Open access peer-reviewed chapter

Fecal Microbiota Transplants as a Treatment Option for Parkinson’s Disease

Written By

Inez A. Flameling and Ger T. Rijkers

Submitted: 03 March 2018 Reviewed: 14 May 2018 Published: 12 December 2018

DOI: 10.5772/intechopen.78666

From the Edited Volume

Gut Microbiota - Brain Axis

Edited by Alper Evrensel and Barış Önen Ünsalver

Chapter metrics overview

1,595 Chapter Downloads

View Full Metrics


Parkinson’s disease (PD) is a progressive neurodegenerative disease with an unknown cause, high prevalence, and no effective therapy. Alterations in gut microbiota composition and function have been found in PD, which could influence the gut-brain axis. Several mechanisms have been proposed and are investigated to explain the link between gut microbiota and PD. In model systems and in individual case reports, modulation of gut microbiota has been associated with improvement of PD. A safe and effective way of gut microbiota manipulation is fecal microbiota transplant (FMT). FMT is used successfully for treatment of recurrent gastrointestinal infections as well as other indications. We advocate randomized clinical trials with FMT as a treatment option for PD.


  • Parkinson’s disease
  • gut microbiota
  • fecal microbiota transplantation
  • clinical trial

1. Introduction

Parkinson’s disease (PD) is a neurodegenerative disease which is accompanied by gastrointestinal dysfunction in 80% of patients [1]. PD has a high prevalence, affecting almost 2% of people over the age of 80 [2] and is currently incurable, although a variety of therapies are available to treat the symptoms [3]. In the last decade, the hypothesis has gained support that PD starts in the gut and spreads through the sympathetic and parasympathetic nervous systems to the substantia nigra and the central nervous system [4, 5]. More recently, it has been recognized that these brain-gut axis interactions in PD may be essentially influenced by gut microbiota.

In this opinion paper we want to encourage the design and initiation of clinical trial using fecal microbiota transplantation (FMT) as a therapeutic intervention for PD. We first elaborate on the evidence for the role of gut microbiota in PD, followed by a short discussion of FMT, and conclude with arguments to support the setup of clinical studies.


2. Alterations in gut microbiota composition in PD patients

A causal link between Helicobacter pylori infections and PD has been suggested for a long time [6, 7]. Even before the discovery of H. pylori, the connection between PD and gastric ulcers has already been reported [8, 9], and it was found that duodenal and gastric ulcers often preceded the onset of PD by many (10–20) years. Since then, numerous studies have reported that the incidence of small intestinal bacterial overgrowth is higher in PD patients than in healthy controls [10, 11, 12, 13] that PD patients have higher H. pylori antibody levels [14] and that H. pylori infections are more prevalent in PD patients than in control groups [15, 16].

Several recent studies show that PD is also preceded or accompanied by changes in the abundance of other bacterial groups. It thus has been found that PD patients harbor lower concentrations of Prevotella bacteria [17, 18, 19, 20, 21], and the number of Prevotella bacteria is negatively correlated with the severity of PD symptoms [20]. Increased numbers of Enterobacteria are found in PD patients [17, 22], and the relative abundance of Enterobacteriaceae is positively associated with the severity of postural instability and gait difficulty [20]. In another study, significantly altered abundances of the Bifidobacteriaceae, Christensenellaceae, (Tissierellaceae), Lachnospiraceae, Lactobacillaceae, Pasteurellaceae, and Verrucomicrobiaceae families were found in PD patients [23]. In PD patients, Lactobacillus numbers were found to be higher and Clostridium coccoides plus Bacteroides fragilis numbers were lower compared to healthy controls, all contributing to a distinct composition of gut microbiota in PD [23]. Concentrations of hydrogen-producing bacteria were also higher in PD patients [24]. It has been suggested that cyanobacteria can be a source of neurotoxins that are related to PD [25, 26]. Molecular analysis of the gut microbiome has shown that 48 operational taxonomic units (OTU’s) of the gastrointestinal microbiota have differential abundancy in PD patients versus healthy controls. Some of these OTUs were significantly related to motor symptoms and depression in PD patients. Functional analysis of gut microbiota also shows differences between PD patients and controls. Increased urinary indoxyl sulfate, a marker of intestinal dysbiosis, is found in PD patients [27].

Besides gut microbiota, microbiota at other ecological niches may also differ. The oral microbiota of PD patients and control subjects had differences in beta diversity and abundances of individual bacterial taxa [28].


3. Mechanistic link between gut microbiota and PD

Various studies suggest that gut microbiota do not just correlate with PD but that PD may actually start within the gut, with gut microbiota as a causative agent. The fact that gastrointestinal dysfunction often precedes motor symptoms by 10–15 years already strongly suggests a role for gut microbiota. In addition, epidemiological studies in Sweden show that gotomy drastically reduces the risk of developing PD [29, 30], suggesting the nervus vagus as vagotomy a route via which PD may travel from the gut to the CNS (see also Figure 1). Sampson and co-workers found that fecal microbiota transplants from human PD patients in a mouse model of PD enhances physical impairments, compared to microbiota transplants of healthy donors [31]; a finding which may indicate that alterations in the human microbiome represent a risk factor for PD.

Figure 1.

Potential mechanisms of interaction between gut microbiota and the brain in Parkinson’s disease.

Various mechanisms and mediators have been proposed for the relation between gut microbiota and development of PD (Figure 1). PD may be initiated by toxins produced by the gut microbiota or because of a failure to produce key essential neuronal dopamine specific nutrients or enzymes, which are required by dopamine-producing cells [32]. For example, decreased numbers of Prevotella are linked to decreased production of important micronutrients like short chain fatty acids, thiamine and folate [19], whereas gut microbes like Bacillus spp. are known to produce dopamine [33]. Cyanobacteria are believed to produce the excitotoxin β-N-methyl amino-L-alanine (BMAA) which has been found to be increased in the brain of PD patients [26].

Since PD is assumed to be characterized by synucleinopathy, another potential mechanism may be that alpha-synuclein produced by gut microbiota spreads upwards from the gut along vagal nerve fibers [34, 35].

It has also been suggested that gut dysbiosis leads to chronic low-grade inflammation in the gut, which may ultimately trigger blood-brain barrier leakage, immune cell activation and inflammation, and ultimately neuroinflammation in the CNS [36]. Increased intestinal permeability has been described in PD, resulting in penetration of E. coli in the intestinal mucosa as well as oxidative stress and increased enteric α-synuclein levels [37].

A more general explanation which has been suggested is that the composition of the gut microbiota changes over the human lifespan, which may play a role in age-related diseases [38].


4. Therapeutic interventions in the microbiome as a treatment option for PD

The effect of interventions in the microbiome on PD has been demonstrated in mouse models. Administration of the antibiotic minocycline prevents nigrostriatal dopaminergic neurodegeneration in a mouse model of PD [39]. Sampson et al. have reported that antibiotic treatment of gut microbiota ameliorates physical impairment, whereas microbial recolonization, or the oral administration of specific microbial metabolites, promotes pathophysiology in a mouse model of PD [31].

In addition, a number of recent clinical studies in human patients show that various treatments of either gastrointestinal dysfunction or gut microbiota composition have a beneficial effect on PD. For example, maintenance laxative usage was associated with apparent stemming of the temporal increase in rigidity in PD [40]. PD patients who were treated for Helicobacter pylori infections experienced prolonged (2–3 years) improvement of motor symptoms compared to a control group [41, 42, 43]. Furthermore, H. pylori-positive PD patients have significantly poorer clinical scores as compared to H. pylori-negative PD patients [16]. Twelve weeks after treatment of the H. pylori infection, improvements in levodopa onset time and effect duration were observed, as well as better scores in motor performance and quality of life measures [16]. A single non peer-reviewed case study described a PD patient that became symptom-free after receiving a fecal microbiota transplant [44].

Other (non-PD related) effects of gut microbiota composition on the nervous system have also been reported. For example, a case report of three MS patients records dramatic improvement of neurological functions after fecal microbiota transplantation [45]. Significant improvement of myoclonus dystonia symptoms was observed in a female patient after receiving fecal microbiota transplantation [46]. Microbiota management via probiotic supplementation significantly reduced overall cognitive reactivity to sad mood in healthy participants of a placebo controlled, randomized clinical trial [47]. Finally, it has been demonstrated that gut microbiota from depressed patients could induce depression-like behavior in microbiota-depleted rats [48].


5. Fecal microbiota transplantation

Given the evidence described above, modification of the gut microbiota could be a valid and attractive treatment option for PD. The most powerful way to modify the gut microbiota is via a fecal microbiota transplantation (FMT). FMT is a relatively new treatment option for gut dysbiosis-related diseases; mainly Clostridium difficile infections, for which it is highly successful with cure rates of over 90% [49, 50]. FMT involves transfer of stool (containing both microbes and the bioactive molecules they produce) from a healthy donor to a patient (see [50] for a review). More recently, the therapy is also offered via orally administered capsules containing a screened sample of donor microbiota in freeze-dried form, which makes the treatment even safer and less invasive.

As of December 2017, nine stool banks have been installed worldwide [51]; the most recent ones being in Madrid and Hong Kong. One of them, OpenBiome, founded by Harvard and MIT microbiologists, also offers treatment via capsules ( For the time being, the stool banks only offer treatments to patients suffering from recurrent C. difficile infections. However, they also cooperate in studies on other diseases. FMT is considered the most cost-effective treatment option in the treatment of recurrent C. difficile infections [52].

FMT is a safe treatment, provided it is performed in a clinical setting and with the use of screened donor feces. Several clinical studies report mild side effects or no side effects at all [49, 53, 54, 55, 56, 57]. Even in high-risk groups, FMT was found to be safe: no adverse effects were found in cancer patients [58] as well as in solid organ transplant recipients [59]. A review by Baxter and Colville [60] on the adverse events associated with FMT concludes that “The vast majority of adverse events of FMT appear to be mild, self-limiting and gastrointestinal in nature.” As for every new treatment, potential long-term negative effects are unknown.

It is important to note that outside clinical settings, there are risks associated with FMT. There is a growing “do it yourself” movement around FMT, where many people are experimenting with FMT as a last resort option for incurable diseases like PD. The Internet is teeming with discussion fora on which people exchange the best DIY techniques, which may involve kitchen blenders and various pumping devices. In a recent review of information regarding FMT on social media, it is concluded that “there is a vast amount of information available about FMT through social media that has the potential for causing harm” [61]. Donor screening does not take place if and when people perform the treatment themselves. This may lead to patients being put at risk to infections or perforations as a result of unprofessional treatment. For example, it has been reported that a child developed aspiration pneumonia as a result of the entrance of fecal matter in the bronchial system after the parents performed FMT without medical supervision [62]. Another case study describes a patient who developed a cytomegalovirus infection, after performing home FMT using unscreened donor feces [63]. These examples underline the importance of FMT to be provided in a clinical setting under controlled conditions.


6. Arguments in favor of an RCT

Given the above considerations, there are strong arguments for initiating a clinical study on the effect of FMT on PD patients.

  1. FMT could potentially provide a treatment option for a disease that affects millions of people worldwide, is currently incurable, and is expected to become more prevalent as a result of an aging population. Given the idea that age-related diseases may be related to aging of the gut microbiota [38], using material from young donors may be especially beneficial.

  2. FMT is considered safe, even in high-risk groups.

  3. FMT is inexpensive

  4. Safe, screened donor feces material can easily be obtained via one of the existing stool banks. A control group can be treated with autologous feces. Alternatively, OpenBiome offers the possibility to assist in designing a setup and provide orally administered capsules.

  5. The best way to stem the DIY movement and prevent dangerous situations as a result of people experimenting with FMT, is to offer a safe and controlled alternative in a hospital setting or to develop safe protocols for home-administered fecal transplantations in a health care setting [49, 56].

So far, only one clinical trial has been initiated ( Identifier: NCT03026231) [64]. However, we argue that more clinical trials are warranted. The argument that the mechanism via which microbiota affect PD is still poorly understood [65, 66, 67] should not block further application of FMT. Aspirin, for example, has been effectively applied for centuries before the mechanism was finally elucidated in the 1970s. Likewise, levodopa has been used for the treatment of PD for decades before its mechanism was unraveled. It may take years before the pathways via which gut microbiota affect the brain are unraveled, and meanwhile a potentially promising treatment option remains unexplored. Given the relative ease and safety of the treatment and the fact that it is already applied on a routine basis to C. difficile patients, including these in high-risk groups like cancer patients or organ transplant recipients, we advocate more clinical studies. Moreover, a clinical study on FMT in PD could lead to a better understanding of the relation between microbiota and the nervous system.

Finally, several authors have already pointed out that FMT is a very promising treatment option for PD. As stated by Mulak and Bonaz: “The close relationship between gut dysbiosis, intestinal permeability and neurological dysfunction suggests that the gut microbiota modification may provide a promising therapeutic option in PD” [68]. Fang also stated that “Microbiota-based interventions that play a regulatory role in the gut microflora exhibit therapeutic potential” (for PD) [69]. Finally, Scheperjans in 2016 comments in an opinion article: “If this endeavor is successful, we may end up with completely new therapeutic approaches that could hopefully turn the ship around toward effective disease modification or even prevention” [70].

It took a long time before FMT was generally accepted as a treatment option for C. difficile infections because physicians were skeptical about this “19th century technique” or wary of any adverse effects [71]. It is unknown how many people died (or are still dying) unnecessarily from otherwise untreatable C. difficile infections or had their colons removed, while it was already known that FMT could cure them. The prognosis has finally changed for the betterment for these patients. In 2010, a study on the effect of FMT on recurrent C. difficile infection in Amsterdam was prematurely terminated because the data and safety monitoring board of the hospital considered it unethical to withhold the treatment from the control group [55]. FMT thus is on the way to becoming a standard treatment for recurrent C. difficile infections in most developed countries.

Given the fact that FMT is a very promising treatment for PD, is safe, not invasive (especially using orally administered capsules) and inexpensive, and people are exposing themselves to risks by performing the treatment themselves without medical supervision, it could be argued that not starting a trial on the effect of FMT on PD would be similarly unethical. The roadmap is clear, and it now just needs to be taken.


Conflict of interest

The authors have no conflict of interest to declare.


  1. 1. Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Parkinsonism & Related Disorders. 2011 Jan;17(1):10-15. DOI: 10.1016/j.parkreldis.2010.08.003
  2. 2. Pringsheim T, Jette N, Frolkis A, Steeves TD. The prevalence of Parkinson's disease: A systematic review and meta-analysis. Movement Disorders. 2014 Nov;29(13):1583-1590. DOI: 10.1002/mds.25945
  3. 3. Radhakrishnan DM, Goyal V. Parkinson's disease: A review. Neurology India. 2018 Mar–Apr;66(Supplement):S26-S35. DOI: 10.4103/0028-3886.226451
  4. 4. Holmqvist S, Chutna O, Bousset L, Aldrin-Kirk P, Li W, Björklund T, Wang ZY, Roybon L, Melki R, Li JY. Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathologica. 2014 Dec;128(6):805-820. DOI: 10.1007/s00401-014-1343-6
  5. 5. Klingelhoefer L, Reichmann H. Pathogenesis of Parkinson disease--the gut-brain axis and environmental factors. Nature Reviews. Neurology. 2015 Nov;11(11):625-636. DOI: 10.1038/nrneurol.2015.197
  6. 6. Altschuler E. Gastric Helicobacter pylori infection as a cause of idiopathic Parkinson disease and non-arteric anterior optic ischemic neuropathy. Medical Hypotheses. 1996 Nov;47(5):413-414
  7. 7. Dobbs SM, Dobbs RJ, Weller C, Charlett A. Link between Helicobacter pylori infection and idiopathic parkinsonism. Medical Hypotheses. 2000 Aug;55(2):93-98
  8. 8. Schwab RS. Symptomatology and medical treatment of Parkinson's disease. International Journal of Neurology. 1961;2:61-75
  9. 9. Strang RR. The association of gastro-duodenal ulceration and Parkinson’s disease. The Medical Journal of Australia. 1965 Jun 5;1(23):842-843
  10. 10. Gabrielli M, Bonazzi P, Scarpellini E, Bendia E, Lauritano EC, Fasano A, Ceravolo MG, Capecci M, Rita Bentivoglio A, Provinciali L, Tonali PA, Gasbarrini A. Prevalence of small intestinal bacterial overgrowth in Parkinson's disease. Movement Disorders. 2011 Apr;26(5):889-892. DOI: 10.1002/mds.23566
  11. 11. Dobbs RJ, Charlett A, Dobbs SM, Weller C, A Ibrahim MA, Iguodala O, Smee C, Plant JM, Lawson AJ, Taylor D, Bjarnason I. Leukocyte-subset counts in idiopathic parkinsonism provide clues to a pathogenic pathway involving small intestinal bacterial overgrowth. A surveillance study. Gut Pathogens. 2012 Oct 19;4(1):12. DOI: 10.1186/1757-4749-4-12
  12. 12. Fasano A, Bove F, Gabrielli M, Petracca M, Zocco MA, Ragazzoni E, Barbaro F, Piano C, Fortuna S, Tortora A, Di Giacopo R, Campanale M, Gigante G, Lauritano EC, Navarra P, Marconi S, Gasbarrini A, Bentivoglio AR. The role of small intestinal bacterial overgrowth in Parkinson's disease. Movement Disorders. 2013 Aug;28(9):1241-1249. DOI: 10.1002/mds.25522
  13. 13. Tan AH, Mahadeva S, Thalha AM, Gibson PR, Kiew CK, Yeat CM, Ng SW, Ang SP, Chow SK, Tan CT, Yong HS, Marras C, Fox SH, Lim SY. Small intestinal bacterial overgrowth in Parkinson's disease. Parkinsonism & Related Disorders. 2014 May;20(5):535-540. DOI: 10.1016/j.parkreldis.2014.02.019
  14. 14. Dobbs RJ, Charlett A, Dobbs SM, Weller C, Peterson DW. Parkinsonism: Differential age-trend in Helicobacter pylori antibody. Alimentary Pharmacology & Therapeutics. 2000 Sep;14(9):1199-1205
  15. 15. Nafisah W, Najman A, Hamizah R, Azmin S, Rabani R, Shah SA, Norlinah MI. High prevalence of Helicobacter pylori infection in Malaysian Parkinson's disease patients. Journal of Parkinsonism and Restless Legs Syndrome. 2013;3:63-67
  16. 16. Hashim H, Azmin S, Razlan H, Yahya NW, Tan HJ, Manaf MR, Ibrahim NM. Eradication of Helicobacter pylori infection improves levodopa action, clinical symptoms and quality of life in patients with Parkinson's disease. PLoS One. 2014 Nov 20;9(11):e112330. DOI: 10.1371/journal.pone.0112330
  17. 17. Unger MM, Spiegel J, Dillmann KU, Grundmann D, Philippeit H, Bürmann J, Faßbender K, Schwiertz A, Schäfer KH. Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls. Parkinsonism & Related Disorders. 2016 Nov;32:66-72. DOI: 10.1016/j.parkreldis.2016.08.019
  18. 18. Cakmak YO. Coffee consumption, smoking, and Parkinson's disease? The beneficial role of hydrogen sulfide. Movement Disorders. 2016 Mar;31(3):429. DOI: 10.1002/mds.26526
  19. 19. Keshavarzian A, Green SJ, Engen PA, Voigt RM, Naqib A, Forsyth CB, Mutlu E, Shannon KM. Colonic bacterial composition in Parkinson's disease. Movement Disorders. 2015 Sep;30(10):1351-1360. DOI: 10.1002/mds.26307
  20. 20. Scheperjans F, Aho V, Pereira PA, Koskinen K, Paulin L, Pekkonen E, Haapaniemi E, Kaakkola S, Eerola-Rautio J, Pohja M, Kinnunen E, Murros K, Auvinen P. Gut microbiota are related to Parkinson's disease and clinical phenotype. Movement Disorders. 2015 Mar;30(3):350-358. DOI: 10.1002/mds.26069
  21. 21. Heintz-Buschart A, Pandey U, Wicke T, Sixel-Döring F, Janzen A, Sittig-Wiegand E, Trenkwalder C, Oertel WH, Mollenhauer B, Wilmes P. The nasal and gut microbiome in Parkinson's disease and idiopathic rapid eye movement sleep behavior disorder. Movement Disorders. 2018 Jan;33(1):88-98. DOI: 10.1002/mds.27105
  22. 22. Ghaisas S, Maher J, Kanthasamy A. Gut microbiome in health and disease: Linking the microbiome-gut-brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases. Pharmacology & Therapeutics. 2016 Feb;158:52-62. DOI: 10.1016/j.pharmthera.2015.11.012
  23. 23. Hill-Burns EM, Debelius JW, Morton JT, Wissemann WT, Lewis MR, Wallen ZD, Peddada SD, Factor SA, Molho E, Zabetian CP, Knight R, Payami H. Parkinson's disease and Parkinson's disease medications have distinct signatures of the gut microbiome. Movement Disorders. 2017 May;32(5):739-749. DOI: 10.1002/mds.26942
  24. 24. Hasegawa S, Goto S, Tsuji H, Okuno T, Asahara T, Nomoto K, Shibata A, Fujisawa Y, Minato T, Okamoto A, Ohno K, Hirayama M. Intestinal dysbiosis and lowered serum lipopolysaccharide-binding protein in Parkinson's disease. PLoS One. 2015 Nov 5;10(11):e0142164. DOI: 10.1371/journal.pone.0142164
  25. 25. Banack SA, Caller TA, Stommel EW. The cyanobacteria derived toxin Beta-N-methylamino-L-alanine and amyotrophic lateral sclerosis. Toxins (Basel). 2010 Dec;2(12):2837-2850. DOI: 10.3390/toxins2122837
  26. 26. Brenner SR. Blue-green algae or cyanobacteria in the intestinal micro-flora may produce neurotoxins such as Beta-N-Methylamino-L-Alanine (BMAA) which may be related to development of amyotrophic lateral sclerosis, Alzheimer's disease and Parkinson-Dementia-Complex in humans and Equine Motor Neuron disease in horses. Medical Hypotheses. 2013 Jan;80(1):103. DOI: 10.1016/j.mehy.2012.10.010
  27. 27. Cassani E, Barichella M, Cancello R, Cavanna F, Iorio L, Cereda E, Bolliri C, Zampella Maria P, Bianchi F, Cestaro B, Pezzoli G. Increased urinary indoxyl sulfate (indican): New insights into gut dysbiosis in Parkinson's disease. Parkinsonism & Related Disorders. 2015 Apr;21(4):389-393. DOI: 10.1016/j.parkreldis.2015.02.004
  28. 28. Pereira PAB, Aho VTE, Paulin L, Pekkonen E, Auvinen P, Scheperjans F. Oral and nasal microbiota in Parkinson's disease. Parkinsonism & Related Disorders. 2017 May;38:61-67. DOI: 10.1016/j.parkreldis.2017.02.026
  29. 29. Svensson E, Horváth-Puhó E, Thomsen RW, Djurhuus JC, Pedersen L, Borghammer P, Sørensen HT. Vagotomy and subsequent risk of Parkinson's disease. Annals of Neurology. 2015 Oct;78(4):522-529. DOI: 10.1002/ana.24448
  30. 30. Liu B, Fang F, Pedersen NL, Tillander A, Ludvigsson JF, Ekbom A, Svenningsson P, Chen H, Wirdefeldt K. Vagotomy and Parkinson disease: A Swedish register-based matched-cohort study. Neurology. 2017 May 23;88(21):1996-2002. DOI: 10.1212/WNL.0000000000003961
  31. 31. Sampson TR, Debelius JW, Thron T, Janssen S, Shastri GG, Ilhan ZE, Challis C, Schretter CE, Rocha S, Gradinaru V, Chesselet MF, Keshavarzian A, Shannon KM, Krajmalnik-Brown R, Wittung-Stafshede P, Knight R, Mazmanian SK. Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease. Cell. 2016 Dec 1;167(6):1469-1480. e12. DOI: 10.1016/j.cell.2016.11.018
  32. 32. Thakur AK, Shakya A, Husain GM, Emerald M, Kumar V. Gut-microbiota and mental health: Current and future perspectives. Journal of Pharmacology & Clinical Toxicology. 2014;2:1016
  33. 33. Eisenhofer G, Aneman A, Friberg P, Hooper D, Fåndriks L, Lonroth H, Hunyady B, Mezey E. Substantial production of dopamine in the human gastrointestinal tract. The Journal of Clinical Endocrinology and Metabolism. 1997 Nov;82(11):3864-3871
  34. 34. Phillips RJ, Walter GC, Wilder SL, Baronowsky EA, Powley TL. Alpha-synuclein-immunopositive myenteric neurons and vagal preganglionic terminals: Autonomic pathway implicated in Parkinson's disease? Neuroscience. 2008 May 15;153(3):733-750. DOI: 10.1016/j.neuroscience.2008.02.074
  35. 35. Gershanik OS. Does Parkinson's disease start in the gut? Arquivos de Neuro-Psiquiatria. 2018 Feb;76(2):67-70. DOI: 10.1590/0004-282X20170188
  36. 36. Nair AT, Ramachandran V, Joghee NM, Antony S, Ramalingam G. Gut microbiota dysfunction as reliable non-invasive early diagnostic biomarkers in the pathophysiology of Parkinson's disease: A critical review. Journal of Neurogastroenterology and Motility. 2018 Jan 30;24(1):30-42. DOI: 10.5056/jnm17105
  37. 37. Forsyth CB, Shannon KM, Kordower JH, Voigt RM, Shaikh M, Jaglin JA, Estes JD, Dodiya HB, Keshavarzian A. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson's disease. PLoS One. 2011;6(12):e28032. DOI: 10.1371/journal.pone.0028032
  38. 38. Santoro A, Ostan R, Candela M, Biagi E, Brigidi P, Capri M, Franceschi C. Gut microbiota changes in the extreme decades of human life: A focus on centenarians. Cellular and Molecular Life Sciences. 2018 Jan;75(1):129-148. DOI: 10.1007/s00018-017-2674-y
  39. 39. Du Y, Ma Z, Lin S, Dodel RC, Gao F, Bales KR, Triarhou LC, Chernet E, Perry KW, Nelson DL, Luecke S, Phebus LA, Bymaster FP, Paul SM. Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease. Proceedings of the National Academy of Sciences of the United States of America. 2001 Dec 4;98(25):14669-14674
  40. 40. Augustin AD, Charlett A, Weller C, Dobbs SM, Taylor D, Bjarnason I, Dobbs RJ. Quantifying rigidity of Parkinson's disease in relation to laxative treatment: A service evaluation. British Journal of Clinical Pharmacology. 2016 Aug;82(2):441-450. DOI: 10.1111/bcp
  41. 41. Dobbs SM, Dobbs RJ, Weller C, Charlett A, Bjarnason IT, Lawson AJ, Letley D, Harbin L, Price AB, Ibrahim MA, Oxlade NL, Bowthorpe J, Leckstroem D, Smee C, Plant JM, Peterson DW. Differential effect of Helicobacter pylori eradication on time-trends in brady/hypokinesia and rigidity in idiopathic parkinsonism. Helicobacter. 2010 Aug;15(4):279-294. DOI: 10.1111/j.1523-5378.2010.00768.x
  42. 42. Dobbs SM, Charlett A, Dobbs RJ, Weller C, Iguodala O, Smee C, Lawson AJ, Taylor D, Bjarnason I. Antimicrobial surveillance in idiopathic parkinsonism: Indication-specific improvement in hypokinesia following Helicobacter pylori eradication and non-specific effect of antimicrobials for other indications in worsening rigidity. Helicobacter. 2013 Jun;18(3):187-196. DOI: 10.1111/hel.12035
  43. 43. Dobbs SM, Dobbs RJ, Weller C, Charlett A, Augustin A, Taylor D, Ibrahim MA, Bjarnason I. Peripheral aetiopathogenic drivers and mediators of Parkinson's disease and co-morbidities: Role of gastrointestinal microbiota. Journal of Neurovirology. 2016 Feb;22(1):22-32. DOI: 10.1007/s13365-015-0357-8
  44. 44. Ananthaswamy A. Faecal transplant eases symptoms of Parkinson’s disease. New Scientist. 2011;209:8-9
  45. 45. Borody TJ, Campbell J, Torres M, Nowak A, Leis S. Reversal of idiopathic thrombocytopenic purpura [ITP] with fecal microbiota transplantation [FMT]. American Journal of Gastroenterology. 2011;106:S352
  46. 46. Borody TJ, Rosen DM, Torres M, Campbell J, Nowak A. Myoclonus-dystonia (M-D) mediated by GI microbiota diarrhoea treatment improves M-D symptoms. The American Journal of Gastroenterology. 2011;106:S352
  47. 47. Steenbergen L, Sellaro R, van Hemert S, Bosch JA, Colzato LS. A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood. Brain, Behavior, and Immunity. 2015 Aug;48:258-264. DOI: 10.1016/j.bbi.2015.04.003
  48. 48. Kelly JR, Borre Y, O' Brien C, Patterson E, El Aidy S, Deane J, Kennedy PJ, Beers S, Scott K, Moloney G, Hoban AE, Scott L, Fitzgerald P, Ross P, Stanton C, Clarke G, Cryan JF, Dinan TG. Transferring the blues: Depression-associated gut microbiota induces neurobehavioural changes in the rat. Journal of Psychiatric Research. 2016 Nov;82:109-118. DOI: 10.1016/j.jpsychires.2016.07.019
  49. 49. Silverman MS, Davis I, Pillai DR. Success of self-administered home fecal transplantation for chronic Clostridium difficile infection. Clinical Gastroenterology and Hepatology. 2010 May;8(5):471-473. DOI: 10.1016/j.cgh.2010.01.007
  50. 50. Merenstein D, El-Nachef N, Lynch SV. Fecal microbial therapy: Promises and pitfalls. Journal of Pediatric Gastroenterology and Nutrition. 2014 Aug;59(2):157-161. DOI: 10.1097/MPG.0000000000000415
  51. 51. Terveer EM, van Beurden YH, Goorhuis A, Seegers JFML, Bauer MP, van Nood E, Dijkgraaf MGW, Mulder CJJ, Vandenbroucke-Grauls CMJE, Verspaget HW, Keller JJ, Kuijper EJ. How to: Establish and run a stool bank. Clinical Microbiology and Infection. 2017 Dec;23(12):924-930. DOI: 10.1016/j.cmi.2017.05.015
  52. 52. Arbel LT, Hsu E, McNally K. Cost-effectiveness of fecal microbiota transplantation in the treatment of recurrent Clostridium difficile infection: A literature review. Cureus. 2017 Aug 23;9(8):e1599. DOI: 10.7759/cureus.1599
  53. 53. Mattila E, Uusitalo-Seppälä R, Wuorela M, Lehtola L, Nurmi H, Ristikankare M, Moilanen V, Salminen K, Seppälä M, Mattila PS, Anttila VJ, Arkkila P. Fecal transplantation, through colonoscopy, is effective therapy for recurrent Clostridium difficile infection. Gastroenterology. 2012 Mar;142(3):490-496. DOI: 10.1053/j.gastro.2011.11.037
  54. 54. Kunde S, Pham A, Bonczyk S, Crumb T, Duba M, Conrad H Jr, Cloney D, Kugathasan S. Safety, tolerability, and clinical response after fecal transplantation in children and young adults with ulcerative colitis. Journal of Pediatric Gastroenterology and Nutrition. 2013 Jun;56(6):597-601. DOI: 10.1097/MPG.0b013e318292fa0d
  55. 55. van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JF, Tijssen JG, Speelman P, Dijkgraaf MG, Keller JJ. Duodenal infusion of donor feces for recurrent Clostridium difficile. The New England Journal of Medicine. 2013 Jan 31;368(5):407-415. DOI: 10.1056/NEJMoa1205037
  56. 56. Duke PS, Fardy J. Recurrent Clostridium difficile infection treated with home fecal transplantation: A case report. Journal of Medical Case Reports. 2014 Nov 28;8:393. DOI: 10.1186/1752-1947-8-393
  57. 57. Bajaj JS, Kassam Z, Fagan A, Gavis EA, Liu E, Cox IJ, Kheradman R, Heuman D, Wang J, Gurry T, Williams R, Sikaroodi M, Fuchs M, Alm E, John B, Thacker LR, Riva A, Smith M, Taylor-Robinson SD, Gillevet PM. Fecal microbiota transplant from a rational stool donor improves hepatic encephalopathy: A randomized clinical trial. Hepatology. 2017 Dec;66(6):1727-1738. DOI: 10.1002/hep.29306
  58. 58. Hefazi M, Patnaik MM, Hogan WJ, Litzow MR, Pardi DS, Khanna S. Safety and efficacy of fecal microbiota transplant for recurrent Clostridium difficile infection in patients with cancer treated with cytotoxic chemotherapy: A single-institution retrospective case series. Mayo Clinic Proceedings. 2017 Nov;92(11):1617-1624. DOI: 10.1016/j.mayocp.2017.08.016
  59. 59. Fischer M, Khan M, Phelps EL, Safdar N, Misch EA, Kaur N, Kowsika SS, Smith JD, Kassam Z, Allegretti JR, Xu H, Kao DH. Fecal microbiota transplantation is safe and effective for the treatment of Clostridium difficile infection in solid organ transplant recipients. Gastroenterology. 2017;152(5 Supp 1):S1005
  60. 60. Baxter M, Colville A. Adverse events in faecal microbiota transplant: A review of the literature. The Journal of Hospital Infection. 2016 Feb;92(2):117-127. DOI: 10.1016/j.jhin.2015.10.024
  61. 61. Segal JP, Abbasi F, Kanagasundaram C, Hart A. Does the internet promote the unregulated use of fecal microbiota transplantation: A potential public health issue? Clinical and Experimental Gastroenterology. 2018;11:179-183
  62. 62. Samuel BP, Crumb TL, LaVigne HD. Nursing assassment for “do it yourself”fecal microbiota transplantation. Gastroenterology Nursing. 2016 Jan–Feb;39(1):60-62. DOI: 10.1097/SGA.0000000000000142
  63. 63. Hohmann EL, Ananthakrishnan AN, Deshpande V. Case records of the Massachusetts General Hospital. Case 25-2014. A 37-year-old man with ulcerative colitis and bloody diarrhea. The New England Journal of Medicine. 2014 Aug 14;371(7):668-675. DOI: 10.1056/NEJMcpc1400842
  64. 64. Identifier: NCT03026231. Characterization of Fecal Microbiome Changes After Administration of PRIM-DJ2727 in Parkinson's Disease Patients. Houston: The University of Texas Health Science Center. [Last Accessed: May 2, 2018]
  65. 65. Scheperjans F, Pekkonen E, Kaakkola S, Auvinen P. Linking smoking, coffee, urate, and Parkinson's disease—A role for gut microbiota? Journal of Parkinson's Disease. 2015;5(2):255-262. DOI: 10.3233/JPD-150557
  66. 66. Fasano A, Visanji NP, Liu LW, Lang AE, Pfeiffer RF. Gastrointestinal dysfunction in Parkinson's disease. Lancet Neurology. 2015 Jun;14(6):625-639. DOI: 10.1016/S1474-4422(15)00007-1
  67. 67. Derkinderen P, Shannon KM, Brundin P. Gut feelings about smoking and coffee in Parkinson's disease. Movement Disorders. 2014 Jul;29(8):976-979. DOI: 10.1002/mds.25882
  68. 68. Mulak A, Bonaz B. Brain-gut-microbiota axis in Parkinson's disease. World Journal of Gastroenterology. 2015 Oct 7;21(37):10609-10620. DOI: 10.3748/wjg.v21.i37.10609
  69. 69. Fang X. Potential role of gut microbiota and tissue barriers in Parkinson's disease and amyotrophic lateral sclerosis. The International Journal of Neuroscience. 2016 Sep;126(9):771-776. DOI: 10.3109/00207454.2015.1096271
  70. 70. Scheperjans F. Can microbiota research change our understanding of neurodegenerative diseases? Neurodegenerative Disease Management. 2016 Apr;6(2):81-85. DOI: 10.2217/nmt-2015-0012
  71. 71. de Vrieze J. Medical research. The promise of poop. Science. 2013 Aug 30;341(6149):954-957. DOI: 10.1126/science.341.6149.954

Written By

Inez A. Flameling and Ger T. Rijkers

Submitted: 03 March 2018 Reviewed: 14 May 2018 Published: 12 December 2018