TY - JOUR
T1 - Gut microbial metabolites in Parkinson's disease
T2 - Association with lifestyle, disease characteristics, and treatment status
AU - Voigt, Robin M.
AU - Wang, Zeneng
AU - Brown, J. Mark
AU - Engen, Phillip A.
AU - Naqib, Ankur
AU - Goetz, Christopher G.
AU - Hall, Deborah A.
AU - Metman, Leo Verhagen
AU - Shaikh, Maliha
AU - Forsyth, Christopher B.
AU - Keshavarzian, Ali
N1 - Funding Information:
This research was in part supported by the NIH including NIA R01 AG056653 (RMV), NIAAA R24 AA026801 (A.K.), NIAAA P50 AA024333 (J.M.B.), NHBLI R01 HL130819 (ZW), NHBLI P01 HL147823 (JMB), and NIDDK R01 DK120679 (JMB), and NIDDK R01 DK130227 (JMB). We would like to thank Mr. and Mrs. Larry Field, Mr. and Mrs. Phillip Glass, Mr. Keehn, and the Alvin Baum Family fund for their philanthropic funding. We would like to thank Christopher Strauch and Belinda Willard in the Cleveland Clinic Metabolomics core for help with quantifying short chain and branched chain fatty acids.
Publisher Copyright:
© 2022 The Authors
PY - 2022/8
Y1 - 2022/8
N2 - There is growing appreciation of the importance of the intestinal microbiota in Parkinson's disease (PD), and one potential mechanism by which the intestinal microbiota can communicate with the brain is via bacteria-derived metabolites. In this study, plasma levels of bacterial-derived metabolites including trimethylamine-N-oxide (TMAO), short chain fatty acids (SCFA), the branched chain fatty acid isovalerate, succinate, and lactate were evaluated in PD subjects (treatment naïve and treated) which were compared to (1) population controls, (2) spousal / household controls (similar lifestyle to PD subjects), and (3) subjects with multiple system atrophy (MSA). Analyses revealed an increase in the TMAO pathway in PD subjects which was independent of medication status, disease characteristics, and lifestyle. Lactic acid was decreased in treated PD subjects, succinic acid positively correlated with disease severity, and the ratio of pro-inflammatory TMAO to the putative anti-inflammatory metabolite butyric acid was significantly higher in PD subjects compared to controls indicating a pro-inflammatory shift in the metabolite profile in PD subjects. Finally, acetic and butyric acid were different between PD and MSA subjects indicating that metabolites may differentiate these synucleinopathies. In summary, (1) TMAO is elevated in PD subjects, a phenomenon independent of disease characteristics, treatment status, and lifestyle and (2) metabolites may differentiate PD and MSA subjects. Additional studies to understand the potential of TMAO and other bacterial metabolites to serve as a biomarker or therapeutic targets are warranted.
AB - There is growing appreciation of the importance of the intestinal microbiota in Parkinson's disease (PD), and one potential mechanism by which the intestinal microbiota can communicate with the brain is via bacteria-derived metabolites. In this study, plasma levels of bacterial-derived metabolites including trimethylamine-N-oxide (TMAO), short chain fatty acids (SCFA), the branched chain fatty acid isovalerate, succinate, and lactate were evaluated in PD subjects (treatment naïve and treated) which were compared to (1) population controls, (2) spousal / household controls (similar lifestyle to PD subjects), and (3) subjects with multiple system atrophy (MSA). Analyses revealed an increase in the TMAO pathway in PD subjects which was independent of medication status, disease characteristics, and lifestyle. Lactic acid was decreased in treated PD subjects, succinic acid positively correlated with disease severity, and the ratio of pro-inflammatory TMAO to the putative anti-inflammatory metabolite butyric acid was significantly higher in PD subjects compared to controls indicating a pro-inflammatory shift in the metabolite profile in PD subjects. Finally, acetic and butyric acid were different between PD and MSA subjects indicating that metabolites may differentiate these synucleinopathies. In summary, (1) TMAO is elevated in PD subjects, a phenomenon independent of disease characteristics, treatment status, and lifestyle and (2) metabolites may differentiate PD and MSA subjects. Additional studies to understand the potential of TMAO and other bacterial metabolites to serve as a biomarker or therapeutic targets are warranted.
KW - MSA
KW - Metabolites
KW - Microbiota
KW - PD
KW - Parkinson's disease
KW - TMAO
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U2 - 10.1016/j.nbd.2022.105780
DO - 10.1016/j.nbd.2022.105780
M3 - Article
C2 - 35654277
AN - SCOPUS:85131361221
SN - 0969-9961
VL - 170
JO - Neurobiology of Disease
JF - Neurobiology of Disease
M1 - 105780
ER -