Enriched Environmental Conditions Modify the Gut Microbiome Composition and Fecal Markers of Inflammation in Parkinson’s Disease

Yogesh Singh,Nicolas Casadei,Mohamed El-Hadidi,Olaf Riess,Julia M. Schulze-Hentrich,Daniel Huson,Ursula Kohlhofer,Jakob Admard,Leticia Quintanilla-Martinez,Zinah Wassouf

doi:10.3389/fnins.2019.01032

Yogesh Singh, Nicolas Casadei + Show 8 more

Open Access

https://doi.org/10.3389/fnins.2019.01032

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Abstract

Recent findings suggest an implication of the gut microbiome in Parkinson’s disease (PD) patients. PD onset and progression has also been linked with various environmental factors such as physical activity, exposure to pesticides, head injury, nicotine, and dietary factors. In this study, we used a mouse model, overexpressing the complete human SNCA gene (SNCA-TG mice) modeling familial and sporadic forms of PD to study whether environmental conditions such as standard vs. enriched environment changes the gut microbiome and influences disease progression. We performed 16S rRNA DNA sequencing on fecal samples for microbiome analysis and studied fecal inflammatory calprotectin from the colon of control and SNCA-TG mice kept under standard environment (SE) and enriched environment (EE) conditions. The overall composition of the gut microbiota was not changed in SNCA-TG mice compared with WT in EE with respect to SE. However, individual gut bacteria at genus level such as Lactobacillus sp. was a significant changed in the SNCA-TG mice. EE significantly reduced colon fecal inflammatory calprotectin protein in WT and SNCA-TG EE compared to SE. Moreover, EE reduces the pro-inflammatory cytokines in the feces and inflammation inducing genes in the colon. Our data suggest that an enriched social environment has a positive effect on the induction of SNCA mediated inflammation in the intestine and by modulating anti-inflammatory gut bacteria.

Highlights

Chronic inflammation is a key process in the progression of Parkinson’s disease (PD) (Li et al, 2016)
We aim to investigate if the expression of α-Syn in the gut of a humanized mouse model of PD can be influenced by EE conditions and explore how EE conditions interact with the gut microbiome to affect the inflammation in the gut
Using IHC, we investigated the expression of the transgenic α-Syn in the gastrointestinal tract of the SNCA-TG mice and observed presence of the human α-Syn protein in the colon and the entire gut including stomach, ileum, cecum, and rectum, respectively (Figure 1A and Supplementary Figure S1)

Summary

Introduction

Chronic inflammation is a key process in the progression of Parkinson’s disease (PD) (Li et al, 2016). Multiple studies showed a progression of the pathology ( termed either α-Synucleinopathy or Synucleinopathy) through the brain (Braak et al, 2003; Visanji et al, 2014), other studies proposed a possible spread of the disease from neurons to neurons via seeding of α-Syn in the peripheral nervous system (Li et al, 2008; Luk et al, 2009). In addition to the genetic factors, external or unknown internal factors inducing α-Syn aggregation or expression such as environmental conditions, diet or lifestyle, bacterial metabolites and self-antigens may trigger or enhance PD (Yamin et al, 2003; Bischoff et al, 2014; Klingelhoefer and Reichmann, 2015; Kotloski and Sutula, 2015; Mulak and Bonaz, 2015; Felice et al, 2016; Sulzer et al, 2017; Caputi and Giron, 2018; Erro et al, 2018). EE conditions could possibly exert neuroprotective effects on neurons and delay pathogenesis in PD (Jadavji et al, 2006; Nithianantharajah and Hannan, 2006; Kotloski and Sutula, 2015)

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