Interaction between bile acids and gut microbiota and their role in Parkinson disease

doi:10.16138/j.1673-6087.2025.04.16

Abstract

Abstract:

Bile acids are amphipathic molecules derived from cholesterol, which facilitate the absorption of lipids, and also serve as signaling molecules in regulating metabolic homeostasis and immune response. Bile acid is modified by intestinal flora, and on the other hand, it alters the composition of gut microbiota and exerts potential effects on the microbiota-gut-brain axis(MGBA). Through this bidirectional communication system, bile acid signaling homeostasis plays a modulatory role for maintaining the physiological function of nervous system. In recent years, increasing evidence indicates that the bile acid associated with dysbiosis in gut microbiota may be an early sign of Parkinson disease (PD), which triggered the exploration of new pathological mechanisms and diagnostic biomarkers for PD. This article reviews the relationship between abnormal bile acid metabolism and PD as well as its potential role in PD treatment from the perspective of interaction between bile acids and intestinal microorganism.

Key words: Bile acids, Gut microbiota, Parkinson disease

CLC Number:

R742.5

LIU Shumeng, AI Penghui, XIAO Qin, YANG Xiaodong. Interaction between bile acids and gut microbiota and their role in Parkinson disease[J]. Journal of Internal Medicine Concepts & Practice, 2025, 20(04): 345-350.

References 42

[1]	Li G, Ma J, Cui S, et al. Parkinson’s disease in China: a forty-year growing track of bedside work[J]. Transl Neurodegener, 2019, 8:22.
[2]	Morris HR, Spillantini MG, Sue CM, et al. The pathogenesis of Parkinson’s disease[J]. Lancet, 2024, 403(10423):293-304. doi: 10.1016/S0140-6736(23)01478-2 pmid: 38245249
[3]	Chiang JYL, Ferrell JM. Bile acids as metabolic regulators and nutrient sensors[J]. Annu Rev Nutr, 2019, 39:175-200. doi: 10.1146/annurev-nutr-082018-124344 pmid: 31018107
[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]	Hurley MJ, Bates R, Macnaughtan J, et al. Bile acids and neurological disease[J]. Pharmacol Ther, 2022, 240:108311.
[6]	Ridlon JM, Harris SC, Bhowmik S, et al. Consequences of bile salt biotransformations by intestinal bacteria[J]. Gut Microbes, 2016, 7(1):22-39. doi: 10.1080/19490976.2015.1127483 pmid: 26939849
[7]	Guzior DV, Quinn RA. Review: Microbial transformations of human bile acids[J]. Microbiome, 2021, 9(1):140. doi: 10.1186/s40168-021-01101-1 pmid: 34127070
[8]	Plass JR, Mol O, Heegsma J, et al. Farnesoid X receptor and bile salts are involved in transcriptional regulation of the gene encoding the human bile salt export pump[J]. Hepatology, 2002, 35(3):589-596. doi: 10.1053/jhep.2002.31724 pmid: 11870371
[9]	Song KH, Li T, Owsley E, et al. Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene expression[J]. Hepatology, 2009, 49(1):297-305.
[10]	Neimark E, Chen F, Li X, et al. Bile acid-induced negative feedback regulation of the human ileal bile acid transporter[J]. Hepatology, 2004, 40(1):149-156. doi: 10.1002/hep.20295 pmid: 15239098
[11]	Sorrentino G, Perino A, Yildiz E, et al. Bile acids signal via TGR5 to activate intestinal stem cells and epithelial regeneration[J]. Gastroenterology, 2020, 159(3):956-968. doi: S0016-5085(20)34739-9 pmid: 32485177
[12]	Liu L, Dong W, Wang S, et al. Deoxycholic acid disrupts the intestinal mucosal barrier and promotes intestinal tumorigenesis[J]. Food Funct, 2018, 9(11):5588-5597. doi: 10.1039/c8fo01143e pmid: 30339173
[13]	Wahlström A, Sayin SI, Marschall HU, et al. Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism[J]. Cell Metab, 2016, 24(1):41-50. doi: 10.1016/j.cmet.2016.05.005 pmid: 27320064
[14]	Monteiro-Cardoso VF, Corliano M, Singaraja RR. Bile acids: a communication channel in the gut-brain axis[J]. Neuromolecular Med, 2021, 23(1):99-117.
[15]	Inagaki T, Moschetta A, Lee YK, et al. Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor[J]. Proc Natl Acad Sci U S A, 2006, 103(10):3920-3925.
[16]	Heintz-Buschart A, Pandey U, Wicke T, et al. The nasal and gut microbiome in Parkinson’s disease and idiopathic rapid eye movement sleep behavior disorder[J]. Mov Disord, 2018, 33(1):88-98.
[17]	Li Z, Liang H, Hu Y, et al. Gut bacterial profiles in Parkinson’s disease: a systematic review[J]. CNS Neurosci Ther, 2023, 29(1):140-157.
[18]	陈施吾, 王刚. 帕金森病与肠道菌群关系的研究进展[J]. 内科理论与实践, 2018, 13(5):316-319.
	Chen SW, Wang G. Advances in research on relationship between Parkinson’s disease and gut microbiota[J]. J Intern Med Concepts Pract, 2018, 13(5):316-319.
[19]	Li P, Killinger BA, Ensink E, et al. Gut microbiota dysbiosis is associated with elevated bile acids in Parkinson’s disease[J]. Metabolites, 2021, 11(1):29.
[20]	Kalecky K, Bottiglieri T. Targeted metabolomic analysis in Parkinson’s disease brain frontal cortex and putamen with relation to cognitive impairment[J]. NPJ Parkinsons Dis, 2023, 9(1):84.
[21]	Shao Y, Li T, Liu Z, et al. Comprehensive metabolic profiling of Parkinson’s disease by liquid chromatography-mass spectrometry[J]. Mol Neurodegener, 2021, 16(1):4.
[22]	Hertel J, Harms AC, Heinken A, et al. Integrated analyses of microbiome and longitudinal metabolome data reveal microbial-host interactions on sulfur metabolism in Parkinson’s disease[J]. Cell Rep, 2019, 29(7):1767-1777.
[23]	Nie K, Li Y, Zhang J, et al. Distinct bile acid signature in Parkinson’s disease with mild cognitive impairment[J]. Front Neurol, 2022, 13:897867.
[24]	Graham SF, Rey NL, Ugur Z, et al. Metabolomic profiling of bile acids in an experimental model of prodromal Parkinson’s disease[J]. Metabolites, 2018, 8(4):71.
[25]	Li Y, Glotfelty EJ, Karlsson T, et al. The metabolite GLP-1 (9-36) is neuroprotective and anti-inflammatory in cellular models of neurodegeneration[J]. J Neurochem, 2021, 159(5):867-886. doi: 10.1111/jnc.15521 pmid: 34569615
[26]	Reich N, Holscher C. The neuroprotective effects of glucagon-like peptide 1 in Alzheimer’s and Parkinson’s disease[J]. Front Neurosci, 2022, 16:970925.
[27]	Huang F, Wang T, Lan Y, et al. Deletion of mouse FXR gene disturbs multiple neurotransmitter systems and alters neurobehavior[J]. Front Behav Neurosci, 2015, 9:70. doi: 10.3389/fnbeh.2015.00070 pmid: 25870546
[28]	Isik S, Yeman Kiyak B, Akbayir R, et al. Microglia mediated neuroinflammation in Parkinson’s disease[J]. Cells, 2023, 12(7):1012.
[29]	Pan RY, He L, Zhang J, et al. Positive feedback regulation of microglial glucose metabolism by histone H4 lysine 12 lactylation in Alzheimer’s disease[J]. Cell Metab, 2022, 34(4):634-648.
[30]	Romero-Ramirez L, Garcia-Rama C, Wu S, et al. Author correction: bile acids attenuate PKM2 pathway activation in proinflammatory microglia[J]. Sci Rep, 2022, 12(1):3399. doi: 10.1038/s41598-022-07497-6 pmid: 35197537
[31]	Kustrimovic N, Comi C, Magistrelli L, et al. Parkinson’s disease patients have a complex phenotypic and functional Th1 bias: Cross-sectional studies of CD4+ Th1/Th2/T17 and Treg in drug-naive and drug-treated patients[J]. J Neuroinflammation, 2018, 15(1):205.
[32]	Hang S, Paik D, Yao L, et al. Bile acid metabolites control T(H)17 and T(reg) cell differentiation[J]. Nature, 2019, 576(7785):143-148.
[33]	Wang L, Gong Z, Zhang X, et al. Gut microbial bile acid metabolite skews macrophage polarization and contributes to high-fat diet-induced colonic inflammation[J]. Gut Microbes, 2020, 12(1):1-20. doi: 10.1080/19490976.2020.1819155 pmid: 33006494
[34]	Chen C, Turnbull DM, Reeve AK. Mitochondrial dysfunction in Parkinson’s disease-cause or consequence?[J]. Biology (Basel), 2019, 8(2):38.
[35]	Huang F, Pariante CM, Borsini A. From dried bear bile to molecular investigation: a systematic review of the effect of bile acids on cell apoptosis, oxidative stress and inflammation in the brain, across pre-clinical models of neurological, neurodegenerative and neuropsychiatric disorders[J]. Brain Behav Immun, 2022, 99:132-146.
[36]	Rosa AI, Fonseca I, Nunes MJ, et al. Novel insights into the antioxidant role of tauroursodeoxycholic acid in experimental models of Parkinson’s disease[J]. Biochim Biophys Acta Mol Basis Dis, 2017, 1863(9):2171-2181.
[37]	Rosa AI, Duarte-Silva S, Silva-Fernandes A, et al. Tauroursodeoxycholic acid improves motor symptoms in a mouse model of Parkinson’s disease[J]. Mol Neurobiol, 2018, 55(12):9139-9155.
[38]	Khalaf K, Tornese P, Cocco A, et al. Tauroursodeoxycholic acid: a potential therapeutic tool in neurodegenerative diseases[J]. Transl Neurodegener, 2022, 11(1):33. doi: 10.1186/s40035-022-00307-z pmid: 35659112
[39]	Sathe AG, Tuite P, Chen C, et al. Pharmacokinetics, safety, and tolerability of orally administered ursodeoxycholic acid in patients with Parkinson’s disease-a pilot study[J]. J Clin Pharmacol, 2020, 60(6):744-750.
[40]	Payne T, Appleby M, Buckley E, et al. A double-blind, randomized, placebo-controlled trial of ursodeoxycholic acid (UDCA) in Parkinson’s disease[J]. Mov Disord, 2023, 38(8):1493-1502.
[41]	Wang K, Liao M, Zhou N, et al. Parabacteroides distasonis alleviates obesity and metabolic dysfunctions via production of succinate and secondary bile acids[J]. Cell Rep, 2019, 26(1):222-235.e5. doi: S2211-1247(18)31958-2 pmid: 30605678
[42]	Ahmed S, Busetti A, Fotiadou P, et al. In vitro characterization of gut microbiota-derived bacterial strains with neuroprotective properties[J]. Front Cell Neurosci, 2019, 13:402. doi: 10.3389/fncel.2019.00402 pmid: 31619962