Objective: Assess the metabolic changes in fecal matter in mice treated with an immunomodulatory therapy.

Background: The cause of neuronal death in Parkinson’s disease (PD) is currently unknown, and to date there are no treatments available to slow the rate of disease progression. Oxidative stress, chronic neuroinflammation and mitochondrial dysfunction likely play a role in PD. Activated microglia are present in PD, likely contributing to sustained inflammation leading to abnormal aggregation of alpha synuclein, a key player in PD pathogenesis. It is also becoming increasingly evident that the gut immunity plays a significant role in PD. Here, we report metabolic changes measured from fecal samples of vaccinated and un-vaccinated transgenic PD mice,.

Method: For lipidomics, a Folch extraction was performed and for metabolomics, a precipitation solution was used for phase separation. For both metabolomics and lipidomics analyses, a Thermo Scientific Q-Exactive Orbitrap Mass Spectrometer coupled to a Dionex UltiMate 3000 system was used. Data was acquired using both positive and negative polarity. Features were detected using MZmine 2, and blank feature filtering was utilized. For lipidomics, LipidMatch and LipidSearch were used for feature identification. For metabolomics, in-house libraries were used for feature identification. Statistical analysis was performed using Metaboanalyst 3.0.

Results: Lipidomics analysis identified significant changes in the triacylglycerides (TGs), and diacylglycerols (DGs). The sum of the intensities of all individual DGs, were found to be significant (p=0.049), with TGs being the most significant class (p=0.016). Metabolomic analysis identified elevated taurine and histamine in treated mice. Methionine, an essential amino acid in humans, was down regulated along with other amino acids and this finding may possibly have been related to a difference in breakdown efficiency of dietary proteins. Metabolites involved in the pyrimidine pathway were significantly different. Cytidine monophosphate (CMP), cytidine, L-glutamine and uridine were up regulated in the PD mice, and deoxycitidine, Deoxyuridine, 5-methylcytosine and ureidopropionic acid were up- regulated in treated mice.

Conclusion: Preliminary data showed that several metabolites were significantly altered in PD indicating that the gut immunity may be altered. It is unknown whether these changes could play a role in therapeutic efficacy.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/metabolomic-analysis-of-fecal-matter-from-parkinsonian-mice/