PDF下载 ( 1507 KB)
短链脂肪酸在肝性脑病中的免疫调节作用及潜在诊疗价值
DOI: 10.12449/JCH250523
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：姚春、陈玮钰负责研究选题并拟定写作思路；毛德文、王涵、付蕾负责设计论文框架；杜洋、冯雯倩负责收集和整理文献材料；陈玮钰负责文章撰写及修改。
Immunomodulatory effect of short-chain fatty acids in hepatic encephalopathy and its potential diagnostic value
-
摘要: 肝性脑病（HE）作为临床常见的严重肝病终末期并发症，其有效救治率亟需提升，发病机制亟待攻克。肝脏是重要的免疫调节中心，免疫稳态失衡在HE的病理机制中占主导地位。短链脂肪酸（SCFA）作为肠道菌群的主要代谢物之一，在先天性免疫和适应性免疫的生物学过程中扮演着重要角色，能够调控免疫细胞的增殖分化、维持肠道微环境稳态和屏障功能完整性。研究表明，SCFA通过免疫调节途径与肝-肠-脑轴进行双向、动态的交互反应和信号传递，在HE的诊疗和预后评估方面具有不可忽视的作用。基于此，本文以SCFA的免疫调节效应为切入点，就SCFA与肝-肠-脑轴的串扰关系，以及SCFA在HE诊疗中的重要意义进行归纳和探讨，以期为优化HE临床防治方案提供新的思路。Abstract: Hepatic encephalopathy （HE） is a common complication of severe liver disease in the end stage， and it is urgently needed to improve the rate of effective treatment and clarify the pathogenesis of HE. The liver is a crucial hub for immune regulation， and disruption of immune homeostasis is a key factor in the pathological mechanisms of HE. As the main metabolites of intestinal flora， short-chain fatty acids （SCFAs） play a vital role in the biological processes of both innate and adaptive immunity and can regulate the proliferation and differentiation of immune cells maintain the homeostasis of intestinal microenvironment and the integrity of barrier function. Studies have shown that SCFAs participate in bidirectional and dynamic interactions with the liver-gut-brain axis through immunomodulatory pathways， thereby playing an important role in the diagnosis， treatment， and prognostic evaluation of HE. Starting from the immunoregulatory effect of SCFAs， this article summarizes and analyzes the crosstalk relationship between SCFAs and the liver-gut-brain axis and the significance of SCFAs in the diagnosis and treatment of HE， in order to provide new ideas for optimizing clinical prevention and treatment strategies.
-
注： JNK，c-jun氨基末端转移酶；IκB，核因子κB抑制因子；Iκκ，IκB激酶。
图 1 SCFA与肝-肠-脑轴的免疫调节路径
Figure 1. Immunomodulatory pathways of SCFA and liver-gut-brain axis
表 1 SCFA对免疫系统的调节作用
Table 1. The regulatory effect of SCFA on immune system
免疫机制 免疫细胞类型 SCFA类型 作用机制 先天性免疫 树突状细胞 丁酸盐 激活GPR109A信号传导和抑制HDAC活性，减少树突状细胞的分化，促进抗炎细胞因子IL-10的表达，抑制促炎细胞因子IL-12、干扰素γ的产生，增强免疫系统对抗原的耐受性［14-15］ 丁酸盐、丙酸盐 下调树突状细胞中IL-6、IL-12和IL-23的表达，抑制抗原特异性CD8+ T细胞的活化，促进初始T细胞分化为Treg，有助于增强树突状细胞的免疫耐受活性［16］ 乙酸盐、丁酸盐 分别激活树突状细胞中的GPR109A和肠上皮细胞中的GPR43，触发SCFA信号传导，增强免疫细胞CD103+树突状细胞的耐受活性，以抑制过度的免疫反应［17］ 巨噬细胞 丁酸盐 抑制HDAC活性，诱导肠道巨噬细胞的糖酵解水平下调，减少肠道内促炎细胞因子的释放，增强巨噬细胞的抗菌功能［18-19］ 丁酸盐、丙酸盐 激活GPR43信号传导和抑制HDAC活性，增加组蛋白H3的乙酰化水平，诱导巨噬细胞由促炎M1表型向抗炎M2表型极化，减轻炎症反应［19-20］ 中性粒细胞 丁酸盐 抑制HDAC活性以减少中性粒细胞来源的趋化因子和促炎细胞因子的释放水平，调节肠道局部免疫以发挥抗炎作用［21］ 丁酸盐、丙酸盐 抑制HDAC活性和NF-κB、MAPK信号通路活化，以及诱导乙酰化组蛋白H3的高表达，从而减少中性粒细胞对趋化因子和炎症介质的释放［22-23］ 丁酸盐、丙酸盐、乙酸盐 抑制NF-κB信号通路活化，减少中性粒细胞释放促炎细胞因子TNF-α、IL-6和IL-1α，拮抗炎症损伤［24］ 嗜酸性粒细胞 丁酸盐、丙酸盐 抑制HDAC活性，诱导嗜酸性粒细胞中线粒体膜电位去极化和Caspase-3/7激活，启动细胞凋亡以抑制嗜酸性粒细胞浸润，促进炎症消退［25］ 嗜碱性粒细胞 丁酸盐、丙酸盐 抑制HDAC活性，诱导IL-13表达增加并减少IL-4产生，介导嗜碱性粒细胞脱颗粒，加速细胞凋亡，从而恢复保护性免疫平衡［26］ ILC 乙酸盐 激活GPR43，从而增强ILC3中IL-1受体的表达，导致IL-1β的分泌增加以诱导IL-22的产生，IL-22能加速黏蛋白的合成以维持屏障功能完整性，实现抗炎作用［27-28］ 丁酸盐 激活GPR41和抑制HDAC活性，能减少ILC2增殖并上调IL-22的表达，促进黏蛋白合成，修复肠道屏障以维持免疫稳态［29-30］ 乙酸盐、丙酸盐 触发GPR43信号传导，进一步介导AKT/STAT3轴差异性激活AKT或ERK信号，导致ILC3丰度增加并促进IL-22分泌，增强肠道稳态和宿主防御［31］ 适应性免疫 T细胞 丁酸盐 一方面通过激活GPR43、GPR109A信号传导和抑制HDAC活性介导FOXP3基因位点乙酰化，驱动FOXP3基因的转录，诱导初始CD4+ T细胞向Treg分化，以及增加IL-10的产生；另一方面通过介导TCA循环与糖酵解的解耦强化细胞能量产生途径，维持CD8+ T细胞的特异性抗原识别功能，协同调节肠道炎症反应和建立免疫稳态［32-35］ 丙酸盐 能够在不影响机体对病原体正常防御性免疫反应的情况下，扩增Treg数量和保护Treg功能，提供积极的抗炎效应［36］ 丁酸盐、丙酸盐 抑制HDAC活性进而增加FOXP3的表达，促进抗炎Treg生成以重建肠道菌群与免疫系统之间的通信网络，恢复促炎和抗炎机制之间的平衡［37］ B细胞 乙酸盐 一方面通过激活GPR43以促进树突状细胞中视黄酸信号传导，进而诱导B细胞协同产生IgA，肠道中的IgA对保护肠道免受炎症损伤具有重要作用；另一方面通过促进乙酰辅酶A的生成与代谢，驱动TCA循环产生能量和翻译后赖氨酸的乙酰化，诱导Breg分泌IL-10，实现免疫保护和维持免疫稳态［38-39］ 丙酸盐 激活GPR43信号传导以诱导GrB的表达，驱动Breg产生IL-10和TTP，其中TTP能加速IL-10的降解，而丙酸盐可诱导GrB与TTP形成复合物以维持IL-10的功能稳定性，从而调节适应性免疫反应［40］ 丁酸盐 既可通过增加血清5-HIAA的水平进而强化Breg的防御功能，又能与5-HIAA协同激活芳香烃受体依赖性基因转录，有助于Breg识别并抑制自身免疫。此外，还能通过调节昼夜节律相关基因的表达诱导Breg分泌IL-10，确保免疫反应的适度和精确性［41-42］ 丁酸盐、丙酸盐 抑制HDAC活性以下调B细胞中免疫应答关键调节剂Aicda和Prdm1的表达，从而延缓B细胞内抗体类别转换重组和浆细胞分化的进程，以防止过度的自身免疫，维持免疫系统平衡［43］ 注：IL，白细胞介素；Treg，调节性T细胞；TNF-α，肿瘤坏死因子α；Caspase，半胱氨酸天冬氨酸蛋白酶；AKT，蛋白激酶B；STAT，信号传导和转录启动因子；ERK，细胞外调节蛋白激酶；FOXP3，叉头框蛋白P3；IgA，免疫球蛋白A；Breg，调节性B细胞；GrB，颗粒酶B；TTP，Tristetraprolin；5-HIAA，5-羟吲哚乙酸；Aicda，活化诱导胞嘧啶核苷脱氨酶；Prdm1，PR结构域锌指蛋白1。
下载: 导出CSV
-
[1] YANNY B, WINTERS A, BOUTROS S, et al. Hepatic encephalopathy challenges, burden, and diagnostic and therapeutic approach[J]. Clin Liver Dis, 2019, 23( 4): 607- 623. DOI: 10.1016/j.cld.2019.07.001. [2] ELSAID MI, RUSTGI VK. Epidemiology of hepatic encephalopathy[J]. Clin Liver Dis, 2020, 24( 2): 157- 174. DOI: 10.1016/j.cld.2020.01.001. [3] TAPPER EB, ABERASTURI D, ZHAO Z, et al. Outcomes after hepatic encephalopathy in population-based cohorts of patients with cirrhosis[J]. Aliment Pharmacol Ther, 2020, 51( 12): 1397- 1405. DOI: 10.1111/apt.15749. [4] MIRZAEI R, BOUZARI B, HOSSEINI-FARD SR, et al. Role of microbiota-derived short-chain fatty acids in nervous system disorders[J]. Biomed Pharmacother, 2021, 139: 111661. DOI: 10.1016/j.biopha.2021.111661. [5] FERNANDES J, SU W, RAHAT-ROZENBLOOM S, et al. Adiposity, gut microbiota and faecal short chain fatty acids are linked in adult humans[J]. Nutr Diabetes, 2014, 4( 6): e121. DOI: 10.1038/nutd.2014.23. [6] YANG HJ, KIM JH. Role of microbiome and its metabolite, short chain fatty acid in prostate cancer[J]. Investig Clin Urol, 2023, 64( 1): 3- 12. DOI: 10.4111/icu.20220370. [7] de VADDER F, 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. [8] BERGMAN EN. Energy contributions of volatile fatty acids from the gastrointestinal tract in various species[J]. Physiol Rev, 1990, 70( 2): 567- 590. DOI: 10.1152/physrev.1990.70.2.567. [9] COMALADA M, BAILÓN E, DE HARO O, et al. The effects of short-chain fatty acids on colon epithelial proliferation and survival depend on the cellular phenotype[J]. J Cancer Res Clin Oncol, 2006, 132( 8): 487- 497. DOI: 10.1007/s00432-006-0092-x. [10] MACHADO MG, PATENTE TA, ROUILLÉ Y, et al. Acetate improves the killing of Streptococcus pneumoniae by alveolar macrophages via NLRP3 inflammasome and glycolysis-HIF-1α axis[J]. Front Immunol, 2022, 13: 773261. DOI: 10.3389/fimmu.2022.773261. [11] LANGE O, PROCZKO-STEPANIAK M, MIKA A. Short-chain fatty acids-a product of the microbiome and its participation in two-way communication on the microbiome-host mammal line[J]. Curr Obes Rep, 2023, 12( 2): 108- 126. DOI: 10.1007/s13679-023-00503-6. [12] YANG M, ZHANG CY. G protein-coupled receptors as potential targets for nonalcoholic fatty liver disease treatment[J]. World J Gastroenterol, 2021, 27( 8): 677- 691. DOI: 10.3748/wjg.v27.i8.677. [13] ZHANG L, SHI XH, QIU HM, et al. Protein modification by short-chain fatty acid metabolites in sepsis: A comprehensive review[J]. Front Immunol, 2023, 14: 1171834. DOI: 10.3389/fimmu.2023.1171834. [14] KAISAR MMM, PELGROM LR, VAN DER HAM AJ, et al. Butyrate conditions human dendritic cells to prime type 1 regulatory T cells via both histone deacetylase inhibition and G protein-coupled receptor 109A signaling[J]. Front Immunol, 2017, 8: 1429. DOI: 10.3389/fimmu.2017.01429. [15] LIU L, LI L, MIN J, et al. Butyrate interferes with the differentiation and function of human monocyte-derived dendritic cells[J]. Cell Immunol, 2012, 277( 1-2): 66- 73. DOI: 10.1016/j.cellimm.2012.05.011. [16] NASTASI C, FREDHOLM S, WILLERSLEV-OLSEN A, et al. Butyrate and propionate inhibit antigen-specific CD8+ T cell activation by suppressing IL-12 production by antigen-presenting cells[J]. Sci Rep, 2017, 7( 1): 14516. DOI: 10.1038/s41598-017-15099-w. [17] TAN J, MCKENZIE C, VUILLERMIN PJ, et al. Dietary fiber and bacterial SCFA enhance oral tolerance and protect against food allergy through diverse cellular pathways[J]. Cell Rep, 2016, 15( 12): 2809- 2824. DOI: 10.1016/j.celrep.2016.05.047. [18] SCHULTHESS J, PANDEY S, CAPITANI M, et al. The short chain fatty acid butyrate imprints an antimicrobial program in macrophages[J]. Immunity, 2019, 50( 2): 432- 445. DOI: 10.1016/j.immuni.2018.12.018. [19] CHANG PV, HAO LM, OFFERMANNS S, et al. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition[J]. Proc Natl Acad Sci U S A, 2014, 111( 6): 2247- 2252. DOI: 10.1073/pnas.1322269111. [20] HUANG CR, DU W, NI YM, et al. The effect of short-chain fatty acids on M2 macrophages polarization in vitro and in vivo[J]. Clin Exp Immunol, 2022, 207( 1): 53- 64. DOI: 10.1093/cei/uxab028. [21] LI GF, LIN J, ZHANG C, et al. Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease[J]. Gut Microbes, 2021, 13( 1): 1968257. DOI: 10.1080/19490976.2021.1968257. [22] AOYAMA M, KOTANI J, USAMI M. Butyrate and propionate induced activated or non-activated neutrophil apoptosis via HDAC inhibitor activity but without activating GPR-41/GPR-43 pathways[J]. Nutrition, 2010, 26( 6): 653- 661. DOI: 10.1016/j.nut.2009.07.006. [23] VINOLO MA, RODRIGUES HG, HATANAKA E, et al. Suppressive effect of short-chain fatty acids on production of proinflammatory mediators by neutrophils[J]. J Nutr Biochem, 2011, 22( 9): 849- 855. DOI: 10.1016/j.jnutbio.2010.07.009. [24] TEDELIND S, WESTBERG F, KJERRULF M, et al. Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: A study with relevance to inflammatory bowel disease[J]. World J Gastroenterol, 2007, 13( 20): 2826- 2832. DOI: 10.3748/wjg.v13.i20.2826. [25] THEILER A, BÄRNTHALER T, PLATZER W, et al. Butyrate ameliorates allergic airway inflammation by limiting eosinophil trafficking and survival[J]. J Allergy Clin Immunol, 2019, 144( 3): 764- 776. DOI: 10.1016/j.jaci.2019.05.002. [26] SHI YB, XU MZ, PAN S, et al. Induction of the apoptosis, degranulation and IL-13 production of human basophils by butyrate and propionate via suppression of histone deacetylation[J]. Immunology, 2021, 164( 2): 292- 304. DOI: 10.1111/imm.13370. [27] FACHI JL, SÉCCA C, RODRIGUES PB, et al. Acetate coordinates neutrophil and ILC3 responses against C. difficile through FFAR2[J]. J Exp Med, 2020, 217( 3): e20190489. DOI: 10.1084/jem.20190489. [28] SERAFINI N, JARADE A, SURACE L, et al. Trained ILC3 responses promote intestinal defense[J]. Science, 2022, 375( 6583): 859- 863. DOI: 10.1126/science.aaz8777. [29] YANG WJ, YU TM, HUANG XS, et al. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity[J]. Nat Commun, 2020, 11( 1): 4457. DOI: 10.1038/s41467-020-18262-6. [30] THIO CL, CHI PY, LAI AC, et al. Regulation of type 2 innate lymphoid cell-dependent airway hyperreactivity by butyrate[J]. J Allergy Clin Immunol, 2018, 142( 6): 1867- 1883. DOI: 10.1016/j.jaci.2018.02.032. [31] CHUN E, LAVOIE S, FONSECA-PEREIRA D, et al. Metabolite-sensing receptor Ffar2 regulates colonic group 3 innate lymphoid cells and gut immunity[J]. Immunity, 2019, 51( 5): 871- 884. DOI: 10.1016/j.immuni.2019.09.014. [32] KIBBIE JJ, DILLON SM, THOMPSON TA, et al. Butyrate directly decreases human gut lamina propria CD4 T cell function through histone deacetylase(HDAC) inhibition and GPR43 signaling[J]. Immunobiology, 2021, 226( 5): 152126. DOI: 10.1016/j.imbio.2021.152126. [33] FURUSAWA Y, OBATA Y, FUKUDA S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells[J]. Nature, 2013, 504( 7480): 446- 450. DOI: 10.1038/nature12721. [34] SINGH N, GURAV A, SIVAPRAKASAM S, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis[J]. Immunity, 2014, 40( 1): 128- 139. DOI: 10.1016/j.immuni.2013.12.007. [35] BACHEM A, MAKHLOUF C, BINGER KJ, et al. Microbiota-derived short-chain fatty acids promote the memory potential of antigen-activated CD8+ T cells[J]. Immunity, 2019, 51( 2): 285- 297. DOI: 10.1016/j.immuni.2019.06.002. [36] MEYER F, SEIBERT FS, NIENEN M, et al. Propionate supplementation promotes the expansion of peripheral regulatory T-Cells in patients with end-stage renal disease[J]. J Nephrol, 2020, 33( 4): 817- 827. DOI: 10.1007/s40620-019-00694-z. [37] ARPAIA N, CAMPBELL C, FAN XY, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation[J]. Nature, 2013, 504( 7480): 451- 455. DOI: 10.1038/nature12726. [38] WU W, SUN M, CHEN F, et al. Microbiota metabolite short-chain fatty acid acetate promotes intestinal IgA response to microbiota which is mediated by GPR43[J]. Mucosal Immunol, 2017, 10( 4): 946- 956. DOI: 10.1038/mi.2016.114. [39] DAÏEN CI, TAN J, AUDO R, et al. Gut-derived acetate promotes B10 cells with antiinflammatory effects[J]. JCI Insight, 2021, 6( 7): e144156. DOI: 10.1172/jci.insight.144156. [40] TIAN GX, PENG KP, YU Y, et al. Propionic acid regulates immune tolerant properties in B Cells[J]. J Cell Mol Med, 2022, 26( 10): 2766- 2776. DOI: 10.1111/jcmm.17287. [41] ROSSER EC, PIPER CJM, MATEI DE, et al. Microbiota-derived metabolites suppress arthritis by amplifying aryl-hydrocarbon receptor activation in regulatory B cells[J]. Cell Metab, 2020, 31( 4): 837- 851. DOI: 10.1016/j.cmet.2020.03.003. [42] KIM DS, WOO JS, MIN HK, et al. Short-chain fatty acid butyrate induces IL-10-producing B cells by regulating circadian-clock-related genes to ameliorate Sjögren’s syndrome[J]. J Autoimmun, 2021, 119: 102611. DOI: 10.1016/j.jaut.2021.102611. [43] SANCHEZ HN, MORONEY JB, GAN HQ, et al. B cell-intrinsic epigenetic modulation of antibody responses by dietary fiber-derived short-chain fatty acids[J]. Nat Commun, 2020, 11( 1): 60. DOI: 10.1038/s41467-019-13603-6. [44] BLOEMEN JG, VENEMA K, van de POLL MC, et al. Short chain fatty acids exchange across the gut and liver in humans measured at surgery[J]. Clin Nutr, 2009, 28( 6): 657- 661. DOI: 10.1016/j.clnu.2009.05.011. [45] LIWINSKI T, CASAR C, RUEHLEMANN MC, et al. A disease-specific decline of the relative abundance of Bifidobacterium in patients with autoimmune hepatitis[J]. Aliment Pharmacol Ther, 2020, 51( 12): 1417- 1428. DOI: 10.1111/apt.15754. [46] KUMMEN M, THINGHOLM LB, RÜHLEMANN MC, et al. Altered gut microbial metabolism of essential nutrients in primary sclerosing cholangitis[J]. Gastroenterology, 2021, 160( 5): 1784- 1798. DOI: 10.1053/j.gastro.2020.12.058. [47] CORNEJO-PAREJA I, AMIAR MR, OCAÑA-WILHELMI L, et al. Non-alcoholic fatty liver disease in patients with morbid obesity: The gut microbiota axis as a potential pathophysiology mechanism[J]. J Gastroenterol, 2024, 59( 4): 329- 341. DOI: 10.1007/s00535-023-02075-7. [48] BRÜSSOW H, PARKINSON SJ. You are what you eat[J]. Nat Biotechnol, 2014, 32( 3): 243- 245. DOI: 10.1038/nbt.2845. [49] DEN BESTEN G, BLEEKER A, GERDING A, et al. Short-chain fatty acids protect against high-fat diet-induced obesity via a PPARγ-dependent switch from lipogenesis to fat oxidation[J]. Diabetes, 2015, 64( 7): 2398- 2408. DOI: 10.2337/db14-1213. [50] DENG MJ, QU F, CHEN L, et al. SCFAs alleviated steatosis and inflammation in mice with NASH induced by MCD[J]. J Endocrinol, 2020, 245( 3): 425- 437. DOI: 10.1530/JOE-20-0018. [51] WEI YR, LI YM, YAN L, et al. Alterations of gut microbiome in autoimmune hepatitis[J]. Gut, 2020, 69( 3): 569- 577. DOI: 10.1136/gutjnl-2018-317836. [52] AWONIYI M, WANG J, NGO B, et al. Protective and aggressive bacterial subsets and metabolites modify hepatobiliary inflammation and fibrosis in a murine model of PSC[J]. Gut, 2023, 72( 4): 671- 685. DOI: 10.1136/gutjnl-2021-326500. [53] SINGH V, YEOH BS, CHASSAING B, et al. Dysregulated microbial fermentation of soluble fiber induces cholestatic liver cancer[J]. Cell, 2018, 175( 3): 679- 694. DOI: 10.1016/j.cell.2018.09.004. [54] BEHARY J, AMORIM N, JIANG XT, et al. Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma[J]. Nat Commun, 2021, 12( 1): 187. DOI: 10.1038/s41467-020-20422-7. [55] PRATT M, FORBES JD, KNOX NC, et al. Microbiome-mediated immune signaling in inflammatory bowel disease and colorectal cancer: Support from meta-omics data[J]. Front Cell Dev Biol, 2021, 9: 716604. DOI: 10.3389/fcell.2021.716604. [56] HANUS M, PARADA-VENEGAS D, LANDSKRON G, et al. Immune system, microbiota, and microbial metabolites: The unresolved triad in colorectal cancer microenvironment[J]. Front Immunol, 2021, 12: 612826. DOI: 10.3389/fimmu.2021.612826. [57] KIRUNDI J, MOGHADAMRAD S, URBANIAK C. Microbiome-liver crosstalk: A multihit therapeutic target for liver disease[J]. World J Gastroenterol, 2023, 29( 11): 1651- 1668. DOI: 10.3748/wjg.v29.i11.1651. [58] CUMMINGS JH, POMARE EW, BRANCH WJ, et al. Short chain fatty acids in human large intestine, portal, hepatic and venous blood[J]. Gut, 1987, 28( 10): 1221- 1227. DOI: 10.1136/gut.28.10.1221. [59] SIVAPRAKASAM S, BHUTIA YD, YANG SP, et al. Short-chain fatty acid transporters: Role in colonic homeostasis[J]. Compr Physiol, 2017, 8( 1): 299- 314. DOI: 10.1002/cphy.c170014. [60] FRANK DN, AMAND AL ST, FELDMAN RA, et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases[J]. Proc Natl Acad Sci U S A, 2007, 104( 34): 13780- 13785. DOI: 10.1073/pnas.0706625104. [61] MIRZAEI R, AFAGHI A, BABAKHANI S, et al. Role of microbiota-derived short-chain fatty acids in cancer development and prevention[J]. Biomed Pharmacother, 2021, 139: 111619. DOI: 10.1016/j.biopha.2021.111619. [62] MA JY, PIAO XS, MAHFUZ S, et al. The interaction among gut microbes, the intestinal barrier and short chain fatty acids[J]. Anim Nutr, 2021, 9: 159- 174. DOI: 10.1016/j.aninu.2021.09.012. [63] PARADA VENEGAS D, de la FUENTE MK, LANDSKRON G, et al. Short chain fatty acids(SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases[J]. Front Immunol, 2019, 10: 277. DOI: 10.3389/fimmu.2019.00277. [64] AGIRMAN G, YU KB, HSIAO EY. Signaling inflammation across the gut-brain axis[J]. Science, 2021, 374( 6571): 1087- 1092. DOI: 10.1126/science.abi6087. [65] ASHIQUE S, MOHANTO S, AHMED MG, et al. Gut-brain axis: A cutting-edge approach to target neurological disorders and potential synbiotic application[J]. Heliyon, 2024, 10( 13): e34092. DOI: 10.1016/j.heliyon.2024.e34092. [66] LIU JM, LI HJ, GONG TY, et al. Anti-neuroinflammatory effect of short-chain fatty acid acetate against Alzheimer’s disease via upregulating GPR41 and inhibiting ERK/JNK/NF-κB[J]. J Agric Food Chem, 2020, 68( 27): 7152- 7161. DOI: 10.1021/acs.jafc.0c02807. [67] CHEN RZ, XU Y, WU P, et al. Transplantation of fecal microbiota rich in short chain fatty acids and butyric acid treat cerebral ischemic stroke by regulating gut microbiota[J]. Pharmacol Res, 2019, 148: 104403. DOI: 10.1016/j.phrs.2019.104403. [68] ERNY D, HRABĚ DE ANGELIS AL, JAITIN D, et al. Host microbiota constantly control maturation and function of microglia in the CNS[J]. Nat Neurosci, 2015, 18( 7): 965- 977. DOI: 10.1038/nn.4030. [69] BRANISTE V, AL-ASMAKH M, KOWAL C, et al. The gut microbiota influences blood-brain barrier permeability in mice[J]. Sci Transl Med, 2014, 6( 263): 263ra158. DOI: 10.1126/scitranslmed.3009759. [70] WYSS MT, MAGISTRETTI PJ, BUCK A, et al. Labeled acetate as a marker of astrocytic metabolism[J]. J Cereb Blood Flow Metab, 2011, 31( 8): 1668- 1674. DOI: 10.1038/jcbfm.2011.84. [71] KOH A, de VADDER F, KOVATCHEVA-DATCHARY P, et al. From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites[J]. Cell, 2016, 165( 6): 1332- 1345. DOI: 10.1016/j.cell.2016.05.041. [72] PABST O, HORNEF MW, SCHAAP FG, et al. Gut-liver axis: Barriers and functional circuits[J]. Nat Rev Gastroenterol Hepatol, 2023, 20( 7): 447- 461. DOI: 10.1038/s41575-023-00771-6. [73] BLOOM PP, TAPPER EB, YOUNG VB, et al. Microbiome therapeutics for hepatic encephalopathy[J]. J Hepatol, 2021, 75( 6): 1452- 1464. DOI: 10.1016/j.jhep.2021.08.004. [74] BLOOM PP, LUÉVANO JM Jr, MILLER KJ, et al. Deep stool microbiome analysis in cirrhosis reveals an association between short-chain fatty acids and hepatic encephalopathy[J]. Ann Hepatol, 2021, 25: 100333. DOI: 10.1016/j.aohep.2021.100333. [75] WANG Q, CHEN CX, ZUO S, et al. Integrative analysis of the gut microbiota and faecal and serum short-chain fatty acids and tryptophan metabolites in patients with cirrhosis and hepatic encephalopathy[J]. J Transl Med, 2023, 21( 1): 395. DOI: 10.1186/s12967-023-04262-9. [76] BAJAJ JS. The role of microbiota in hepatic encephalopathy[J]. Gut Microbes, 2014, 5( 3): 397- 403. DOI: 10.4161/gmic.28684. [77] JUANOLA O, FERRUSQUÍA-ACOSTA J, GARCÍA-VILLALBA R, et al. Circulating levels of butyrate are inversely related to portal hypertension, endotoxemia, and systemic inflammation in patients with cirrhosis[J]. FASEB J, 2019, 33( 10): 11595- 11605. DOI: 10.1096/fj.201901327R. [78] ZHU RR, LIU LW, ZHANG GZ, et al. The pathogenesis of gut microbiota in hepatic encephalopathy by the gut-liver-brain axis[J]. Biosci Rep, 2023, 43( 6): BSR20222524. DOI: 10.1042/BSR20222524. -
本文二维码
图(1) / 表(1)
计量
- 文章访问数: 123
- HTML全文浏览量: 46
- PDF下载量: 11
- 被引次数: 0
