Treating the Gut in Parkinson’s Disease
Post by Christopher Chen
The takeaway
A common symptom in people with Parkinson’s Disease (PD) is a compromised, pro-inflammatory gut bacteria profile that may lead to neuroinflammation and neurodegeneration associated with PD. Clinicians found that a short-term regimen of prebiotic fiber helped restore the gut’s anti-inflammatory environment in patients with PD and may even attenuate clinical symptoms.
What's the science?
Though classified as a neurodegenerative disease, Parkinson’s Disease (PD) also manifests itself in the gut microbiota. Specifically, patients with PD express increased levels of pro-inflammatory bacteria (family Enterobacteriaceae) and decreased levels of anti-inflammatory bacteria (family Lachnospiraceae). This imbalance may lead to intestinal “leakiness” which allows for the infiltration of harmful substances like lipopolysaccharide (LPS) which may increase neurodegeneration. However, research has shown that anti-inflammatory bacteria can restore gut balance by producing molecules called short-chain fatty acids (SCFA). Scientists know that the body’s breakdown of substances called prebiotic fibers recruits the helpful bacteria that generate SCFAs. Recently in Nature Communications, Hall and colleagues investigate whether treating PD patients with prebiotic fiber can increase SCFA production, decrease pro-inflammatory bacteria, and potentially alleviate clinical symptoms of PD.
How did they do it?
The researchers first determined the effects of different prebiotic fibers on SCFA production. To do so, they treated the stool of age-matched healthy controls and patients with PD with different types of prebiotic fiber and measured how much each fiber increased SCFA. Based on this data, the scientists created an edible bar containing an optimized mixture of prebiotic fibers (30% resistant starch, 30% resistant maltodextrin, 30% stabilized rice bran, and 10% agave branched inulin).
Over the course of ten days, the bar was given to two groups of PD patients, the first group being newly diagnosed and non-medicated PD patients and the second being medicated PD patients. Following the ten-day regimen, researchers assessed participant stool to assess microbiota composition and also assessed participants on a range of symptoms linked to gastrointestinal and neurological function, including UPDRS, a neurological assessment specifically linked to PD symptomology. These results were then compared to data from the same assessments taken prior to the prebiotic fiber intervention.
What did they find?
Following treatment, both participant groups exhibited changes at the microbiome and cellular level as well as in behavioral assessments. In terms of microbiome composition, patient stool showed a decrease in the overall abundance of pro-inflammatory bacteria and an increase in the overall abundance of anti-inflammatory, SCFA-producing bacteria. Researchers also took blood samples from patients, which showed an increase in SCFA following the treatment. Additionally, a metabolic pathway linked to acetyl-CoA fermentation known to be upregulated in PD was downregulated following prebiotic fiber intervention. It should be noted, however, that while the overall amount of SCFA-producing bacteria increased, several species of SCFA-producing bacteria were downregulated following the treatment. In terms of neurological effects, no neuroinflammation markers showed decreases in patients, though levels of a neurodegeneration marker called NfL were reduced.
Finally, an exploratory analysis was conducted to assess the effects of the prebiotic fiber regimen on clinical and behavioral outcomes. Most notably, both patient groups had minimal GI discomfort and scored significantly lower on the UPDRS following treatment, suggesting an improvement in PD symptomology.
What's the impact?
Taken together, evidence from this study suggests that diets high in prebiotic fiber may be conducive to restoring anti-inflammatory, SCFA-producing bacteria in patients with PD. Furthermore, the resulting increase in SCFA-producing bacteria may be linked to functionally significant decreases in PD symptomology. Though this study was conducted on a relatively small patient group (twenty total participants) and the long-term effects of prebiotic fiber remain unclear, it offers a compelling glimpse into the therapeutic potential of non-pharmacological, microbiome-centric treatments for neurological disorders such as PD.