肠道菌群在类风湿关节炎治疗中的研究进展
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摘要
随着新一代测序技术的发展,肠道菌群与人体各个疾病的关系受到学者们广泛关注,肠道菌群失调与类风湿关节炎(RA)、糖尿病、炎症性肠病等自身免疫性疾病有关。恢复正常肠道菌群可能阻止RA进展,甚至改善其症状。传统抗风湿药因其可能存在明显药物不良反应或部分RA患者对药物疗效不显著,使得大部分患者病情不能完全缓解,故RA的治疗受到一定限制。目前,关于RA治疗的新方法仍在不断探索中,未来调节肠道正常菌群将为RA的治疗带来新思路。
With the development of a new generation of gene sequencing technology,the relationship between intestinal flora and various diseases of the human body has been extensively concerned by scholars. The intestinal flora imbalance is associated with autoimmune diseases,such as rheumatoid arthritis( RA),diabetes and inflammatory bowel disease and so on. Restoring normal intestinal flora may prevent RA progression and even improve the symptoms. Traditional anti-rheumatic drugs may have obvious adverse drug reactions and no significant effect in some patients,which results in the incomplete alleviation of most patietns,so the treatment of RA is limited. At present,new methods for the treatment of RA are still being explored,and regulating the intestinal flora will bring new ideas in the future.
With the development of a new generation of gene sequencing technology,the relationship between intestinal flora and various diseases of the human body has been extensively concerned by scholars. The intestinal flora imbalance is associated with autoimmune diseases,such as rheumatoid arthritis( RA),diabetes and inflammatory bowel disease and so on. Restoring normal intestinal flora may prevent RA progression and even improve the symptoms. Traditional anti-rheumatic drugs may have obvious adverse drug reactions and no significant effect in some patients,which results in the incomplete alleviation of most patietns,so the treatment of RA is limited. At present,new methods for the treatment of RA are still being explored,and regulating the intestinal flora will bring new ideas in the future.
引文
[1] de Oliveira GLV,Leite AZ,Higuchi BS,et al. Intestinal dysbiosisand probiotic applications in autoimmune diseases[J]. Immunology,2017,152(1):1-12.
[2]何毓珏,林锦膘,欧启水.口腔和肠道微生物在类风湿关节炎发病中的研究进展[J].中华风湿病学杂志,2017,21(2):126-128.
[3] Reinoso Webb C,Koboziev I,Furr KL,et al. Protective and pro-inflammatory roles of intestinal bacteria[J]. Pathophysiology,2016,23(2):67-80.
[4] Donaldson GP,Lee SM,Mazmanian SK. Gut biogeography of thebacterial microbiota[J]. Nat Rev Microbiol,2015,14(1):20-32.
[5] Conlon MA,Bird AR. The impact of diet and lifestyle on gutmicrobiota and human health[J]. Nutrients,2014,7(1):17-44.
[6] Rinaldi E,Consonni A,Guidesi E,et al. Gut microbiota and probio-tics:Novel immune system modulators in myasthenia gravis?[J].Ann N Y Acad Sci,2018,1413(1):49-58.
[7] Kelly D,Mulder IE. Microbiome and immunological interactions[J].Nutr Rev,2012,70 Suppl 1:S18-30.
[8] Maeda Y,Kurakawa T,Umemoto E,et al. Dysbiosis contributes toarthritis development via activation of autoreactive T cells in theintestine[J]. Arthritis Rheumatol,2016,68(11):2646-2661.
[9]董幼丹,王晓非.肠道菌群的功与过:类风湿关节炎诊治中的新思考[J].中华风湿病学杂志,2017,21(3):145-148.
[10] Yang BH,Hagemann S,Mamareli P,et al. Foxp3+T cells expressingRORγt represent a stable regulatory T-cell effector lineage withenhanced suppressive capacity during intestinal inflammation[J].Mucosal Immunol,2016,9(2):444-457.
[11] Miossec P,Korn T,Kuchroo VK. Interleukin-17 and type 17 helperT cells[J]. N Engl J Med,2009,361(9):888-898.
[12] Samson M,Audia S,Janikashvili N,et al. Brief report:Inhibitionof interleukin-6 function corrects Th17/Treg cell imbalance inpatients with rheumatoid arthritis[J]. Arthritis Rheum,2012,64(8):2499-2503.
[13] Chen J,Wright K,Davis JM,et al. An expansion of rare lineageintestinal microbes characterizes rheumatoid arthritis[J]. GenomeMed,2016,8(1):43.
[14] Smith PM,Howitt MR,Panikov N,et al. The microbial metabolites,short chain fatty acids,regulate colonic Treg cell homeostasis[J].Science,2013,341(6145):569-573.
[15] Scher JU,Sczesnak A,Longman RS,et al. Expansion of intestinalPrevotella copri correlates with enhanced susceptibility to arthri-tis[J]. Elife,2013,2:e01202.
[16] Koeth RA,Wang Z,Levison BS,et al. Intestinal microbiotametabolism of L-carnitine,a nutrient in red meat,promotes athero-sclerosis[J]. Nat Med,2013,19(5):576-585.
[17] Abdollahiroodsaz S,Abramson SB,Scher JU. The metabolic role ofthe gut microbiota in health and rheumatic disease:Mechanismsand interventions[J]. Nat Rev Rheumatol,2016,12(8):446-455.
[18] Goh CE,Kopp J,Papapanou PN,et al. Association between serumantibodies to periodontal bacteria and rheumatoid factor in thethird national health and nutrition examination survey[J]. ArthritisRheumatol,2016,68(10):2384-2393.
[19] Vaahtovou J,Munukka E,Korkeamaki M,et al. Fecal microbiotain early rheumatoid arthritis[J]. J Rheumatol,2008,35(8):1500-1505.
[20] Zhang X,Zhang D,Jia H,et al. The oral and gut microbiomes areperturbed in rheumatoid arthritis and partly normalized after treat-ment[J]. Nat Med,2015,21(8):895-905.
[21] Vaghef-Mehrabany E,Alipour B,Homayouni-Rad A,et al. Probioticsupplementation improves inflammatory status in patients withrheumatoid arthritis[J]. Nutrition,2014,30(4):430-435.
[22]zdemir. Any role for probiotics in the therapy or prevention ofautoimmune diseases? Up-to-date review[J]. J Complement IntegrMed,2013,10(1):229-250.
[23] Liu X,Zou Q,Zeng B,et al. Analysis of fecal Lactobacillus com-munity structure in patients with early rheumatoid arthritis[J].Curr Microbiol,2013,67(2):170-176.
[24] Pineda Mde L,Thompson SF,Summers K,et al. A randomized,double-blinded,placebo-controlled pilot study of probiotics inactive rheumatoid arthritis[J]. Med Sci Monit,2011,17(6):CR347-354.
[25] Vaghef-Mehrabani E,Homayouni-Rad A,Alipour B,et al. Formu-lation and design of probiotic supplements for rheumatoid arthritispatients[J]. Pharm Sci,2018,24:44-51.
[26] Kim JE,Chae CS,Kim GC,et al. Lactobacillus helveticus,sup-presses experimental rheumatoid arthritis by reducing inflammatoryT cell responses[J]. J Funct Foods,2015,13:350-362.
[27] Abhari K,Shekarforoush SS,Hosseinzadeh S,et al. The effects oforally administered Bacillus coagulans and inulin on preventionand progression of rheumatoid arthritis in rats[J]. Food NutrRes,2016,60:30876.
[28] Zamani B,Golkar HR,Farshbaf S,et al. Clinical and metabolicresponse to probiotic supplementation in patients with rheumatoidarthritis:A randomized,double blind,placebo controlled trial[J].Int J Rheum Dis,2016,19(9):869-879.
[29] Ogrendik M. Antibiotics for the treatment of rheumatoid arthritis[J].Int J Gen Med,2013,7:43-47.
[30] Brusca SB,Abramson SB,Scher JU. Microbiome,and mucosal,inflammation as extra-articular triggers for rheumatoid arthritis andautoimmunity[J]. Curr Opin Rheumatol,2014,26(1):101-107.
[31] Monsarrat P,Vergnes JN,Cantagrel A,et al. Effect of periodontaltreatment on the clinical parameters of patients with rheumatoidarthritis:Study protocol of the randomized,controlled ESPERAtrial[J]. Trials,2013,14:253.
[32] O'Dell JR,Haire CE,Palmer W,et al. Treatment of early rheuma-toid arthritis with minocycline or placebo:Results of a rando-mized,double-blind,placebo-controlled trial[J]. Arthritis Rheum,1997,40(5):842-848.
[33] Saviola G,Abdi-Ali L,Campostrini L,et al. Clarithromycin inrheumatoid arthritis:The addition to methotrexate and low-dosemethylprednisolone induces a significant additive value-a 24-monthsingle-blind pilot study[J]. Rheumatol Int,2013,33(11):2833-2838.
[34] Vindigni SM,Surawicz CM. Fecal microbiota transplantation[J].Gastroenterol North Am,2017,46(1):171-185.
[35] Moayyedi P,Surette MG,Kim PT,et al. Fecal microbiota trans-plantation induces remission in patients with active ulcerativecolitis in a randomized controlled trial[J]. Gastroenterology,2015,149(1):102-109.
[36] Choi HH,Cho YS. Fecal microbiota transplantation:Currentapplications,effectiveness,and future perspectives[J]. ClinEndosc,2016,49(3):257-265.
[37] Peppercorn MA,Goldman P. The role of intestinal bacteria in themetabolism of salicylazosulfapyridine[J]. J Pharmacol Exp Ther,1972,181(3):555-562.
[38] Maurice CF,Haiser HJ,Turnbaugh PJ. Xenobiotics shape thephysiology and gene expression of the active human gut micro-biome[J]. Cell,2013,152(1/2):39-50.
[39] Kabuyama Y,Kitamura T,Yamaki J,et al. Involvement of thiore-doxin reductase 1 in the regulation of redox balance and viabilityof rheumatoid synovial cells[J]. Biochem Biophys Res Commun,2008,367(2):491-496.
[40] Viaud S,Saccheri F,Mignot G,et al. The intestinal microbiotamodulates the anticancer immune effects of cyclophosphamide[J].Science,2013,342(6161):971-976.
[41] van Roon EN,van de Laar MA. Methotrexate bioavailability[J].Clin Exp Rheumatol,2010,28(5 Suppl 61):S27-32.
[42] Forslund K,Hildebrand F,Nielsen T,et al. Disentangling type 2diabetes and metformin treatment signatures in the human gutmicrobiota[J]. Nature,2015,528(7581):262-266.
[43] Maslowski KM,Vieira AT,Ng A,et al. Regulation of inflammatoryresponses by gut microbiota and chemoattractant receptor GPR43[J].Nature,2009,461(7268):1282-1286.
[44] Kim EK,Lee SH,Lee SY,et al. Metformin ameliorates experimen-tal-obesity-associated autoimmune arthritis by inducing FGF21expression and brown adipocyte differentiation[J]. Exp Mol Med,2018,50(1):e432.
[2]何毓珏,林锦膘,欧启水.口腔和肠道微生物在类风湿关节炎发病中的研究进展[J].中华风湿病学杂志,2017,21(2):126-128.
[3] Reinoso Webb C,Koboziev I,Furr KL,et al. Protective and pro-inflammatory roles of intestinal bacteria[J]. Pathophysiology,2016,23(2):67-80.
[4] Donaldson GP,Lee SM,Mazmanian SK. Gut biogeography of thebacterial microbiota[J]. Nat Rev Microbiol,2015,14(1):20-32.
[5] Conlon MA,Bird AR. The impact of diet and lifestyle on gutmicrobiota and human health[J]. Nutrients,2014,7(1):17-44.
[6] Rinaldi E,Consonni A,Guidesi E,et al. Gut microbiota and probio-tics:Novel immune system modulators in myasthenia gravis?[J].Ann N Y Acad Sci,2018,1413(1):49-58.
[7] Kelly D,Mulder IE. Microbiome and immunological interactions[J].Nutr Rev,2012,70 Suppl 1:S18-30.
[8] Maeda Y,Kurakawa T,Umemoto E,et al. Dysbiosis contributes toarthritis development via activation of autoreactive T cells in theintestine[J]. Arthritis Rheumatol,2016,68(11):2646-2661.
[9]董幼丹,王晓非.肠道菌群的功与过:类风湿关节炎诊治中的新思考[J].中华风湿病学杂志,2017,21(3):145-148.
[10] Yang BH,Hagemann S,Mamareli P,et al. Foxp3+T cells expressingRORγt represent a stable regulatory T-cell effector lineage withenhanced suppressive capacity during intestinal inflammation[J].Mucosal Immunol,2016,9(2):444-457.
[11] Miossec P,Korn T,Kuchroo VK. Interleukin-17 and type 17 helperT cells[J]. N Engl J Med,2009,361(9):888-898.
[12] Samson M,Audia S,Janikashvili N,et al. Brief report:Inhibitionof interleukin-6 function corrects Th17/Treg cell imbalance inpatients with rheumatoid arthritis[J]. Arthritis Rheum,2012,64(8):2499-2503.
[13] Chen J,Wright K,Davis JM,et al. An expansion of rare lineageintestinal microbes characterizes rheumatoid arthritis[J]. GenomeMed,2016,8(1):43.
[14] Smith PM,Howitt MR,Panikov N,et al. The microbial metabolites,short chain fatty acids,regulate colonic Treg cell homeostasis[J].Science,2013,341(6145):569-573.
[15] Scher JU,Sczesnak A,Longman RS,et al. Expansion of intestinalPrevotella copri correlates with enhanced susceptibility to arthri-tis[J]. Elife,2013,2:e01202.
[16] Koeth RA,Wang Z,Levison BS,et al. Intestinal microbiotametabolism of L-carnitine,a nutrient in red meat,promotes athero-sclerosis[J]. Nat Med,2013,19(5):576-585.
[17] Abdollahiroodsaz S,Abramson SB,Scher JU. The metabolic role ofthe gut microbiota in health and rheumatic disease:Mechanismsand interventions[J]. Nat Rev Rheumatol,2016,12(8):446-455.
[18] Goh CE,Kopp J,Papapanou PN,et al. Association between serumantibodies to periodontal bacteria and rheumatoid factor in thethird national health and nutrition examination survey[J]. ArthritisRheumatol,2016,68(10):2384-2393.
[19] Vaahtovou J,Munukka E,Korkeamaki M,et al. Fecal microbiotain early rheumatoid arthritis[J]. J Rheumatol,2008,35(8):1500-1505.
[20] Zhang X,Zhang D,Jia H,et al. The oral and gut microbiomes areperturbed in rheumatoid arthritis and partly normalized after treat-ment[J]. Nat Med,2015,21(8):895-905.
[21] Vaghef-Mehrabany E,Alipour B,Homayouni-Rad A,et al. Probioticsupplementation improves inflammatory status in patients withrheumatoid arthritis[J]. Nutrition,2014,30(4):430-435.
[22]zdemir. Any role for probiotics in the therapy or prevention ofautoimmune diseases? Up-to-date review[J]. J Complement IntegrMed,2013,10(1):229-250.
[23] Liu X,Zou Q,Zeng B,et al. Analysis of fecal Lactobacillus com-munity structure in patients with early rheumatoid arthritis[J].Curr Microbiol,2013,67(2):170-176.
[24] Pineda Mde L,Thompson SF,Summers K,et al. A randomized,double-blinded,placebo-controlled pilot study of probiotics inactive rheumatoid arthritis[J]. Med Sci Monit,2011,17(6):CR347-354.
[25] Vaghef-Mehrabani E,Homayouni-Rad A,Alipour B,et al. Formu-lation and design of probiotic supplements for rheumatoid arthritispatients[J]. Pharm Sci,2018,24:44-51.
[26] Kim JE,Chae CS,Kim GC,et al. Lactobacillus helveticus,sup-presses experimental rheumatoid arthritis by reducing inflammatoryT cell responses[J]. J Funct Foods,2015,13:350-362.
[27] Abhari K,Shekarforoush SS,Hosseinzadeh S,et al. The effects oforally administered Bacillus coagulans and inulin on preventionand progression of rheumatoid arthritis in rats[J]. Food NutrRes,2016,60:30876.
[28] Zamani B,Golkar HR,Farshbaf S,et al. Clinical and metabolicresponse to probiotic supplementation in patients with rheumatoidarthritis:A randomized,double blind,placebo controlled trial[J].Int J Rheum Dis,2016,19(9):869-879.
[29] Ogrendik M. Antibiotics for the treatment of rheumatoid arthritis[J].Int J Gen Med,2013,7:43-47.
[30] Brusca SB,Abramson SB,Scher JU. Microbiome,and mucosal,inflammation as extra-articular triggers for rheumatoid arthritis andautoimmunity[J]. Curr Opin Rheumatol,2014,26(1):101-107.
[31] Monsarrat P,Vergnes JN,Cantagrel A,et al. Effect of periodontaltreatment on the clinical parameters of patients with rheumatoidarthritis:Study protocol of the randomized,controlled ESPERAtrial[J]. Trials,2013,14:253.
[32] O'Dell JR,Haire CE,Palmer W,et al. Treatment of early rheuma-toid arthritis with minocycline or placebo:Results of a rando-mized,double-blind,placebo-controlled trial[J]. Arthritis Rheum,1997,40(5):842-848.
[33] Saviola G,Abdi-Ali L,Campostrini L,et al. Clarithromycin inrheumatoid arthritis:The addition to methotrexate and low-dosemethylprednisolone induces a significant additive value-a 24-monthsingle-blind pilot study[J]. Rheumatol Int,2013,33(11):2833-2838.
[34] Vindigni SM,Surawicz CM. Fecal microbiota transplantation[J].Gastroenterol North Am,2017,46(1):171-185.
[35] Moayyedi P,Surette MG,Kim PT,et al. Fecal microbiota trans-plantation induces remission in patients with active ulcerativecolitis in a randomized controlled trial[J]. Gastroenterology,2015,149(1):102-109.
[36] Choi HH,Cho YS. Fecal microbiota transplantation:Currentapplications,effectiveness,and future perspectives[J]. ClinEndosc,2016,49(3):257-265.
[37] Peppercorn MA,Goldman P. The role of intestinal bacteria in themetabolism of salicylazosulfapyridine[J]. J Pharmacol Exp Ther,1972,181(3):555-562.
[38] Maurice CF,Haiser HJ,Turnbaugh PJ. Xenobiotics shape thephysiology and gene expression of the active human gut micro-biome[J]. Cell,2013,152(1/2):39-50.
[39] Kabuyama Y,Kitamura T,Yamaki J,et al. Involvement of thiore-doxin reductase 1 in the regulation of redox balance and viabilityof rheumatoid synovial cells[J]. Biochem Biophys Res Commun,2008,367(2):491-496.
[40] Viaud S,Saccheri F,Mignot G,et al. The intestinal microbiotamodulates the anticancer immune effects of cyclophosphamide[J].Science,2013,342(6161):971-976.
[41] van Roon EN,van de Laar MA. Methotrexate bioavailability[J].Clin Exp Rheumatol,2010,28(5 Suppl 61):S27-32.
[42] Forslund K,Hildebrand F,Nielsen T,et al. Disentangling type 2diabetes and metformin treatment signatures in the human gutmicrobiota[J]. Nature,2015,528(7581):262-266.
[43] Maslowski KM,Vieira AT,Ng A,et al. Regulation of inflammatoryresponses by gut microbiota and chemoattractant receptor GPR43[J].Nature,2009,461(7268):1282-1286.
[44] Kim EK,Lee SH,Lee SY,et al. Metformin ameliorates experimen-tal-obesity-associated autoimmune arthritis by inducing FGF21expression and brown adipocyte differentiation[J]. Exp Mol Med,2018,50(1):e432.