Identification of gut metabolites associated with Parkinson's disease using bioinformatic analyses

Jun Yan; Xia Feng; Xia Zhou; Mengjie Zhao; Hong Xiao; Rui Li; Hong Shen

doi:10.3389/fnagi.2022.927625

Identification of gut metabolites associated with Parkinson's disease using bioinformatic analyses

Front Aging Neurosci. 2022 Jul 26:14:927625. doi: 10.3389/fnagi.2022.927625. eCollection 2022.

Authors

Jun Yan¹, Xia Feng², Xia Zhou³, Mengjie Zhao³, Hong Xiao³, Rui Li⁴, Hong Shen³

Affiliations

¹ Department of Geriatric, Nanjing Medical University Affiliated Brain Hospital, Nanjing, China.
² Department of Pharmacy, Nanjing Medical University Affiliated Brain Hospital, Nanjing, China.
³ Institute of Neuropsychiatry, Nanjing Medical University Affiliated Brain Hospital, Nanjing, China.
⁴ School of Pharmacy, Nanjing Medical University, Nanjing, China.

Abstract

Background: Parkinson's disease (PD) is a common neurodegenerative disease affecting the movement of elderly patients. Environmental exposures are the risk factors for PD; however, gut environmental risk factors for PD are critically understudied. The proof-of-concept study is to identify gut metabolites in feces, as environmental exposure risk factors, that are associated with PD and potentially increase the risk for PD by using leverage of known toxicology results.

Materials and methods: We collected the data regarding the gut metabolites whose levels were significantly changed in the feces of patients with PD from the original clinical studies after searching the following databases: EBM Reviews, PubMed, Embase, MEDLINE, and Elsevier ClinicalKey. We further searched each candidate metabolite-interacting PD gene set by using the public Comparative Toxicogenomics Database (CTD), identified and validated gut metabolites associated with PD, and determined gut metabolites affecting specific biological functions and cellular pathways involved in PD by using PANTHER tools.

Results: Sixteen metabolites were identified and divided into the following main categories according to their structures and biological functions: alcohols (ethanol), amino acids (leucine, phenylalanine, pyroglutamic acid, glutamate, and tyrosine), short-chain fatty acids (propionate and butyrate), unsaturated fatty acids (linoleic acid and oleic acid), energy metabolism (lactate, pyruvate, and fumarate), vitamins (nicotinic acid and pantothenic acid), and choline metabolism (choline). Finally, a total of three identified metabolites, including butyrate, tyrosine, and phenylalanine, were validated that were associated with PD.

Conclusion: Our findings identified the gut metabolites that were highly enriched for PD genes and potentially increase the risk of developing PD. The identification of gut metabolite exposures can provide biomarkers for disease identification, facilitate an understanding of the relationship between gut metabolite exposures and response, and present an opportunity for PD prevention and therapies.

Keywords: Comparative Toxicogenomics Database; Parkinson’s disease; environmental exposures; gut metabolites; visual analyses.