Diseases and Disorders

Fecal Microbiota Transplantation for Parkinson’s Disease

Annika Zhou


Abstract

Parkinson’s disease (PD) is a long-term degenerative neurological disorder of the central nervous system that mainly affects the motor system and the control of movement. A primary form of Parkinsonism, a group of disorders where there is progressive loss of motor function due to the degeneration of neurons, the idiopathic disease affects ten million people worldwide with more than sixty-thousand diagnosed cases per year [1]. Parkinson’s disease is known for its high prevalence, especially in the aging population, its eventual resistance to drug treatments, and lack of effective therapy. Recent research has shown, however, that alterations in gut microbiota composition and dysbiosis are linked to a disruption in the gut-brain axis [2]. Experiments have further indicated that the enteric nervous system is involved in PD progression toward the central nervous system and that modulation of gut microbiota has been associated with improvements in neuropsychiatric and neurological disorders [2]. A safe and effective way of manipulating gut microbiota is through fecal microbiota transplants. FMT has been used successfully as a treatment for irritable bowel syndrome (IBS) and autism in addition to numerous other disorders [3]. This article seeks to advocate for clinical trials and experiments with FMT as a treatment option for Parkinson’s disease. 


 

Parkinson’s Motor and Non-Motor Symptoms

Parkinson’s disease, a neurodegenerative disease, is typically diagnosed from physical symptoms, such as tremors. Symptoms consist of tremors of a limb, often beginning in the hands or fingers. Parkinson’s disease is, for the majority of the time, diagnosed based on motor symptoms like the aforementioned tremors. However, non-motor symptoms such as constipation, abdominal pain, IBS, and gastrointestinal dysfunction have drawn little attention in research. While Parkinson’s disease is characterized by cardinal motor impairments, this wide range of non-motor symptoms typically precede the motor symptoms. In a study performed by China Medical University in Taiwan, the prevalence of constipation and abdominal pain in PD are 46.7%-52.5% and approximately 28% respectively [4]. Several studies, such as the Chinese Medical University study, have also indicated that there is a correlation between IBS and the risk of PD [4]. By following the medical history of 23,875 patients with newly diagnosed IBS and 95,500 subjects without IBS to compare, the incidence of PD was 1.76 times higher in the IBS group than in the non-IBS group; further data suggests that patients with IBS have a 48% higher chance of getting PD than the population without IBS [4]. In the last decade, hypotheses concerning the concept of a gut-brain axis and the idea that Parkinson’s disease begins in the gut have gained much more support [5]. It has been recognized that such gut-brain axis interactions in Parkinson’s disease may be influenced by an imbalance in gut microbiota, which explains why gastrointestinal dysfunction typically precedes the motor symptoms of Parkinson’s disease. 

 

 The Gut-Brain Axis

The gut-brain axis or the GBA consists of bidirectional communication between the enteric and central nervous system, linking the emotional and cognitive centres of the brain with peripheral intestinal functions [2]. The bidirectional link is a complex form of communication that not only ensures the maintenance of gastrointestinal homeostasis, but also affects the mood, motivation, and higher cognitive functions of an individual [2]. The maintenance of homeostasis is theorized to be an important part of maintaining a healthy mental state. Dysbiosis, a microbial imbalance, is highly associated with mood disorders and is linked to a disruption of the gut-brain axis [2]. Current treatments like levodopa are based on restoring dopaminergic neurotransmission and alleviating motor symptoms like tremors but leave non-motor symptoms untreated. Accumulating evidence suggests that the enteric nervous system is involved in Parkinson’s disease progression toward the central nervous system. In this sense, perhaps by altering an individuals dietary components or through fecal transplants, we may influence the gut-brain axis by altering the microbial composition of the enteric nervous system. 

 

Figure 1. A diagram illustrating the gut-brain axis connection [6].

 

Past Usage of Fecal Transplantation in Other Diseases

In the past, fecal transplants have been tested and researched in patients of several other neurological disorders and gastrointestinal diseases. While commonly used as a treatment for gastrointestinal diseases, such as Clostridium difficile infection, Crohn’s disease, and ulcerative colitis, the application of fecal transplants has been experimentally used in the treatment of metabolic and autoimmune disorders as well [7]. Case reports also exist showing that fecal transplants have been effective in treating multiple sclerosis, chronic fatigue syndrome, and IBS. The implementation of fecal transplants is not only cheap and reliable, unlike other forms of treatment for Parkinson’s disease, such as long-term Levodopa use or invasive surgery, but also tends to maintain its effect over long periods of time (usually multiple years). The long-term effect of fecal transplants is visible in usage for numerous gastrointestinal disorders and diseases. According to Linda Lee, Director of the Johns Hopkins Integrative Medicine and Digestive Center, the procedure of fecal transplantation is simple, and in treatment for C. difficile, for example, fecal transplants are effective in 90% of patients [8]. Lee further reports that “70% of people who receive fecal transplants for C. difficile report an improvement of symptoms within just three days” and that fecal transplants have the potential to “[improve] the quality of life [8].” Studies regarding C. difficile infections have shown that 30% of patients relapse when treated with rounds of antibiotics, which means that patients are spending significant amounts of money for repeated courses of antibiotics and are not getting better; in contrast, fecal transplants are not only effective, but also cost-friendly in treating gut infections, making it a better option [8]. If a single fecal transplant treatment can be effective for numerous years, it can easily replace the standard drug treatment of Levodopa. 

 

Limitations of Fecal Transplantation

While fecal transplantation has shown potential in becoming a treatment for Parkinson’s disease among many other diseases and disorders, such an innovative and new treatment is not without any risk. Lee compares the beginning of fecal transplantation use to “the early days of blood transfusion,” reminding readers that researchers could be unaware of deadly microbiota like they had been unaware of hepatitis C at the time [8]. Scientists have not yet discovered all the organisms or the full composition of humans’ gut microbiota, so if the theory that gut bacteria play an important role in diseases is true, fecal transplantation could have unanticipated dangers and consequences. Long-term effects of fecal transplantation cannot be predicted at this time; however, treatments have so far been effective with only minor side effects like constipation and bloating [8]. 

 

The Application of Fecal Transplants in Neurological and Neuropsychiatric Disorders 

Promising advancements in autism research involve the gut-brain axis and gut microbiome, the collection of microbes that live in our intestines and helps digest food and prevent the overgrowth of bacteria. Similar to Parkinson’s disease, roughly 30% to 50% of autistic individuals experience gastrointestinal problems, such as constipation and diarrhea [3]. These statistics further reinforce earlier statements regarding the connection between neurological disorders and dysbiosis. Research performed on children with autism with gastrointestinal problems have indicated that children with worse gastrointestinal problems also have worse autism-related symptoms [3]. When gastrointestinal problems are relieved, behaviour improves. Research conducted has further shown long-term beneficial effects for children diagnosed with ASD treated through Microbiota Transfer Therapy (MTT), a specific type of fecal transplant [3]. Fecal transplants in the experiment eventually lead to improvements in gut health and symptoms that persisted for years following the initial treatment [3]. Two years post-treatment, most initial improvements in gut symptoms remained, and ASD symptoms steadily reduced over the next two years; professional evaluators indicated a 45% reduction in core ASD symptoms in terms of language, social interaction, and behaviour [3]. In this case study, by transferring healthy microbiota to individuals lacking certain gut bacteria, it was possible to create a more diverse population of bacteria in a patient and improve gut and neurological health. Besides ASD, chronic fatigue syndrome and multiple sclerosis are other examples of neuropsychiatric and neurological diseases and illnesses that have been effectively treated with fecal transplants [7]. Considering the similarity in symptoms and the similar effects of the GBA in PD and autism specifically, it can be inferred that fecal transplants have the potential to alleviate Parkinson’s symptoms or be used as a preventative treatment or a method of early diagnosis.

 

Conclusion

The gut, according to Patrik Brundin MD, PhD, Van Andel Research Institute and J. William Langston MD, Stanford Udall Center, Department of Pathology, Stanford University, both Editors-in-Chief of the Journal of Parkinson’s Disease, “has emerged as one of the new frontiers in PD research [5].” The gut-brain axis among other research developments has demonstrated the possibility and great potential of fecal transplants as a treatment for Parkinson’s disease. Fecal transplantation has demonstrated its potential impact in neurological disorders, as it has demonstrated its ability to ameliorate symptoms in gastrointestinal diseases related to PD and other neurological disorders, such as multiple sclerosis and autism. Given the similarities in symptoms and the similar gut-brain axis connection in the two diseases, it is reasonable to predict that fecal transplants can not only be used as a preventative treatment or method of early diagnosis, but can also be used to relieve motor symptoms in Parkinson’s disease.


References


  1. Inside Tract - The Benefits of Fecal Transplant. (n.d.). https://www.hopkinsmedicine.org/news/publica tions/inside_tract/inside_tract_fall_2013/the_benefits_of_fecal_transplant. Retrieved; 06/07/2019.

  2. Evrensel, A., & Ceylan, M. E. (2016). Fecal Microbiota Transplantation and Its Usage in Neuropsychiatric Disorders. Clinical Psychopharmacology and Neuroscience, 14(3), 231-237. doi:10.9758/cpn.2016.14.3.231

  3. Gut Feeling. (n.d.). Retrieved from https://pulse.embs.org/november-2017/link-depression-gut-bacteria/

  4. Science daily. The involvement of the gut in Parkinson's disease: Hype or hope? (07/02/2019). https://www.sciencedaily.com/releases/2019/02/190207115006.htm. Retrieved; 05/31/2019.

  5. Lai, S., Liao, K., Lin, C., & Sung, F. (2014). Irritable bowel syndrome correlates with increased risk of Parkinson’s disease in Taiwan. European Journal of Epidemiology, 29(1), 57-62. doi:10.1007/s10654-014-9878-3

  6. Kang, D., Adams, J. B., Coleman, D. M., Pollard, E. L., Maldonado, J., Mcdonough-Means, S., . . . Krajmalnik-Brown, R. (2019). Long-term benefit of Microbiota Transfer Therapy on autism symptoms and gut microbiota. Scientific Reports, 9(1). doi:10.1038/s41598-019-42183-0

  7. Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of gastroenterology, 28(2), 203–209.

  8. Mayo clinic. (30/06/2018). Parkinson’s disease. Mayoclinic. https://www.mayoclinic.org/diseases-conditions/parkinsons-disease/symptoms-causes/syc-20376055. Retrieved; 06/20/2019.

Annika Zhou

Annika Zhou


gr11 high school student with a passion for neuroscience and medicine