Fecal Microbiota Transplantation in Neurological Disorders

Karuna E W Vendrik, Rogier E Ooijevaar, Pieter R C de Jong, Jon D Laman, Bob W van Oosten, Jacobus J van Hilten, Quinten R Ducarmon, Josbert J Keller, Eduard J Kuijper, Maria Fiorella Contarino, Karuna E W Vendrik, Rogier E Ooijevaar, Pieter R C de Jong, Jon D Laman, Bob W van Oosten, Jacobus J van Hilten, Quinten R Ducarmon, Josbert J Keller, Eduard J Kuijper, Maria Fiorella Contarino

Abstract

Background: Several studies suggested an important role of the gut microbiota in the pathophysiology of neurological disorders, implying that alteration of the gut microbiota might serve as a treatment strategy. Fecal microbiota transplantation (FMT) is currently the most effective gut microbiota intervention and an accepted treatment for recurrent Clostridioides difficile infections. To evaluate indications of FMT for patients with neurological disorders, we summarized the available literature on FMT. In addition, we provide suggestions for future directions. Methods: In July 2019, five main databases were searched for studies and case descriptions on FMT in neurological disorders in humans or animal models. In addition, the ClinicalTrials.gov website was consulted for registered planned and ongoing trials. Results: Of 541 identified studies, 34 were included in the analysis. Clinical trials with FMT have been performed in patients with autism spectrum disorder and showed beneficial effects on neurological symptoms. For multiple sclerosis and Parkinson's disease, several animal studies suggested a positive effect of FMT, supported by some human case reports. For epilepsy, Tourette syndrome, and diabetic neuropathy some studies suggested a beneficial effect of FMT, but evidence was restricted to case reports and limited numbers of animal studies. For stroke, Alzheimer's disease and Guillain-Barré syndrome only studies with animal models were identified. These studies suggested a potential beneficial effect of healthy donor FMT. In contrast, one study with an animal model for stroke showed increased mortality after FMT. For Guillain-Barré only one study was identified. Whether positive findings from animal studies can be confirmed in the treatment of human diseases awaits to be seen. Several trials with FMT as treatment for the above mentioned neurological disorders are planned or ongoing, as well as for amyotrophic lateral sclerosis. Conclusions: Preliminary literature suggests that FMT may be a promising treatment option for several neurological disorders. However, available evidence is still scanty and some contrasting results were observed. A limited number of studies in humans have been performed or are ongoing, while for some disorders only animal experiments have been conducted. Large double-blinded randomized controlled trials are needed to further elucidate the effect of FMT in neurological disorders.

Keywords: Parkinson's disease; autism spectrum disorder; autoimmunity; fecal microbiota transplantation; gastrointestinal microbiome; gut-brain axis; nervous system diseases; neurodegenerative.

Copyright © 2020 Vendrik, Ooijevaar, de Jong, Laman, van Oosten, van Hilten, Ducarmon, Keller, Kuijper and Contarino.

Figures

Figure 1
Figure 1
Potential effects of FMT in patients with neurological disorders and in animal models for neurological disorders. The figure includes studies in which patients with a neurological disorder or animal models for a neurological disorder received FMT with feces from a healthy donor. Tourette syndrome was not included as this contains only one case report. Blue areas include cognitive symptoms, yellow areas include motor and sensory symptoms or effects and orange areas include other effects. The outer parts contain results from human studies and the inner parts from animal studies. Statements in bold are found by more than one study, excluding case descriptions. N: the number of studies identified per neurological disorder, subdivided in human and animal studies. *based on case reports/series only (very limited evidence). **inconsistent results.

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