鼠李糖乳杆菌抗炎机制及其在防治家畜疾病中的应用前景

doi:10.11843/j.issn.0366-6964.2023.11.010

摘要/Abstract

摘要： 抗生素是目前防治家畜疾病的主要手段之一,抗生素的滥用导致了致病菌耐药性的增加,畜禽产品中抗生素残留等问题,给食品安全及疾病防治带来了巨大挑战。随着人们对兽用抗生素滥用问题认识的加深,越来越多的目光聚焦于如何找到抗生素替代品来防止细菌感染、保证食品安全。鼠李糖乳杆菌多分离于人和动物的肠道内容物、粪便和阴道中,也常在牛奶及乳制品中发现。鼠李糖乳杆菌的使用可以减少抗生素的使用量,缓解致病菌耐药性的问题,对家畜的生长和胃肠道微生物的平衡也有一定的促进作用。本文综述了鼠李糖乳杆菌调节微生物菌群平衡、维持上皮细胞完整性、增强免疫力、抑制炎症和凋亡发生、限制病原体生长和黏附的作用机制,同时阐述了鼠李糖乳杆菌在预防奶牛乳房炎、奶牛子宫内膜炎、仔猪肠胃炎和中毒等疾病上的应用。本综述旨在为鼠李糖乳杆菌作为潜在的替抗药物在家畜健康养殖中的应用提供参考。

关键词: 鼠李糖乳杆菌, 奶牛乳房炎, 奶牛子宫内膜炎, 仔猪胃肠炎, 中毒

Abstract: Antibiotics are currently one of the main means of preventing and treating livestock diseases. With the abuse of antibiotics, the resistance of pathogenic bacteria has increased and antibiotic residues in livestock and poultry products have brought great challenges to food safety and disease prevention. As people’s understanding of the abuse of veterinary antibiotics, more and more attention is focused on how to find alternatives to reduce the use of antibiotics. Lactobacillus rhamnosus is mostly found in human and animal intestinal contents, stool, and vagina, also in milk and dairy products. The use of Lactobacillus rhamnosus can reduce the abuse of antibiotics, reduce the problem of drug resistance of pathogenic bacteria, and also promote the growth of livestock and the balance of gastrointestinal microorganisms. The present article reviews the mechanism of Lactobacillus rhamnosus in regulating the balance of microbial flora, maintaining the integrity of epithelial cells, enhancing immunity, inhibiting inflammation and apoptosis, and inhibiting the growth and adhesion of pathogens. At the same time, the application of Lactobacillus rhamnosus in the prevention of dairy cow mastitis, dairy cow endometritis, piglet gastroenteritis and poisoning was described, aiming to provide reference for the application of Lactobacillus rhamnosus as a potential alternative drug in healthy breeding of livestock.

Key words: Lactobacillus rhamnosus, dairy cow endometritis, dairy cow mastitis, piglet gastroenteritis, poison

中图分类号:

S859.79.7

单强, 王雪, 朱要宏, 王九峰. 鼠李糖乳杆菌抗炎机制及其在防治家畜疾病中的应用前景[J]. 畜牧兽医学报, 2023, 54(11): 4537-4550.

SHAN Qiang, WANG Xue, ZHU Yaohong, WANG Jiufeng. Application Prospect of Anti-inflammatory Mechanism of Lactobacillus rhamnosus and Its Prevention and Treatment in Livestock Diseases[J]. Acta Veterinaria et Zootechnica Sinica, 2023, 54(11): 4537-4550.

参考文献 78

[1]	PELLEGRINO M, BERARDO N, GIRAUDO J, et al. Bovine mastitis prevention:humoral and cellular response of dairy cows inoculated with lactic acid bacteria at the dry-off period[J]. Benef Microbes, 2017, 8(4):589-596.
[2]	PETROVA M I, REID G, TER HAAR J A. Lacticaseibacillus rhamnosus GR-1, a. k. a. Lactobacillus rhamnosus GR-1:past and future perspectives[J]. Trends Microbiol, 2021, 29(8):747-761.
[3]	崔志文. 鼠李糖乳杆菌影响仔猪肠道屏障功能的研究[D]. 杭州:浙江大学, 2013.CUI Z W. Effects of Lactobacillus rhamnosus on intestinal barrier in piglets[D]. Hangzhou:Zhejiang University, 2013. (in Chinese)
[4]	REID G, COOK R L, BRUCE A W. Examination of strains of Lactobacilli for properties that may influence bacterial interference in the urinary tract[J]. J Urol, 1987, 138(2):330-335.
[5]	MILLSAP K, REID G, VAN DER MEI H C, et al. Displacement of Enterococcus faecalis from hydrophobic and hydrophilic substrata by Lactobacillus and Streptococcus spp. As studied in a parallel plate flow chamber[J]. Appl Environ Microbiol, 1994, 60(6):1867-1874.
[6]	KÖHLER G A, ASSEFA S, REID G. Probiotic interference of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 with the opportunistic fungal pathogen Candida albicans[J]. Infect Dis Obstet Gynecol, 2012, 2012:636474.
[7]	MCMILLAN A, DELL M, ZELLAR M P, et al. Disruption of urogenital biofilms by lactobacilli[J]. Colloids Surf B Biointerfaces, 2011, 86(1):58-64.
[8]	VELRAEDS M M C, VAN DE BELT-GRITTER B, VAN DER MEI H C, et al. Interference in initial adhesion of uropathogenic bacteria and yeasts to silicone rubber by a Lactobacillus acidophilus biosurfactant[J]. J Med Microbiol, 1998, 47(12):1081-1085.
[9]	REID G, YOUNES J A, VAN DER MEI H C, et al. Microbiota restoration:natural and supplemented recovery of human microbial communities[J]. Nat Rev Microbiol, 2011, 9(1):27-38.
[10]	苏帅, 孙会, 于航宇, 等. 鼠李糖乳杆菌的生物学功能[J]. 动物营养学报, 2019, 31(1):97-101.SU S, SUN H, YU H Y, et al. Biological function of Lactobacillus rhamnosus[J]. Chinese Journal of Animal Nutrition, 2019, 31(1):97-101. (in Chinese)
[11]	SHAN Q, LIU N, WANG X, et al. Lactobacillus rhamnosus GR-1 attenuates foodborne Bacillus cereus-induced NLRP3 inflammasome activity in bovine mammary epithelial cells by protecting intercellular tight junctions[J]. J Anim Sci Biotechnol, 2022, 13(1):101.
[12]	LI Y N, ZHU Y H, CHU B X, et al. Lactobacillus rhamnosus GR-1 prevents Escherichia coli-induced apoptosis through pink1/parkin-mediated mitophagy in bovine mastitis[J]. Front Immunol, 2021, 12:715098.
[13]	WU Q, ZHU Y H, XU J, et al. Lactobacillus rhamnosus GR-1 ameliorates Escherichia coli-induced activation of NLRP3 and NLRC4 inflammasomes with differential requirement for ASC[J]. Front Microbiol, 2018, 9:1661.
[14]	WU Q, LIU M C, YANG J, et al. Lactobacillus rhamnosus GR-1 ameliorates Escherichia coli-induced inflammation and cell damage via attenuation of ASC-independent NLRP3 inflammasome activation[J]. Appl Environ Microbiol, 2016, 82(4):1173-1182.
[15]	LIU N, WANG X, SHAN Q, et al. Lactobacillus rhamnosus ameliorates multi-drug-resistant Bacillus cereus-induced cell damage through inhibition of NLRP3 inflammasomes and apoptosis in bovine endometritis[J]. Microorganisms, 2022, 10(1):137.
[16]	刘宁. 乳酸杆菌限制K+外排缓解细菌诱发子宫内膜上皮细胞NLRP3激活的机理[D]. 北京:中国农业大学, 2022.LIU N. The mechanism of Lactobacillus inhibiting K+ efflux to regulating the activation of NLRP3 pathway in endometrial epithelial cells infected by bacteria[D]. Beijing:China Agricultural University, 2022. (in Chinese)
[17]	LIU M C, WU Q, WANG M L, et al. Lactobacillus rhamnosus GR-1 limits Escherichia coli-induced inflammatory responses via attenuating MyD88-dependent and MyD88-independent pathway activation in bovine endometrial epithelial cells[J]. Inflammation, 2016, 39(4):1483-1494.
[18]	刘佳玮, 冯晓微, 焦玉兰, 等. 鼠李糖乳杆菌GR-1介导MAPK信号通路抗大肠杆菌诱导奶牛子宫内膜上皮细胞炎性损伤[J]. 河北农业大学学报, 2022, 45(2):99-106.LIU J W, FENG X W, JIAO Y L, et al. Protective effect of MAPK signal pathway mediated by Lactobacillus rhamnosus GR-1 against inflammatory injury of bovine endometrial epithelial cells induced by E. coli[J]. Journal of Hebei Agricultural University, 2022, 45(2):99-106. (in Chinese)
[19]	LIU J W, FENG X W, LI B T, et al. Lactobacillus rhamnosus GR-1 alleviates Escherichia coli-induced inflammation via NF-κB and MAPKs signaling in bovine endometrial epithelial cells[J]. Front Cell Infect Microbiol, 2022, 12:809674.
[20]	ZHANG L Y, JIANG X, LIU X, et al. Growth, health, rumen fermentation, and bacterial community of holstein calves fed Lactobacillus rhamnosus GG during the preweaning stage[J]. J Anim Sci, 2019, 97(6):2598-2608.
[21]	EWASCHUK J B, NAYLOR J M, CHIRINO-TREJO M, et al. Lactobacillus rhamnosus strain GG is a potential probiotic for calves[J]. Can J Vet Res, 2004, 68(4):249-253.
[22]	EWASCHUK J B, WALKER J W, DIAZ H, et al. Bioproduction of conjugated linoleic acid by probiotic bacteria occurs in vitro and in vivo in mice[J]. J Nutr, 2006, 136(6):1483-1487.
[23]	CATOZZI C, CUSCÓ A, LECCHI C, et al. Impact of intramammary inoculation of inactivated Lactobacillus rhamnosus and antibiotics on the milk microbiota of water buffalo with subclinical mastitis[J]. PLoS One, 2019, 14(1):e0210204.
[24]	ZHANG L Y, LIU S, ZHAO X J, et al. Lactobacillus rhamnosus GG modulates gastrointestinal absorption, excretion patterns, and toxicity in Holstein calves fed a single dose of aflatoxin B1[J]. J Dairy Sci, 2019, 102(2):1330-1340.
[25]	ZHANG W, ZHU Y H, YANG G Y, et al. Lactobacillus rhamnosus GG affects microbiota and suppresses autophagy in the intestines of pigs challenged with Salmonella infantis[J]. Front Microbiol, 2017, 8:2705.
[26]	GAO K, WANG C, LIU L, et al. Immunomodulation and signaling mechanism of Lactobacillus rhamnosus GG and its components on porcine intestinal epithelial cells stimulated by lipopolysaccharide[J]. J Microbiol Immunol Infect, 2017, 50(5):700-713.
[27]	YU J, ZHU Y H, YANG G Y, et al. Anti-inflammatory capacity of Lactobacillus rhamnosus GG in monophasic variant Salmonella infected piglets is correlated with impeding NLRP6-mediated host inflammatory responses[J]. Vet Microbiol, 2017, 210:91-100.
[28]	YANG G Y, YU J, SU J H, et al. Oral administration of Lactobacillus rhamnosus GG ameliorates Salmonella infantis-induced inflammation in a pig model via activation of the IL-22bp/IL-22/stat3 pathway[J]. Front Cell Infect Microbiol, 2017, 7:323.
[29]	ZHANG L, XU Y Q, LIU H Y, et al. Evaluation of Lactobacillus rhamnosus GG using an Escherichia coli k88 model of piglet diarrhoea:effects on diarrhoea incidence, faecal microflora and immune responses[J]. Vet Microbiol, 2010, 141(1-2):142-148.
[30]	MAO J D, QI S R, CUI Y J, et al. Lactobacillus rhamnosus GG attenuates lipopolysaccharide-induced inflammation and barrier dysfunction by regulating MAPK/NF-κB signaling and modulating metabolome in the piglet intestine[J]. J Nutr, 2020, 150(5):1313-1323.
[31]	ZHANG W, WU Q, ZHU Y H, et al. Probiotic Lactobacillus rhamnosus GG induces alterations in ileal microbiota with associated CD3-CD19-T-bet+IFNγ+/- cell subset homeostasis in pigs challenged with Salmonella enterica serovar 4,
[5]	, 12:i:-[J]. Front Microbiol, 2019, 10:977.
[32]	SPLICHALOVA A, JENISTOVA V, SPLICHALOVA Z, et al. Colonization of preterm gnotobiotic piglets with probiotic Lactobacillus rhamnosus GG and its interference with Salmonella typhimurium[J]. Clin Exp Immunol, 2019, 195(3):381-394.
[33]	JIN Y B, CAO X, SHI C W, et al. Lactobacillus rhamnosus GG promotes early B lineage development and IgA production in the lamina propria in piglets[J]. J Immunol, 2021, 207(8):2179-2191.
[34]	WANG Y, GONG L, WU Y P, et al. Oral administration of Lactobacillus rhamnosus GG to newborn piglets augments gut barrier function in pre-weaning piglets[J]. J Zhejiang Univ Sci B, 2019, 20(2):180-192.
[35]	焦连国. 猪源沙门菌分离鉴定及鼠李糖乳杆菌预防断奶仔猪腹泻效果研究[D]. 北京:中国农业大学, 2019.JIAO L G. Isolation and identification of Salmonella isolated from pigs and effects of Lactobacillus rhamnosus in preventing weaned diarrhea in piglets[D]. Beijing:China Agricultural University, 2019. (in Chinese)
[36]	MAO X B, GU C S, HU H Y, et al. Dietary Lactobacillus rhamnosus GG supplementation improves the mucosal barrier function in the intestine of weaned piglets challenged by porcine rotavirus[J]. PLoS One, 2016, 11(1):e0146312.
[37]	WU S P, YUAN L J, ZHANG Y G, et al. Probiotic Lactobacillus rhamnosus GG mono-association suppresses human rotavirus-induced autophagy in the gnotobiotic piglet intestine[J]. Gut Pathog, 2013, 5(1):22.
[38]	LIU F N, LI G H, WEN K, et al. Lactobacillus rhamnosus GG on rotavirus-induced injury of ileal epithelium in gnotobiotic pigs[J]. J Pediatr Gastroenterol Nutr, 2013, 57(6):750-758.
[39]	WEN K, TIN C, WANG H F, et al. Probiotic Lactobacillus rhamnosus GG enhanced TH1 cellular immunity but did not affect antibody responses in a human gut microbiota transplanted neonatal gnotobiotic pig model[J]. PLoS One, 2014, 9(4):e94504.
[40]	MA K D, BAI Y S, LI J B, et al. Lactobacillus rhamnosus GG ameliorates deoxynivalenol-induced kidney oxidative damage and mitochondrial injury in weaned piglets[J]. Food Funct, 2022, 13(7):3905-3916.
[41]	BAI Y S, MA K D, LI J B, et al. Lactobacillus rhamnosus GG ameliorates DON-induced intestinal damage depending on the enrichment of beneficial bacteria in weaned piglets[J]. J Anim Sci Biotechnol, 2022, 13(1):90.
[42]	GARCÍA G R, PAYROS D, PINTON P, et al. Intestinal toxicity of deoxynivalenol is limited by Lactobacillus rhamnosus RC007 in pig jejunum explants[J]. Arch Toxicol, 2018, 92(2):983-993.
[43]	LI J Z, LI Q K, GAO N, et al. Exopolysaccharides produced by Lactobacillus rhamnosus GG alleviate hydrogen peroxide-induced intestinal oxidative damage and apoptosis through the Keap1/Nrf2 and Bax/Bcl-2 pathways in vitro[J]. Food Funct, 2021, 12(20):9632-9641.
[44]	ZHANG W, ZHU Y H, YANG J C, et al. A selected Lactobacillus rhamnosus strain promotes EGFR-independent AKT activation in an enterotoxigenic Escherichia coli K88-infected IPEC-J2 cell model[J]. PLoS One, 2015, 10(4):e0125717.
[45]	WU T, SHI Y T, ZHANG Y Y, et al. Lactobacillus rhamnosus LB1 alleviates enterotoxigenic Escherichia coli-induced adverse effects in piglets by improving host immune response and anti-oxidation stress and restoring intestinal integrity[J]. Front Cell Infect Microbiol, 2021, 11:724401.
[46]	THOMAS D J, HUSMANN R J, VILLAMAR M, et al. Lactobacillus rhamnosus HN001 attenuates allergy development in a pig model[J]. PLoS One, 2011, 6(2):e16577.
[47]	GOOD M, SODHI C P, OZOLEK J A, et al. Lactobacillus rhamnosus HN001 decreases the severity of necrotizing enterocolitis in neonatal mice and preterm piglets:evidence in mice for a role of TLR9[J]. Am J Physiol Gastrointest Liver Physiol, 2014, 306(11):G1021-G1032.
[48]	GENG T T, HE F, SU S, et al. Probiotics Lactobacillus rhamnosus GG ATCC53103 and lactobacillus plantarum JL01 induce cytokine alterations by the production of TCDA, DHA, and succinic and palmitic acids, and enhance immunity of weaned piglets[J]. Res Vet Sci, 2021, 137:56-67.
[49]	SOLANO-AGUILAR G I, LAKSHMAN S, JANG S, et al. The effect of feeding cocoa powder and Lactobacillus rhamnosus on the composition and function of pig intestinal microbiome[J]. Curr Dev Nutr, 2018, 2(5):nzy011.
[50]	PHILIPPEAU C, LETTAT A, MARTIN C, et al. Effects of bacterial direct-fed microbials on ruminal characteristics, methane emission, and milk fatty acid composition in cows fed high- or low-starch diets[J]. J Dairy Sci, 2017, 100(4):2637-2650.
[51]	GENÍS S, BACH À, ARÍS A. Effects of intravaginal lactic acid bacteria on bovine endometrium:implications in uterine health[J]. Vet Microbiol, 2017, 204:174-179.
[52]	GENÍS S, SÀNCHEZ-CHARDI A, BÀCH A, et al. A combination of lactic acid bacteria regulates Escherichia coli infection and inflammation of the bovine endometrium[J]. J Dairy Sci, 2017, 100(1):479-492.
[53]	GENÍS S, BACH À, FÀBREGAS F, et al. Potential of lactic acid bacteria at regulating Escherichia coli infection and inflammation of bovine endometrium[J]. Theriogenology, 2016, 85(4):625-637.
[54]	BARKO P C, MCMICHAEL M A, SWANSON K S, et al. The gastrointestinal microbiome:a review[J]. J Vet Intern Med, 2018, 32(1):9-25.
[55]	MCFALL-NGAI M. Adaptive immunity:care for the community[J]. Nature, 2007, 445(7124):153.
[56]	GOMAA E Z. Human gut microbiota/microbiome in health and diseases:a review[J]. Antonie Van Leeuwenhoek, 2020, 113(12):2019-2040.
[57]	BRUCE A W, REID G. Intravaginal instillation of Lactobacilli for prevention of recurrent urinary tract infections[J]. Can J Microbiol, 1988, 34(3):339-343.
[58]	SHELDON I M, CRONIN J G, BROMFIELD J J. Tolerance and innate immunity shape the development of postpartum uterine disease and the impact of endometritis in dairy cattle[J]. Annu Rev Anim Biosci, 2019, 7:361-384.
[59]	LEBEER S, BRON P A, MARCO M L, et al. Identification of probiotic effector molecules:present state and future perspectives[J]. Curr Opin Biotechnol, 2018, 49:217-223.
[60]	吴琼. 乳酸杆菌减轻大肠杆菌诱发奶牛乳腺上皮细胞炎性损伤的机理[D]. 北京:中国农业大学, 2018.WU Q. Lactobacillus attenuates inflammatory damage of bovine mammary epithelial cells infected with Escherichia coli[D]. Beijing:China Agricultural University, 2018. (in Chinese)
[61]	VECKMAN V, MIETTINEN M, PIRHONEN J, et al. Streptococcus pyogenes and Lactobacillus rhamnosus differentially induce maturation and production of Th1-type cytokines and chemokines in human monocyte-derived dendritic cells[J]. J Leukoc Biol, 2004, 75(5):764-771.
[62]	YOUNES J A, LIEVENS E, HUMMELEN R, et al. Women and their microbes:the unexpected friendship[J]. Trends Microbiol, 2018, 26(1):16-32.
[63]	SWIDSINSKI A, MENDLING W, LOENING-BAUCKE V, et al. An adherent Gardnerella vaginalis biofilm persists on the vaginal epithelium after standard therapy with oral metronidazole[J]. Am J Obstet Gynecol, 2008, 198(1):97. e1-97. e6.
[64]	VAN DE WIJGERT J, VERWIJS M C. Lactobacilli-containing vaginal probiotics to cure or prevent bacterial or fungal vaginal dysbiosis:a systematic review and recommendations for future trial designs[J]. BJOG Int J Obstet Gynaecol, 2020, 127(2):287-299.
[65]	MATSUBARA V H, BANDARA H M H N, MAYER M P A, et al. Probiotics as antifungals in mucosal candidiasis[J]. Clin Infect Dis, 2016, 62(9):1143-1153.
[66]	REID G, KIM S O, KÖHLER G A. Selecting, testing and understanding probiotic microorganisms[J]. FEMS Immunol Med Microbiol, 2006, 46(2):149-157.
[67]	PETROVA M I, LIEVENS E, VERHOEVEN T L A, et al. The lectin-like protein 1 in Lactobacillus rhamnosus GR-1 mediates tissue-specific adherence to vaginal epithelium and inhibits urogenital pathogens[J]. Sci Rep, 2016, 6:37437.
[68]	CORFIELD A P, BERRY M. Glycan variation and evolution in the eukaryotes[J]. Trends Biochem Sci, 2015, 40(7):351-359.
[69]	REID G, LAM D, BRUCE A W, et al. Adhesion of Lactobacilli to urinary catheters and diapers:effect of surface properties[J]. J Biomed Mater Res, 1994, 28(6):731-734.
[70]	REID G, TIESZER C, LAM D. Influence of lactobacilli on the adhesion of Staphylococcus aureus and Candida albicans to fibers and epithelial cells[J]. J Ind Microbiol, 1995, 15(3):248-253.
[71]	RAINARD P, FOUCRAS G. A critical appraisal of probiotics for mastitis control[J]. Front Vet Sci, 2018, 5:251.
[72]	PELLEGRINO M S, FROLA I D, NATANAEL B, et al. In vitro characterization of lactic acid bacteria isolated from bovine milk as potential probiotic strains to prevent bovine mastitis[J]. Probiotics Antimicrob Proteins, 2019, 11(1):74-84.
[73]	HU X Y, LI S M, FU Y H, et al. Targeting gut microbiota as a possible therapy for mastitis[J]. Eur J Clin Microbiol Infect Dis, 2019, 38(8):1409-1423.
[74]	刘明超. 奶牛子宫内膜炎早期诊断及益生菌抗大肠杆菌诱导的子宫内膜上皮细胞炎性损伤作用机理[D]. 北京:中国农业大学, 2017.LIU M C. Early diagnosis of endometritis of dairy cows and the mechanism of probiotics against inflammatory injury of bovine endometrial epithelial cells induced by Escherichia coli[D]. Beijing:China Agricultural University, 2017. (in Chinese)
[75]	DAVIES D, MEADE K G, HERATH S, et al. Toll-like receptor and antimicrobial peptide expression in the bovine endometrium[J]. Reprod Biol Endocrinol, 2008, 6:53.
[76]	何贝贝, 李天天, 朱玉华, 等. 不同生长性能猪肠道菌群差异分析[J]. 动物营养学报, 2014, 26(8):2327-2334.HE B B, LI T T, ZHU Y H, et al. Differential analysis of intestinal microflora in pigs with different growth performance[J]. Chinese Journal of Animal Nutrition, 2014, 26(8):2327-2334. (in Chinese)
[77]	BISANZ J E, ENOS M K, MWANGA J R, et al. Randomized open-label pilot study of the influence of probiotics and the gut microbiome on toxic metal levels in Tanzanian pregnant women and school children[J]. mBio, 2014, 5(5):e01580-14.
[78]	DAISLEY B A, MONACHESE M, TRINDER M, et al. Immobilization of cadmium and lead by Lactobacillus rhamnosus GR-1 mitigates apical-to-basolateral heavy metal translocation in a Caco-2 model of the intestinal epithelium[J]. Gut Microbes, 2019, 10(3):321-333.