Abstract
ObjectiveEmerging evidence suggests that gut microbiome composition alterations affect neurodegeneration through neuroinflammation in the pathogenesis of Parkinson’s disease (PD). Here, we evaluate gut microbiota alterations and host cytokine responses in a population of Taiwanese patients with PD.MethodsFecal microbiota communities from 80 patients with PD and 77 age and gender-matched controls were assessed by sequencing the V3–V4 region of the 16S ribosomal RNA gene. Diet and comorbidities were controlled in the analyses. Plasma concentrations of IL-1β, IL-2, IL-4, IL-6, IL-13, IL-18, GM-CSF, IFNγ, and TNFα were measured by a multiplex immunoassay and relationships between microbiota, clinical characteristics, and cytokine levels were analyzed in the PD group. We further examined the cytokine changes associated with the altered gut microbiota seen in patients with PD in another independent cohort of 120 PD patients and 120 controls.ResultsMicrobiota from patients with PD was altered relative to controls and dominated by Verrucomicrobia, Mucispirillum, Porphyromonas, Lactobacillus, and Parabacteroides. In contrast, Prevotella was more abundant in controls. The abundances of Bacteroides were more increased in patients with non-tremor PD subtype than patients with tremor subtype. Bacteroides abundance was correlated with motor symptom severity defined by UPDRS part III motor scores (rho = 0.637 [95% confidence interval 0.474 to 0.758], P < 0.01). Altered microbiota was correlated with plasma concentrations of IFNγ and TNFα. There was a correlation between Bacteroides and plasma level of TNFα (rho = 0.638 [95% CI: 0.102–0.887], P = 0.02); and a correlation between Verrucomicrobia abundance and plasma concentrations of IFNγ (rho = 0.545 [95% CI − 0.043–0.852], P = 0.05). The elevated plasma cytokine responses were confirmed in an additional independent 120 patients with PD and 120 controls (TNFα: PD vs. control 8.51 ± 4.63 pg/ml vs. 4.82 ± 2.23 pg/ml, P < 0.01; and IFNγ: PD vs. control: 38.45 ± 7.12 pg/ml vs. 32.79 ± 8.03 pg/ml, P = 0.03).ConclusionsThis study reveals altered gut microbiota in PD and its correlation with clinical phenotypes and severity in our population. The altered plasma cytokine profiles associated with gut microbiome composition alterations suggest aberrant immune responses may contribute to inflammatory processes in PD.
Highlights
Parkinson’s disease (PD) is a common neurodegenerative disorder and is caused by a combination of genetic and environmental risk factors [1]
Altered cytokine responses in PD patients with alterations in taxonomic compositions of the gut microbiota Because gut microbial dysbioses are often accompanied by abnormal production of inflammatory cytokines such as IL-1β, IL-22, and IFNγ [15, 20], we investigated whether there are specific cytokine responses correlated with the relative abundances of the candidate genera associated with risk for or motor severity of PD, including Verrucomicrobia, Prevotella, Mucispirillum, Porphyromonas, Lactobacillus, Parabacteroides, and Bacteroides
Our results demonstrate that specific genera of gut microbiota may associate with the risk and severity of PD in our population, and extend the current knowledge to glimpse the complexity of the interaction between gut microbiome composition alterations and host immune responses in PD pathogenesis
Summary
Parkinson’s disease (PD) is a common neurodegenerative disorder and is caused by a combination of genetic and environmental risk factors [1]. Emerging evidence suggests that gut microbiota may act as environmental triggers to promote neuronal degeneration and motor dysfunction through microglial activation in α-synuclein-overexpressing mice [4]. These observations are consistent with the altered gut microbiomes reported in patients with PD [5,6,7,8,9,10,11,12], the reported gut bacterial profiles are heterogeneous. We characterize fecal microbiota and peripheral cytokine alterations in a Taiwanese PD population and analyze the relationships between changes of fecal microbiota and PD clinical characteristics
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