Alteration of Gut Microbial Metabolites in the Systemic Circulation of Patients with Parkinson’s Disease

Article type: Research Article

Authors: Chen, Szu-Ju^{a; b; c} | Chen, Chieh-Chang^{c; d} | Liao, Hsin-Yu^e | Wu, Yu-Wei^f | Liou, Jyh-Ming^d | Wu, Ming-Shiang^d | Kuo, Ching-Hua^{e; g; h; *} | Lin, Chin-Hsien^{a; *}

Affiliations: [a] Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan | [b] Department of Neurology, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan | [c] Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan | [d] Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan | [e] School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. | [f] Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan | [g] The Metabolomics Core Laboratory, NTU Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan | [h] Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan

Correspondence: [*] Correspondence to: Ching-Hua Kuo, PhD, School of Pharmacy, National Taiwan University, Taipei, Taiwan. Tel.: +886 2 33668766; Fax: +886 2 23919098; E-mail: kuoch@ntu.edu.tw and Chin-Hsien Lin, MD, PhD, Department of Neurology, National Taiwan University Hospital, Taipei 100, Taiwan. Tel.: +886 2 23123456 ext 65335; Fax: +886 2 23418395; E-mail: chlin@ntu.edu.tw.

Abstract: Background:Emerging evidence suggests that gut dysbiosis contributes to Parkinson’s disease (PD) by signaling through microbial metabolites. Hippuric acid (HA), indole derivatives, and secondary bile acids are among the most common gut metabolites. Objective:To examine the relationship of systemic concentrations of these microbial metabolites associated with changes of gut microbiota, PD status, and severity of PD. Methods:We enrolled 56 patients with PD and 43 age- and sex-matched healthy participants. Motor and cognitive severity were assessed with Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III motor score and the Mini-Mental State Examination (MMSE), respectively. Plasma concentrations of targeted gut metabolites were measured with liquid chromatography-tandem mass spectrometry. Gut microbiota was analyzed with shotgun metagenomic sequencing. Results:Compared with controls, PD patients had significantly higher plasma levels of HA, indole-3-propionic acid (IPA), deoxycholic acid (DCA), and glycodeoxycholic acid (GDCA). After adjustment for age and sex in a multivariate logistic regression analysis, plasma levels of HA (odds ratio [OR] 3.21, p < 0.001), IPA (OR 2.59, p = 0.031), and GDCA (OR 2.82, p = 0.036) were associated with positive PD status. Concentrations of these gut metabolites did not correlate with MDS-UPDRS part III score or MMSE after adjustment for confounders. Microbial metabolite levels were associated with the relative abundance of pro-inflammatory gut bacteria. Conclusion:Aberrant gut microbial metabolites of HA, indole derivatives and secondary bile acids associated with specific gut microbiota changes were observed in patients with PD.

Keywords: Parkinson’s disease, microbial metabolite, gut microbiota, gut–brain axis, bile acid, hippuric acid, indole derivative

DOI: 10.3233/JPD-223179

Journal: Journal of Parkinson's Disease, vol. 12, no. 4, pp. 1219-1230, 2022