# Nocardia cyriacigeorgica Elicits Gut Disturbances in a Leaky Gut Model of Colitis, but Not the Harmful Cascade Leading to Gut-First Parkinson’s Disease

## TL;DR

This study explores how a specific bacterium affects gut health and its potential link to Parkinson’s disease, but finds it doesn’t trigger the harmful cascade leading to the disease.

## Contribution

The novel finding is that mitochondrial dysfunction and aSyn aggregation alone, without gut leakage, do not cause gut-first Parkinson’s disease.

## Key findings

- Nocardia cyriacigeorgica causes gut disturbances in a colitis model.
- The harmful cascade leading to gut-first Parkinson’s disease is not triggered by aSyn aggregation and mitochondrial dysfunction alone.
- Intestinal barrier leakage is a necessary factor for gut-first Parkinson’s disease onset.

## Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder with an unknown cause. Recent research has highlighted the importance of the gut in neuronal and immune maturation through the exchange of nutrients and cellular signals. This has led to the “gut-first PD” hypothesis, which aims to explain many of the sporadic cases and their prodromal intestinal symptoms, such as constipation and intestinal α-synuclein (aSyn) aggregation. The link between mitochondrial dysfunction and aSyn deposition is central to PD pathophysiology, since they can also trigger pro-inflammatory signals associated with aSyn deposition, potentially contributing to the onset of PD. As mitochondria are derived from ancestral alpha-proteobacteria, other bacteria may specifically target this organelle. We sought to use Nocardia cyriacigeorgica, a bacterium previously associated with parkinsonism, and dextran sulfate sodium (DSS) as pro-inflammatory modulators to gain further insight into the onset of PD. This study indicates that aSyn aggregation plus mitochondrial dysfunction without intestinal barrier leakage are not sufficient to trigger gut-first PD.