综述 REVIEW

霉菌毒素对动物肠道功能的影响及其作用机制研究进展

  • 陈豪 ,
  • 何流琴 ,
  • 刘娣 ,
  • 杨玲媛
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  • 1. 湖南农业大学动物科学与技术学院, 长沙 410128;
    2. 湖南师范大学生命科学学院, 动物肠道功能 湖南省重点实验室, 长沙 410081;
    3. 黑龙江省农业科学院畜牧研究所, 哈尔滨 150086
陈豪(1997-),男,湖南常德人,硕士研究生,从事动物营养研究。E-mail:chenyichen11@sina.com

收稿日期: 2021-07-18

  网络出版日期: 2022-02-15

基金资助

中国科协青年托举人才项目(2019QNRC001);广西桂林市科技计划项目(2020010901);广西重点研发计划(桂科AB19259012);国家自然科学基金面上项目(31872370);湖湘高层次人才聚集工程项目(2018RS3111);湖南省动物肠道生态与健康国际科技创新合作基地开放基金项目

Research Progress of Effects of Mycotoxin on Intestinal Function and Its Mechanism

  • CHEN Hao ,
  • HE Liuqin ,
  • LIU Ti ,
  • YANG Linyuan
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  • 1. College of Animal Science and Technology, Hunan Agricultural University, Changsha 410128, China;
    2. Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, College of Life Science, Hunan Normal University, Changsha 410081, China;
    3. Institute of Animal Husbandry, Heilongjiang Academy of Agricultural Sciences, Harbin 150086, China

Received date: 2021-07-18

  Online published: 2022-02-15

摘要

霉菌毒素属于霉菌次级代谢产物,具有种类多、分布广、毒性大的特点。霉菌毒素作为畜牧业中的"隐形杀手",不仅严重降低了饲料品质,而且常存在于饲料原料中,影响动物机体健康,直接或间接造成食品安全问题。肠道作为消化吸收的主要场所,对霉菌毒素的刺激具有强烈的抵御和免疫作用,同时也深受霉菌毒素的损伤。玉米是主要的饲料原料之一,而黄曲霉毒素、脱氧雪腐镰刀菌烯醇和玉米赤霉烯酮是玉米中主要出现的霉菌毒素,因此了解这3种霉菌毒素的毒性机制显得尤为重要。本文综合国内外研究进展,主要以这3种霉菌毒素为例,就霉菌毒素对肠道屏障、免疫机能、抗氧化功能、微生态平衡和营养物质代谢等的影响及其作用机制研究进行综述,为降低饲料中霉菌毒素的危害和开发降解霉菌毒素产品提供新的思路和理论依据,同时也对提升我国畜禽肉品质和粮食战略安全具有重要意义。

本文引用格式

陈豪 , 何流琴 , 刘娣 , 杨玲媛 . 霉菌毒素对动物肠道功能的影响及其作用机制研究进展[J]. 动物营养学报, 2022 , 34(2) : 772 -782 . DOI: 10.3969/j.issn.1006-267x.2022.02.012

Abstract

Mycotoxins are secondary metabolites of fungi, which are characterized by many kinds, wide distribution and high toxicity. Mycotoxins, as the "invisible killer" in animal husbandry, not only seriously reduce the quality of feed, but also often exist in feed materials, affecting animal health and directly or indirectly causing food safety problems. As the main place of digestion and absorption, intestinal tract has strong resistance and immunity to the stimulation of mycotoxins, and it is also deeply affected by mycotoxins. Maize is one of the main feed materials, and aflatoxin, deoxynivalenol and zearalenone are the main mycotoxins in maize, therefore, it is particularly important to understand the toxic mechanism of these three mycotoxins. In this paper, based on the research status at home and abroad, take these three mycotoxins as examples, the effects of mycotoxins on Intestinal barrier, immune function, antioxidant function, microecological balance and nutrient metabolism were reviewed, which provided new ideas and theoretical basis for reducing the harm of mycotoxins in feed and developing products for degrading mycotoxins. At the same time, it also has great significance to improve the quality of livestock and poultry meat and food strategic security in China.

参考文献

[1] MARTINDAH E, BAHRI S.Mycotoxin contamination in the food chain[J].Indonesian Bulletin of Animal and Veterinary Sciences, 2017, 26(3):115.
[2] YANG C, SONG G, LIM W.Effects of mycotoxin-contaminated feed on farm animals[J].Journal of Hazardous Materials, 2020, 389:122087.
[3] 黄志伟.12种植物性饲料原料中霉菌毒素污染状况的调查分析[J].粮食与饲料工业, 2019(1):58-60. HUANG Z W.Investigation and analysis of mycotoxin contamination in 12 plant feed ingredients[J].Cereal & Feed Industry, 2019(1):58-60.(in Chinese)
[4] 黄俊恒, 黄广明.2017年21省市饲料及饲料原料霉菌毒素污染状况分析[J].养猪, 2018(3):20-22. HUANG J H, HUANG G M.Analysis on mycotoxin pollution of feed and feed raw materials in 21 provinces and cities in 2017[J].Swine Production, 2018(3):20-22.(in Chinese)
[5] STREIT E, NAEHRER K, RODRIGUES I, et al.Mycotoxin occurrence in feed and feed raw materials worldwide:long-term analysis with special focus on Europe and Asia[J].Journal of the Science of Food and Agriculture, 2013, 93(12):2892-2899.  
[6] WU N, OU W, ZHANG Z D, et al.Recent advances in detoxification strategies for zearalenone contamination in food and feed[J].Chinese Journal of Chemical Engineering, 2021, 30:168-177.
[7] JIA R, SADIQ F A, LIU W B, et al.Protective effects of Bacillus subtilis ASAG 216 on growth performance, antioxidant capacity, gut microbiota and tissues residues of weaned piglets fed deoxynivalenol contaminated diets[J].Food and Chemical Toxicology, 2021, 148:111962.
[8] XIA S, ZHU P, PI F W, et al.Development of a simple and convenient cell-based electrochemical biosensor for evaluating the individual and combined toxicity of DON, ZEN and AFB1[J].Biosensors & Bioelectronics, 2017, 97:345-351.
[9] HOLANDA D M, KIM S W.Investigation of the efficacy of mycotoxin-detoxifying additive on health and growth of newly-weaned pigs under deoxynivalenol challenges[J].Animal Bioscience, 2021, 34(3):405-416.  
[10] PAYROS D, MÉNARD S, LAFFITTE J, et al.The food contaminant, deoxynivalenol, modulates the Thelper/Treg balance and increases inflammatory bowel diseases[J].Archives of Toxicology, 2020, 94(9):3173-3184.  
[11] RIAHI I, MARQUIS V, RAMOS A J, et al.Effects of deoxynivalenol-contaminated diets on productive, morphological, and physiological indicators in broiler chickens[J].Animals, 2020, 10(10):1795.
[12] LUCKE A, BÖHM J, ZEBELI Q, et al.Dietary deoxynivalenol and oral lipopolysaccharide challenge differently affect intestinal innate immune response and barrier function in broiler chickens[J].Journal of Animal Science, 2018, 96(12):5134-5143.
[13] VAN LE THANH B, LESSARD M, CHORFI Y, et al.The efficacy of anti-mycotoxin feed additives in preventing the adverse effects of wheat naturally contaminated with Fusarium mycotoxins on performance, intestinal barrier function and nutrient digestibility and retention in weanling pigs[J].Canadian Journal of Animal Science, 2015, 95(2):197-209.  
[14] KOWALSKA K, HABROWSKA-GÓRCZYŃSKA D E, PIASTOWSKA-CIESIELSKA A W.Zearalenone as an endocrine disruptor in humans[J].Environmental Toxicology and Pharmacology, 2016, 48:141-149.
[15] BINDER S B, SCHWARTZ-ZIMMERMANN H E, VARGA E, et al.Metabolism of zearalenone and its major modified forms in pigs[J].Toxins, 2017, 9(2):56.
[16] PRZYBYLSKA-GORNOWICZ B, LEWCZUK B, PRUSIK M, et al.The effects of deoxynivalenol and zearalenone on the pig large intestine.A light and electron microscopy study[J].Toxins, 2018, 10(4):148.
[17] GREGORIEFF A, CLEVERS H.Wnt signaling in the intestinal epithelium:from endoderm to cancer[J].Genes & Development, 2005, 19(8):877-890.  
[18] FRAUNGRUBER P, KALTOFEN T, HEUBLEIN S, et al.G protein-coupled estrogen receptor correlates with Dkk2 expression and has prognostic impact in ovarian cancer patients[J].Frontiers in Endocrinology, 2021, 12:564002.
[19] CHO N L, JAVID S H, CAROTHERS A M, et al.Estrogen receptors alpha and beta are inhibitory modifiers of Apc-dependent tumorigenesis in the proximal colon of Min/+ mice[J].Cancer Research, 2007, 67(5):2366-2372.  
[20] PASTERNAK J A, AIYER V I A, HAMONIC G, et al.Molecular and physiological effects on the small intestine of weaner pigs following feeding with deoxynivalenol-contaminated feed[J].Toxins, 2018, 10(1):40.
[21] PINTON P, NOUGAYRÈDE J P, DEL RIO J C, et al.The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression[J].Toxicology and Applied Pharmacology, 2009, 237(1):41-48.  
[22] ALIZADEH A, BRABER S, AKBARI P, et al.Deoxynivalenol impairs weight gain and affects markers of gut health after low-dose, short-term exposure of growing pigs[J].Toxins, 2015, 7(6):2071-2095.  
[23] MANDA G, MOCANU M A, MARIN D E, et al.Dual effects exerted in vitro by micromolar concentrations of deoxynivalenol on undifferentiated Caco-2 cells[J].Toxins, 2015, 7(2):593-603.  
[24] LUO S, TERCIOLO C, BRACARENSE A P F L, et al.In vitro and in vivo effects of a mycotoxin, deoxynivalenol, and a trace metal, cadmium, alone or in a mixture on the intestinal barrier[J].Environment International, 2019, 132:105082.
[25] LI R N, LI Y S, SU Y T, et al.Short-term ingestion of deoxynivalenol in naturally contaminated feed alters piglet performance and gut hormone secretion[J].Animal Science Journal, 2018, 89(8):1134-1143.  
[26] PIERRON A, MIMOUN S, MURATE L S, et al.Intestinal toxicity of the masked mycotoxin deoxynivalenol-3-β-D-glucoside[J].Archives of Toxicology, 2016, 90(8):2037-2046.  
[27] MORRIS O, JASPER H.Reactive oxygen species in intestinal stem cell metabolism, fate and function[J].Free Radical Biology & Medicine, 2021, 166:140-146.
[28] NAGAI H, TATARA H, TANAKA-FURUHASHI K, et al.Homeostatic regulation of ROS-triggered Hippo-Yki pathway via autophagic clearance of Ref(2)P/p62 in the Drosophila intestine[J].Developmental Cell, 2021, 56(1):81-94.e10.  
[29] MARIN D E, PISTOL G C, GRAS M A, et al.Comparative effect of ochratoxin A on inflammation and oxidative stress parameters in gut and kidney of piglets[J].Regulatory Toxicology and Pharmacology, 2017, 89:224-231.
[30] ADESSO S, AUTORE G, QUARONI A, et al.The food contaminants nivalenol and deoxynivalenol induce inflammation in intestinal epithelial cells by regulating reactive oxygen species release[J].Nutrients, 2017, 9(12):1343.
[31] LIU M, GAO R, MENG Q W, et al.Toxic effects of maternal zearalenone exposure on intestinal oxidative stress, barrier function, immunological and morphological changes in rats[J].PLoS One, 2014, 9(9):e106412.
[32] ARAB H H, GAD A M, REDA E J, et al.Activation of autophagy by sitagliptin attenuates cadmium-induced testicular impairment in rats:targeting AMPK/mTOR and Nrf2/HO-1 pathways[J].Life Sciences, 2021, 269:119031.
[33] SARRAMI S, JAFARI P, TAJABADI EBRAHIMI M, et al. Effects of various Toxeat concentrations on growth performance, immune response, cecal microflora, and gut morphology in broilers fed with aflatoxin contaminated diets[J].Turkish Journal of Veterinary and Animal Sciences, 2019, 43(3):299-305.  
[34] HOU L J, TONG X, LIN S Y, et al.MiR-221/222 ameliorates deoxynivalenol-induced apoptosis and proliferation inhibition in intestinal epithelial cells by targeting PTEN[J].Frontiers in Cell and Developmental Biology, 2021, 9:652939.
[35] JI J, WANG Q Y, WU H, et al.Insights into cellular metabolic pathways of the combined toxicity responses of Caco-2 cells exposed to deoxynivalenol, zearalenone and aflatoxin B1[J].Food and Chemical Toxicology, 2019, 126:106-112.
[36] SUN C J, SHEN H K, CAI H M, et al.Intestinal guard:human CXCL17 modulates protective response against mycotoxins and CXCL17-mimetic peptides development[J].Biochemical Pharmacology, 2021, 188:114586.
[37] ZHAO Y J, GUO W Y, GU X L, et al.Repression of deoxynivalenol-triggered cytotoxicity and apoptosis by mannan/β-glucans from yeast cell wall:involvement of autophagy and PI3K-AKT-mTOR signaling pathway[J].International Journal of Biological Macromolecules, 2020, 164:1413-1421.
[38] MENDIETA C R, GÓMEZ G V, DEL RÍO J C G, et al.Effect of the addition of Saccharomyces cerevisiae yeast cell walls to diets with mycotoxins on the performance and immune responses of broilers[J].The Journal of Poultry Science, 2018, 55(1):38-46.  
[39] GAO Y A, YE Q Y, BAO X Y, et al.Transcriptomic and proteomic profiling reveals the intestinal immunotoxicity induced by aflatoxin M1 and ochratoxin A[J].Toxicon, 2020, 180:49-61.
[40] LUONGO D, SEVERINO L, BERGAMO P, et al.Interactive effects of fumonisin B1 and alpha-zearalenol on proliferation and cytokine expression in Jurkat T cells[J].Toxicology in Vitro, 2006, 20(8):1403-1410.  
[41] JIANG M, PENG X, FANG J, et al.Effects of aflatoxin B1 on T-cell subsets and mRNA expression of cytokines in the intestine of broilers[J].International Journal of Molecular Sciences, 2015, 16(4):6945-6959.
[42] JIANG M, FANG J, PENG X, et al.Effect of aflatoxin B1 on IgA+ cell number and immunoglobulin mRNA expression in the intestine of broilers[J].Immunopharmacology and Immunotoxicology, 2015, 37(5):450-457.  
[43] LIU D D, WANG Q, HE W M, et al.Two-way immune effects of deoxynivalenol in weaned piglets and porcine alveolar macrophages:due mainly to its exposure dosage[J].Chemosphere, 2020, 249:126464.
[44] LESSARD M, SAVARD C, DESCHENE K, et al.Impact of deoxynivalenol (DON) contaminated feed on intestinal integrity and immune response in swine[J].Food and Chemical Toxicology, 2015, 80:7-16.
[45] VAN DE WALLE J, ROMIER B, LARONDELLE Y, et al.Influence of deoxynivalenol on NF-kappaB activation and IL-8 secretion in human intestinal Caco-2 cells[J].Toxicology Letters, 2008, 177(3):205-214.  
[46] 陈祥兴, 张崇玉, 黄丽波, 等.镰刀菌毒素对断奶仔猪肠道IL-1β和IL-6分布和表达的影响[J].畜牧兽医学报, 2016, 47(10):2126-2135. CHEN X X, ZHANG C Y, HUANG L B, et al.Effects of Fusarium toxins on IL-1β and IL-6 in post-weaning piglets[J].Acta Veterinaria et Zootechnica Sinica, 2016, 47(10):2126-2135.(in Chinese)
[47] WANG S, YANG J C, ZHANG B Y, et al.Deoxynivalenol impairs porcine intestinal host defense peptide expression in weaned piglets and IPEC-J2 cells[J].Toxins, 2018, 10(12):541.
[48] GRAZIANI F, PUJOL A, NICOLETTI C, et al.The food-associated ribotoxin deoxynivalenol modulates inducible NO synthase in human intestinal cell model[J].Toxicological Sciences, 2015, 145(2):372-382.  
[49] WANG X, YU H, SHAN A S, et al.Toxic effects of zearalenone on intestinal microflora and intestinal mucosal immunity in mice[J].Food and Agricultural Immunology, 2018, 29(1):1002-1011.  
[50] LIN R Q, SUN Y, YE W C, et al.T-2 toxin inhibits the production of mucin via activating the IRE1/XBP1 pathway[J].Toxicology, 2019, 424:152230.
[51] MAKOWSKA K, OBREMSKI K, GONKOWSKI S.The impact of T-2 toxin on vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) nerve structures in the wall of the porcine stomach and duodenum[J].Toxins, 2018, 10(4):138.
[52] SCHMUTZ C, CENK E, MARKO D.The alternaria mycotoxin alternariol triggers the immune response of IL-1β-stimulated, differentiated Caco-2 cells[J].Molecular Nutrition & Food Research, 2019, 63(20):e1900341.
[53] WU L, WANG W C, YAO K, et al.Effects of dietary arginine and glutamine on alleviating the impairment induced by deoxynivalenol stress and immune relevant cytokines in growing pigs[J].PLoS One, 2013, 8(7):e69502.
[54] METZGER R N, KRUG A B, EISENÄCHER K.Enteric virome sensing-its role in intestinal homeostasis and immunity[J].Viruses, 2018, 10(4):146.
[55] AWAD W A, RUHNAU D, HESS C, et al.Feeding of deoxynivalenol increases the intestinal paracellular permeability of broiler chickens[J].Archives of Toxicology, 2019, 93(7):2057-2064.  
[56] YANG X A, LIU L L, CHEN J, et al.Response of intestinal bacterial flora to the long-term feeding of aflatoxin B1 (AFB1) in mice[J].Toxins, 2017, 9(10):317.
[57] REDDY K E, KIM M, KIM K H, et al.Effect of commercially purified deoxynivalenol and zearalenone mycotoxins on microbial diversity of pig cecum contents[J].Animal Bioscience, 2021, 34(2):243-255.  
[58] EL-NEZAMI H S, CHREVATIDIS A, AURIOLA S, et al.Removal of common Fusarium toxins in vitro by strains of Lactobacillus and Propionibacterium[J].Food Additives and Contaminants, 2002, 19(7):680-686.  
[59] ALI-VEHMAS T, RIZZO A, WESTERMARCK T, et al.Measurement of antibacterial activities of T-2 toxin, deoxynivalenol, ochratoxin A, aflatoxin B1 and fumonisin B1 using microtitration tray-based turbidimetric techniques[J].Zentralblatt Fur Veterinarmedizin.Reihe A, 1998, 45(8):453-458.
[60] MIRÓ-ABELLA E, TORRELL H, HERRERO P, et al.Monitoring and evaluation of the interaction between deoxynivalenol and gut microbiota in Wistar rats by mass spectrometry-based metabolomics and next-generation sequencing[J].Food and Chemical Toxicology, 2018, 121:124-130.
[61] VIGNAL C, DJOUINA M, PICHAVANT M, et al.Chronic ingestion of deoxynivalenol at human dietary levels impairs intestinal homeostasis and gut microbiota in mice[J].Archives of Toxicology, 2018, 92(7):2327-2338.  
[62] LIU M, ZHANG L, CHU X H, et al.Effects of deoxynivalenol on the porcine growth performance and intestinal microbiota and potential remediation by a modified HSCAS binder[J].Food and Chemical Toxicology, 2020, 141:111373.
[63] PIOTROWSKA M, SLIŻEWSKA K, NOWAK A, et al.The effect of experimental Fusarium mycotoxicosis on microbiota diversity in porcine ascending colon contents[J].Toxins, 2014, 6(7):2064-2081.  
[64] GALARZA-SEEBER R, LATORRE J D, BIELKE L R, et al.Leaky gut and mycotoxins:aflatoxin B1 does not increase gut permeability in broiler chickens[J].Frontiers in Veterinary Science, 2016, 3:10.
[65] DANG H A, ZSOLNAI A, KOVACS M, et al.In vitro interaction between fumonisin B1 and the intestinal microflora of pigs[J].Polish Journal of Microbiology, 2017, 66(2):245-250.  
[66] ZHENG W J, JI X, ZHANG Q, et al.Intestinal microbiota ecological response to oral administrations of hydrogen-rich water and lactulose in female piglets fed a Fusarium toxin-contaminated diet[J].Toxins, 2018, 10(6):246.
[67] RICHARDS J D, GONG J, DE LANGE C F M.The gastrointestinal microbiota and its role in monogastric nutrition and health with an emphasis on pigs:current understanding, possible modulations, and new technologies for ecological studies[J].Canadian Journal of Animal Science, 2005, 85(4):421-435.  
[68] WANG Y, ZHANG J, WANG Y L, et al.Isolation and characterization of the Bacillus cereus BC7 strain, which is capable of zearalenone removal and intestinal flora modulation in mice[J].Toxicon, 2018, 155:9-20.
[69] WU L, LIAO P, HE L Q, et al.Dietary L-arginine supplementation protects weanling pigs from deoxynivalenol-induced toxicity[J].Toxins, 2015, 7(4):1341-1354.  
[70] WU L, LIAO P, HE L Q, et al.Growth performance, serum biochemical profile, jejunal morphology, and the expression of nutrients transporter genes in deoxynivalenol (DON)-challenged growing pigs[J].BMC Veterinary Research, 2015, 11:144.
[71] MELOCHE J L, SMITH T K.Altered tissue amino acid metabolism in acute T-2 toxicosis[J].Proceedings of the Society for Experimental Biology and Medicine, 1995, 210(3):260-265.  
[72] YIN J, REN W K, DUAN J L, et al.Dietary arginine supplementation enhances intestinal expression of SLC7A7 and SLC7A1 and ameliorates growth depression in mycotoxin-challenged pigs[J].Amino Acids, 2014, 46(4):883-892.  
[73] ZHANG Z Q, WANG S B, WANG R G, et al.Phosphoproteome analysis reveals the molecular mechanisms underlying deoxynivalenol-induced intestinal toxicity in IPEC-J2 cells[J].Toxins, 2016, 8(10):270.
[74] AWAD W A, VAHJEN W, ASCHENBACH J R, et al.A diet naturally contaminated with the Fusarium mycotoxin deoxynivalenol (DON) downregulates gene expression of glucose transporters in the intestine of broiler chickens[J].Livestock Science, 2011, 140(1/3):72-79.
[75] NOSSOL C, LANDGRAF P, KAHLERT S, et al.Deoxynivalenol affects cell metabolism and increases protein biosynthesis in intestinal porcine epithelial cells (IPEC-J2):DON increases protein biosynthesis[J].Toxins, 2018, 10(11):464.
[76] KRISHNASWAMY R, DEVARAJ S N, PADMA V V.Lutein protects HT-29 cells against deoxynivalenol-induced oxidative stress and apoptosis:prevention of NF-kappaB nuclear localization and down regulation of NF-kappaB and cyclo-oxygenase-2 expression[J].Free Radical Biology & Medicine, 2010, 49(1):50-60.  
[77] ZHOU J, TANG L L, WANG J C, et al.Aflatoxin B1 disrupts gut-microbial metabolisms of short-chain fatty acids, long-chain fatty acids, and bile acids in male F344 rats[J].Toxicological Sciences, 2018, 164(2):453-464.  
[78] AWAD W A, ZENTEK J.The feed contaminant deoxynivalenol affects the intestinal barrier permeability through inhibition of protein synthesis[J].Archives of Toxicology, 2015, 89(6):961-965.  
[79] ACOSTA J A, JONES G M, PATIENCE J F.165 Impact of mycotoxin contamination of feed on growth performance and blood metabolites of growing pigs[J].Journal of Animal Science, 2019, 97(Suppl.2):93.
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