Advances in Gut Microbiota in Heart Failure Combined with Depression

doi:10.12114/j.issn.1007-9572.2023.0638

Abstract

Abstract:

Heart failure patients are prone to depression, and interact with each other, leading to lower quality of life and poor prognosis of patients. As the largest microecosystem in the human body, changes in the composition, structure and function of the gut microbiota are closely related to the physiological and pathological states of the host. Currently, the "gut-heart/brain axis" has been used to explain the link between gut microbiota, cardiovascular diseases, and mood states, which is an important comorbid basis for heart failure and depression. In this paper, we reviewed the mechanisms of gut microbiota, metabolites, and vagus nerve in the development of heart failure and depression, and propose that mediterranean diet, probiotics, and microbiota transplantation have the potential to improve the "microbiota-gut-heart/brain axis", providing a new perspective for the treatment of heart failure patients comorbid with depression.

Key words: Heart failure, Depression, Gut microbiota, Metabolite, Review

摘要：

心力衰竭患者容易罹患抑郁，二者相互影响，导致患者生活质量降低与预后不良。肠道菌群作为人体最大的微生态系统，其组成、结构及功能变化与宿主的生理和病理状态密切相关。目前，"肠-心/脑轴"已用于解释肠道微生物、血管疾病及情绪状态之间的联系，是心力衰竭与抑郁的重要共病基础。本文综述了肠道微生物、代谢产物、迷走神经等在心力衰竭与抑郁发生、发展中的作用机制，提出地中海饮食、益生菌、菌群移植等具有改善微生物-肠-心/脑轴的潜力，为心力衰竭共病抑郁患者的治疗提供了新的切入点。

关键词: 心力衰竭, 抑郁, 肠道菌群, 代谢产物, 综述

CLC Number:

R 541.62

HUANG Kai,ZHANG Yi,YANG Chun, et al. Advances in Gut Microbiota in Heart Failure Combined with Depression[J]. Chinese General Practice, 2024, 27(35): 4455-4461. DOI: 10.12114/j.issn.1007-9572.2023.0638.
黄凯,张浥,杨春等. 肠道菌群与心力衰竭合并抑郁的研究进展[J]. 中国全科医学, 2024, 27(35): 4455-4461. DOI: 10.12114/j.issn.1007-9572.2023.0638.

References 77

[1]	WANG H, CHAI K, DU M H, et al. Prevalence and incidence of heart failure among urban patients in China：a national population-based analysis[J]. Circ Heart Fail，2021，14(10):e008406. DOI：10.1161/CIRCHEARTFAILURE.121.008406.
[2]	中华医学会心血管病学分会心力衰竭学组，中国医师协会心力衰竭专业委员会，中华心血管病杂志编辑委员会. 中国心力衰竭诊断和治疗指南2018[J]. 中华心血管病杂志，2018，46(10):760-789. DOI：10.3760/cma.j.issn.0253-3758.2018.10.004.
[3]	BURG M M. Depression and HeartFailure：what then must we do?[J]. JACC Heart Fail，2022，10(4):263-265. DOI：10.1016/j.jchf.2021.12.003.
[4]	SMITH K. Mental health：a world of depression[J]. Nature，2014，515(7526):181. DOI：10.1038/515180a.
[5]	GUSTAD L T, LAUGSAND L E, JANSZKY I, et al. Symptoms of anxiety and depression and risk of heart failure：the HUNT Study[J]. Eur J Heart Fail，2014，16(8):861-870. DOI：10.1002/ejhf.133.
[6]	REGAN J A, KITZMAN D W, LEIFER E S, et al. Impact of age on comorbidities and outcomes in HeartFailure with ReducedEjection fraction[J]. JACC Heart Fail，2019，7(12):1056-1065. DOI：10.1016/j.jchf.2019.09.004.
[7]	SBOLLI M, FIUZAT M, CANI D, et al. Depression and heart failure：the lonely comorbidity[J]. Eur J Heart Fail，2020，22(11):2007-2017. DOI：10.1002/ejhf.1865.
[8]	CHEN Z J, WU Y S, DUAN J H, et al. The cholinergic anti-inflammatory pathway could be an important mechanism underling the comorbidity of depression and cardiovascular disease：a comment to Shao et al[J]. Psychiatry Res，2020，286:112881. DOI：10.1016/j.psychres.2020.112881.
[9]	TRØSEID M, ANDERSEN G Ø, BROCH K, et al. The gut microbiome in coronary artery disease and heart failure：current knowledge and future directions[J]. EBioMedicine，2020，52:102649. DOI：10.1016/j.ebiom.2020.102649.
[10]	薛炳清，李春艳，朱灿. 肠道菌群对心血管疾病患者合并焦虑抑郁影响的研究进展[J]. 吉首大学学报（自然科学版），2021，42(1):83-89. DOI：10.13438/j.cnki.jdzk.2021.01.013.
[11]	BERMON S, PETRIZ B, KAJĖNIENĖ A, et al. The microbiota：an exercise immunology perspective[J]. Exerc Immunol Rev，2015，21:70-79.
[12]	SENDER R, FUCHS S, MILO R. Revised estimates for the number of human and bacteria cells in the body[J]. PLoS Biol，2016，14(8):e1002533. DOI：10.1371/journal.pbio.1002533.
[13]	COSTELLO E K, LAUBER C L, HAMADY M, et al. Bacterial community variation in human body habitats across space and time[J]. Science，2009，326(5960):1694-1697. DOI：10.1126/science.1177486.
[14]	CARMODY R N, GERBER G K, LUEVANO J M Jr, et al. Diet dominates host genotype in shaping the murine gut microbiota[J]. Cell Host Microbe，2015，17(1):72-84. DOI：10.1016/j.chom.2014.11.010.
[15]	SEKIROV I, RUSSELL S L, ANTUNES L C, et al. Gut microbiota in health and disease[J]. Physiol Rev，2010，90(3):859-904. DOI：10.1152/physrev.00045.2009.
[16]	TREMAROLI V, BÄCKHED F. Functional interactions between the gut microbiota and host metabolism[J]. Nature，2012，489(7415):242-249. DOI：10.1038/nature11552.
[17]	TANG W H W, LI D Y, HAZEN S L. Dietary metabolism，the gut microbiome，and heart failure[J]. Nat Rev Cardiol，2019，16(3):137-154. DOI：10.1038/s41569-018-0108-7.
[18]	HAMILTON M K, BOUDRY G, LEMAY D G, et al. Changes in intestinal barrier function and gut microbiota in high-fat diet-fed rats are dynamic and region dependent[J]. Am J Physiol Gastrointest Liver Physiol，2015，308(10):G840-G851. DOI：10.1152/ajpgi.00029.2015.
[19]	BUNKER J J, FLYNN T M, KOVAL J C, et al. Innate and adaptive humoral responses coat distinct commensal bacteria with immunoglobulin A[J]. Immunity，2015，43(3):541-553. DOI：10.1016/j.immuni.2015.08.007.
[20]	DE OLIVEIRA G L V, LEITE A Z, HIGUCHI B S, et al. Intestinal dysbiosis and probiotic applications in autoimmune diseases[J]. Immunology，2017，152(1):1-12. DOI：10.1111/imm.12765.
[21]	MEINITZER S, BARANYI A, HOLASEK S, et al. Sex-specific associations of trimethylamine-N-oxide and zonulin with signs of depression in carbohydrate malabsorbers and nonmalabsorbers[J]. Dis Markers，2020，2020:7897240. DOI：10.1155/2020/7897240.
[22]	DU Q, WANG Y H, ZHAO H Q, et al. Damages and its mechanism of the blood brain barrier in rats with diabetes mellitus with depression[J]. Zhongguo Ying Yong Sheng Li Xue Za Zhi，2016，32(6):558-562. DOI：10.13459/j.cnki.cjap.2016.06.016.
[23]	HOU K J, WU Z X, CHEN X Y, et al. Microbiota in health and diseases[J]. Signal Transduct Target Ther，2022，7(1):135. DOI：10.1038/s41392-022-00974-4.
[24]	LUEDDE M, WINKLER T, HEINSEN F A, et al. Heart failure is associated with depletion of core intestinal microbiota[J]. ESC Heart Fail，2017，4(3):282-290. DOI：10.1002/ehf2.12155.
[25]	JIN L, SHI X M, YANG J, et al. Gut microbes in cardiovascular diseases and their potential therapeutic applications[J]. Protein Cell，2021，12(5):346-359. DOI：10.1007/s13238-020-00785-9.
[26]	SUN W J, DU D B, FU T Z, et al. Alterations of the gut microbiota in patients with severe chronic heart failure[J]. Front Microbiol，2021，12:813289. DOI：10.3389/fmicb.2021.813289.
[27]	YANG J, ZHENG P, LI Y F, et al. Landscapes of bacterial and metabolic signatures and their interaction in major depressive disorders[J]. Sci Adv，2020，6(49):eaba8555. DOI：10.1126/sciadv.aba8555.
[28]	LIANG S S, SIN Z Y, YU J L, et al. Multi-cohort analysis of depression-associated gut bacteria sheds insight on bacterial biomarkers across populations[J]. Cell Mol Life Sci，2022，80(1):9. DOI：10.1007/s00018-022-04650-2.
[29]	KELLY J R, BORRE Y, O' BRIEN C, et al. Transferring the blues：depression-associated gut microbiota induces neurobehavioural changes in the rat[J]. J Psychiatr Res，2016，82:109-118. DOI：10.1016/j.jpsychires.2016.07.019.
[30]	LI B, WANG H Y, HUANG J H, et al. Polysaccharide，the active component of Dendrobium officinale，ameliorates metabolic hypertension in rats via regulating intestinal flora-SCFAs-vascular axis[J]. Front Pharmacol，2022，13:935714. DOI：10.3389/fphar.2022.935714.
[31]	CARLEY A N, MAURYA S K, FASANO M, et al. Short-chain fatty acids outpace ketone oxidation in the failing heart[J]. Circulation，2021，143(18):1797-1808. DOI：10.1161/CIRCULATIONAHA.120.052671.
[32]	SKONIECZNA-ŻYDECKA K, GROCHANS E, MACIEJEWSKA D, et al. Faecal short chain fatty acids profile is changed in Polish depressive women[J]. Nutrients，2018，10(12):1939. DOI：10.3390/nu10121939.
[33]	SONG L J, SUN Q H, ZHENG H N, et al. Roseburia hominis alleviates neuroinflammation via short-chain fatty acids through histone deacetylase inhibition[J]. Mol Nutr Food Res，2022，66(18):e2200164. DOI：10.1002/mnfr.202200164.
[34]	SELBER-HNATIW S, SULTANA T, TSE W, et al. Metabolic networks of the human gut microbiota[J]. Microbiology，2020，166(2):96-119. DOI：10.1099/mic.0.000853.
[35]	WILSON TANG W H, WANG Z N, FAN Y Y, et al. Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure：refining the gut hypothesis[J]. J Am Coll Cardiol，2014，64(18):1908-1914. DOI：10.1016/j.jacc.2014.02.617.
[36]	LI Z H, WU Z Y, YAN J Y, et al. Gut microbe-derived metabolite trimethylamine N-oxide induces cardiac hypertrophy and fibrosis[J]. Lab Invest，2019，99(3):346-357. DOI：10.1038/s41374-018-0091-y.
[37]	MAKRECKA-KUKA M, VOLSKA K, ANTONE U, et al. Trimethylamine N-oxide impairs pyruvate and fatty acid oxidation in cardiac mitochondria[J]. Toxicol Lett，2017，267:32-38. DOI：10.1016/j.toxlet.2016.12.017.
[38]	BARANYI A, ENKO D, VON LEWINSKI D, et al. Assessment of trimethylamine N-oxide（TMAO）as a potential biomarker of severe stress in patients vulnerable to posttraumatic stress disorder（PTSD）after acute myocardial infarction[J]. Eur J Psychotraumatol，2021，12(1):1920201. DOI：10.1080/20008198.2021.1920201.
[39]	HERNANDEZ L, WARD L J, AREFIN S, et al. Blood-brain barrier and gut barrier dysfunction in chronic kidney disease with a focus on circulating biomarkers and tight junction proteins[J]. Sci Rep，2022，12(1):4414. DOI：10.1038/s41598-022-08387-7.
[40]	MENG F Q, LI N, LI D L, et al. The presence of elevated circulating trimethylamine N-oxide exaggerates postoperative cognitive dysfunction in aged rats[J]. Behav Brain Res，2019，368:111902. DOI：10.1016/j.bbr.2019.111902.
[41]	LIANG S, WANG T, HU X, et al. Administration of Lactobacillus helveticus NS8 improves behavioral，cognitive，and biochemical aberrations caused by chronic restraint stress[J]. Neuroscience，2015，310:561-577. DOI：10.1016/j.neuroscience.2015.09.033.
[42]	LUKIĆ I, GETSELTER D, KOREN O, et al. Role of tryptophan in microbiota-induced depressive-like behavior：evidence from tryptophan depletion study[J]. Front Behav Neurosci，2019，13:123. DOI：10.3389/fnbeh.2019.00123.
[43]	KRAUTKRAMER K A, FAN J, BÄCKHED F. Gut microbial metabolites as multi-Kingdom intermediates[J]. Nat Rev Microbiol，2021，19(2):77-94. DOI：10.1038/s41579-020-0438-4.
[44]	SONG P, RAMPRASATH T, WANG H, et al. Abnormal kynurenine pathway of tryptophan catabolism in cardiovascular diseases[J]. Cell Mol Life Sci，2017，74(16):2899-2916. DOI：10.1007/s00018-017-2504-2.
[45]	DSCHIETZIG T B, KELLNER K H, SASSE K, et al. Plasma kynurenine predicts severity and complications of heart failure and associates with established biochemical and clinical markers of disease[J]. Kidney Blood Press Res，2019，44(4):765-776. DOI：10.1159/000501483.
[46]	CHAAR D, DUMONT B, VULESEVIC B, et al. Neutrophils pro-inflammatory and anti-inflammatory cytokine release in patients with heart failure and reduced ejection fraction[J]. ESC Heart Fail，2021，8(5):3855-3864. DOI：10.1002/ehf2.13539.
[47]	LI Y, FENG Y F, LIU X T, et al. Songorine promotes cardiac mitochondrial biogenesis via Nrf2 induction during sepsis[J]. Redox Biol，2021，38:101771. DOI：10.1016/j.redox.2020.101771.
[48]	QIN X Y, SHAN Q H, FANG H, et al. PSD-93 up-regulates the synaptic activity of corticotropin-releasing hormone neurons in the paraventricular nucleus in depression[J]. Acta Neuropathol，2021，142(6):1045-1064. DOI：10.1007/s00401-021-02371-7.
[49]	HUO J Y, JIANG W Y, YIN T, et al. Intestinal barrier dysfunction exacerbates neuroinflammation via the TLR4 pathway in mice with heart failure[J]. Front Physiol，2021，12:712338. DOI：10.3389/fphys.2021.712338.
[50]	CHEN B C, HUNG M Y, WANG H F, et al. GABA tea attenuates cardiac apoptosis in spontaneously hypertensive rats（SHR）by enhancing PI3K/Akt-mediated survival pathway and suppressing Bax/Bak dependent apoptotic pathway[J]. Environ Toxicol，2018，33(7):789-797. DOI：10.1002/tox.22565.
[51]	CAULEY E, WANG X, DYAVANAPALLI J, et al. Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure[J]. Am J Physiol Heart Circ Physiol，2015，309(8):H1281-H1287. DOI：10.1152/ajpheart.00445.2015.
[52]	STRANDWITZ P, KIM K H, TEREKHOVA D, et al. GABA-modulating bacteria of the human gut microbiota[J]. Nat Microbiol，2019，4(3):396-403. DOI：10.1038/s41564-018-0307-3.
[53]	FUCHS T, JEFFERSON S J, HOOPER A, et al. Disinhibition of somatostatin-positive GABAergic interneurons results in an anxiolytic and antidepressant-like brain state[J]. Mol Psychiatry，2017，22(6):920-930. DOI：10.1038/mp.2016.188.
[54]	OSADCHIY V, MARTIN C R, MAYER E A. The gut-brain axis and the microbiome：mechanisms and clinical implications[J]. Clin Gastroenterol Hepatol，2019，17(2):322-332. DOI：10.1016/j.cgh.2018.10.002.
[55]	NEUFELD K M, KANG N, BIENENSTOCK J, et al. Reduced anxiety-like behavior and central neurochemical change in germ-free mice[J]. Neurogastroenterol Motil，2011，23(3):255-264,e119. DOI：10.1111/j.1365-2982.2010.01620.x.
[56]	REDWINE L S, WIRTZ P H, HONG S Z, et al. Depression as a potential modulator of Beta-adrenergic-associated leukocyte mobilization in heart failure patients[J]. J Am Coll Cardiol，2010，56(21):1720-1727. DOI：10.1016/j.jacc.2010.04.064.
[57]	ADELBORG K, SCHMIDT M, SUNDBØLL J, et al. Mortality risk among heart failure patients with depression：a nationwide population-based cohort study[J]. J Am Heart Assoc，2016，5(9):e004137. DOI：10.1161/JAHA.116.004137.
[58]	WANG Y, ZHAN G F, CAI Z W, et al. Vagus nerve stimulation in brain diseases：therapeutic applications and biological mechanisms[J]. Neurosci Biobehav Rev，2021，127:37-53. DOI：10.1016/j.neubiorev.2021.04.018.
[59]	VADDER F D, KOVATCHEVA-DATCHARY P, GONCALVES D, et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits[J]. Cell，2014，156(1/2):84-96. DOI：10.1016/j.cell.2013.12.016.
[60]	EGEROD K L, PETERSEN N, TIMSHEL P N, et al. Profiling of G protein-coupled receptors in vagal afferents reveals novel gut-to-brain sensing mechanisms[J]. Mol Metab，2018，12:62-75. DOI：10.1016/j.molmet.2018.03.016.
[61]	BERCIK P, PARK A J, SINCLAIR D, et al. The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication[J]. Neurogastroenterol Motil，2011，23(12):1132-1139. DOI：10.1111/j.1365-2982.2011.01796.x.
[62]	BRAVO J A, FORSYTHE P, CHEW M V, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve[J]. Proc Natl Acad Sci U S A，2011，108(38):16050-16055. DOI：10.1073/pnas.1102999108.
[63]	HAN W F, TELLEZ L A, PERKINS M H, et al. A neural circuit for gut-induced reward[J]. Cell，2018，175(3):887-888. DOI：10.1016/j.cell.2018.10.018.
[64]	VEST A R, CHAN M, DESWAL A, et al. Nutrition，obesity，and Cachexia in patients with heart failure：a consensus statement from the heart failure society of America scientific statements committee[J]. J Card Fail，2019，25(5):380-400. DOI：10.1016/j.cardfail.2019.03.007.
[65]	BAYERLE P, BEYER S, TEGTBUR U, et al. Exercise capacity，iron status，body composition，and Mediterranean diet in patients with chronic heart failure[J]. Nutrients，2022，15(1):36. DOI：10.3390/nu15010036.
[66]	WALKER M E, O'DONNELL A A, HIMALI J J, et al. Associations of the mediterranean-dietary approaches to stop hypertension intervention for neurodegenerative delay diet with cardiac remodelling in the community：the Framingham Heart Study[J]. Br J Nutr，2021，126(12):1888-1896. DOI：10.1017/S0007114521000660.
[67]	GEORGOUSOPOULOU E N, KASTORINI C M, MILIONIS H J, et al. Association between Mediterranean diet and non-fatal cardiovascular events，in the context of anxiety and depression disorders：a case/case-control study[J]. Hellenike Kardiologike Epitheorese，2014，55(1):24-31.
[68]	HUANG R X, WANG K, HU J N. Effect of probiotics on depression：a systematic review and meta-analysis of randomized controlled trials[J]. Nutrients，2016，8(8):483. DOI：10.3390/nu8080483.
[69]	GAN X T, ETTINGER G, HUANG C X, et al. Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat[J]. Circ Heart Fail，2014，7(3):491-499. DOI：10.1161/CIRCHEARTFAILURE.113.000978.
[70]	VLASOV A A, SHPERLING M I, TERKIN D A, et al. Effect of prebiotic complex on gut microbiota and endotoxemia in female rats with modeled heart failure[J]. Bull Exp Biol Med，2020，168(4):435-438. DOI：10.1007/s10517-020-04726-8.
[71]	LIM S H. Larch Arabinogalactan attenuates myocardial injury by inhibiting apoptotic cascades in a rat model of ischemia-reperfusion[J]. J Med Food，2017，20(7):691-699. DOI：10.1089/jmf.2016.3886.
[72]	MOLUDI J, KHEDMATGOZAR H, NACHVAK S M, et al. The effects of co-administration of probiotics and prebiotics on chronic inflammation，and depression symptoms in patients with coronary artery diseases：a randomized clinical trial[J]. Nutr Neurosci，2022，25(8):1659-1668. DOI：10.1080/1028415X.2021.1889451.
[73]	YAN T X, NIAN T T, LIAO Z Z, et al. Antidepressant effects of a polysaccharide from okra（Abelmoschus esculentus（L）Moench）by anti-inflammation and rebalancing the gut microbiota[J]. Int J Biol Macromol，2020，144:427-440. DOI：10.1016/j.ijbiomac.2019.12.138.
[74]	RAO J J, QIAO Y, XIE R N, et al. Fecal microbiota transplantation ameliorates stress-induced depression-like behaviors associated with the inhibition of glial and NLRP3 inflammasome in rat brain[J]. J Psychiatr Res，2021，137:147-157. DOI：10.1016/j.jpsychires.2021.02.057.
[75]	GUO Q Q, LIN H, CHEN P C, et al. Dynamic changes of intestinal flora in patients with irritable bowel syndrome combined with anxiety and depression after oral administration of enterobacteria capsules[J]. Bioengineered，2021，12(2):11885-11897. DOI：10.1080/21655979.2021.1999374.
[76]	ZHANG Y, ZHANG S, LI B L, et al. Gut microbiota dysbiosis promotes age-related atrial fibrillation by lipopolysaccharide and glucose-induced activation of NLRP3-inflammasome[J]. Cardiovasc Res，2022，118(3):785-797. DOI：10.1093/cvr/cvab114.
[77]	ZHONG H J, ZENG H L, CAI Y L, et al. Washed microbiota transplantation lowers blood pressure in patients with hypertension[J]. Front Cell Infect Microbiol，2021，11:679624. DOI：10.3389/fcimb.2021.679624.