益生菌对非酒精性脂肪肝治疗的潜在作用

doi:10.3969/j.issn.1674-490X.2017.01.011

摘要/Abstract

摘要： 非酒精性脂肪肝(NAFLD)是最常见的慢性肝病之一,其发病率在中国居民中呈迅速上升趋势,但疗效显著的临床治疗手段依旧缺乏。由于肠道与肝脏在结构和功能上存在密切关系,越来越多的证据显示肠道菌群在NAFLD的发生和进展过程中扮演着重要角色。由环境因素引起的肠道菌群失调可造成肝脏受损。目前,多项动物实验结果支持益生菌对NAFLD的预防和抑制作用,采用益生菌对NAFLD患者进行干预的临床随机对照试验数量较少,但现有数据均显示服用益生菌可改善患者症状。今后需开展更大规模的多中心随机双盲安慰剂对照临床试验,为临床应用提供更可靠的依据。

关键词: 非酒精性脂肪肝, 益生菌, 肠道菌群

Abstract: Non-alcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases.Although the incidence rate of NAFLD is rising rapidly in our country,effective clinical treatment is still lacking.Due to the close anatomical and functional relationship between the gut and the liver,emerging evidence suggests an important role of gut microbiota in the initiation and progression of NAFLD.Altered gut microbiota due to environmental factors can lead to liver damage.Results of animal studies strongly support the protective effect of probiotics against NAFLD.Currently,there is only a small number of randomized controlled clinical trials evaluating the effectiveness of probiotics on NAFLD treatment;nonetheless,findings show intake of probiotics can improve symptoms of the disease.More multi-centre large-scale randomized controlled trials are needed in order to provide evidence for clinical application of probiotics.

Key words: non-alcoholic fatty liver disease, probiotics, gut microbiota

中图分类号:

梁玉竹,张霞,杨霞,杨兰. 益生菌对非酒精性脂肪肝治疗的潜在作用[J]. 医学研究与教育, 2017, 34(1): 49-55.

参考文献

[1] FRASINARIU O E,CECCARELLI S,ALISI A,et al.Gut-liver axis and fibrosis in nonalcoholic fatty liver disease: an input for novel therapies[J].Dig Liver Dis,2013,45(7): 543.DOI:10.1016/j.dld.2012.11.010.
[2] 中华医学会肝病学分会脂肪肝和酒精性肝病学组.非酒精性脂肪性肝病诊疗指南(2010年修订版)[J].中华肝脏病杂志,2010,18(3): 163.DOI:10.3760/cma.j.issn.1007-3418.2010.03.002.
[3] CHITTURI S,FARRELL G C,HASHIMOTO E,et al.Asia-Pacific Working Party on NAFLD.Non-alcoholic fatty liver disease in the Asia-Pacific region: definitions and overview of proposed guidelines[J].J Gastroenterol Hepatol,2007,22(6): 778.DOI:10.1111/j.1440-1746.2007.05001.x.
[4] GITTO S,VITALE G,VILLA E,et al.Treatment of nonalcoholic steatohepatitis in adults: present and future[J].Gastroenterol Res Pract,2015(2015): 732870.DOI:10.1155/2015/732870.
[5] LI D Y,YANG M,EDWARDS S,et al.Nonalcoholic fatty liver disease: for better or worse,blame the gut microbiota?[J].JPEN J Parenter Enteral Nutr,2013,37(6): 787-793.DOI:10.1177/0148607113481623.
[6] BUSS C,VALLE-TOVO C,MIOZZO S,et al.Probiotics and synbiotics may improve liver aminotransferases levels in non-alcoholic fatty liver disease patients[J].Ann Hepatol,2014,13(5): 482-488.
[7] TILG H,MOSCHEN A R.Evolution of inflammation in nonalcoholic fatty liver disease: the multiple parallel hits hypothesis[J].Hepatology,2010,52(5): 1836-1846.DOI:10.1002/hep.24001.
[8] CESARO C,TISO A,DEL PRETE A,et al.Gut microbiota and probiotics in chronic liver diseases[J].Dig Liver Dis,2011,43(6): 431.DOI:10.1016/j.dld.2010.10.015.
[9] PAOLELLA G,MANDATO C,PIERRI L,et al.Gut-liver axis and probiotics: their role in non-alcoholic fatty liver disease[J].World J Gastroenterol,2014,20(42): 15518-15531.DOI:10.3748/wjg.v20.i42.15518.
[10] MOUZAKI M,COMELLI E M,ARENDT B M,et al.Intestinal microbiota in patients with nonalcoholic fatty liver disease[J].Hepatology,2013,58(1): 120.DOI:10.1002/hep.26319.
[11] ESLAMPARAST T,EGHTESAD S,HEKMATDOOST A,et al.Probiotics and nonalcoholic fatty liver disease[J].Middle East J Dig Dis,2013,5(3): 130.
[12] ARON-WISNEWSKY J,GABORIT B,DUTOUR A,et al.Gut microbiota and non-alcoholic fatty liver disease: new insights[J].Clin Microbiol Infect,2013,19(4).DOI:10.1111/1469-0691.12140.
[13] WIGG A J,ROBERTS-THOMSON I C,DYMOCK R B,et al.The role of small intestinal bacterial overgrowth,intestinal permeability,endotoxaemia,and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis[J].Gut,2001,48(2): 206-211.
[14] SOLGA S F,DIEHL A M.Non-alcoholic fatty liver disease: lumen-liver interactions and possible role for probiotics[J].J Hepatol,2003,38(5): 681-687.DOI:10.1016/S0168-8278(03)00097-7.
[15] 卢伟娜,冯丽英.肠道微生物在非酒精性脂肪性肝病发病中的作用[J].世界华人消化杂志,2014,22(3): 341.DOI:http://dx.doi.org/10.11569/wcjd.v22.i3.340.
[16] ALISI A,CECCARELLI S,PANERA N,et al.Causative role of gut microbiota in non-alcoholic fatty liver disease pathogenesis[J].Front Cell Infect Microbiol,2012,2(132): 1-2.DOI:10.3389/fcimb.2012.00132.
[17] COMPARE D,COCCOLI P,ROCCO A,et al.Gut-liver axis: the impact of gut microbiota on non alcoholic fatty liver disease[J].Nutr Metab Cardiovasc Dis,2012,22(6): 471-476.DOI:10.1016/j.numecd.2012.02.007.
[18] MIELE L,VALENZA V,LA TORRE G,et al.Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease[J].Hepatology,2009,49(6): 1877-1887.DOI:10.1002/hep.22848.
[19] MIURA K,OHNISHI H.Role of gut microbiota and Toll-like receptors in nonalcoholic fatty liver disease[J].World J Gastroenterol,2014,20(23): 7382.DOI:10.3748/wjg.v20.i23.7381.
[20] LI Z,YANG S,LIN H,et al.Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease[J].Hepatology,2003,37(2): 343-350.DOI:10.1053/jhep.2003.50048.
[21] MA X,HUA J,LI Z.Probiotics improve high fat diet-induced hepatic steatosis and insulin resistance by increasing hepatic NKT cells[J].J Hepatol,2008,49(5): 821-830.DOI:10.1016/j.jhep.2008.05.025.
[22] ESPOSITO E,IACONO A,BIANCO G,et al.Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats[J].J Nutr,2009,139(5): 905-911.DOI:10.3945/jn.108.101808.
[23] MENCARELLI A,CIPRIANI S,RENGA B,et al.VSL#3 resets insulin signaling and protects against NASH and atherosclerosis in a model of genetic dyslipidemia and intestinal inflammation[J].PLoS One,2012,7(9): e45425.DOI:10.1371/journal.pone.0045425.
[24] NARDONE G,COMPARE D,LIGUORI E,et al.Protective effects of Lactobacillus paracasei F19 in a rat model of oxidative and metabolic hepatic injury[J].Am J Physiol Gastrointest Liver Physiol,2010,299(3): G669-G676.DOI:10.1152/ajpgi.00188.2010.
[25] LI C,NIE S P,ZHU K X,et al.Lactobacillus plantarum NCU116 improves liver function,oxidative stress and lipid metabolism in rats with high fat diet induced non-alcoholic fatty liver disease[J].Food Funct,2014,5(12): 3216-3223.DOI:10.1039/c4fo00549j.
[26] RITZE Y,BARDOS G,CLAUS A,et al.Lactobacillus rhamnosus GG protects against non-alcoholic fatty liver disease in mice[J].PLoS One,2014,9(1): e80169.DOI:10.1371/journal.pone.0080169.
[27] RASO G M,SIMEOLI R,IACONO A,et al.Effects of a Lactobacillus paracasei B21060 based synbiotic on steatosis,insulin signaling and toll-like receptor expression in rats fed a high-fat diet[J].J Nutr Biochem,2014,25(1): 81-90.DOI:10.1016/j.jnutbio.2013.09.006.
[28] WAGNERBERGER S,SPRUSS A,KANURI G,et al.Lactobacillus casei Shirota protects from fructose-induced liver steatosis: a mouse model[J].J Nutr Biochem,2013,24(3): 531-538. DOI:10.1016/j.jnutbio.2012.01.014.
[29] XU R Y,WAN Y P,FANG Q Y,et al.Supplementation with probiotics modifies gut flora and attenuates liver fat accumulation in rat nonalcoholic fatty liver disease model[J].J Clin Biochem Nutr,2012,50(1): 72-77.DOI:10.3164/jcbn.11-38.
[30] ENDO H,NIIOKA M,KOBAYASHI N,et al.Butyrate-producing probiotics reduce nonalcoholic fatty liver disease progression in rats: new insight into the probiotics for the gut-liver axis[J].PLoS One,2013,8(5): e63388.DOI:10.1371/journal.pone.0063388.
[31] REICHOLD A,BRENNER S A,SPRUSS A,et al.Bifidobacterium adolescentis protects from the development of nonalcoholic steatohepatitis in a mouse model[J].J Nutr Biochem,2014,25(2): 118-125.DOI:10.1016/j.jnutbio.2013.09.011.
[32] ALLER R,DE LUIS D A,IZAOLA O,et al.Effect of a probiotic on liver aminotransferases in nonalcoholic fatty liver disease patients: a double blind randomized clinical trial[J].Eur Rev Med Pharmacol Sci,2011,15(9): 1090-1095.
[33] VAJRO P,MANDATO C,LICENZIATI M R,et al.Effects of Lactobacillus rhamnosus strain GG in pediatric obesity-related liver disease[J].J Pediatr Gastroenterol Nutr,2011,52(6): 740-743.DOI:10.1097/MPG.0b013e31821f9b85.
[34] ALISI A,BEDOGNI G,BAVIERA G,et al.Randomised clinical trial: The beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis[J].Aliment Pharmacol Ther,2014,39(11): 1276-1285.DOI:10.1111/apt.12758.
[35] MALAGUARNERA M,VACANTE M,ANTIC T,et al.Bifidobacterium longum with fructo-oligosaccharides in patients with non alcoholic steatohepatitis[J].Dig Dis Sci,2012,57(2): 545-553.DOI:10.1007/s10620-011-1887-4.
[36] WONG V W,WON G L,CHIM A M,et al.Treatment of nonalcoholic steatohepatitis with probiotics.A proof-of-concept study[J].Ann Hepatol,2013,12(2): 256-262.
[37] ESLAMPARAST T,POUSTCHI H,ZAMANI F,et al.Synbiotic supplementation in nonalcoholic fatty liver disease: a randomized,double-blind,placebo-controlled pilot study[J].Am J Clin Nutr,2014,99(3): 535-542.DOI:10.3945/ajcn.113.068890.