Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls
Introduction
Parkinson's disease (PD) is a neurodegenerative disorder clinically characterized by motor and non-motor symptoms. The pathohistological hallmark of PD is the presence of aggregated proteins (Lewy bodies) in the nervous system. Lewy body pathology in PD is found in structures of the central nervous system (CNS) as well as in the peripheral autonomic [1] and enteric nervous system (ENS) [2], [3], [4], [5]. PD patients frequently exhibit non-motor symptoms, including signs and symptoms of gastrointestinal dysmotility (e.g. delayed gastric emptying [6], [7], [8], constipation [9], [10]). Lewy body pathology in the ENS might represent the pathohistological correlate for gastrointestinal symptoms in PD. Current hypotheses suggest that the ENS might be one of the first sites where Lewy body pathology appears in PD [2], [11]. Interestingly, an animal model of PD shows that chronic intragastric administration of rotenone, a complex-1-inhibitor, results in a spatio-temporal distribution of alpha-synuclein immunoreactivity that is compatible with the above mentioned hypotheses [12], [13]. A similar trigger might be responsible for the formation of Lewy bodies in humans.
Due to the immediate vicinity of the ENS with feces, gut microbiota and microbiota's metabolic products are among potential candidates that could initiate a process that eventually results in the formation of Lewy bodies in the ENS. Two recent studies showed an association between the abundance of certain gut microbiota and PD [14], [15]: amongst others, bacteria that have the capacity to produce short chain fatty acids (SCFA) were reduced in PD. SCFA modulate the activity of the ENS and thereby increase gastrointestinal motility [16]. Hence, altered concentrations of SCFA might contribute to gastrointestinal dysmotility in PD.
We hypothesized that a shift in gut microbiota might be associated with a shift in gut microbiota's metabolic products, e.g. SCFA. We therefore analyzed microbiota and SCFA in fecal samples of patients with PD and age-matched healthy controls.
Section snippets
Subjects and methods
This study was approved by the Ethics committee of the medical association of Saarland. All enrolled subjects provided written informed consent.
Results
The percentage of bacterial phyla and bacterial groups in fecal samples of PD patients and age-matched controls were determined by quantitative PCR. Results are shown in Fig. 1: The bacterial phylum Bacteroidetes was significantly reduced in fecal samples of PD patients. Prevotellaceae (a bacterial family assigned to the phylum Bacteroidetes) were also descriptively reduced in PD patients compared to controls.
The phylum Firmicutes was the most abundant phylum and showed a similar relative
Discussion
Gastrointestinal symptoms as well as Lewy body pathology in the ENS occur at early stages of PD. Current hypotheses discuss the gut as the origin of the pathological process that underlies PD [11]. Gut microbiota and their metabolic products are among potential candidates that could ignite a process that eventually leads to Lewy body formation in the ENS. Two recent studies showed that the abundance of certain gut microbiota differs between PD patients and controls [14], [15].
Here we report
Conflict of interest/disclosure
All authors declare that there is no conflict of interest regarding this work. All authors have approved the final article.
Authors' contributions to the article
- 1)
a) conception, design; b) data acquisition; c) analysis, interpretation.
- 2)
a) drafting the article; b) revising the article critically.
- 3)
a) final approval of the version to be submitted.
Marcus M. Unger: 1a), 1b), 1c), 2a), 3a).
Jörg Spiegel: 1b), 2b), 3a).
Klaus-Ulrich Dillmann: 1b), 2b), 3a).
David Grundmann: 1c), 2b), 3a).
Hannah Philippeit: 1b), 2b), 3a).
Jan Bürmann: 1b), 2b), 3a).
Klaus Faβbender: 1b), 2b), 3a).
Andreas Schwiertz: 1a), 1c), 2b), 3a).
Karl-Herbert Schäfer: 1a), 1c), 2b), 3a).
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Both authors contributed equally.