Gut microbiota and metabolites of α-synuclein transgenic monkey models with early stage of Parkinson’s disease

Abstract

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease. However, it is unclear whether microbiota and metabolites have demonstrated changes at early PD due to the difficulties in diagnosis and identification of early PD in clinical practice. In a previous study, we generated A53T transgenic monkeys with early Parkinson’s symptoms, including anxiety and cognitive impairment. Here we analyzed the gut microbiota by metagenomic sequencing and metabolites by targeted gas chromatography. The gut microbiota analysis showed that the A53T monkeys have higher degree of diversity in gut microbiota with significantly elevated Sybergistetes, Akkermansia, and Eggerthella lenta compared with control monkeys. Prevotella significantly decreased in A53T transgenic monkeys. Glyceric acid, L-Aspartic acid, and p-Hydroxyphenylacetic acid were significantly elevated, whereas Myristic acid and 3-Methylindole were significantly decreased in A53T monkeys. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (KO0131) and the oxidative phosphorylation reaction (KO2147) were significantly increased in metabolic pathways of A53T monkeys. Our study suggested that the transgenic A53T and α-syn aggregation may affect the intestine microbiota and metabolites of rhesus monkeys, and the identified five compositional different metabolites that are mainly associated with mitochondrial dysfunction may be related to the pathogenesis of PD.

The Gut–Brain Axis and Its Relation to Parkinson’s Disease: A Review

“…Various studies over the past few decades have observed distinct differences in microbiota composition between individuals with and without PD, as well as between individuals with different PD phenotypes of symptomology (Heintz-Buschart et al, 2018;Heinzel et al, 2021). A recent study observed differences in the microbiota (elevated Akkermansia, Eggerthella, and Synergistetes; depleted Prevotella) between A53T transgenic monkeys with early-stage PD and control monkeys (Yan et al, 2021a). These results extend upon commonly observed microbiota differences between human PD patients and healthy controls to an earlier timepoint of disease progression.…”

Mechanistic Insights Into Gut Microbiome Dysbiosis-Mediated Neuroimmune Dysregulation and Protein Misfolding and Clearance in the Pathogenesis of Chronic Neurodegenerative Disorders

“…The genus Akkermansia is consistently enriched in human PD patients versus healthy controls, and the data corroborate recent findings in an A53T α-synuclein Tg non-human primate model. Investigators noted a higher diversity of microbial flora with significant increases in abundance of Akkermansia, Sybergistetes, and Eggerthella lenta (Nishiwaki et al, 2020;Yan et al, 2021). As a mucin-degrading bacteria, Akkermansia spp.…”

Dietary fibre deprivation and bacterial curli exposure shift gut microbiome and exacerbate Parkinson's disease-like pathologies in an alpha-synuclein-overexpressing mouse

“…diet, impact the gut microbiome (Bernardo-Cravo et al 2020;Singh et al 2019). Changes in gut microbial composition in PD has been described extensively in humans (Boertien et al 2019;Gerhardt and Mohajeri 2018;Heintz-Buschart et al 2018;Keshavarzian et al 2015;Scheperjans et al 2015;Shen et al 2021;Unger et al 2016), but also more and more in different animal models (Gorecki et al 2019;Sampson et al 2016;Yan et al 2021). Using 16S rRNA amplicon sequencing, our goal was to understand how the disease challenges affected, independently or in combination, the microbial phenotype in our mice.…”