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

Abstract

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.

Protective Effects of Polysaccharides in Neurodegenerative Diseases

“…Such as, polysaccharide chitosan as the only essentially natural cationic polysaccharide is useful for chemical modification and electrostatic interactions in drug delivery systems in NDs ( Sarvaiya and Agrawal, 2015 ; Liu et al, 2017 ; Raj et al, 2018 ). Starch is a glucose-based polysaccharide produced by many green plants to store energy, often as an excipient in pharmaceutical products, have been used to modify the properties of drug delivery systems to improve sustained release and directly to enhance drug delivery in PD ( Odeniyi et al, 2018 ; Becker et al, 2021 ). An energy storage polysaccharide Inulin is found in plants of the Compositae family, and also indigestible to humans and digested by the enzymes of bacteria in the gut, allowing to be exploited for colon targeted delivery ( Castelli et al, 2008 ).…”

The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment

“…Moreover, it is now evident that GM dysbiosis is a factor that takes part in the development of several neurological diseases, including PD, AD, multiple sclerosis, autism spectrum disorders (ASD), anxiety, depression, schizophrenia, and other mental illnesses [ 314 , 315 ]. Concerning PD, as previously mentioned, altered GM could contribute to the onset of some PD-related complications, such as constipation, the most common non-motor symptom [ 316 ]. Therefore, modulation of the microbiota-gut-brain axis using probiotics could be a promising complementary approach to traditional methods to prevent or counteract these disorders, including PD, as widely reported in literature [ 315 , 317 , 318 , 319 , 320 ].…”

“…Concerning PD, to date, few studies have been conducted to evaluate the effects of prebiotics on PD animal models and patients ( Table 2 ) [ 316 , 346 , 372 , 373 , 374 , 375 ]. In a mouse model of PD, Perez–Pardo et al found that prebiotic fibers (FOS, GOS and nutriose, a soluble corn fibre) can normalize motor symptoms, reduce α-synuclein levels, and restore GI dysfunction, inflammation and dopamine transporter expression [ 372 ]; further, it has been shown that the prebiotic polymannuronic acid can prevent dopaminergic neuronal loss via SCFAs-mediated anti-inflammatory and anti-apoptotic mechanisms [ 373 ].…”

“…Indeed, both Astarloa et al, by administering wheat, pectin, and dimethylpolyoxyhexane-900, and Ashraf et al, by using psyllium, found a significant improvement in constipation [ 374 , 375 ]. Finally, another study investigated the effects of an oral supplementation with resistant starch, whose fermentation by anaerobic bacteria leads to the production of SCFAs, finding an increased butyrate concentration, as well as an improvement in non-motor symptoms [ 316 ].…”

Gastrointestinal Involvement in Extra-Digestive Disease: Which Is the Role of Fecal Calprotectin?

“…In addition, epidemiological data suggest an association between IBD and PD. Hor et al [ 32 ] published an interesting paper highlighting the increased levels of FC in patients with PD and MSA compared to controls. The levels are higher in MSA and in patients older than 65 years.…”