肠道菌群对畜禽免疫系统的影响研究进展

doi:10.16431/j.cnki.1671-7236.2025.07.038

摘要/Abstract

摘要： 免疫系统由免疫器官、免疫细胞和免疫活性物质组成，可识别清除病原体与异常细胞，肠道菌群则参与机体消化吸收和代谢、调节免疫系统和神经系统等。肠道菌群是由肠道内所有微生物构成的复杂群落，在长期共同进化过程中，肠道菌群与宿主免疫系统之间存在动态互作，影响宿主肠道健康和免疫功能，肠道菌群失调会引起宿主炎症反应和疾病发生。同时，肠道菌群能够代谢蛋白质、膳食纤维、初级胆汁酸、亚油酸和碳水化合物等物质，产生大量的代谢产物，如短链脂肪酸、胆汁酸和吲哚等化合物，影响肠道上皮细胞和免疫细胞之间的互作，包括宿主代谢、肠道屏障和免疫功能等。现阶段对于畜禽肠道菌群的研究仍存在不足，如对肠道菌群多样性认识不全面、功能和协作机制不明确、研究方法局限以及调控手段缺乏等问题。笔者系统综述了畜禽肠道菌群及其代谢物和肠道菌群失调对免疫系统的影响，旨在更好地理解畜禽肠道菌群与免疫系统之间的复杂相互作用，为制定预防和治疗相关疾病的新策略和方法提供理论依据。

关键词: 肠道菌群; 免疫系统; 代谢; 炎症反应

Abstract: The immune system consists of immune organs,immune cells and immunologically active substances,which can recognize and eliminate pathogens and abnormal cells.The intestinal flora is involved in the body’s digestion,absorption and metabolism,and the regulation of the immune system and nervous system.Intestinal flora is a complex community composed of all microorganisms in the intestinal tract.During the long-term co-evolutionary process,there is a dynamic interplay between the intestinal flora and the host immune system,which affects the host’s intestinal health and immune function,and dysregulation of the intestinal flora can cause inflammatory reactions and diseases in the host.At the same time,intestinal flora can metabolize protein,dietary fiber,primary bile acids,linoleic acids and carbohydrates,and produce a large number of metabolites,such as short-chain fatty acids,bile acids and indole，which affect the interaction between intestinal epithelial cells and immune cells,including host metabolism,intestinal barrier and immune function.At present,there are still some shortcomings in the study of intestinal flora in livestock and poultry,such as incomplete understanding of intestinal flora diversity,unclear function and cooperation mechanism,limitations in research methods and lack of regulatory means.In this paper,the effects of intestinal flora and its metabolites on the immune system of livestock and poultry were systematically reviewed in order to better understand the complex interaction between intestinal flora and immune system of livestock and poultry,and provide theoretical basis for developing new strategies and methods for the prevention and treatment of related diseases.

Key words: intestinal flora; immune system; metabolism; inflammatory response

中图分类号:

S852.4

王豪杰, 华添, 陈世豪, 毕瑜林, 江勇, 王志秀, 陈国宏, 白皓, 常国斌. 肠道菌群对畜禽免疫系统的影响研究进展[J]. 中国畜牧兽医, 2025, 52(7): 3398-3408.

WANG Haojie, HUA Tian, CHEN Shihao, BI Yulin, JIANG Yong, WANG Zhixiu, CHEN Guohong, BAI Hao, CHANG Guobin. Research Progress on Effects of Intestinal Flora on Immune System of Livestock and Poultry[J]. China Animal Husbandry & Veterinary Medicine, 2025, 52(7): 3398-3408.

参考文献

[1] MALYS M K,CAMPBELL L,MALYS N.Symbiotic and antibiotic interactions between gut commensal microbiota and host immune system[J].Medicina (Kaunas)，2015，51(2):69-75.
[2] LIU Y,FENG Y,YANG X,et al.Mining chicken ileal microbiota for immunomodulatory microorganisms[J].ISME Journal，2023，17(5):758-774.
[3] LI R,ZHANG L,TANG Z,et al.Effects of fungal polysaccharide on oxidative damage and TLR4 pathway to the central immune organs in cadmium intoxication in chickens[J].Biological Trace Element Research，2019,191(2):464-473.
[4] HOUTEN S M,VIOLANTE S,VENTURA F V,et al.The biochemistry and physiology of mitochondrial fatty acid β-oxidation and its genetic disorders[J].Annual Review of Physiology,2016，78:23-44.
[5] PEARCE E L，PEARCE E J.Metabolic pathways in immune cell activation and quiescence[J].Immunity,2013,38(4):633-643.
[6] 华兆琳,侯百东.“自我”与“非我”免疫识别新机理与创新疫苗发展[J].中国科学基金,2020,34(5):565-572.HUA Z L,HOU B D.New mechanism of “self” and “not-self” immune recognition and the development of innovative vaccines[J].China Science Foundation,2020,34(5):565-572.(in Chinese)
[7] EYERICH S,EYERICH K,TRAIDL-HOFFMANN C,et al.Cutaneous barriers and skin immunity:Differentiating a connected network[J].Trends in Immunology，2018,39(4):315-327.
[8] FARHOOD B,NAJAFI M,MORTEZAEE K.CD8^＋ cytotoxic T lymphocytes in cancer immunotherapy:A review[J].Journal of Cellular Physiology， 2019，234(6):8509-8521.
[9] 张瑞萍.表达嵌合T细胞受体的T淋巴细胞介导的肿瘤过继性免疫治疗作用机理研究[D].上海：中国人民解放军海军军医大学,2005.ZHANG R P.Study on the mechanism of tumor relay immunotherapy mediated by T lymphocytes expressing chimeric T cell receptor[D].Shanghai：People’s Liberation Army Naval Military Medical University,2005.(in Chinese)
[10] 杨丽萍,马臻棋,王学红,等.肠道菌群与人体健康的研究进展[J].临床医学进展,2021,11(5):2221-2227.YANG L P,MA Z Q,WANG X H,et al.Progress of research on intestinal flora and human health[J].Progress in Clinical Medicine,2021,11(5):2221-2227.(in Chinese)
[11] 雷燕,曹霞飞,黄志深,等.双歧杆菌生理生化特性及调控大鼠肠道菌群,脂质代谢功能的研究进展[J].中国食品卫生杂志,2023,35(9):1395-1400.LEI Y,CAO X F,HUANG Z S,et al.Progress of physiological and biochemical properties of Bifidobacterium bifidum and its function in regulating intestinal flora and lipid metabolism in rats[J]. Chinese Journal of Food Hygiene,2023,35(9):1395-1400.(in Chinese)
[12] HASAN N,YANG H.Factors affecting the composition of the gut microbiota,and its modulation[J]. PeerJ，2019,7:e7502.
[13] SUN Y,YU K,ZHOU L,et al.Metabolomic and transcriptomic responses induced in the livers of pigs by the long-term intake of resistant starch[J]. Journal of Animal Science， 2016,94(3):1083-1094.
[14] 杜蕾,孙静,葛良鹏,等.肠道菌群对动物免疫系统早期发育的影响[J].中国畜牧杂志,2017，53(6):10-14.DU L,SUN J,GE L P,et al.Effects of intestinal flora on the early development of animal immune system[J].Chinese Journal of Animal Science,2017，53(6):10-14.(in Chinese)
[15] 张家豪,吕冰洁,程翔.肠道菌群通过调节免疫细胞参与肠外疾病的研究进展[J].中华内科杂志,2024,63(1):100-106.ZHANG Z H,LYU B J,CHENG X.Progress of intestinal flora involved in extraintestinal diseases by regulating immune cells[J].Chinese Journal of Internal Medicine,2024,63(1):100-106.(in Chinese)
[16] 张萌萌.肠道微生物对肠道屏障功能完整性的维护机制研究概况[J].微生物学通报,2020,47(3):8.ZHANG M M.Overview of research on the mechanism of intestinal microbial maintenance of the functional integrity of the intestinal barrier[J].Microbiology Bulletin,2020,47(3):8.(in Chinese)
[17] OEMCKE L A,ANDERSON R C,ALTERMANN E,et al.The role of segmented filamentous bacteria in immune barrier maturation of the small intestine at weaning[J].Frontiers in Nutrition， 2021,8:759137.
[18] IVANOV I I,ATARASHI K,MANEL N,et al.Induction of intestinal Th17 cells by segmented filamentous bacteria[J]. Cell，2009,139(3):485-498.
[19] WU H J,IVANOV I I,DARCE J,et al.Gut-residing segmented filamentous bacteria drive autoimmune arthritis via T helper 17 cells[J].Immunity，2010,32(6):815-827.
[20] ATARASHI K,TANOUE T,ANDO M,et al.Th17 cell induction by adhesion of microbes to intestinal epithelial cells[J].Cell，2015,163(2):367-380.
[21] TENG F,KLINGER C N,FELIX K M,et al.Gut microbiota drive autoimmune arthritis by promoting differentiation and migration of peyer’s patch T follicular helper cells[J]. Immunity，2016,44(4):875-888.
[22] SUN S,LUO L,LIANG W,et al.Bifidobacterium alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade[J]. Proceedings of the National Academy of Sciences of the United States of America， 2020,117(44):27509-27515.
[23] ALESSANDRI G,VAN SINDEREN D,VENTURA M.The genus bifidobacterium:From genomics to functionality of an important component of the mammalian gut microbiota running title:Bifidobacterial adaptation to and interaction with the host[J].Computational and Structural Biotechnology Journal， 2021,19:1472-1487.
[24] MAZMANIAN S K,LIU C H,TZIANABOS A O,et al.An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system[J].Cell，2005,2(1):107-118.
[25] HE B,XU W,SANTINI P A,et al.Intestinal bacteria trigger T cell-independent immunoglobulin A(2) class switching by inducing epithelial-cell secretion of the cytokine APRIL[J].Immunity，2007,26(6):812-826.
[26] ERTURK-HASDEMIR D,KASPER D L.Finding a needle in a haystack:Bacteroides fragilis polysaccharide A as the archetypical symbiosis factor[J]. Annals of the New York Academy of Sciences，2018,1417(1):116-129.
[27] MAZMANIAN S K,ROUND J L,KASPER D L.A microbial symbiosis factor prevents intestinal inflammatory disease[J].Nature,2008,453(7195):620-625.
[28] NUTSCH K M,HSIEH C S.T cell tolerance and immunity to commensal bacteria[J].Current Opinion in Immunology，2012,24(4):385-391.
[29] STEWART A G,THOMAS B,KOFF J.TGF-β:Master regulator of inflammation and fibrosis[J]. Respirology，2018,23(12):1096-1097.
[30] SCHLENNER S M,WEIGMANN B,RUAN Q,et al.Smad3 binding to the Foxp3 enhancer is dispensable for the development of regulatory T cells with the exception of the gut[J]. Journal of Experimental Medicine， 2012,209(9):1529-1535.
[31] GOODWIN A C,DESTEFANO SHIELDS C E,WU S,et al.Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis[J]. Proceedings of the National Academy of Sciences of the United States of America，2011,108(37):15354-15359.
[32] SHU Z,ZHANG J,ZHOU Q,et al.Effects of inactivated Lactobacillus rhamnosus on growth performance,serum indicators,and colonic microbiota and metabolism of weaned piglets[J]. BMC Veterinary Research，2024,20(1):422.
[33] 马梓毓.粪菌移植通过调节空肠Th17/Treg细胞平衡改善鸡生长性能的机理研究[D].武汉：华中农业大学,2023.MA Z Y.Mechanism of faecal bacterial transplantation to improve chicken growth performance by regulating jejunal Th17/Treg cell balance[D].Wuhan：Huazhong Agricultural University,2023.(in Chinese)
[34] ALIZADEH M,SHOJADOOST B,BOODHOO N,et al.Molecular and cellular characterization of immunity conferred by lactobacilli against necrotic enteritis in chickens[J].Frontiers in Immunology，2023,14:1301980.
[35] HAVERSON K,REHAKOVA Z,SINKORA J,et al.Immune development in jejunal mucosa after colonization with selected commensal gut bacteria:A study in germ-free pigs[J]. Veterinary Immunology and Immunopathology，2007,119(3-4):243-253.
[36] BUTLER J E,SUN J,WEBER P,et al.Antibody repertoire development in fetal and newborn piglets,Ⅲ.Colonization of the gastrointestinal tract selectively diversifies the preimmune repertoire in mucosal lymphoid tissues[J].Immunology，2000,100(1):119-130.
[37] PACENTRA A,GRASSELLI F,BUSSOLATI S,et al.The effect of pathogen-associated molecular patterns on the swine granulosa cells[J].Theriogenology，2020,145:207-216.
[38] TAKEDA K,AKIRA S.Toll-like receptors in innate immunity[J].International Immunology，2005,17(1):1-14.
[39] MACPHERSON A J,GANAL-VONARBURG S C.Checkpoint for gut microbes after birth[J]. Nature，2018,560(7719):436-438.
[40] JANG J Y,KIM S,KWON M S,et al.Rotavirus-mediated alteration of gut microbiota and its correlation with physiological characteristics in neonatal calves[J].Journal of Microbiology，2019,57(2):113-121.
[41] MORRISON D J,PRESTON T.Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism[J]. Gut Microbes，2016,7(3):189-200.
[42] 陈福,何邵平,田科雄,等.短链脂肪酸的生理功能及其在畜禽生产中的应用[J].动物营养学报,2019,31(7):3039-3048.CHEN F,HE S P,TIAN K X,et al.Physiological functions of short-chain fatty acids and their applications in livestock and poultry production[J].Chinese Journal of Animal Nutrition,2019,31(7):3039-3048.(in Chinese)
[43] GEVA-ZATORSKY N,SEFIK E,KUA L,et al.Mining the human gut microbiota for immunomodulatory organisms[J].Cell，2017,168(5):928-943.
[44] 倪萍,张海波,廖晓鹏,等.短链脂肪酸、色氨酸代谢物及两性离子多糖A调控动物炎性肠病通路的研究进展[J].中国畜牧杂志,2021,57(6):78-83.NI P,ZHANG H B,LIAO X P,et al.Progress of short-chain fatty acids,tryptophan metabolites and amphoteric polysaccharide A in regulating inflammatory bowel disease pathway in animals[J].Chinese Journal of Animal Science,2021,57(6):78-83.(in Chinese)
[45] KIM M,QIE Y,PARK J,et al.Gut microbial metabolites fuel host antibody responses[J].Cell Host Microbe,2016,20(2):202-214.
[46] TAKEUCHI T,MIYAUCHI E,KANAYA T,et al.Acetate differentially regulates IgA reactivity to commensal bacteria[J]. Nature,2021,595(7868):560-564.
[47] LIANG L,LIU L,ZHOU W,et al.Gut microbiota-derived butyrate regulates gut mucus barrier repair by activating the macrophage/Wnt/ERK signaling pathway[J].Clinical Science,2022,136(4):291-307.
[48] LI X,WANG C,ZHU J,et al.Sodium butyrate ameliorates oxidative stress-induced intestinal epithelium barrier injury and mitochondrial damage through AMPK-mitophagy pathway[J].Oxidative Medicine and Cellular Longevity，2022，2022:3745135.
[49] CHEN L,SUN M,WU W,et al.Microbiota metabolite butyrate differentially regulates Th1 and Th17 cells’ differentiation and function in induction of colitis[J]. Inflammatory Bowel Diseases,2019,25(9):1450-1461.
[50] AGUS A,PLANCHAIS J,SOKOL H.Gut microbiota regulation of tryptophan metabolism in health and disease[J].Cell Host Microbe,2018,23(6):716-724.
[51] MACPHERSON A,GANAL-VONARBURG S C.Checkpoint for gut microbes after birth[J].Nature,2018,560(7719):436-438.
[52] KRISHNAN S,DING Y,SAEDI N,et al.Gut microbiota-derived tryptophan metabolites modulate inflammatory response in hepatocytes and macrophages[J].Cell Reports, 2018,23(4):1099-1111.
[53] COLLINS S L,STINE J G,BISANZ J E,et al.Bile acids and the gut microbiota:Metabolic interactions and impacts on disease[J]. Nature Reviews Microbiology,2023,21(4):236-247.
[54] HU J,WANG C,HUANG X,et al.Gut microbiota-mediated secondary bile acids regulate dendritic cells to attenuate autoimmune uveitis through TGR5 signaling[J].Cell Reports,2021,36(12):109726.
[55] GUO C,XIE S,CHI Z,et al.Bile acids control inflammation and metabolic disorder through inhibition of NLRP3 inflammasome[J].Immunity,2016,45(4):802-816.
[56] SONG X,SUN X,OH S F,et al.Microbial bile acid metabolites modulate gut RORγ^＋ regulatory T cell homeostasis[J]. Nature, 2020,577(7790):410-415.
[57] YU T,YANG W,YAO S,et al.STING promotes intestinal IgA production by regulating acetate-producing bacteria to maintain host-microbiota mutualism[J]. Inflammatory Bowel Diseases,2023,29(6):946-959.
[58] SONG X,ZHANG H,ZHANG Y,et al.Gut microbial fatty acid isomerization modulates intraepithelial T cells[J].Nature,2023,619(7971):837-843.
[59] MAINARDI E,CORINO C,ROSSI R.The effect of vitamins on the immune systems of pigs[J].Animals (Basel),2024,14(14):2126.
[60] REDDING L E,BERRY A S,INDUGU N,et al.Gut microbiota features associated with Clostridioides difficile colonization in dairy calves[J].PLoS One,2021,16(12):e0251999.
[61] VIDEVALL E,SONG S J,BENSCH H M,et al.Early-life gut dysbiosis linked to juvenile mortality in ostriches[J].Microbiome, 2020,8(1):147.
[62] DE VOS W M,TILG H,VAN HUL M,et al.Gut microbiome and health:Mechanistic insights[J].Gut,2022,71(5):1020-1032.
[63] GASKINS H R,CROIX J A,NAKAMURA N,et al.Impact of the intestinal microbiota on the development of mucosal defense[J]. Clinical Infectious Diseases,2008,46(Suppl 2):S80-S86.
[64] BROOM L J,KOGUT M H.The role of the gut microbiome in shaping the immune system of chickens[J].Veterinary Immunology and Immunopathology, 2018,204:44-51.
[65] CHELED-SHOVAL S L,GAMAGE N S,AMIT-ROMACH E,et al.Differences in intestinal mucin dynamics between germ-free and conventionally reared chickens after mannan-oligosaccharide supplementation[J].Poultry Science, 2014,93(3):636-644.
[66] 甘元涛,赵少勇.肠黏膜屏障损伤与紧密连接蛋白ZO-1的关系研究进展[J].现代医药卫生,2016,32(7):3.GAN Y T,ZHAO S Y.Research progress on the relationship between intestinal mucosal barrier damage and tight junction protein ZO-1[J].Modern Medicine and Health,2016,32(7):3.(in Chinese)
[67] WILLING B P,VAN KESSEL A G.Enterocyte proliferation and apoptosis in the caudal small intestine is influenced by the composition of colonizing commensal bacteria in the neonatal gnotobiotic pig[J].Journal of Animal Science,2007,85(12):3256-3266.
[68] SPLICHALOVA A,SLAVIKOVA V,SPLICHALOVA Z,et al.Preterm life in sterile conditions:A study on preterm,germ-free piglets[J].Frontiers in Immunology,2018,9:220.
[69] 焦禹豪,陈蓓迪,张烜.肠道菌群在天然免疫系统中的作用[J].协和医学杂志,2019,10(3):6.JIAO Y H,CHEN B D,ZHANG X.The role of intestinal flora in the natural immune system[J].Journal of Concordant Medicine,2019,10(3):6.(in Chinese)
[70] LIEW F Y.T_H1 and T_H2 cells:A historical perspective[J].Nature Reviews Microbiology，2002,2(1):55-60.
[71] CHEN H,LI H,LIU Z.Interplay of intestinal microbiota and mucosal immunity in inflammatory bowel disease:A relationship of frenemies[J]. Therapeutic Advances in Gastroenterology，2020,13:1756284820935188.
[72] LIU B,WANG C,HUASAI S,et al.Compound probiotics improve the diarrhea rate and intestinal microbiota of newborn calves[J].Animals (Basel)， 2022,12(3):322.
[73] FAN Y,PEDERSEN O.Gut microbiota in human metabolic health and disease[J].Nature Reviews Microbiology，2021,19(1):55-71.
[74] HONNEFFER J B,MINAMOTO Y,SUCHODOLSKI J S.Microbiota alterations in acute and chronic gastrointestinal inflammation of cats and dogs[J].World Journal of Gastroenterology， 2014,20(44):16489-16497.
[75] 国康琳,余佳佳,刘瑛.金黄色葡萄球菌感染相关毒力因子研究进展[J].中华临床感染病杂志,2022,15(1):7.GUO K L,YU J J,LIU Y.Progress in the study of virulence factors associated with Staphylococcus aureus infection[J].Chinese Journal of Clinical Infectious Diseases,2022,15(1):7.(in Chinese)