Gut Feeling: Unraveling the Parkinson’s Disease–Microbiome Connection
- Website Tech
- Sep 19
- 7 min read
Written by: Emma Reid
Edited by: Fahad Hassan Shah
Introduction
When we think of Parkinson’s Disease, we often think of slow movement, stiffness, and cognitive decline. But what if the earliest signs of this neurodegenerative disease started outside your brain—in the gut?
The Gut-Brain Connection
The gut-brain axis has been a central point of research for decades. The gut-brain axis mainly consists of the vagus nerve: a cranial nerve that directly connects the digestive system to the brain (and vice versa). The vagus nerve regulates involuntary bodily responses, such as hunger and inflammation, through the transport of neuromodulators and metabolites. A deeper understanding of this two-way bodily system has led to developments in treatments for mental health disorders and immune system regulation. One of the most notable recent findings from studying this connection is the possibility of identifying brain diseases, such as Parkinson’s disease, with the gut microbiome long before physical symptoms appear (Fasano et al., 2015).
Parkinson’s Disease: An Overview
The origin of Parkinson’s Disease (PD) has typically been defined as sporadic, or having no known common, identifiable cause. There are no genetic risk factors, family history, or environmental factors that can directly account for causing this disease in an individual. Recent studies over the years have only been able to find possible identifiable markers of Parkinson’s in the body. One of the most well-known and driving markers of the disease is the presence of a misfolded protein called alpha-synuclein, or α-synuclein (Stefanis, 2012). α-Synuclein aggregates into abnormal clumps called Lewy bodies in the brain, which results in neuron malfunction and ultimately neuronal death. The spread of α-synuclein continues throughout several progressive stages in the brain, leading to the neurodegenerative disease known as Parkinson’s (Braak et al., 2003).
Trust Your Gut: Parkinson’s Disease and the Gut
It has been hypothesized that inflammation and oxidative stress contribute to the accumulation of abnormal α-synuclein in the body, but the origin of these pathological processes has been a topic of speculation for years (Hawkes et al., 2010). The substantial loss of dopamine neurons in brain regions such as the substantia nigra leads to the characteristic symptoms of tremors and motor impairment that are associated with Parkinson’s Disease. However, studies over the last decade have suggested that another potential culprit may be at play: the gut. Gastrointestinal dysfunction is a common symptom found across Parkinson’s patients, often occurring years before motor symptoms even appear. (Pfeiffer, 2003). Unsurprisingly, patients with Parkinson’s have been found to have a heightened concentration of α-synuclein throughout their entire gastrointestinal tract, ranging from the salivary glands in the mouth to the colon and rectum (Fasano et al., 2015). In addition, other studies have shown that early α-synuclein deposition is found in parasympathetic nerves innervating the gut, including nerves such as the vagus nerve (Bloch et al., 2006). Therefore, according to the deposition trail of α-synuclein in the body, it has been hypothesized that these abnormal proteins may originate in the gut, then travel up the vagus nerve to the brain in order to progressively spread α-synuclein throughout the brain and body (Braak et al., 2003).
The Gut Microbiome: Playing More Than Just A ‘Micro’ Role in PD
The presence of α-synuclein in the gut is not the only symptom affecting the GI tract in patients with Parkinson's disease. The human microbiome—the collection of microorganisms in the gut—is significantly different in patients with Parkinson’s disease compared to healthy adults. For instance, one study found that there was a significant decrease in helpful bacteria such as Prevotella in the microbiome of Parkinson’s patients compared to a healthy control group (Scheperjans et al., 2015). In addition, the amount of short-chain fatty acids (SCFAs) found in the gut was less in Parkinson’s patients compared to adults without Parkinson’s disease (Jin et al., 2019). SCFAs play a crucial role in regulating the blood-brain barrier and inhibiting inflammation, suggesting that a deficiency of SCFAs in Parkinson’s patients may contribute to increased neuroinflammation in the brain (Aho et al., 2021). Ultimately, Parkinson’s patients seem to have a distinct and unique microbial makeup in their bodies compared to healthy adults.
Further research has been conducted over the years to not only study the microbiome in Parkinson’s patients but also to test for a causal link between the microbiome and Parkinson’s. For instance, the transfer of gut bacteria from human Parkinson's donors into mouse models resulted in enhanced motor impairment compared to mouse models injected with healthy human microbiota in a 2016 study by Sampson et al. This finding suggests that there may be a causal link between the microbiome of an individual and the onset of Parkinson’s Disease. Moreover, the gut may not just play a minor role in Parkinson’s as a symptom but rather facilitate the development of the disease as a whole.
Figure 1
Note. Microbes in the gut play a crucial role in regulating the responses of microglia in the brain. With altered microbes due to PD, microglia can not be successfully activated to manage neuroinflammation, causing motor dysfunction in the brain (Sampson et al., 2016).
Treating Parkinson’s With the Microbiome
The discovery of the gut microbiome having a prominent effect on the brain provides promising avenues for treatment and prevention. For instance, several studies have investigated the effects of vitamin B supplements on Parkinson’s patients. These studies have found that vitamin supplements can improve motor symptoms associated with Parkinson’s disease by releasing dopamine in patients, as well as providing neuroprotective effects to slow the progression of the disease in the brain (Haghdoost-Yazdi et al., 2012; Luong & Nguyen, 2013). Additionally, a diet consisting of fish oil and nutrient supplements has been shown to prevent motor and non-motor symptoms, such as gastrointestinal dysfunction, in Parkinson’s patients (Perez-Pardo et al., 2017). There has even been additional research involving transferring gut bacteria from healthy controls into Parkinson’s patients through fecal microbiota transplants, or FMT. When FMTs were used in Parkinson’s patients, there was a significant increase in the diversity of their microbiome and a decrease in their gastrointestinal symptoms, such as constipation and lessened gut motility. Motor-related symptoms associated with Parkinson’s were reduced as well (DuPont et al., 2023).
Conclusion
Ultimately, it seems that the gut does not take a backseat as a secondary symptom in Parkinson’s anymore. Research over the past two decades has explored the intriguing and unexpected connection between the gut and the brain, leading to new opportunities for diagnosing and treating this disease. While it is still unclear whether the gut causes Parkinson’s in patients or results from it, it is now obvious that the gut plays a key role in neurological health.
References
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