[72]	WEI Z K, XIAO C, GUO C M, et al. Sodium acetate inhibits Staphylococcus aureus internalization into bovine mammary epithelial cells by inhibiting NF-κB activation[J]. Microb Pathog, 2017, 107:116-121.
[73]	RATAJCZAK W, RYŁ A, MIZERSKI A, et al. Immunomodulatory potential of gut microbiome-derived short-chain fatty acids (SCFAs)[J]. Acta Biochim Pol, 2019, 66(1):1-12.
[74]	WANG J J, WEI Z K, ZHANG X, et al. Propionate protects against lipopolysaccharide-induced mastitis in mice by restoring blood-milk barrier disruption and suppressing inflammatory response[J]. Front Immunol, 2017, 8:1108.
[75]	CORRÊA-OLIVEIRA R, FACHI J L, VIEIRA A, et al. Regulation of immune cell function by short-chain fatty acids[J]. Clin Trans Immunol, 2016, 5(4):e73.
[76]	RANJBAR R, VAHDATI S N, TAVAKOLI S, et al. Immunomodulatory roles of microbiota-derived short-chain fatty acids in bacterial infections[J]. Biomed Pharmacother, 2021, 141:111817.
[77]	TAN J, MCKENZIE C, POTAMITIS M, et al. The role of short-chain fatty acids in health and disease[J]. Adv Immunol, 2014, 121:91-119.
[78]	KIM C H. Control of lymphocyte functions by gut microbiota-derived short-chain fatty acids[J]. Cell Mol Immunol, 2021, 18(5):1161-1171.
[79]	GOZHO G N, KRAUSE D O, PLAIZIER J C. Ruminal lipopolysaccharide concentration and inflammatory response during grain-induced subacute ruminal acidosis in dairy cows[J]. J Dairy Sci, 2007, 90(2):856-866.
[80]	GUO J, MU R Y, LI S, et al. Characterization of the bacterial community of rumen in dairy cows with laminitis[J]. Genes (Basel), 2021, 12(12):1996.
[81]	宋朋杰, 武小虎, 张世栋, 等. 微生态制剂防治奶牛子宫内膜炎研究进展[J]. 中国兽医学报, 2020, 40(1):210-215, 224.SONG P J, WU X H, ZHANG S D, et al. Research progress of microecological preparation for the prevention and treatment of endometritis in dairy cows[J]. Chinese Journal of Veterinary Science, 2020, 40(1):210-215, 224. (in Chinese)
[82]	BILAL M S, ABAKER J A, UL AABDIN Z, et al. Lipopolysaccharide derived from the digestive tract triggers an inflammatory response in the uterus of mid-lactating dairy cows during SARA[J]. BMC Vet Res, 2016, 12(1):284.
[83]	HAMESCH K, BORKHAM-KAMPHORST E, STRNAD P, et al. Lipopolysaccharide-induced inflammatory liver injury in mice[J]. Lab Anim, 2015, 49(1 Suppl):37-46.
[84]	ABAKER J A, XU T L, JIN D, et al. Lipopolysaccharide derived from the digestive tract provokes oxidative stress in the liver of dairy cows fed a high-grain diet[J]. J Dairy Sci, 2017, 100(1):666-678.
[85]	GUO J F, CHANG G J, ZHANG K, et al. Rumen-derived lipopolysaccharide provoked inflammatory injury in the liver of dairy cows fed a high-concentrate diet[J]. Oncotarget, 2017, 8(29):46769-46780.