| 678 | 0 | 44 |
| 下载次数 | 被引频次 | 阅读次数 |
抑郁症不仅是一种中枢神经系统疾病，还与肝功能密切相关。研究表明，抑郁症患者出现肝脏代谢异常，同时肝病患者患有抑郁症的风险显著升高。肠-肝-脑轴是一个重要的代谢和信号传导途径，通过调节胆汁酸、脂质和氨基酸代谢，使肝脏对抑郁症的发展产生影响。目前的研究主要集中于肠道菌群在抑郁症中的作用，而肝脏的调节作用尚未得到充分探讨。本研究系统地回顾了肝脏代谢如何通过肠-肝-脑轴调节抑郁症，并提出了基于肝脏代谢调节抑郁症的潜在干预策略，包括饮食调节和中医药疗法，为抑郁症的临床诊断和治疗提供了新的视角。
Abstract：Depression is not only a central nervous system disorder but is also closely related to liver function. Research indicates that individuals with depression frequently show hepatic metabolic abnormalities, and those suffering from liver diseases present a significantly elevated risk for developing depressive symptoms. The gut-liver-brain axis is a crucial metabolic and signaling pathway. It allows the liver to impact the development of depression by regulating the metabolism of bile acids, lipids, and amino acids. Current research primarily focuses on the role of gut microbiota in depression, while the liver′s regulatory roles have not been adequately explored. This study systematically reviews how hepatic metabolism affects depression through the gut-liver-brain axis and proposes potential intervention strategies based on hepatic metabolic regulation for depression, including dietary modification and Chinese medicine therapy, offering novel perspectives for the clinical diagnosis and treatment of depression.
1 World Health Organization. Depressive disorder(depres-sion)[EB/OL].[2023-03-31]https：//www. who. int/news-room/fact-sheets/detail/depression.
2 Pilmeyer J, Lamerichs R, Schielen S, et al. Multi-mod-al MRI for objective diagnosis and outcome prediction indepression[J]. Neuroimage Clin, 2024, 44:103682.
3 Kronsten VT, Tranah TH, Pariante C, et al. Gut-de-rived systemic inflammation as a driver of depression inchronic liver disease[J]. J Hepatol, 2022, 76(3):665-680.
4 Jia S, Wang R, Zhang D, et al. Quercetin modulates theliver metabolic profile in a chronic unpredictable mildstress rat model based on metabolomics technology[J].Food Funct, 2023, 14(3):1726-1739.
5 Ding JH, Jin Z, Yang XX, et al. Role of gut microbiotavia the gut-liver-brain axis in digestive diseases[J].World J Gastroenterol, 2020, 26(40):6141-6162.
6 Fuchs CD, Simbrunner B, Baumgartner M, et al. Bileacid metabolism and signalling in liver disease[J]. JHepatol, 2025, 82(1):134-153.
7 Monteiro-Cardoso VF, CorlianòM, Singaraja RR. Bileacids:A communication channel in the gut-brain axis[J]. Neuromolecular Med, 2021, 23(1):99-117.
8 Sun N, Zhang J, Wang J, et al. Abnormal gut microbio-ta and bile acids in patients with first-episode major de-pressive disorder and correlation analysis[J]. PsychiatryClin Neurosci, 2022, 76(7):321-328.
9 Wang J, Zang J, Yu Y, et al. Lingguizhugan oral solu-tion alleviates MASLD by regulating bile acids metabo-lism and the gut microbiota through activating FXR/TGR5 signaling pathways[J]. Front Pharmacol, 2024,15:1426049.
10 Chen WG, Zheng JX, Xu X, et al. Hippocampal FXRplays a role in the pathogenesis of depression:A prelimi-nary study based on lentiviral gene modulation[J]. Psy-chiatry Res, 2018, 264:374-379.
11 Ortega-Martínez S. A new perspective on the role of theCREB family of transcription factors in memory consoli-dation via adult hippocampal neurogenesis[J]. FrontMol Neurosci, 2015, 8:46.
12 Hu W, Wu J, Ye T, et al. Farnesoid X receptor-mediat-ed cytoplasmic translocation of CRTC2 disrupts CREB-BDNF signaling in hippocampal CA1 and leads to the de-velopment of depression-like behaviors in mice[J]. Int JNeuropsychopharmacol, 2020, 23(10):673-686.
13 Li H, Zhu X, Xu J, et al. The FXR mediated anti-de-pression effect of CDCA underpinned its therapeutic po-tentiation for MDD[J]. Int Immunopharmacol, 2023,115:109626.
14 Kim YK, Kim OY, Song J. Alleviation of depression byglucagon-like peptide 1 through the regulation of neuroin-flammation, neurotransmitters, neurogenesis, and syn-aptic function[J]. Front Pharmacol, 2020, 11:1270.
15 Wang H, Tan YZ, Mu RH, et al. Takeda G protein-coupled receptor 5 modulates depression-like behaviorsvia hippocampal CA3 pyramidal neurons afferent to dor-solateral septum[J]. Biol Psychiatry, 2021, 89(11):1084-1095.
16 Tao Y, Zhou H, Li Z, et al. TGR5 deficiency-inducedanxiety and depression-like behaviors:The role of gutmicrobiota dysbiosis[J]. J Affect Disord, 2024, 344:219-232.
17 Li XY, Zhang SY, Hong YZ, et al. TGR5-mediated lat-eral hypothalamus-dCA3-dorsolateral septum circuit reg-ulates depressive-like behavior in male mice[J]. Neu-ron, 2024, 112(11):1795-1814.e10.
18 Song Z, Cai Y, Lao X, et al. Taxonomic profiling andpopulational patterns of bacterial bile salt hydrolase(BSH) genes based on worldwide human gut microbi-ome[J]. Microbiome, 2019, 7(1):9.
19 Vital M, Rud T, Rath S, et al. Diversity of bacteria ex-hibiting bile Acid-inducible 7α-dehydroxylation genes inthe human gut[J]. Comput Struct Biotechnol J, 2019,17:1016-1019.
20 Su X, Gao Y, Yang R. Gut microbiota derived bile acidmetabolites maintain the homeostasis of gut and systemicimmunity[J]. Front Immunol, 2023, 14:1127743.
21 Wang L, Gong Z, Zhang X, et al. Gut microbial bile ac-id metabolite skews macrophage polarization and contrib-utes to high-fat diet-induced colonic inflammation[J].Gut Microbes, 2020, 12(1):1-20.
22 Anwar SD, Foster C, Ashraf A. Lipid disorders andmetabolic-associated fatty liver disease[J]. EndocrinolMetab Clin North Am, 2023, 52(3):445-457.
23 Xu K, Zheng P, Zhao S, et al. MANF/EWSR1/ANXA6 pathway might as the bridge between hypolipid-emia and major depressive disorder[J]. Transl Psychia-try, 2022, 12(1):527.
24 Zhou L, Xiong JY, Chai YQ, et al. Possible antidepres-sant mechanisms of omega-3 polyunsaturated fatty acidsacting on the central nervous system[J]. Front Psychia-try, 2022, 13:933704.
25 Pifferi F, Laurent B, Plourde M. Lipid transport and me-tabolism at the blood-brain interface:Implications inhealth and disease[J]. Front Physiol, 2021, 12:645646.
26 Wang J, Li S, Wang D, et al. Effects of omega-3 PU-FAs on lipid profiles and antioxidant response in de-pressed adolescents:A metabolomic and lipidomic study[J]. Redox Biol, 2025, 82:103617.
27 Guu TW, Mischoulon D, Sarris J, et al. Internationalsociety for nutritional psychiatry research practice guide-lines for omega-3 fatty acids in the treatment of major de-pressive disorder[J]. Psychother Psychosom, 2019, 88(5):263-273.
28 Fu Y, Wang Y, Gao H, et al. Associations among di-etary omega-3 polyunsaturated fatty acids, the gut micro-biota, and intestinal immunity[J]. Mediators Inflamm,2021, 2021:8879227.
29 Gammoh O, Aljabali AAA, Tambuwala MM. Plasmaamino acids in major depressive disorder:Between pa-thology to pharmacology[J]. Excli J, 2024, 23:62-78.
30 Ho CSH, Tay GWN, Wee HN, et al. The utility ofamino acid metabolites in the diagnosis of major depres-sive disorder and correlations with depression severity[J]. Int J Mol Sci, 2023, 24(3):2231.
31 Mora D, Arioli S. Microbial urease in health and disease[J]. PLoS Pathog, 2014, 10(12):e1004472.
32 Wang P, Wu PF, Wang HJ, et al. Gut microbiome-de-rived ammonia modulates stress vulnerability in the host[J]. Nat Metab, 2023, 5(11):1986-2001.
33 Gallego-Durán R, Hadjihambi A, Ampuero J, et al.Ammonia-induced stress response in liver disease pro-gression and hepatic encephalopathy[J]. Nat Rev Gas-troenterol Hepatol, 2024, 21(11):774-791.
34 Yan T, Li F, Xiong W, et al. Nootkatone improves anx-iety-and depression-like behavior by targeting hyperam-monemia-induced oxidative stress in D-galactosaminemodel of liver injury[J]. Environ Toxicol, 2021, 36(4):694-706.
35 Limón ID, Angulo-Cruz I, Sánchez-Abdon L, et al.Disturbance of the glutamate-glutamine cycle, secondaryto hepatic damage, compromises memory function[J].Front Neurosci, 2021, 15:578922.
36 Reshetova M, Markin P, Appolonova S, et al. Trypto-phan metabolites in the progression of liver diseases[J].Biomolecules, 2024, 14(11):1449.
37 Zeng G, Krishnamurthy S, Staats Pires A, et al. Activa-tion of the kynurenine pathway identified in individualswith covert hepatic encephalopathy[J]. Hepatol Com-mun, 2024, 8(12):e0559.
38 Zeng QB, Huang XB, Xu R, et al. Kynurenine pathwaymetabolites predict antianhedonic effects of electroconvul-sive therapy in patients with treatment-resistant depres-sion[J]. J Affect Disord, 2025, 379:764-771.
39 Yu Z, Lin Y, Wu L, et al. Bisphenol F exposure induc-es depression-like changes:Roles of the kynurenine met-abolic pathway along the"liver-brain"axis[J]. EnvironPollut, 2024, 346:123356.
40 Correia AS, Vale N. Tryptophan metabolism in depres-sion:A narrative review with a focus on serotonin andkynurenine pathways[J]. Int J Mol Sci, 2022, 23(15):8493.
41 Wu L, Tang Z, Chen H, et al. Mutual interaction be-tween gut microbiota and protein/amino acid metabolismfor host mucosal immunity and health[J]. Anim Nutr,2021, 7(1):11-16.
42 Xie J, Wang Y, Zhong Q, et al. Associations betweendisordered microbial metabolites and changes of neu-rotransmitters in depressed mice[J]. Front Cell InfectMicrobiol, 2022, 12:906303.
43 Xie Y, Shang S, Luan W, et al. Apple polyphenol ex-tracts attenuated depressive-like behaviors of high-su-crose diet feeding mice by farnesoid X receptor-mediatedmodulation of bile acid circulation within the liver-gut-brain axis[J]. J Agric Food Chem, 2024, 72(45):25118-25134.
44 Yang Y, Eguchi A, Mori C, et al. Dietary sulforaphaneglucosinolate mitigates depression-like behaviors in micewith hepatic ischemia/reperfusion injury:A role of thegut-liver-brain axis[J]. J Psychiatr Res, 2024, 176:129-139.
45 Li B, Yan Y, Zhang T, et al. Quercetin reshapes gut mi-crobiota homeostasis and modulates brain metabolic pro-file to regulate depression-like behaviors induced byCUMS in rats[J]. Front Pharmacol, 2024, 15:1362464.
46 Ma C, Yuan D, Renaud SJ, et al. Chaihu-shugan-san al-leviates depression-like behavior in mice exposed tochronic unpredictable stress by altering the gut microbio-ta and levels of the bile acids hyocholic acid and 7-ketoD-CA[J]. Front Pharmacol, 2022, 13:1040591.
47 Jung J, Lee SM, Lee MJ, et al. Lipidomics reveals thatacupuncture modulates the lipid metabolism and inflam-matory interaction in a mouse model of depression[J].Brain Behav Immun, 2021, 94:424-436.
基本信息:
DOI：10.13210/j.cnki.jhmu.20250610.003
中图分类号:R749.4
引用信息:
[1]贾欢欢,吴民民,滕丽丽,等.肝脏代谢通过肠-肝-脑轴调控抑郁症的机制研究[J].海南医科大学学报,2025,31(22):1745-1753.DOI:10.13210/j.cnki.jhmu.20250610.003.
基金信息:
国家自然科学基金（82174477）~~
2025-06-11
2025-06-11
2025-06-11