Current pharmacological treatments for Parkinson’s disease (PD) provide relief for motor
symptoms but fail to alleviate prevalent non-motor symptoms (NMS)- such as gastrointestinal
(GI) dysfunction which often occurs before the development of motor symptoms. Strategies to
slow the progression of PD have been proposed, but so far none has proven successful. PD
patients display changes in gut microbiome composition believed to contribute to disease
pathology. The PD microbiome is differentiated by a greater number of opportunistic pathogens
and a pro-inflammatory profile, which may be mediated by the decreased proportion of butyrate
producing bacteria and lower gut concentration of short chain fatty acids. Given the diversity of
known byproducts of bacterium and commensal relationships, the gut microbiota can be seen as
a metabolic reservoir to utilize in the treatment of disease. This study describes the effect of
butyrogenic dietary interventions- inulin, guar gum, and probiotic C. butyricum- on PD asynuclein brain pathology, motor deficits, and constipation in PD transgenic (Tg) mice.
Stemming from our prior work, we compared the disease-modifying efficacy of oral butyrate and
butyrogenic dietary treatments to see if microbiome-targeted therapies serve as an alternative
route to delay the progression of PD.
Our findings show that a combined prebiotic and probiotic approach, i.e, synbiotic,
reduces alpha-synuclein aggregation in the brains of aged Tg mice to a greater extent than found
iv with oral butyrate therapy. Treatment with prebiotic alone was less effective at reducing
aggregates of alpha-synuclein. Behaviorally, both prebiotic and synbiotic treatments prevented
the decline in motor function as Tg mice aged. In contrast, prebiotic and probiotic therapies
exclusively improve bowel transit time and stool composition. Lastly, we discovered that oral
butyrate treatments do not significantly change microbiota diversity, whereas prebiotic and
probiotic interventions generally decreased or enriched microbiota diversity, respectively.
Moreover, differences in bacterial relative abundance identified bacterial taxa associated with
disease or treatments.
In total, results from this work suggest that synbiotic therapy may be the best therapeutic
approach to treat PD, as oral butyrate dosing did not improve constipation. This work provides a
starting point and highlights an avenue for the development of neuroprotective therapies for PD
which act via the microbiota-gut-brain axis. CLICK TO REVIEW