Probiotics Applications in Parkinson’s Disease Treatment

Diseases have appeared, disappeared, increased, or decreased throughout human history. These epidemiological trends occur strongly with infectious diseases but also manifest in chronic diseases. In the past three or four decades, researchers have reported changes in the epidemiology of neurological diseases. In some high-income and developing countries, the risk of stroke and cognitive decline has reduced, while the risks of Parkinson’s disease, progressive supranuclear palsy, and multiple system atrophy have increased again.

The global burden of Parkinson’s disease has more than doubled in 26 years, from 2.5 million patients in 1990 to 6.1 million patients in 2016. This trend is expected to continue, reaching over 12 million patients worldwide by around 2050 [1-4]. Part of this increase is due to the aging population (increased life expectancy) and also longer disease duration, and potential changes in environmental or social risk factors, such as smoking or head injury, all considered underlying risk factors for Parkinson’s disease [4].

Parkinson’s disease is a progressive movement disorder affecting motor functions. It is characterized by tremors, muscle rigidity, slowed movements, pain, and gastrointestinal (GI) dysfunction. Currently, there is no cure for Parkinson’s disease, only temporary treatment options. Scientists are striving to find ways to prevent this fatal disease. One treatment option being researched is the use of probiotics to restore the nervous system [5,6]. The complexity of Parkinson’s disease and the diverse combination of markers would be ideal for enhancing accurate diagnosis and use of better drugs for Parkinson’s. Besides Levodopa, the most widely used drug for treating Parkinson’s motor symptoms, other options may include types like Monoamine oxidase B inhibitors, Amantadine, and Anticholinergics [7,8].

However, they have certain side effects, such as movement disorders and gastrointestinal dysfunction. Some researchers have suggested treatment methods for Parkinson’s, including gene and disease-modifying approaches to reduce abnormal accumulation and synthesis of α-synuclein, tyrosine hydroxylase dysfunction, lysosomal protein function, neural inflammation blockade, and nerve regeneration enhancement. Alongside new compounds and targeted drugs, cell therapy, immune therapy, and vaccines have emerged, along with non-pharmacological approaches like gene therapy, some of which have entered clinical trials [9]. Researchers have recently conducted evaluations that have opened up a brighter future for Parkinson’s in the coming years. These evaluations suggest that the disease may be slowed, halted, or reversed. Recently, the gut-brain axis, enteric nervous system (ENS), gut microbiota, and the brain-gut connection have become illuminating as essential for the underlying mechanism of Parkinson’s disease.

Gut Bacterial Disorders in Parkinson’s Disease

Clinicians have clinically identified a range of GI dysfunctions related to Parkinson’s, including weight loss, gastric pain, constipation, and colonic disorders [10]. These dysfunctions are potential contributors to Parkinson’s. This is because α-synuclein appears early in the ENS and then progresses to the brain via nerve pathways. Notably, normal elderly individuals also have α-synuclein in their ENS, but it is more prevalent in Parkinson’s patients. Once the disease is manifest, it is associated and fueled by the gut microbiota, which is released extracellularly and involves adjacent cells, including nerve cells, which can internalize and form α-synuclein pathology. Release mechanisms like the ubiquitin-proteasome system to clear damaged proteins have been shown to be ineffective in genetic Parkinson’s and autonomic progression. Gut microbiota alterations are thus an apparent causative factor in Parkinson’s disease.

Using Probiotics to Support Parkinson’s Disease Treatment

Preclinical/clinical evidence of probiotic (beneficial bacteria) effects in Parkinson’s remains limited. It is anticipated why probiotics, prebiotics, and synbiotics are beneficial in Parkinson’s. Probiotics may be a tool to alter the Parkinson’s disease-associated microbiota to improve GI function, bacterial migration, and neural inflammation in the ENS. The first clinical study conducted demonstrated that Parkinson’s patients with chronic constipation using yogurt containing Lactobacillus casei Shirota for five weeks improved symptoms, bloating, and abdominal pain [11]. This study elevated the value of probiotic use in improving Parkinson’s in patients. Additionally, this study demonstrated that probiotics in capsule form reduced abdominal pain and bloating in Parkinson’s patients for several months [12]. A recent study (ClinicalTrials.gov) assessed the impact of capsule-form probiotics (containing Lactobacillus acidophilus, Bifidobacterium bifidum, Lactobacillus reuteri, and Lactobacillus fermentum) on clinical and biochemical profiles (including metabolic parameters) in Parkinson’s [13]. Furthermore, these studies demonstrated that probiotic use reduced insulin levels, insulin resistance, and increased insulin sensitivity compared to placebo. Using Symprove (a clinical trial of Symprove probiotics), a drinkable live bacteria probiotic aiming to deliver beneficial live bacteria to the gut. Symprove is a multi-strain liquid probiotic intended to deliver live beneficial bacteria through the acidic stomach. Six patients were tested for three months. It’s highly likely that the effects are through multiple mechanisms, such as improving digestive symptoms through altering the gut environment or inhibiting harmful gut bacteria. For instance, probiotics may adjust the lower prevalence of Prevotella in Parkinson’s patients’ feces that has been reported. Another example involves Parkinson’s patients infected with Helicobacter pylori. Eliminating Helicobacter pylori with the assistance of probiotics may be helpful for these patients. Probiotic Bifidobacterium bifidum affects Helicobacter pylori and may be a potential option for future research on Parkinson’s. Supplementing Lactobacillus reuteri has an anti-Helicobacter pylori effect and holds some future potential for Parkinson’s. The lower quantity of Bifidobacterium found in the feces of progressive Parkinson’s patients indicates probiotics’ usefulness in this scenario [14].

Prospects of Probiotics in Parkinson’s Disease Treatment

Studies have indicated the bidirectional support of the gut-brain axis and bacterial disturbances in Parkinson’s disease. A healthy gut microbiota might reduce the risk of developing certain disorders in individuals, likely including Parkinson’s. The pre-inflammatory environment in conditions of bacterial disturbances might transmit signals to the brain through the nervous system and the blood-brain barrier. Therefore, the immune system imbalance in subjects could be a contributing factor, or partly responsible, for both motor and non-motor symptoms of Parkinson’s. Probiotics, prebiotics, and synbiotics have been studied for their impact on GI functional disorders as options for regulating gut bacterial disorders. An overview of clinical and preclinical data suggests that the gut microbiota might directly or indirectly support the brain through various mechanisms, like the nervous, immune, and endocrine systems. This also suggests that treating neurodegenerative disorders such as Parkinson’s might involve a combination of tailored adjustments for each process to optimize outcomes. Future research on Parkinson’s should consider the gut-brain axis and the nervous system’s modulation of the gut microbiota and microbial metabolism. Although recent evidence suggests that the gut microbiota might regulate the immune response of the central nervous system, microglia, neurological physiological processes (e.g., nerve conduction), behavior, and the integrity of the blood-brain barrier, a deeper understanding of these mechanisms is crucial. Maintaining a healthy gut microbiota may face limitations and challenges, but the current potential is highly promising. We still need to understand the effects of exogenously used probiotics on bacterial populations and the gut microbial environment in Parkinson’s patients. There should also be more consistency in designing studies concerning probiotic strains, their combinations, intervention durations, and dosages applied. Personalized approaches may yield more reliable results when considering the high variability of the gut microbiota and the observed high variability in the effects of probiotics.

References:

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