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中华临床医师杂志(电子版) ›› 2024, Vol. 18 ›› Issue (02) : 219 -222. doi: 10.3877/cma.j.issn.1674-0785.2024.02.018

综述

肠道菌群-胆汁酸代谢轴在慢性肾脏病中的研究进展
韦美菊1, 潘玲1,()   
  1. 1. 530021 南宁,广西医科大学第一附属医院肾内科
  • 收稿日期:2023-11-17 出版日期:2024-02-15
  • 通信作者: 潘玲
  • 基金资助:
    广西自然科学基金(2022GXNSFAA035458)

Role of gut microbiota-bile acid metabolism axis in chronic kidney disease

Meiju Wei1, Ling Pan1,()   

  1. 1. Department of Nephrology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
  • Received:2023-11-17 Published:2024-02-15
  • Corresponding author: Ling Pan
引用本文:

韦美菊, 潘玲. 肠道菌群-胆汁酸代谢轴在慢性肾脏病中的研究进展[J]. 中华临床医师杂志(电子版), 2024, 18(02): 219-222.

Meiju Wei, Ling Pan. Role of gut microbiota-bile acid metabolism axis in chronic kidney disease[J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(02): 219-222.

肠道菌群失衡是慢性肾脏病(CKD)的常见表现及重要发病机制,肠道菌群可调节胆汁酸代谢途径,肠道菌群失衡引起异常胆汁酸代谢物增多。另一方面,胆汁酸代谢也在胆汁酸受体的调节下影响肠道菌群组成及肠道免疫应答,肠道菌群-胆汁酸代谢的相互作用在CKD发生发展中发挥重要的作用。肠道微生态-胆汁酸代谢轴的平衡是CKD免疫稳态的保障。本文通过总结肠道菌群-胆汁酸代谢轴在CKD中的作用及机制等方面的国内外文献,对相关研究新进展进行综述。

Imbalance of the gut microbiota is an important factor in the pathogenesis of chronic kidney disease (CKD). On one hand, the gut microbiota can regulate the metabolism of bile acid. On the other hand, bile acid metabolism that is regulated by bile acid receptors also affects the composition of the gut microbiota and the immune response of the intestinal mucosa, thus playing an important role in the development of CKD. The balance of the gut microbiota-bile acid metabolism axis is beneficial for intestinal immune homeostasis in CKD. In this review, we discuss the role of the gut microbiota-bile acid metabolism axis in CKD.

图1 肠道菌群-胆汁酸代谢轴在CKD中的作用 注:CA为胆酸;CDCA为鹅去氧胆酸;DCA为去氧胆酸;FXR为法尼醇X受体;PXR为孕烷X受体;LCA为石胆酸;LPS为脂多糖;SCFAS为短链脂肪酸;VDR为维生素D受体
1
Wang X, Yang S, Li S, et al. Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents[J]. Gut, 2020, 69(12): 2131-2142.
2
Rukavina Mikusic NL, Kouyoumdzia NM, Choi MR. Gut microbiota and chronic kidney disease: evidences and mechanisms that mediate a new communication in the gastrointestinal-renal axis[J]. Pflugers Arch, 2020, 472(3): 303-320.
3
Kuipers F, de Boer JF, Staels B. Microbiome modulation of the host adaptive immunity through bile acid modification[J]. Cell Metab, 2020, 31(3): 445-447.
4
Cai J, Rimal B, Jiang C, et al. Bile acid metabolism and signaling, the microbiota, and metabolic disease[J]. Pharmacol Ther, 2022, 237: 108238.
5
Luxenburger A, Harris LD, Ure EM, et al. The discovery of 12beta-methyl-17-epi-18-nor-bile acids as potent and selective TGR5 agonists[J]. Eur J Med Chem, 2023, 250: 115143.
6
Ticho AL, Malhotra P, Dudeja PK, et al. Bile acid receptors and gastrointestinal functions[J]. Liver Res, 2019, 3(1): 31-39.
7
姚柏宇, 田忠. 胆汁酸及其相关核受体对肠黏膜屏障的影响[J]. 中华肝胆外科杂志, 2020, 26(02): 158-160.
8
Tiratterra E, Franco P, Porru E, et al. Role of bile acids in inflammatory bowel disease[J]. Ann Gastroenterol, 2018, 31(3): 266-272.
9
牛鹏飞, 王延召, 曾庆敏, 等. 肠黏膜屏障功能及损伤机制研究进展[J/OL]. 中华临床医师杂志(电子版), 2020, 14(9): 735-739.
10
Fiorucci S, Distrutti E, Carino A, et al. Bile acids and their receptors in metabolic disorders[J]. Prog Lipid Res, 2021, 82: 101094.
11
Bakke D, Sun J. Ancient nuclear receptor VDR with new functions: microbiome and inflammation[J]. Inflamm Bowel Dis, 2018, 24(6): 1149-1154.
12
Fiorucci S, Carino A, Baldoni M, et al. Bile acid signaling in inflammatory bowel diseases[J]. Dig Dis Sci, 2021, 66(3): 674-693.
13
Yang S, Li A, Wang J, et al. Vitamin D receptor: A novel therapeutic target for kidney diseases[J]. Curr Med Chem, 2018, 25(27): 3256-3271.
14
李舒, 刘文奇, 傅鹂婕, 等. 溃疡性结肠炎肠道微生物的研究进展[J/OL]. 中华临床医师杂志(电子版), 2015, 9(4): 674-677.
15
饶翀, 肖新华. 肠道菌群和脂代谢异常[J/OL]. 中华临床医师杂志(电子版), 2016, 10(8): 1053-1055.
16
Mertowska P, Mertowski S, Wojnicka J, et al. A link between chronic kidney disease and gut microbiota in immunological and nutritional aspects[J]. Nutrients, 2021, 13(10): 3637.
17
Krukowski H, Valkenburg S, Madella A-M, et al. Gut microbiome studies in CKD: opportunities, pitfalls and therapeutic potential[J]. Nature Reviews Nephrology, 2022, 19(2): 87-101.
18
Lohia S, Vlahou A, Zoidakis J. Microbiome in chronic kidney disease (CKD): An omics perspective[J]. Toxins (Basel), 2022, 14(3): 176.
19
Wang F, Li N, Ni S, et al. The effects of specific gut microbiota and metabolites on IgA nephropathy-based on mendelian randomization and clinical validation[J]. Nutrients, 2023, 15(10).
20
He JW, Zhou XJ, Lv JC, et al. Perspectives on how mucosal immune responses, infections and gut microbiome shape IgA nephropathy and future therapies[J]. Theranostics, 2020, 10(25): 11462-11478.
21
Coppo R. The gut-renal connection in IgA nephropathy[J]. Semin Nephrol, 2018, 38(5): 504-512.
22
Gesualdo L, Di Leo V, Coppo R. The mucosal immune system and IgA nephropathy[J]. Semin Immunopathol, 2021, 43(5): 657-668.
23
Chemouny JM, Gleeson PJ, Abbad L, et al. Modulation of the microbiota by oral antibiotics treats immunoglobulin A nephropathy in humanized mice[J]. Nephrol Dial Transplant, 2019, 34(7): 1135-1144.
24
Sallustio F, Curci C, Chaoul N, et al. High levels of gut-homing immunoglobulin A+ B lymphocytes support the pathogenic role of intestinal mucosal hyperresponsiveness in immunoglobulin A nephropathy patients[J]. Nephrology Dialysis Transplantation, 2021, 36(3): 452-464.
25
Wei H, Wang L, An Z, et al. QiDiTangShen granules modulated the gut microbiome composition and improved bile acid profiles in a mouse model of diabetic nephropathy[J]. Biomedicine & Pharmacotherapy, 2021, 133: 111061.
26
朱艺平, 陈一平, 赵艳英, 等. 二十味沉香丸调控糖尿病肾病大鼠肠道菌群益生菌构成的机制研究[J/OL]. 中华临床医师杂志(电子版), 2022, 16(6): 572-578.
27
张大涯, 陈世锔, 陈润祥, 等. 肠道微生物群对代谢相关脂肪性肝病发展的影响[J/OL]. 中华临床医师杂志(电子版), 2023, 17(7): 828-833.
28
Li X, Wang L, Ma S, et al. Combination of oxalobacter formigenes and veillonella parvula in gastrointestinal microbiota related to bile-acid metabolism as a biomarker for hypertensive nephropathy[J]. Int J Hypertens, 2022, 2022: 5999530.
29
Chen TH, Cheng CY, Huang CK, et al. Exploring the relevance between gut microbiota-metabolites profile and chronic kidney disease with distinct pathogenic factor[J]. Microbiol Spectr, 2023, 11(1): e0280522.
30
Guan Y, Chen K, Quan D, et al. The combination of scutellaria baicalensis Georgi and Sophora japonica L. ameliorate renal function by regulating gut microbiota in spontaneously hypertensive rats[J]. Front Pharmacol, 2021, 11: 575294.
31
Li T, Chiang JY. Nuclear receptors in bile acid metabolism[J]. Drug Metab Rev, 2013, 45(1): 145-155.
32
邱宇翔, 亢宁苏, 郑露, 等. 胆汁酸核受体与肾脏疾病的研究进展[J]. 国际泌尿系统杂志, 2021, 41(1): 180-182.
33
Hu H, Shao W, Liu Q, et al. Gut microbiota promotes cholesterol gallstone formation by modulating bile acid composition and biliary cholesterol secretion[J]. Nat Commun, 2022, 13(1): 252.
34
Mori H, Svegliati Baroni G, et al. Farnesoid X receptor, bile acid metabolism, and gut microbiota[J]. Metabolites, 2022, 12(7): 647.
35
Liu Y, Kang W, Liu S, et al. Gut microbiota-bile acid-intestinal Farnesoid X receptor signaling axis orchestrates cadmium-induced liver injury[J]. Sci Total Environ, 2022, 849: 157861.
36
Liu Y, Chen K, Li F, et al. Probiotic lactobacillus rhamnosus GG prevents liver fibrosis through inhibiting hepatic bile acid synthesis and enhancing bile acid excretion in mice[J]. Hepatology, 2020, 71(6): 2050-2066.
37
Schneider KM, Candels LS, Hov JR, et al. Gut microbiota depletion exacerbates cholestatic liver injury via loss of FXR signalling[J]. Nat Metab, 2021, 3(9): 1228-1241.
38
Ratziu V, Harrison SA, Loustaud-Ratti V, et al. Hepatic and renal improvements with FXR agonist vonafexor in individuals with suspected fibrotic NASH[J]. J Hepatol, 2023, 78(3): 479-492.
39
Wei H, Wang L, An Z, et al. QiDiTangShen granules modulated the gut microbiome composition and improved bile acid pro fi les in a mouse model of diabetic nephropathy[J]. Biomed Pharmacother, 2021, 133: 111061.
40
Chatterjee I, Lu R, Zhang Y, et al. Vitamin D receptor promotes healthy microbial metabolites and microbiome[J]. Sci Rep, 2020, 10(1): 7340.
41
Lu R, Zhang YG, Xia Y, et al. Paneth cell alertness to pathogens maintained by vitamin D receptors[J]. Gastroenterology, 2021, 160(4): 1269-1283.
42
Zhang YG, Lu R, Wu S, et al. Vitamin D receptor protects against dysbiosis and tumorigenesis via the JAK/STAT pathway in intestine[J]. Cell Mol Gastroenterol Hepatol, 2020, 10(4): 729-746.
43
Wang F, Hu R, Zhang J, et al. High-dose vitamin D3 supplementation ameliorates renal fibrosis by vitamin D receptor activation and inhibiting TGF-beta1/Smad3 signaling pathway in 5/6 nephrectomized rats[J]. Eur J Pharmacol, 2021, 907: 174271.
44
Li A, Yi B, Han H, et al. Vitamin D-VDR (vitamin D receptor) regulates defective autophagy in renal tubular epithelial cell in streptozotocin-induced diabetic mice via the AMPK pathway[J]. Autophagy, 2022, 18(4): 877-890.
45
Martínez-Arias L, Panizo S, Alonso-Montes C, et al. Effects of calcitriol and paricalcitol on renal fibrosis in CKD[J]. Nephrol Dial Transplant, 2021, 36(5): 793-803.
46
Li X, Fan QL, Ma TK, et al. MYCT1 attenuates renal fibrosis and tubular injury in diabetic kidney disease[J]. iScience, 2023, 26(9): 107609.
47
Lv Y, Luo YY, Ren HW, et al. The role of pregnane X receptor (PXR) in substance metabolism[J]. Front Endocrinol (Lausanne), 2022, 13: 959902.
48
窦景云, 古月瑜, 刘旭生. 孕烷X受体在肾脏疾病中的研究进展[J]. 中国现代应用药学, 2022, 39(11): 1503-1508.
49
Oladimeji PO, Chen T. PXR: More than just a master xenobiotic receptor[J]. Mol Pharmacol, 2018, 93(2): 119-127.
50
Watanabe A, Marumo T, Kawarazaki W, et al. Berrant DNA methylation of pregnane X receptor underlies metabolic gene alterations in the diabetic kidney[J]. Am J Physiol Renal Physiol, 2018, 314(4): F551-F560.
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