乳酸菌缓解伴侣动物肠道炎症的作用机制及研究进展

doi:10.16431/j.cnki.1671-7236.2025.05.046

摘要/Abstract

摘要： 炎症性肠病(IBD)是一种威胁伴侣动物健康的胃肠道炎症疾病，临床症状主要表现为呕吐、腹泻、腹痛、黏液性血便和体重下降等。目前并没有完全治愈炎症性肠病的方法，其确切发病机制尚不清楚。乳酸菌作为一类重要的益生菌，对炎症因子有抑制作用，其可通过调节炎症信号通路、抑制炎症介质释放等机制治疗肠道炎症。其可直接或间接调节代谢产物，增加短链脂肪酸含量，利用乙酸、丙酸、丁酸等对肠黏膜屏障进行保护和对肠上皮细胞直接提供能量，从而抑制肠道炎症。乳酸菌可抑制TLR4/NF-κB信号通路的表达，下调促炎细胞因子的产生，降低紧密连接蛋白ZO-1、Occludin和Claudin 1的表达。同时乳酸菌可通过芳烃受体(AhR)上调白细胞介素-22(IL-22)表达，影响T细胞和B细胞等免疫细胞的活性，进而影响机体的免疫应答。乳酸菌在肠道定植后，一般会产生肠道菌群的正向变化，重塑并增加肠道有益微生物群的多样性。乳酸菌还可通过修改某些microRNA的表达，在转录后对先天免疫反应产生积极影响，保持肠道屏障完整性，并减少促炎细胞因子的产生，调节Th1、Th17和Treg相关细胞因子的表达，对炎症性肠病起到治疗和干预作用。笔者通过探讨乳酸菌的作用机制，以期为未来乳酸菌用于治疗炎症性肠病提供更多理论支持。

关键词: 炎症性肠病; 乳酸菌; 短链脂肪酸; 作用机制; 炎症

Abstract: Inflammatory bowel disease (IBD) is a gastrointestinal inflammatory condition that poses significant health risks to companion animals.The primary clinical manifestations include vomiting,diarrhea,abdominal pain,bloody mucous stools,and weight loss.Currently,there is no definitive cure for IBD,and its precise pathogenesis remains unclear.Lactic acid bacteria (LAB),recognized as essential probiotics,have the potential to modulate gut inflammatory disorders by influencing relevant signaling pathways and inhibiting the release of inflammatory mediators.LAB can directly or indirectly regulate metabolites,thereby increasing the concentration of short-chain fatty acids (SCFAs) such as acetic acid,propionic acid and butyric acid,which play a pivotal role in protecting the intestinal mucosa and intestinal epithelial cells by providing direct energy,and consequently mitigating intestinal inflammation.LAB can suppress Toll-like receptor 4 (TLR4) signaling pathway,thereby reducing the production of pro-inflammatory cytokines,and diminishing the expression of tight junction proteins such as ZO-1 and Occludin,as well as Claudin 1.Furthermore,LAB have been shown up-regulating interleukin-22 (IL-22) through the aryl hydrocarbon receptor (AhR),which subsequently impacts the activity of immune cells,including T cells and B cells,thereby influencing the overall immune response.Following in the gut,LAB generally induce beneficial alterations in the intestinal microbiota by reshaping and enhancing the diversity of beneficial microbial populations.They can also modulate certain microRNAs (miRNAs),after transcription,exert positive effects on innate immune responses,help maintain intestinal barrier,and reduce the production of proinflammatory cytokines.Additionally,LAB regulate the expression of Th1,Th17 and Treg-related cytokines,and play a therapeutic and intervention role in inflammatory bowel disease.By exploring the mechanism of action of LAB,we hope to provide more theoretical support for the future use of LAB in the treatment of IBD.

Key words: inflammatory bowel disease; lactic acid bacteria; short chain fatty acids; mechanism; inflammatory

中图分类号:

孙晋涛, 顾鑫淑, 王金全, 王秀敏, 陶慧, 王振龙, 韩冰. 乳酸菌缓解伴侣动物肠道炎症的作用机制及研究进展[J]. 中国畜牧兽医, 2025, 52(5): 2442-2448.

SUN Jintao, GU Xinshu, WANG Jinquan, WANG Xiumin, TAO Hui, WANG Zhenlong, HAN Bing. Mechanisms and Recent Advances of Lactic Acid Bacteria in Treating Intestinal Inflammation in Companion Animals[J]. China Animal Husbandry and Veterinary Medicine, 2025, 52(5): 2442-2448.

参考文献

[1] BRUNER L P,WHITE A M,PROKSELL S.Inflammatory bowel disease[J]. Primary Care，2023,50(3):411-427.
[2] JERGENS A E.Feline idiopathic inflammatory bowel disease:What we know and what remains to be unraveled[J]. Journal of Feline Medicine and Surgery,2012，14(7):445-458.
[3] ZHANG X F,GUAN X X,TANG Y J,et al.Clinical effects and gut microbiota changes of using probiotics,prebiotics or synbiotics in inflammatory bowel disease:A systematic review and Meta-analysis[J].European Journal of Clinical Nutrition,2021,60(5):2855-2875.
[4] DAY M J,BILZER T,MANSELL J,et al.Histopathological standards for the diagnosis of gastrointestinal inflammation in endoscopic biopsy samples from the dog and cat:A report from the world small animal veterinary association gastrointestinal standardization group[J].Journal of Comparative Pathology，2008,138 Suppl 1:S1-S43.
[5] KOPPER J J,IENNARELLA-SERVANTEZ C,JERGENS A E,et al.Harnessing the biology of canine intestinal organoids to heighten understanding of inflammatory bowel disease pathogenesis and accelerate drug discovery:A one health approach[J].Frontiers in Toxicology,2021,3:773953.
[6] DI SABATINO A,LENTI M V,GIUFFRIDA P,et al.New insights into immune mechanisms underlying autoimmune diseases of the gastrointestinal tract[J].Autoimmunity Reviews，2015,14(12):1161-1169.
[7] KHOR B,GARDET A,XAVIER R J.Genetics and pathogenesis of inflammatory bowel disease[J].Nature,2011，474(7351):307-317.
[8] KUCHARZIK T,WALSH S V,CHEN J,et al.Neutrophil transmigration in inflammatory bowel disease is associated with differential expression of epithelial intercellular junction proteins[J].American Journal of Pathology,2001,159(6):2001-2009.
[9] ZEN K,LIU Y,MCCALL I C,et al.Neutrophil migration across tight junctions is mediated by adhesive interactions between epithelial coxsackie and Adenovirus receptor and a junctional adhesion molecule-like protein on neutrophils[J]. Molecular Biology of the Cell,2005,16(6):2694-2703.
[10] OPPENHEIM J J,ZACHARIAE C O,MUKAIDA N,et al.Properties of the novel proinflammatory supergene "intercrine" cytokine family[J].Annual Review of Immunology,1991,9:617-648.
[11] BEIL W J,WELLER P F,PEPPERCORN M A,et al.Ultrastructural immunogold localization of subcellular sites of TNF-alpha in colonic Crohn’s disease[J].Journal of Leukocyte Biology,1995,58(3):284-298.
[12] BRAZIL J C,LOUIS N A,PARKOS C A.The role of polymorphonuclear leukocyte trafficking in the perpetuation of inflammation during inflammatory bowel disease[J].Inflammatory Bowel Diseases,2013,19(7):1556-1565.
[13] YANG D,CHEN Q,CHERTOV O,et al.Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells[J].Journal of Leukocyte Biology,2000,68(1):9-14.
[14] BRAZIL J C,LEE W Y,KOLEGRAFF K N,et al.Neutrophil migration across intestinal epithelium:Evidence for a role of CD44 in regulating detachment of migrating cells from the luminal surface[J].Journal of Immunology,2010,185(11):7026-7036.
[15] GARCÍA-SANCHO M,RODRÍGUEZ-FRANCO F,SAINZ A,et al.Evaluation of clinical,macroscopic,and histopathologic response to treatment in nonhypoproteinemic dogs with lymphocytic-plasmacytic enteritis[J].Journal of Veterinary Internal Medicine，2007,21(1):11-17.
[16] AGULLA B,VILLAESCUSA A,SAINZ Á,et al.Peripheral and intestinal T lymphocyte subsets in dogs with chronic inflammatory enteropathy[J]. Journal of Veterinary Internal Medicine,2024,38(3):1437-1448.
[17] MENG Y,WANG J,WANG Z,et al.Lactobacillus plantarum KLDS1.0318 ameliorates impaired intestinal immunity and metabolic disorders in cyclophosphamide-treated mice[J].Frontiers in Microbiology，2019,10:731.
[18] SONG Y,SUN M,MA F,et al.Lactiplantibacillus plantarum DLPT4 protects against cyclophosphamide-induced immunosuppression in mice by regulating immune response and intestinal flora[J]. Probiotics and Antimicrobial Proteins,2024,16(2):321-333.
[19] YAN F,LI N,SHI J,et al. Lactobacillus acidophilus alleviates type 2 diabetes by regulating hepatic glucose,lipid metabolism and gut microbiota in mice[J].Food & Function，2019,10(9)：5804-5815.
[20] SATISH KUMAR C S,KONDAL REDDY K,BOOBALAN G,et al.Protective effect of Lactobacillus plantarum,21,a probiotic on trinitrobenzenesulfonic acid-induced ulcerative colitis in rats[J].International Immunopharmacology,2015,25:504-510.
[21] ZHANG J,XIAO Y,WANG H,et al.Lactic acid bacteria-derived exopolysaccharide:Formation,immunomodulatory ability,health effects,and structure-function relationship[J]. Microbiological Research,2023,274:127432.
[22] MARKOWIAK-KOPEĆ P, ŚLIŻEWSKA K.The effect of probiotics on the production of short-chain fatty acids by human intestinal microbiome[J]. Nutrients，2020,12(4):1107.
[23] CHERBUT C.Motor effects of short-chain fatty acids and lactate in the gastrointestinal tract[J].Proceedingsof the Nutrition Society，2003,62(1):95-99.
[24] LI M,VAN ESCH B C A M,WAGENAAR G T M,et al.Pro- and anti-inflammatory effects of short chain fatty acids on immune and endothelial cells[J]. European Journal of Pharmacology,2018,831:52-59.
[25] ELCE A,AMATO F,ZARRILLI F,et al.Butyrate modulating effects on pro-inflammatory pathways in human intestinal epithelial cells[J]. Beneficial Microbes,2017,8(5):841-847.
[26] KUCZY AN＇G SKA B,WASILEWSKA A,BICZYSKO M,et al.Krótkołańcuchowe kwasy tłuszczowe-mechanizm działania,potencjalne zastosowanie kliniczne oraz zalecenia dietetyczne[J]. Instytut Mikrobiomiki,2011,80:299-304.
[27] MOENS F,VAN DEN ABBEELE P,BASIT A W,et al.A four-strain probiotic exerts positive immunomodulatory effects by enhancing colonic butyrate production in vitro[J].International Journal of Pharmaceutics，2019,555:1-10.
[28] WANG L,ZHANG J,GUO Z,et al.Effect of oral consumption of probiotic Lactobacillus planatarum P-8 on fecal microbiota,SIgA,SCFAs,and TBAs of adults of different ages[J].Nutrition,2014,30(7-8):776-783.
[29] LAURINDO L F,SANTOS A R O D,CARVALHO A C A,et al.Phytochemicals and regulation of NF-κB in inflammatory bowel diseases:An overview of in vitro and in vivo effects[J].Metabolites,2023,13(1):96.
[30] ATREYA I,ATREYA R,NEURATH M F.NF-kappaB in inflammatory bowel disease[J].Journal of Internal Medicine,2008,263(6):591-596.
[31] DONG K,ZHANG Y,JI H R,et al.Dexamethasone-loaded lipid calcium phosphate nanoparticles treat experimental colitis by regulating macrophage polarization in inflammatory sites[J].International Journal of Nanomedicine,2024,19:993-1016.
[32] KANG Y,KANG X,YANG H,et al.Lactobacillus acidophilus ameliorates obesity in mice through modulation of gut microbiota dysbiosis and intestinal permeability[J].Pharmacological Research,2022,175:106020.
[33] KIM A Y,PARK Y J,PAN X,et al.Obesity-induced DNA hypermethylation of the adiponectin gene mediates insulin resistance[J]. Nature Communications，2015,6:7585.
[34] KIM K J,KYUNG S,JIN H,et al.Lactic acid bacteria isolated from human breast milk improve colitis induced by 2,4,6-trinitrobenzene sulfonic acid by inhibiting NF-κB signaling in mice[J].Journal of Microbiology and Biotechnology,2023,33(8):1057-1065.
[35] JANG S E,MIN S W.Lactobacillus sakei S1 improves colitis induced by 2,4,6-trinitrobenzene sulfonic acid by the inhibition of NF-κB signaling in mice[J]. Journal of Microbiology and Biotechnology,2020,30(1):71-78.
[36] JANG S E,HAN M J,KIM S Y,et al. Lactobacillus plantarum CLP-0611 ameliorates colitis in mice by polarizing M1 to M2-like macrophages[J]. International Immunopharmacology,2014,21(1):186-192.
[37] IKUTA T,KUROSUMI M,YATSUOKA T,et al.Tissue distribution of aryl hydrocarbon receptor in the intestine:Implication of putative roles in tumor suppression[J]. Experimental Cell Research,2016,343(2):126-134.
[38] VÁZQUEZ-GÓMEZ G,PETRÁŠ J,DVOŘ ÁK Z,et al.Aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR) play both distinct and common roles in the regulation of colon homeostasis and intestinal carcinogenesis[J].Biochemical Pharmacology，2023,216:115797.
[39] TAN Y Q,WANG Y N,FENG H Y,et al.Host/microbiota interactions-derived tryptophan metabolites modulate oxidative stress and inflammation via aryl hydrocarbon receptor signaling[J]. Free Radical Biology and Medicine,2022,184:30-41.
[40] NOHARA K,PAN X,TSUKUMO S,et al.Constitutively active aryl hydrocarbon receptor expressed specifically in T-lineage cells causes thymus involution and suppresses the immunization-induced increase in splenocytes[J].The Journal of Immunology，2005,174(5):2770-2777.
[41] SAKAMOTO R,TAKADA A,YAMAKADO S,et al.Release from persistent T cell receptor engagement and blockade of aryl hydrocarbon receptor activity enhance IL-6-dependent mouse follicular helper T-like cell differentiation in vitro[J].PLoS One，2023,18(6):e0287746.
[42] BENDER M J,MCPHERSON A C,PHELPS C M,et al.Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment[J].Cell,2023,186(9):1846-1862.
[43] MONTGOMERY T L,ECKSTROM K,LILE K H,et al.Lactobacillus reuteri tryptophan metabolism promotes host susceptibility to CNS autoimmunity[J].Microbiome,2022,10(1):198.
[44] LAMAS B,NATIVIDAD J M,SOKOL H.Aryl hydrocarbon receptor and intestinal immunity[J].Mucosal Immunology，2018,11(4):1024-1038.
[45] MONTELEONE I,RIZZO A,SARRA M,et al.Aryl hydrocarbon receptor-induced signals up-regulate IL-22 production and inhibit inflammation in the gastrointestinal tract[J].Gastroenterology，2011,141(1):237-248.
[46] ZELANTE T,IANNITTI RG,CUNHA C,et al.Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22[J].Immunity，2013,39(2):372-385.
[47] GAO J,XU K,LIU H,et al.Impact of the gut microbiota on intestinal immunity mediated by tryptophan metabolism[J].Frontiers in Cellular and Infection Microbiology,2018,8:13.
[48] SEO S K,KWON B.Immune regulation through tryptophan metabolism[J].Experimental and Molecular Medicine，2023,55(7):1371-1379.
[49] SUN M,MA N,HE T,et al.Tryptophan (Trp) modulates gut homeostasis via aryl hydrocarbon receptor (AhR)[J]. Critical Reviews in Food Science and Nutrition，2020，60(10):1760-1768.
[50] ÖZÇAM M,TOCMO R,OH J H,et al.Gut symbionts Lactobacillus reuteri r2lc and 2010 encode a polyketide synthase cluster that activates the mammalian aryl hydrocarbon receptor[J].Applied and Environmental Microbiology,2019,85(10):e01661-18.
[51] DONG F,HAO F,MURRAY I A,et al.Intestinal microbiota-derived tryptophan metabolites are predictive of Ah receptor activity[J]. Gut Microbes，2020,12(1):1-24.
[52] JANG Y J,KIM W K,HAN D H,et al.Lactobacillus fermentum species ameliorate dextran sulfate sodium-induced colitis by regulating the immune response and altering gut microbiota[J]. Gut Microbes，2019，10(6):696-711.
[53] RODRÍGUEZ-NOGALES A,ALGIERI F,GARRIDO-MESA J,et al.Intestinal anti-inflammatory effect of the probiotic Saccharomyces boulardii in DSS-induced colitis in mice:Impact on microRNAs expression and gut microbiota composition[J].Journal of Nutritional Biochemistry,2018,61:129-139.
[54] LI A,LIU A,WANG J,et al.The prophylaxis functions of Lactobacillus fermentum GLF-217 and Lactobacillus plantarum FLP-215 on ulcerative colitis via modulating gut microbiota of mice[J].Journal of the Science of Food and Agriculture,2024,104(10):5816-5825.
[55] ZHANG W Q,QUAN K Y,FENG C J,et al.The Lactobacillus gasseri g098 strain mitigates symptoms of DSS-induced inflammatory bowel disease in mice[J].Nutrients，2022,14(18):3745.
[56] LIU Y,LIU G,FANG J.Progress on the mechanisms of Lactobacillus plantarum to improve intestinal barrier function in ulcerative colitis[J].Journal of Nutritional Biochemistry,2024,124:109505.
[57] ZHAO H,ZHAO C,DONG Y,et al.Inhibition of miR122a by Lactobacillus rhamnosus GG culture supernatant increases intestinal occludin expression and protects mice from alcoholic liver disease[J]. Toxicology Letters,2015,234(3):194-200.
[58] KALIYAMOORTHY V,JACOP J P,THIRUGNANASAMBANTHAM K,et al.The synergic impact of lignin and Lactobacillus plantarum on DSS-induced colitis model via regulating CD44 and miR199a alliance[J]. World Journal of Microbiology and Biotechnology，2022,38(12):233.