Effects of Resistant Starch on Symptoms,Fecal Markers,and Gut Microbiota in Parkinson’s Disease—The RESISTA-PD Trial

The composition of the gut microbiota is linked to multiple diseases,including Parkinson’s disease(PD).Abundance of bacteria producing short-chain fatty acids(SCFAs)and fecal SCFA concentrations are reduced in PD.SCFAs exert various beneficial functions in humans.In the interventional,monocentric,open-label clinical trial “Effects of Resistant Starch on Bowel Habits,Short Chain Fatty Acids and Gut Microbiota in Parkinson’s Disease”(RESISTA-PD;ID:NCT02784145),we aimed at altering fecal SCFAs by an 8-week prebiotic intervention with resistant starch(RS).We enrolled 87 subjects in three study-arms:32 PD patients received RS(PD+RS),30 control subjects received RS,and 25 PD patients received solely dietary instructions.We performed paired-end 100 bp length metagenomic sequencing of fecal samples using the BGISEQ platform at an average of 9.9 GB.RS was well-tolerated.In the PD+RS group,fecal butyrate concentrations increased significantly,and fecal calprotectin concentrations dropped significantly after 8 weeks of RS intervention.Clinically,we observed a reduction in non-motor symptom load in the PD+RS group.The reference-based analysis of metagenomes highlighted stable alpha-diversity and beta-diversity across the three groups,including bacteria producing SCFAs.Reference-free analysis suggested punctual,yet pronounced differences in the metagenomic signature in the PD+RS group.RESISTA-PD highlights that a prebiotic treatment with RS is safe and well-tolerated in PD.The stable alpha-diversity and beta-diversity alongside altered fecal butyrate and calprotectin concentrations call for long-term studies,also investigating whether RS is able to modify the clinical course of PD.