肝性脑病的肠道菌群调节及饮食治疗途径

乐滢玉; 张荣臻; 肖伟松; 覃小宾; 曾胜澜; 毛德文

doi:10.3969/j.issn.1001-5256.2021.07.046

肝性脑病的肠道菌群调节及饮食治疗途径

DOI: 10.3969/j.issn.1001-5256.2021.07.046

1.
广西中医药大学研究生学院，南宁 530222
2.
广西中医药大学第一附属医院肝病一区，南宁 530023

基金项目:

国家自然科学基金面上项目 (81774236);

国家自然科学基金项目 (81960841);

广西自然科学基金课题 (2018GXNSFAA281096);

广西科技计划项目-广西科技基地和人才专项 (Guike AD17129001);

广西研究生教育创新计划资助项目 (YCXJ2021038)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：乐滢玉、毛德文负责研究选题; 张荣臻、肖伟松负责设计论文框架，起草论文; 乐滢玉负责拟定写作思路，撰写文章; 覃小宾、曾胜澜负责修订论文; 毛德文负责指导撰写文章并最后定稿。

详细信息

通信作者:
毛德文，mdwboshi2005@163.com

中图分类号: R575
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- 被引次数: 0
出版历程
- 收稿日期: 2020-12-18
- 录用日期: 2021-02-08
- 出版日期: 2021-07-20

Gut microbiota regulation and diet therapy for hepatic encephalopathy

1.
Graduate School of Guangxi University of Chinese Medicine, Nanning 530222, China
2.
First Department of Hepatology, The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China

Research funding:

National Natural Science Foundation of China(General Program) (81774236);

National Natural Science Foundation of China (81960841);

Natural Science Foundation of Guangxi (2018GXNSFAA281096);

Guangxi Science and Technology Plan Project - Guangxi Science and Technology Base and Talents Special Project (Guike AD17129001);

Guangxi Postgraduate Education Innovation Program (YCXJ2021038)

摘要

摘要: 肝性脑病(HE)在很大程度上增加了肝病患者的经济负担，严重影响了患者的生活质量。HE病理基础复杂且影响因素繁多，发病机理尚未完全明晰。其临床治疗尚无特异有效的方法，药物治疗临床疗效欠佳，许多药物耐受性差、依从性低，不良反应普遍。就HE的蛋白质类食物和调节肠道菌群的药物治疗途径进行分析与归纳，以期为HE临床治疗提供新思路及优质方案。
- 肝性脑病 /
- 胃肠道微生物组 /
- 健康膳食 /
- 治疗学
Abstract: Hepatic encephalopathy (HE) greatly increases the economic burden of patients with liver disease and seriously affects their quality of life. HE has a complex pathological basis and various influencing factors, and its pathogenesis has not been fully clarified. There is still no specific effective therapy for this disease, and drug therapy often has an unsatisfactory clinical effect, as many drugs have poor tolerability, low compliance, and common adverse effects. This article analyzes and summarizes the non-drug therapies for hepatic encephalopathy including protein food and gut microbiota regulation, in order to provide new ideas and high-quality regimens for clinical treatment.
- Hepatic Encephalopathy /
- Gastrointestinal Microbiome /
- Healthy Diet /
- Therapeutics

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参考文献(51)

[1]	American Association for the Study of Liver Diseases; European Association for the Study of the Liver. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases[J]. J Hepatol, 2014, 61(3): 642-659. DOI: 10.1016/j.jhep.2014.05.042.
[2]	RIDOLA L, CARDINALE V, RIGGIO O. The burden of minimal hepatic encephalopathy: From diagnosis to therapeutic strategies[J]. Ann Gastroenterol, 2018, 31(2): 151-164. DOI: 10.20524/aog.2018.0232.
[3]	RIDOLA L, NARDELLI S, GIOIA S, et al. Quality of life in patients with minimal hepatic encephalopathy[J]. World J Gastroenterol, 2018, 24(48): 5446-5453. DOI: 10.3748/wjg.v24.i48.5446.
[4]	ZHANG JC, WANG YG, LIN F, et al. The pathogenesis of hepatic encephalopathy[J/CD]. Chin J Liver Dis (Electronic Version), 2019, 11(1): 6-11. DOI: 10.3969/j.issn.1674-7380.2019.01.002. 张军昌, 王永刚, 林芳, 等. 肝性脑病发病机制新进展[J/CD]. 中国肝脏病杂志(电子版), 2019, 11(1): 6-11. DOI: 10.3969/j.issn.1674-7380.2019.01.002.
[5]	YAN ML, ZHANG Z, QIN YP, et al. progress of drug therapy for hepatic encephalopathy[J]. Tianjin Pharmacy, 2019, 31(3): 55-59. DOI: 10.3969/j.issn.1006-5687.2019.03.019. 闫美玲, 张正, 秦寅鹏, 等. 肝性脑病的药物治疗研究进展[J]. 天津药学, 2019, 31(3): 55-59. DOI: 10.3969/j.issn.1006-5687.2019.03.019.
[6]	JAWARO T, YANG A, DIXIT D, et al. Management of hepatic encephalopathy: A primer[J]. Ann Pharmacother, 2016, 50(7): 569-577. DOI: 10.1177/1060028016645826.
[7]	SHARMA P, SHARMA BC. Lactulose for minimal hepatic encephalopathy in patients with extrahepatic portal vein obstruction[J]. Saudi J Gastroenterol, 2012, 18(3): 168-172. DOI: 10.4103/1319-3767.96448.
[8]	European Association for the Study of the Liver. EASL clinical practice guidelines on nutrition in chronic liver disease[J]. J Hepatol, 2019, 70(1): 172-193. DOI: 10.1016/j.jhep.2018.06.024.
[9]	PLAUTH M, BERNAL W, DASARATHY S, et al. ESPEN guideline on clinical nutrition in liver disease[J]. Clin Nutr, 2019, 38(2): 485-521. DOI: 10.1016/j.clnu.2018.12.022.
[10]	PEARLMAN M, AKPOTAIRE O. Diet and the role of food in common gastrointestinal diseases[J]. Med Clin North Am, 2019, 103(1): 101-110. DOI: 10.1016/j.mcna.2018.08.008.
[11]	SUMMERSKILL WH, WOLFE SJ, DAVIDSON CS. The management of hepatic coma in relation to protein withdrawal and certain specific measures[J]. Am J Med, 1957, 23(1): 59-76. DOI: 10.1016/0002-9343(57)90358-3.
[12]	CÓRDOBA J, LÓPEZ-HELLÍN J, PLANAS M, et al. Normal protein diet for episodic hepatic encephalopathy: Results of a randomized study[J]. J Hepatol, 2004, 41(1): 38-43. DOI: 10.1016/j.jhep.2004.03.023.
[13]	FENTON JC, KNIGHT EJ, HUMPHERSON PL. Milk-and-cheese diet in portal-systemic encephalopathy[J]. Lancet, 1966, 1(7430): 164-166. DOI: 10.1016/s0140-6736(66)90696-9.
[14]	CHATAURET N, DESJARDINS P, ZWINGMANN C, et al. Direct molecular and spectroscopic evidence for increased ammonia removal capacity of skeletal muscle in acute liver failure[J]. J Hepatol, 2006, 44(6): 1083-1088. DOI: 10.1016/j.jhep.2005.11.048.
[15]	CLEMMESEN JO, KONDRUP J, OTT P. Splanchnic and leg exchange of amino acids and ammonia in acute liver failure[J]. Gastroenterology, 2000, 118(6): 1131-1139. DOI: 10.1016/s0016-5085(00)70366-0.
[16]	KAWAGUCHI T, TANIGUCHI E, SATA M. Effects of oral branched-chain amino acids on hepatic encephalopathy and outcome in patients with liver cirrhosis[J]. Nutr Clin Pract, 2013, 28(5): 580-588. DOI: 10.1177/0884533613496432.
[17]	HOLECEK M. Ammonia and amino acid profiles in liver cirrhosis: Effects of variables leading to hepatic encephalopathy[J]. Nutrition, 2015, 31(1): 14-20. DOI: 10.1016/j.nut.2014.03.016.
[18]	DEJONG CH, van de POLL MC, SOETERS PB, et al. Aromatic amino acid metabolism during liver failure[J]. J Nutr, 2007, 137(6 Suppl 1): 1579s-1585s; discussion 1597S-1598S. DOI: 10.1093/jn/137.6.1579S.
[19]	GLUUD LL, DAM G, BORRE M, et al. Lactulose, rifaximin or branched chain amino acids for hepatic encephalopathy: What is the evidence?[J]. Metab Brain Dis, 2013, 28(2): 221-225. DOI: 10.1007/s11011-012-9372-0.
[20]	LES I, DOVAL E, GARCÍA-MARTÍNEZ R, et al. Effects of branched-chain amino acids supplementation in patients with cirrhosis and a previous episode of hepatic encephalopathy: A randomized study[J]. Am J Gastroenterol, 2011, 106(6): 1081-1088. DOI: 10.1038/ajg.2011.9.
[21]	KIRCHEIS G, LVTH S. Pharmacokinetic and pharmacodynamic properties of L-Ornithine L-Aspartate (LOLA) in hepatic encephalopathy[J]. Drugs, 2019, 79(Suppl 1): 23-29. DOI: 10.1007/s40265-018-1023-2.
[22]	BUTTERWORTH RF, KIRCHEIS G, HILGER N, et al. Efficacy of l-Ornithine l-Aspartate for the treatment of hepatic encephalopathy and hyperammonemia in cirrhosis: Systematic review and meta-analysis of randomized controlled trials[J]. J Clin Exp Hepatol, 2018, 8(3): 301-313. DOI: 10.1016/j.jceh.2018.05.004.
[23]	BUTTERWORTH RF, MCPHAIL M. L-Ornithine L-Aspartate (LOLA) for hepatic encephalopathy in cirrhosis: Results of randomized controlled trials and meta-analyses[J]. Drugs, 2019, 79(Suppl 1): 31-37. DOI: 10.1007/s40265-018-1024-1.
[24]	VARAKANAHALLI S, SHARMA BC, SRIVASTAVA S, et al. Secondary prophylaxis of hepatic encephalopathy in cirrhosis of liver: A double-blind randomized controlled trial of L-ornithine L-aspartate versus placebo[J]. Eur J Gastroenterol Hepatol, 2018, 30(8): 951-958. DOI: 10.1097/MEG.0000000000001137.
[25]	GOH ET, STOKES CS, SIDHU SS, et al. L-ornithine L-aspartate for prevention and treatment of hepatic encephalopathy in people with cirrhosis[J]. Cochrane Database Syst Rev, 2018, 5(5): CD012410. DOI: 10.1002/14651858.CD012410.pub2.
[26]	STRAVITZ RT, GOTTFRIED M, DURKALSKI V, et al. Safety, tolerability, and pharmacokinetics of l-ornithine phenylacetate in patients with acute liver injury/failure and hyperammonemia[J]. Hepatology, 2018, 67(3): 1003-1013. DOI: 10.1002/hep.29621.
[27]	MARTÍNEZ GARCÍA RM, JIMÉNEZ ORTEGA AI, LÓPEZ SOBALER AM, et al. Nutrition strategies that improve cognitive function[J]. Nutr Hosp, 2018, 35(Spec No6): 16-19. DOI: 10.20960/nh.2281.
[28]	PERES WA, CHAVES GV, GONÇALVES JC, et al. Vitamin A deficiency in patients with hepatitis C virus-related chronic liver disease[J]. Br J Nutr, 2011, 106(11): 1724-1731. DOI: 10.1017/S0007114511002145.
[29]	KATAYAMA K, SAITO M, KAWAGUCHI T, et al. Effect of zinc on liver cirrhosis with hyperammonemia: A preliminary randomized, placebo-controlled double-blind trial[J]. Nutrition, 2014, 30(11-12): 1409-1414. DOI: 10.1016/j.nut.2014.04.018.
[30]	GUEVARA M, BACCARO ME, TORRE A, et al. Hyponatremia is a risk factor of hepatic encephalopathy in patients with cirrhosis: A prospective study with time-dependent analysis[J]. Am J Gastroenterol, 2009, 104(6): 1382-1389. DOI: 10.1038/ajg.2009.293.
[31]	SHEN TD. Diet and gut microbiota in health and disease[J]. Nestle Nutr Inst Workshop Ser, 2017, 88: 117-126. DOI: 10.1159/000455220.
[32]	WOODHOUSE CA, PATEL VC, SINGANAYAGAM A, et al. Review article: The gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease[J]. Aliment Pharmacol Ther, 2018, 47(2): 192-202. DOI: 10.1111/apt.14397.
[33]	GIBSON GR, HUTKINS R, SANDERS ME, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics[J]. Nat Rev Gastroenterol Hepatol, 2017, 14(8): 491-502. DOI: 10.1038/nrgastro.2017.75.
[34]	PINZONE MR, CELESIA BM, di ROSA M, et al. Microbial translocation in chronic liver diseases[J]. Int J Microbiol, 2012, 2012: 694629. DOI: 10.1155/2012/694629.
[35]	CHEN C, LI L, WU Z, et al. Effects of lactitol on intestinal microflora and plasma endotoxin in patients with chronic viral hepatitis[J]. J Infect, 2007, 54(1): 98-102. DOI: 10.1016/j.jinf.2005.11.013.
[36]	STADLBAUER V, MOOKERJEE RP, HODGES S, et al. Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis[J]. J Hepatol, 2008, 48(6): 945-951. DOI: 10.1016/j.jhep.2008.02.015.
[37]	LATA J, JURANKOVA J, KOPACOVA M, et al. Probiotics in hepatology[J]. World J Gastroenterol, 2011, 17(24): 2890-2896. DOI: 10.3748/wjg.v17.i24.2890.
[38]	LUNIA MK, SHARMA BC, SHARMA P, et al. Probiotics prevent hepatic encephalopathy in patients with cirrhosis: A randomized controlled trial[J]. Clin Gastroenterol Hepatol, 2014, 12(6): 1003-1008. e1. DOI: 10.1016/j.cgh.2013.11.006.
[39]	DHIMAN RK, RANA B, AGRAWAL S, et al. Probiotic VSL#3 reduces liver disease severity and hospitalization in patients with cirrhosis: A randomized, controlled trial[J]. Gastroenterology, 2014, 147(6): 1327-1337. e3. DOI: 10.1053/j.gastro.2014.08.031.
[40]	CAO Q, YU CB, YANG SG, et al. Effect of probiotic treatment on cirrhotic patients with minimal hepatic encephalopathy: A meta-analysis[J]. Hepatobiliary Pancreat Dis Int, 2018, 17(1): 9-16. DOI: 10.1016/j.hbpd.2018.01.005.
[41]	SAJI S, KUMAR S, THOMAS V. A randomized double blind placebo controlled trial of probiotics in minimal hepatic encephalopathy[J]. Trop Gastroenterol, 2011, 32(2): 128-132.
[42]	LIU Q, DUAN ZP, HA DK, et al. Synbiotic modulation of gut flora: Effect on minimal hepatic encephalopathy in patients with cirrhosis[J]. Hepatology, 2004, 39(5): 1441-1449. DOI: 10.1002/hep.20194.
[43]	BAJAJ JS, SAEIAN K, CHRISTENSEN KM, et al. Probiotic yogurt for the treatment of minimal hepatic encephalopathy[J]. Am J Gastroenterol, 2008, 103(7): 1707-1715. DOI: 10.1111/j.1572-0241.2008.01861.x.
[44]	LIU JE, ZHANG Y, ZHANG J, et al. Probiotic yogurt effects on intestinal flora of patients with chronic liver disease[J]. Nurs Res, 2010, 59(6): 426-432. DOI: 10.1097/NNR.0b013e3181fa4dc6.
[45]	CAMPION D, PONZO P, ALESSANDRIA C, et al. The role of microbiota in autism spectrum disorders[J]. Minerva Gastroenterol Dietol, 2018, 64(4): 333-350. DOI: 10.23736/S1121-421X.18.02493-5.
[46]	PIWOWARCZYK A, HORVATH A, ŁUKASIK J, et al. Gluten- and casein-free diet and autism spectrum disorders in children: A systematic review[J]. Eur J Nutr, 2018, 57(2): 433-440. DOI: 10.1007/s00394-017-1483-2.
[47]	BALZOLA F, SANNA C, OTTOBRELLI A, et al. Chronic hepatic encephalopaty (HE) in patients with severe liver cirrhosis: Efficacy of the wheat and milk protein free diet in the reduction of clinical episodes[J]. J Hepatol, 2011, 54: s64. DOI: 10.1016/S0168-8278(11)60148-7.
[48]	WANG WW, ZHANG Y, HUANG XB, et al. Fecal microbiota transplantation prevents hepatic encephalopathy in rats with carbon tetrachloride-induced acute hepatic dysfunction[J]. World J Gastroenterol, 2017, 23(38): 6983-6994. DOI: 10.3748/wjg.v23.i38.6983.
[49]	BAJAJ JS, KASSAM Z, FAGAN A, et al. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial[J]. Hepatology, 2017, 66(6): 1727-1738. DOI: 10.1002/hep.29306.
[50]	BAJAJ JS, FAGAN A, GAVIS EA, et al. Long-term outcomes of fecal microbiota transplantation in patients with cirrhosis[J]. Gastroenterology, 2019, 156(6): 1921-1923. e3. DOI: 10.1053/j.gastro.2019.01.033.
[51]	DEFILIPP Z, BLOOM PP, TORRES SOTO M, et al. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant[J]. N Engl J Med, 2019, 381(21): 2043-2050. DOI: 10.1056/NEJMoa1910437.