Proceedings of the Texas A&M Medical Student Grand Rounds

Understanding the Extent to Which The Gut-to-Brain Axis Contributes to the Pathogenesis of Parkinson’s Disease

June 23, 2022 Lindsay Wiseman

Lindsay Wiseman

Introduction. Parkinson’s disease (PD) is a central nervous system pathology caused by aggregations of ɑ-synuclein, called Lewy bodies, in dopaminergic neurons of the substantia nigra in the brain.1,2,3 This causes cognitive and motor deficits in PD patients.2 PD is a neurodegenerative disease that cannot be cured yet, but pharmacological therapies for motor symptoms, like levodopa, are available.2,4 Aho et al. 2021 identified the possible roles of the microbiota-gut-brain-axis (MGBA) in PD. The composition of the gut microbiota is different in PD patients compared to normal individuals, so research must be conducted to understand the influence this microbial change has on disease cause and/or progression.5 Methods. There is evidence that the gut is linked to the brain, so researchers are determining the role that the MGBA has on PD patients. A clinical study measured levels of gut microbiota and their products, along with cognitive and pathological data of PD patients.5 In another study, a PD animal model was given oral vancomycin pre-treatment, and the levels of dopamine break-down enzyme, MAO-B, were measured.6 Another PD animal study used oral polymannuronic acid (PM) treatment to identify its effects on the gut and microbiota, and indirectly the effects on the brain.7 Many PD studies are focused on methods to reduce inflammation in the gut.8 Results. Higher levels of short-chain fatty acids, which are commonly produced by gut bacteria, were associated with later age of onset of PD in a clinical study.5 Furthermore, oral vancomycin and its effects on the gut significantly decreased the amount of dopamine metabolism in the brain by decreasing levels of MAO-B.6 Therefore, this change in gut microbiota after vancomycin treatment is correlated with an improved disease state in PD. PM treatment decreased inflammation in the gut, which was associated with decreased inflammation in the brain. This is a possible mechanism to prevent destruction of dopaminergic neurons via the gut.7,8 Conclusion. Each of these studies analyzed how either the existing gut microbiota or the adjustment of gut microbiota in PD patients affected the brain. The MGBA exists and plays a role in the pathogenesis of PD. It will be important for future research to explore gut treatment and prevention methods for PD.6,7,9

  1. Raza C, Anjum R, Shakeel NUA. Parkinson’s disease: Mechanisms, translational models and management strategies. Life Sci. 2019;226:77-90. doi:10.1016/j.lfs.2019.03.057
  2. Jankovic J, Tan EK. Parkinson’s disease: etiopathogenesis and treatment. J Neurol Neurosurg Psychiatry. 2020;91(8):795-808. doi:10.1136/jnnp-2019-322338
  3. Cacabelos R. Parkinson’s Disease: From Pathogenesis to Pharmacogenomics. Int J Mol Sci. 2017;18(3):551. Published 2017 Mar 4. doi:10.3390/ijms18030551
  4. Armstrong MJ, Okun MS. Diagnosis and Treatment of Parkinson Disease: A Review. JAMA. 2020;323(6):548-560. doi:10.1001/jama.2019.22360
  5. Aho VTE, Houser MC, Pereira PAB, et al. Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson’s disease. Mol Neurodegener. 2021;16(1):6. Published 2021 Feb 8. doi:10.1186/s13024-021-00427-6
  6. Cui C, Hong H, Shi Y, et al. Vancomycin Pretreatment on MPTP-Induced Parkinson’s Disease Mice Exerts Neuroprotection by Suppressing Inflammation Both in Brain and Gut [published online ahead of print, 2022 Jan 29]. J Neuroimmune Pharmacol. 2022;10.1007/s11481-021-10047-y. doi:10.1007/s11481-021-10047-y
  7. Dong XL, Wang X, Liu F, et al. Polymannuronic acid prevents dopaminergic neuronal loss via brain-gut-microbiota axis in Parkinson’s disease model. Int J Biol Macromol. 2020;164:994-1005. doi:10.1016/j.ijbiomac.2020.07.180
  8. Li W, Zhao Q, Wang J, Wang Y, Wen T. Dcf1 deletion presents alterations in gut microbiota of mice similar to Parkinson’s disease. Biochem Biophys Res Commun. 2020;529(4):1137-1144. doi:10.1016/j.bbrc.2020.06.150
  9. Srivastav S, Neupane S, Bhurtel S, et al. Probiotics mixture increases butyrate, and subsequently rescues the nigral dopaminergic neurons from MPTP and rotenone-induced neurotoxicity. J Nutr Biochem. 2019;69:73-86. doi:10.1016/j.jnutbio.2019.03.021
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