Abstract

Animal models indicate that butyrate might reduce motor symptoms in Parkinson’s disease. Some dietary fibers are butyrogenic, but in Parkinson’s disease patients their butyrate stimulating capacity is unknown. Therefore, we investigated different fiber supplements’ effects on short-chain fatty acid production, along with potential underlying mechanisms, in Parkinson’s patients and age-matched healthy controls. Finally, it was investigated if this butyrate production could be confirmed by using fiber-rich vegetables. Different fibers (n = 40) were evaluated by in vitro fermentation experiments with fecal samples of Parkinson’s patients (n = 24) and age-matched healthy volunteers (n = 39). Short-chain fatty acid production was analyzed by headspace solid-phase micro-extraction gas chromatography-mass spectrometry. Clostridium coccoides and C. leptum were quantified through 16S-rRNA gene-targeted group-specific qPCR. Factors influencing short-chain fatty acid production were investigated using linear mixed models. After fiber fermentation, butyrate concentration varied between 25.6 ± 16.5 µmol/g and 203.8 ± 91.9 µmol/g for Parkinson’s patients and between 52.7 ± 13.0 µmol/g and 229.5 ± 42.8 µmol/g for controls. Inulin had the largest effect, while xanthan gum had the lowest production. Similar to fiber supplements, inulin-rich vegetables, but also fungal β-glucans, stimulated butyrate production most of all vegetable fibers. Parkinson’s disease diagnosis limited short-chain fatty acid production and was negatively associated with butyrate producers. Butyrate kinetics during 48 h fermentation demonstrated a time lag effect in Parkinson’s patients, especially in fructo-oligosaccharide fermentation. Butyrate production can be stimulated in Parkinson’s patients, however, remains reduced compared to healthy controls. This is a first step in investigating dietary fiber’s potential to increase short-chain fatty acids in Parkinson’s disease.

Highlights

  • As reviewed by Elfil et al (2020), changes in the gut microbiome composition are thought to play a role in the pathophysiology of Parkinson’s disease (PD) and could be a potential target in future therapies[1]

  • Our results demonstrated that all fiber types stimulated short-chain fatty acids (SCFA) production, in both PD and healthy controls (HC)

  • Both fermentation experiments found similar results regarding the limited SCFA production capacity of PD patients compared to HC

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Summary

Introduction

As reviewed by Elfil et al (2020), changes in the gut microbiome composition are thought to play a role in the pathophysiology of Parkinson’s disease (PD) and could be a potential target in future therapies[1]. The gut microbiome composition of PD patients is characterized by a lower number of butyrate-producing bacteria and a more pro-inflammatory profile[2,3,4,5,6,7], combined with lower fecal short-chain fatty acids (SCFA) concentrations[5]. Matt et al (2018) showed that both intra-peritoneal butyrate administration and a high dietary fiber diet resulted in reduced expression of pro-inflammatory genes in aged mice’s brains[14]. Results by Sampson et al (2016) demonstrated that administration of an SCFA mixture promoted neuroinflammation in a germ-free PD mouse model[15]. Beneficial effects of administration of a low dose of butyrate in a mouse model of autism have been reported, whereas a high dose did not exert any effects[17]. The hypothesis is that enhancing colonic SCFA production would be beneficial in PD

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