Parkinson's disease patients' short chain fatty acids production capacity after in vitro fecal fiber fermentation

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.

Fig. 1. Overview of mean SCFA production per fiber in Parkinson’s Disease patients and healthy controls.

a inulins; (b) oligosaccharides; (c) resistant starch/dextrin, polydextrose; (d) pectins; (e) gums; (f) hemicelluloses, cellulose, lignin; (g) vegetable soluble dietary fiber; (h) vegetable/quinoa insoluble dietary fiber; SDF soluble dietary fiber, IDF insoluble dietary fiber, PD Parkinson’s patients, HC healthy controls. Potential effects of factors on SCFA production were analyzed using linear mixed models, sex, fiber type, and PD diagnosis were added as fixed factors, the participant was added as a random factor. PD diagnosis resulted in an overall reduction of acetic acid (p = 0.002), butyric acid (p = 0.0001), and total SCFA (p = 0.004), compared to HC for the fiber supplement experiments (a–f). Similar effects of PD diagnosis on acetic acid (p = 0.01), butyric acid (p = 0.097), and total SCFA (p = 0.08) were observed in the vegetable/quinoa fiber experiments (g–h). Fibers significantly (p < 2.0E−16) influenced the production of all SCFA in both experiments.

Fig. 2. Mean butyrate concentration after 24h fermentation with different types of fiber supplements.

Results presented as mean ± SD; different letters indicate significant differences in butyrate production between fiber types; RS resistant starch, RD resistant dextrin, oligosaccharides are fructo-, galacto- and human milk oligosaccharides; rest group comprises fibers consisting of hemicelluloses, cellulose, and lignin. Differences between fiber types were post-hoc analyzed by pairwise comparisons, using Tukey to correct for multiple testing. All significant differences observed, had a p-value < 0.0001.

Fig. 3. Kinetics of butyrate production during 48h fermentation of Orafti HP, Actilight P950 and Novelose 330 in Parkinson’s disease patients and healthy controls.

Results are shown as median ± range, PD Parkinson’s disease patients, HC healthy controls, Orafti HP is inulin; Actilight P950 is FOS; Novelose 330 is resistant starch. Butyrate kinetics were analyzed using linear mixed models per time point, sex, fiber type, PD diagnosis and interaction effect of fiber type, and PD diagnosis were added as fixed factors, the participant was added as a random factor. The kinetic profile indicated that 3–12 h after inulin, RS, and FOS fermentation, PD had lower butyrate production compared to HC.