The gut-brain axis: is intestinal inflammation a silent driver of Parkinson’s disease pathogenesis?

Abstract

The state of the intestinal environment can have profound effects on the activity of the central nervous system through the physiological contributions of the microbiota, regulation of intestinal barrier function, and altered activity of peripheral neurons. The common language employed for much of the gut-brain communication is the modulation of immune activity. Chronic proinflammatory immune activity is increasingly being recognized as a fundamental element of neurodegenerative disorders, and in Parkinson’s disease, inflammation in the intestine appears particularly relevant in pathogenesis. We review the evidence that intestinal dysfunction is present in Parkinson’s disease and that it may reflect the earliest manifestations of Parkinson’s disease pathology, and we link these findings to dysregulated immune activity. Based on this, we present a model for Parkinson’s disease pathogenesis in which the disorder originates in the intestine and progresses with inflammation as its underlying mechanism. More in-depth investigations into the physiological mechanisms underlying peripheral pre-motor symptoms in Parkinson’s disease are expected to lead to the development of novel diagnostic and therapeutic measures that can slow or limit progression of the disease to more advanced stages involving debilitating motor and cognitive symptoms.

Which way does the axis tip? IBD increases the risk of Parkinson’s disease

“…These findings are consistent with basic research implicating the link between the central and enteric nervous system, also known as the gut–brain axis, in parkinsonism 2. Intestinal inflammation, a characteristic of uncontrolled IBD, may lead to a neural inflammation via the gut–brain biochemical signalling.…”

Inflammatory bowel disease increases the risk of Parkinson’s disease: a Danish nationwide cohort study 1977–2014

“…This so-called ‘gut-brain axis’ is believed to link functions of the brain with peripheral intestinal functions 2. Especially, unbalances in the intestinal microbiome in relation to neurological diseases have recently taken the spotlight, with studies relating PD with a more proinflammatory gut milieu 21.…”

“…IBD is characterised by chronic proinflammatory immune activity, a trait which is now also suggested to be a fundamental element of neurodegenerative disorders. Intestinal inflammation may be of particular relevance in the pathogenesis of parkinsonism, including Parkinson’s disease (PD)2 and multiple system atrophy (MSA).…”

Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson's Disease: A Critical Review

“…146 The hypothetical basis for this theory is that the gut bacteria may be responsible for chemicals which are over activating parts of the brain, 147 leading to a-synuclein damage and its deposition which ultimately causes neurodegeneration in the brain resulting in PD. 148 It is important, therefore, to have a forward step to define the specific gut microbes that may contribute to the development of PD, as this could translate into novel biomarkers to identify at-risk patients at a very early stage in the disease progression. These findings may possibly lead to novel therapeutic approaches that avoid the existing complications of drugs delivered to the brain and may also become safer and more effective to the ailing patients.…”