Department of Neurology, Saarland University, D-66421 Homburg, Germany.
Chair for Clinical Bioinformatics, Saarland University, D-66123 Saarbrücken, Germany.
Genomics Proteomics Bioinformatics. 2022 Apr;20(2):274-287. doi: 10.1016/j.gpb.2021.08.009. Epub 2021 Nov 25.
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'sDisease" (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.
肠道微生物群的组成与多种疾病有关,包括帕金森病(PD)。产生短链脂肪酸(SCFA)的细菌丰度和粪便 SCFA 浓度在 PD 中降低。SCFA 在人体中发挥多种有益作用。在干预性、单中心、开放性临床试验“抗性淀粉对帕金森病肠道习惯、短链脂肪酸和肠道微生物群的影响”(RESISTA-PD;ID:NCT02784145)中,我们旨在通过抗性淀粉(RS)的 8 周益生元干预来改变粪便 SCFA。我们将 87 名受试者分为三组:32 名 PD 患者接受 RS(PD+RS),30 名对照受试者接受 RS,25 名 PD 患者仅接受饮食指导。我们使用 BGISEQ 平台对粪便样本进行了平均长度为 9.9GB 的配对末端 100bp 宏基因组测序。RS 耐受性良好。在 PD+RS 组中,粪便丁酸盐浓度显著增加,RS 干预 8 周后粪便钙卫蛋白浓度显著下降。临床上,我们观察到 PD+RS 组非运动症状负荷减少。宏基因组的基于参考的分析突出了三组之间稳定的 alpha 多样性和 beta 多样性,包括产生 SCFA 的细菌。无参考分析表明,PD+RS 组的宏基因组特征存在明显但短暂的差异。RESISTA-PD 强调,RS 的益生元治疗在 PD 中是安全且耐受良好的。稳定的 alpha 多样性和 beta 多样性以及粪便丁酸盐和钙卫蛋白浓度的改变,需要进行长期研究,还需要研究 RS 是否能够改变 PD 的临床病程。
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