<p>Early diagnosis of Parkinson’s disease (PD) and distinguishing it from essential tremor (ET) remains a significant challenge. We analyzed fecal samples (gut microbiota via 16S rRNA gene sequencing with DADA2-denoising/OTU-clustering) and short-chain fatty acids (SCFAs) in 104 drug-naïve early PD patients (73 test/31 validation), 69 ET patients (48/21), and 61 healthy controls (HC; 43/18). Differential taxa were identified using ANCOM, ANCOM-BC, ALDEx2, MaAsLin2, and LEfSe; top diagnostic potential was selected by random forest and assessed by ROC curve analysis. Compared to HC, PD showed reduced <i>Citrobacter/Haemophilus</i>, increased <i>Eggerthella</i>, and elevated isovaleric/isobutyric acids (validation AUC = 0.864). PD vs. ET exhibited decreased <i>Bilophila/Bacteroides/Haemophilus</i> with elevated isovaleric/isobutyric/valeric acids (validation AUC = 0.825). Tremor-dominant PD (TD-PD) was distinguished from ET by lower <i>Lachnoclostridium/Haemophilus/Bilophila</i> and higher <i>isovaleric/isobutyric</i> acids (validation AUC = 0.780), while non-TD-PD differed from TD-PD only in decreased Dialister (validation AUC = 0.802). Gut microbiota and SCFAs might serve as specific, non-invasive candidate biomarkers for early PD diagnosis.</p>

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Gut microbiota and SCFA biomarkers for early diagnosis of PD patients and differentiation of its motor subtypes

  • Pingchen Zhang,
  • Juanjuan Du,
  • Chao Gao,
  • Jin Liu,
  • Maoxin Huang,
  • Hongxia Li,
  • Xin Shen,
  • Yuyan Tan,
  • Shengdi Chen,
  • Pei Huang

摘要

Early diagnosis of Parkinson’s disease (PD) and distinguishing it from essential tremor (ET) remains a significant challenge. We analyzed fecal samples (gut microbiota via 16S rRNA gene sequencing with DADA2-denoising/OTU-clustering) and short-chain fatty acids (SCFAs) in 104 drug-naïve early PD patients (73 test/31 validation), 69 ET patients (48/21), and 61 healthy controls (HC; 43/18). Differential taxa were identified using ANCOM, ANCOM-BC, ALDEx2, MaAsLin2, and LEfSe; top diagnostic potential was selected by random forest and assessed by ROC curve analysis. Compared to HC, PD showed reduced Citrobacter/Haemophilus, increased Eggerthella, and elevated isovaleric/isobutyric acids (validation AUC = 0.864). PD vs. ET exhibited decreased Bilophila/Bacteroides/Haemophilus with elevated isovaleric/isobutyric/valeric acids (validation AUC = 0.825). Tremor-dominant PD (TD-PD) was distinguished from ET by lower Lachnoclostridium/Haemophilus/Bilophila and higher isovaleric/isobutyric acids (validation AUC = 0.780), while non-TD-PD differed from TD-PD only in decreased Dialister (validation AUC = 0.802). Gut microbiota and SCFAs might serve as specific, non-invasive candidate biomarkers for early PD diagnosis.