한빛사
>
한빛사논문
한빛사논문
- 조회167
Microbiome, Apr 30 2025, 13 (1) 108 | https://doi.org/10.1186/s40168-025-02095-w
Distinct gut microbiome characteristics and dynamics in patients with Parkinson's disease based on the presence of premotor rapid-eye movement sleep behavior disorders
Jae-Yun Lee 1,†, Sungyang Jo 2,†, Jihyun Lee 2, Moongwan Choi 2, Kijeong Kim 2, Sangjin Lee 2, Hyun Sik Kim 1, Jin-Woo Bae 1,*, Sun Ju Chung 2,*
1Department of Biology and Department of Life and Nanopharmaceutical Science, Kyung Hee University, Seoul, 02447 Republic of Korea
2Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505 Republic of Korea
2Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505 Republic of Korea
†These authors contributed equally
*Corresponding authors: correspondence to Jin-Woo Bae or Sun Ju Chung
*Corresponding authors: correspondence to Jin-Woo Bae or Sun Ju Chung
Abstract
Background
Alpha-synuclein aggregation, a hallmark of Parkinson’s disease (PD), is hypothesized to often begin in the enteric or peripheral nervous system in “body-first” PD and progresses through the vagus nerve to the brain, therefore REM sleep behavior disorder (RBD) precedes the PD diagnosis. In contrast, “brain-first” PD begins in the central nervous system. Evidence that gut microbiome imbalances observed in PD and idiopathic RBD exhibit similar trends supports body-first and brain-first hypothesis and highlights the role of microbiota in PD pathogenesis. However, further investigation is needed to understand distinct microbiome changes in body-first versus brain-first PD over the disease progression.
Results
Our investigation involved 104 patients with PD and 85 of their spouses as healthy controls (HC), with 57 patients (54.8%) categorized as PD-RBD(+) and 47 patients (45.2%) as PD-RBD(−) based on RBD presence before the PD diagnosis. We evaluated the microbiome differences between these groups over the disease progression through taxonomic and functional differential abundance analyses and carbohydrate-active enzyme (CAZyme) profiles based on metagenome-assembled genomes. The PD-RBD(+) gut microbiome showed a relatively stable microbiome composition irrespective of disease stage. In contrast, PD-RBD(−) microbiome exhibited a relatively dynamic microbiome change as the disease progressed. In early-stage PD-RBD(+), Escherichia and Akkermansia, associated with pathogenic biofilm formation and host mucin degradation, respectively, were enriched, which was supported by functional analysis. We discovered that genes of the UDP-GlcNAc synthesis/recycling pathway negatively correlated with biofilm formation; this finding was further validated in a separate cohort. Furthermore, fiber intake-associated taxa were decreased in early-stage PD-RBD(+) and the biased mucin-degrading capacity of CAZyme compared to fiber degradation.
Conclusion
We determined that the gut microbiome dynamics in patients with PD according to the disease progression depend on the presence of premotor RBD. Notably, early-stage PD-RBD(+) demonstrated distinct gut microbial characteristics, potentially contributing to exacerbation of PD pathophysiology. This outcome may contribute to the development of new therapeutic strategies targeting the gut microbiome in PD.
Alpha-synuclein aggregation, a hallmark of Parkinson’s disease (PD), is hypothesized to often begin in the enteric or peripheral nervous system in “body-first” PD and progresses through the vagus nerve to the brain, therefore REM sleep behavior disorder (RBD) precedes the PD diagnosis. In contrast, “brain-first” PD begins in the central nervous system. Evidence that gut microbiome imbalances observed in PD and idiopathic RBD exhibit similar trends supports body-first and brain-first hypothesis and highlights the role of microbiota in PD pathogenesis. However, further investigation is needed to understand distinct microbiome changes in body-first versus brain-first PD over the disease progression.
Results
Our investigation involved 104 patients with PD and 85 of their spouses as healthy controls (HC), with 57 patients (54.8%) categorized as PD-RBD(+) and 47 patients (45.2%) as PD-RBD(−) based on RBD presence before the PD diagnosis. We evaluated the microbiome differences between these groups over the disease progression through taxonomic and functional differential abundance analyses and carbohydrate-active enzyme (CAZyme) profiles based on metagenome-assembled genomes. The PD-RBD(+) gut microbiome showed a relatively stable microbiome composition irrespective of disease stage. In contrast, PD-RBD(−) microbiome exhibited a relatively dynamic microbiome change as the disease progressed. In early-stage PD-RBD(+), Escherichia and Akkermansia, associated with pathogenic biofilm formation and host mucin degradation, respectively, were enriched, which was supported by functional analysis. We discovered that genes of the UDP-GlcNAc synthesis/recycling pathway negatively correlated with biofilm formation; this finding was further validated in a separate cohort. Furthermore, fiber intake-associated taxa were decreased in early-stage PD-RBD(+) and the biased mucin-degrading capacity of CAZyme compared to fiber degradation.
Conclusion
We determined that the gut microbiome dynamics in patients with PD according to the disease progression depend on the presence of premotor RBD. Notably, early-stage PD-RBD(+) demonstrated distinct gut microbial characteristics, potentially contributing to exacerbation of PD pathophysiology. This outcome may contribute to the development of new therapeutic strategies targeting the gut microbiome in PD.
논문정보
- Research article
- 2025년 04월 (BRIC 등록일 2025-05-07)
- 국내 연구진
- 생명과학 > 미생물학
댓글 작성 로그인
팝업 닫기관련 링크
관련분야 연구자보기
관련분야 논문보기
