{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:43:26Z","timestamp":1792172606399,"version":"4.4.0"},"reference-count":67,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T00:00:00Z","timestamp":1609718400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Farmer Family Foundation"},{"DOI":"10.13039\/100000005","name":"Department of Defense","doi-asserted-by":"publisher","award":["W81XWH1810512"],"award-info":[{"award-number":["W81XWH1810512"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1R21NS112614-01"],"award-info":[{"award-number":["1R21NS112614-01"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1R01NS113894-01A1"],"award-info":[{"award-number":["1R01NS113894-01A1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1R01NS114409-01A1"],"award-info":[{"award-number":["1R01NS114409-01A1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["1R01NS110838-01A1"],"award-info":[{"award-number":["1R01NS110838-01A1"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Gibby &amp; Friends vs. Parky Award"},{"name":"National Institutes on Aging","award":["1R21AG067083-01"],"award-info":[{"award-number":["1R21AG067083-01"]}]},{"name":"Alzheimer\u2019s Association","award":["AARG-17-530020"],"award-info":[{"award-number":["AARG-17-530020"]}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation","doi-asserted-by":"publisher","award":["MJFF16201"],"award-info":[{"award-number":["MJFF16201"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>The gut microbiome can impact brain health and is altered in Parkinson\u2019s disease (PD). The vermiform appendix is a lymphoid tissue in the cecum implicated in the storage and regulation of the gut microbiota. We sought to determine whether the appendix microbiome is altered in PD and to analyze the biological consequences of the microbial alterations. We investigated the changes in the functional microbiota in the appendix of PD patients relative to controls (n = 12 PD, 16 C) by metatranscriptomic analysis. We found microbial dysbiosis affecting lipid metabolism, including an upregulation of bacteria responsible for secondary bile acid synthesis. We then quantitatively measure changes in bile acid abundance in PD relative to the controls in the appendix (n = 15 PD, 12 C) and ileum (n = 20 PD, 20 C). Bile acid analysis in the PD appendix reveals an increase in hydrophobic and secondary bile acids, deoxycholic acid (DCA) and lithocholic acid (LCA). Further proteomic and transcriptomic analysis in the appendix and ileum corroborated these findings, highlighting changes in the PD gut that are consistent with a disruption in bile acid control, including alterations in mediators of cholesterol homeostasis and lipid metabolism. Microbially derived toxic bile acids are heightened in PD, which suggests biliary abnormalities may play a role in PD pathogenesis.<\/jats:p>","DOI":"10.3390\/metabo11010029","type":"journal-article","created":{"date-parts":[[2021,1,4]],"date-time":"2021-01-04T08:35:19Z","timestamp":1609749319000},"page":"29","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":141,"title":["Gut Microbiota Dysbiosis Is Associated with Elevated Bile Acids in Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"11","author":[{"given":"Peipei","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan A.","family":"Killinger","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA"},{"name":"Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7309-9943","authenticated-orcid":false,"given":"Elizabeth","family":"Ensink","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Beddows","sequence":"additional","affiliation":[{"name":"Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Metabolomics Department, Beaumont Health, Royal Oak, MI 48073, USA"},{"name":"Department of Obstetrics and Gynecology, Oakland University-William Beaumont School Medicine, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Lubben","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7187-7657","authenticated-orcid":false,"given":"Jared","family":"Lamp","sequence":"additional","affiliation":[{"name":"Integrated Mass Spectrometry Unit, Department of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Schilthuis","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irving E.","family":"Vega","sequence":"additional","affiliation":[{"name":"Integrated Mass Spectrometry Unit, Department of Translational Neuroscience, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy","family":"Woltjer","sequence":"additional","affiliation":[{"name":"Department of Pathology, Oregon Health &amp; Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Andrew","family":"Pospisilik","sequence":"additional","affiliation":[{"name":"Department of Epigenetics, Van Andel Institute, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Brundin","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA"},{"name":"Division of Psychiatry and Behavioral Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Brundin","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA"},{"name":"Division of Psychiatry and Behavioral Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1001-0002","authenticated-orcid":false,"given":"Stewart F.","family":"Graham","sequence":"additional","affiliation":[{"name":"Metabolomics Department, Beaumont Health, Royal Oak, MI 48073, USA"},{"name":"Department of Obstetrics and Gynecology, Oakland University-William Beaumont School Medicine, Rochester, MI 48309, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviane","family":"Labrie","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI 49503, USA"},{"name":"Division of Psychiatry and Behavioral Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/S1474-4422(16)30230-7","article-title":"The epidemiology of Parkinson\u2019s disease: Risk factors and prevention","volume":"15","author":"Ascherio","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","article-title":"Parkinson\u2019s disease","volume":"386","author":"Kalia","year":"2015","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1002\/ana.24648","article-title":"Pathological \u03b1-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients","volume":"79","author":"Stokholm","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/s00401-013-1214-6","article-title":"Accumulation of \u03b1-synuclein in the bowel of patients in the pre-clinical phase of Parkinson\u2019s disease","volume":"127","author":"Hilton","year":"2014","journal-title":"Acta Neuropathol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.neuron.2019.05.035","article-title":"Transneuronal Propagation of Pathologic \u03b1-Synuclein from the Gut to the Brain Models Parkinson\u2019s Disease","volume":"103","author":"Kim","year":"2019","journal-title":"Neuron"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s00401-019-02040-w","article-title":"Evidence for bidirectional and trans-synaptic parasympathetic and sympathetic propagation of alpha-synuclein in rats","volume":"138","author":"Ferreira","year":"2019","journal-title":"Acta Neuropathol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Killinger, B.A., Madaj, Z., Sikora, J.W., Rey, N., Haas, A.J., Vepa, Y., Lindqvist, D., Chen, H., Thomas, P.M., and Brundin, P. (2018). The vermiform appendix impacts the risk of developing Parkinson\u2019s disease. Sci. Transl. Med., 10.","DOI":"10.1126\/scitranslmed.aar5280"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1002\/mds.26670","article-title":"Appendectomy in mid and later life and risk of Parkinson\u2019s disease: A population-based study","volume":"31","author":"Marras","year":"2016","journal-title":"Mov. Disord."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"510","DOI":"10.3389\/fneur.2020.00510","article-title":"Appendectomy, Tonsillectomy and Parkinson\u2019s Disease Risk: A Swedish Register-Based Study","volume":"11","author":"Liu","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1038\/nrmicro3552","article-title":"Gut biogeography of the bacterial microbiota","volume":"14","author":"Donaldson","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S345","DOI":"10.3233\/JPD-191703","article-title":"The Appendix in Parkinson\u2019s Disease: From Vestigial Remnant to Vital Organ?","volume":"9","author":"Killinger","year":"2019","journal-title":"J. Parkinson\u2019s Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nn.4476","article-title":"Interactions between the microbiota, immune and nervous systems in health and disease","volume":"20","author":"Fung","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/mds.26069","article-title":"Gut microbiota are related to Parkinson\u2019s disease and clinical phenotype","volume":"30","author":"Scheperjans","year":"2015","journal-title":"Mov. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13073-017-0428-y","article-title":"Functional implications of microbial and viral gut metagenome changes in early stage L-DOPA-na\u00efve Parkinson\u2019s disease patients","volume":"9","author":"Bedarf","year":"2017","journal-title":"Genome Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1136\/gutjnl-2018-316844","article-title":"Role of TLR4 in the gut-brain axis in Parkinson\u2019s disease: A translational study from men to mice","volume":"68","author":"Dodiya","year":"2019","journal-title":"Gut"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1002\/ana.25788","article-title":"Gut Microbiome Signatures of Risk and Prodromal Markers of Parkinson Disease","volume":"88","author":"Heinzel","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Jackson, H.T., Mongodin, E.F., Davenport, K.P., Fraser, C.M., Sandler, A.D., and Zeichner, S.L. (2014). Culture-independent evaluation of the appendix and rectum microbiomes in children with and without appendicitis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0095414"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.tim.2018.08.009","article-title":"Bowel Biofilms: Tipping Points between a Healthy and Compromised Gut?","volume":"27","author":"Tytgat","year":"2019","journal-title":"Trends Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3704","DOI":"10.1038\/ncomms4704","article-title":"Generation of colonic IgA-secreting cells in the caecal patch","volume":"5","author":"Masahata","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Sanchez-Alcoholado, L., Fernandez-Garcia, J.C., Gutierrez-Repiso, C., Bernal-Lopez, M.R., Ocana-Wilhelmi, L., Garcia-Fuentes, E., Moreno-Indias, I., and Tinahones, F.J. (2020). Incidental Prophylactic Appendectomy Is Associated with a Profound Microbial Dysbiosis in the Long-Term. Microorganisms, 8.","DOI":"10.3390\/microorganisms8040609"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.tins.2018.09.007","article-title":"Triggers, Facilitators, and Aggravators: Redefining Parkinson\u2019s Disease Pathogenesis","volume":"42","author":"Johnson","year":"2019","journal-title":"Trends Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"S359","DOI":"10.3233\/JPD-191780","article-title":"Bacterial Metabolites Mirror Altered Gut Microbiota Composition in Patients with Parkinson\u2019s Disease","volume":"9","year":"2019","journal-title":"J. Parkinsons Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.immuni.2018.12.018","article-title":"The Short Chain Fatty Acid Butyrate Imprints an Antimicrobial Program in Macrophages","volume":"50","author":"Schulthess","year":"2019","journal-title":"Immunity"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.immuni.2019.06.002","article-title":"Microbiota-Derived Short-Chain Fatty Acids Promote the Memory Potential of Antigen-Activated CD8(+) T Cells","volume":"51","author":"Bachem","year":"2019","journal-title":"Immunity"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.immuni.2019.09.014","article-title":"Metabolite-Sensing Receptor Ffar2 Regulates Colonic Group 3 Innate Lymphoid Cells and Gut Immunity","volume":"51","author":"Chun","year":"2019","journal-title":"Immunity"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cmet.2016.05.005","article-title":"Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism","volume":"24","author":"Sayin","year":"2016","journal-title":"Cell Metabolism."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1983","DOI":"10.1152\/physrev.00054.2017","article-title":"Guts and Gall: Bile Acids in Regulation of Intestinal Epithelial Function in Health and Disease","volume":"98","author":"Hegyi","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3658","DOI":"10.1096\/fj.201600275R","article-title":"Effects of bile acids on neurological function and disease","volume":"30","author":"McMillin","year":"2016","journal-title":"FASEB J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/s41385-019-0162-4","article-title":"Emerging roles of bile acids in mucosal immunity and inflammation","volume":"12","author":"Chen","year":"2019","journal-title":"Mucosal Immunol"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1111\/apt.13333","article-title":"Systematic review: Bile acids and intestinal inflammation-luminal aggressors or regulators of mucosal defence?","volume":"42","author":"Pavlidis","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0016-5085(94)95519-0","article-title":"Pathogenic factors in early recurrence of cholesterol gallstones","volume":"106","author":"Berr","year":"1994","journal-title":"Gastroenterology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41586-019-1785-z","article-title":"Bile acid metabolites control TH17 and Treg cell differentiation","volume":"576","author":"Hang","year":"2019","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/s41586-019-1865-0","article-title":"Microbial bile acid metabolites modulate gut ROR\u03b3+ regulatory T cell homeostasis","volume":"577","author":"Song","year":"2020","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/bioinformatics\/btr709","article-title":"Robust rank aggregation for gene list integration and meta-analysis","volume":"28","author":"Kolde","year":"2012","journal-title":"Bioinformatics"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/s41531-019-0100-x","article-title":"Effect of Parkinson\u2019s disease and related medications on the composition of the fecal bacterial microbiota","volume":"5","author":"Weis","year":"2019","journal-title":"NPJ Parkinson\u2019s Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1053\/j.gastro.2012.09.055","article-title":"The receptor TGR5 mediates the prokinetic actions of intestinal bile acids and is required for normal defecation in mice","volume":"144","author":"Alemi","year":"2013","journal-title":"Gastroenterology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1111\/apt.15950","article-title":"The benefit of elobixibat in chronic constipation is associated with faecal deoxycholic acid but not effects of altered microbiota","volume":"52","author":"Misawa","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/s41598-017-00612-y","article-title":"Potential role of fecal microbiota from patients with slow transit constipation in the regulation of gastrointestinal motility","volume":"7","author":"Ge","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1038\/nn.4030","article-title":"Host microbiota constantly control maturation and function of microglia in the CNS","volume":"18","author":"Erny","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/j.cell.2016.11.018","article-title":"Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson\u2019s Disease","volume":"167","author":"Sampson","year":"2016","journal-title":"Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.tim.2006.04.006","article-title":"Burkholderia cepacia complex species: Health hazards and biotechnological potential","volume":"14","author":"Chiarini","year":"2006","journal-title":"Trends Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.3389\/fnins.2019.01365","article-title":"Tryptophan Metabolism by Gut Microbiome and Gut-Brain-Axis: An in silico Analysis","volume":"13","author":"Kaur","year":"2019","journal-title":"Front. Neurosci"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1002\/mds.28202","article-title":"Tryptophan Metabolites Are Associated With Symptoms and Nigral Pathology in Parkinson\u2019s Disease","volume":"35","author":"Heilman","year":"2020","journal-title":"Mov. Disord."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"13632","DOI":"10.1038\/s41598-018-31778-8","article-title":"Burkholderia pseudomallei-loaded cells act as a Trojan horse to invade the brain during endotoxemia","volume":"8","author":"Hsueh","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2681","DOI":"10.1128\/IAI.00361-16","article-title":"Burkholderia pseudomallei Rapidly Infects the Brain Stem and Spinal Cord via the Trigeminal Nerve after Intranasal Inoculation","volume":"84","author":"Walkden","year":"2016","journal-title":"Infect. Immun."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Wallner, A., King, E., Ngonkeu, E.L.M., Moulin, L., and B\u00e9na, G. (2019). Genomic analyses of Burkholderia cenocepacia reveal multiple species with differential host-adaptation to plants and humans. BMC Genom., 20.","DOI":"10.1186\/s12864-019-6186-z"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s12017-019-08539-5","article-title":"Chronic Mild Gut Inflammation Accelerates Brain Neuropathology and Motor Dysfunction in \u03b1-Synuclein Mutant Mice","volume":"21","author":"Kishimoto","year":"2019","journal-title":"Neuromolecular. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1159\/000477990","article-title":"A Role for Neuronal Alpha-Synuclein in Gastrointestinal Immunity","volume":"9","author":"Stolzenberg","year":"2017","journal-title":"J. Innate Immun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7063","DOI":"10.1039\/C9FO01334B","article-title":"Effects of theabrownin on serum metabolites and gut microbiome in rats with a high-sugar diet","volume":"10","author":"Yue","year":"2019","journal-title":"Food Funct."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"6142","DOI":"10.2174\/1381612822666160906161513","article-title":"Gut Permeability and Microbiota in Parkinson\u2019s Disease: Role of Depression, Tryptophan Catabolites, Oxidative and Nitrosative Stress and Melatonergic Pathways","volume":"22","author":"Anderson","year":"2016","journal-title":"Curr. Pharm. Des."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1136\/gutjnl-2012-302578","article-title":"Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases","volume":"62","author":"Duboc","year":"2013","journal-title":"Gut"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.immuni.2016.09.008","article-title":"Bile Acids Control Inflammation and Metabolic Disorder through Inhibition of NLRP3 Inflammasome","volume":"45","author":"Guo","year":"2016","journal-title":"Immunity"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Ma, C., Han, M., Heinrich, B., Fu, Q., Zhang, Q., Sandhu, M., Agdashian, D., Terabe, M., Berzofsky, J.A., and Fako, V. (2018). Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science, 360.","DOI":"10.1126\/science.aan5931"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Praslickova, D., Torchia, E.C., Sugiyama, M.G., Magrane, E.J., Zwicker, B.L., Kolodzieyski, L., and Agellon, L.B. (2012). The ileal lipid binding protein is required for efficient absorption and transport of bile acids in the distal portion of the murine small intestine. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050810"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1136\/gutjnl-2018-317842","article-title":"Microbial bile salt hydrolases mediate the efficacy of faecal microbiota transplant in the treatment of recurrent Clostridioides difficile infection","volume":"68","author":"Mullish","year":"2019","journal-title":"Gut"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1007\/BF03401914","article-title":"Ursodeoxycholic acid may inhibit deoxycholic acid-induced apoptosis by modulating mitochondrial transmembrane potential and reactive oxygen species production","volume":"4","author":"Rodrigues","year":"1998","journal-title":"Mol. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1412","DOI":"10.1016\/S0016-5085(19)30493-7","article-title":"Effect of high and low doses of ursodeoxycholic acid on gallstone dissolution in humans","volume":"78","author":"Salen","year":"1980","journal-title":"Gastroenterology"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1212\/WNL.0000000000001905","article-title":"UDCA exerts beneficial effect on mitochondrial dysfunction in LRRK2(G2019S) carriers and in vivo","volume":"85","author":"Mortiboys","year":"2015","journal-title":"Neurology"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1002\/jcph.1575","article-title":"Pharmacokinetics, Safety, and Tolerability of Orally Administered Ursodeoxycholic Acid in Patients With Parkinson\u2019s Disease-A Pilot Study","volume":"60","author":"Sathe","year":"2020","journal-title":"J. Clin. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/nmeth.2066","article-title":"Metagenomic microbial community profiling using unique clade-specific marker genes","volume":"9","author":"Segata","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1038\/s41592-018-0176-y","article-title":"Species-level functional profiling of metagenomes and metatranscriptomes","volume":"15","author":"Franzosa","year":"2018","journal-title":"Nat. Methods"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1038\/nmeth.2658","article-title":"Differential abundance analysis for microbial marker-gene surveys","volume":"10","author":"Paulson","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: A web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/s41596-018-0103-9","article-title":"Pathway enrichment analysis and visualization of omics data using g:Profiler, GSEA, Cytoscape and EnrichmentMap","volume":"14","author":"Reimand","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Pan, X., Elliott, C.T., McGuinness, B., Passmore, P., Kehoe, P.G., Holscher, C., McClean, P.L., Graham, S.F., and Green, B.D. (2017). Metabolomic Profiling of Bile Acids in Clinical and Experimental Samples of Alzheimer\u2019s Disease. Metabolites, 7.","DOI":"10.3390\/metabo7020028"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/1\/29\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:06:41Z","timestamp":1760159201000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/11\/1\/29"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,4]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["metabo11010029"],"URL":"https:\/\/doi.org\/10.3390\/metabo11010029","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,4]]}}}