Expert Comment: Susanna Lindvall from European Parkinson’s Disease AssociationPrint this page 30 Jun 2014
Susanna Lindvall, Vice-President of the European Parkinson’s Disease Association, shares her thoughts on possible explanations for the negative association between coffee and Parkinson’s disease for our quarterly news bulletin.
New hypothesis regarding coffee consumption in Parkinson’s disease
We know from existing literature that coffee drinkers have a lower risk of Parkinson’s disease. The explanation for this finding is not known but there are two main hypotheses. One is that people with Parkinson’s dislike drinking coffee, while the other that caffeine is neuroprotective.
A recent publication1, however – by Pascal Derkinderen, Kathleen M Shannon and Patrik Brundin – proposes an alternative hypothesis, in which coffee consumption changes the composition of the gut flora in a way that it decreases intestinal inflammation. This, in turn, would lead to less misfolding of the protein alphasynuclein, thereby reducing the risk of Parkinson’s by minimising propagation of the protein aggregates to the central nervous system, where they otherwise can induce neurodegeneration.
The authors suggest that the explanation lies in the digestive tract and, more precisely, in the gut flora, which consists of around a hundred trillion microorganisms surpassing the metabolic potential of our body.2 The influence of the gut flora is not limited to local effects but also extends to remote organs, particularly the brain.3,4
In healthy subjects, the intestinal gut flora is generally stable over time, but compositional changes might occur after antibiotic usage or dietary modifications.2 Diseases associated with impaired gastrointestinal motility, such as diabetes mellitus and Parkinson’s, are predisposed for small intestinal bacterial overgrowth, a malabsorption syndrome associated with increased bacterial density in the gut.5,6
Braak et al put forth the so-called “dual hit hypothesis”, stipulating that Parkinson’s may be triggered by a hitherto unknown neurotropic agent, presumed to be a virus, which initially affects the gut and the olfactory system, causing alpha-synuclein aggregation.7 Thereafter, according to the hypothesis, the neurotropic agent propagates through the nervous system, giving rise to Lewy pathological conditions on the way and eventually, after several years, reaching the substantia nigra. A possible explanation comes from the anti-inflammatory properties of some bacterial stains such as Bifidobacterium, whose activity and proportion are upregulated by coffee drinking.8
One therefore might suggest that in the absence of coffee drinking, the microbiota would shift toward a pro-inflammatory state. This would promote chronic gastrointestinal inflammation and an enteric glial reaction, which actually have been shown to occur in the early stage of Parkinson’s.9 Coffee consumption – by decreasing the release of proinflammatory cytokines from the gut to the bloodstream – may reduce central nervous system neurodegeneration.
The authors suggest that complex studies would be required to determine whether a link exists between drinking coffee, changes in the gut microbe composition, and a lower risk of Parkinson’s.
1. Gut feelings about smoking and coffee in Parkinson’s disease. Derkinderen P, Shannon KM, Brundin P., Mov Disord. 2014 Apr 21. doi: 10.1002/mds.25882. [Epub ahead of print]
2. Lozupone CA, Stombaugh JI, Gordon JI, et al. Diversity, stability and resilience of the human gut microbiota. Nature 2012;489:220-230.
3. Forsythe P, Kunze WA, Bienenstock J. On communication between gut microbes and the brain. Curr Opin Gastroenterol 2012;28:557-562.
4. Collins SM, Surette M, Bercik P. The interplay between the intestinal microbiota and the brain. Nat Rev Microbiol 2012;10:735-742.
5. Gabrielli M, Bonazzi P, Scarpellini E, et al. Prevalence of small intestinal bacterial overgrowth in Parkinson’s disease. Mov Disord 2011;26:889-892.
6. Fasano A, Bove F, Gabrielli M, et al. The role of small intestinal bacterial overgrowth in Parkinson’s disease. Mov Disord 2013;28:1241-1249.
7. Hawkes CH, Del Tredici K, Braak H. Parkinson’s disease: a dualhit hypothesis. Neuropathol Appl Neurobiol 2007;33:599-614.
8. Jaquet M, Rochat I, Moulin J, et al. Impact of coffee consumption on the gut microbiota: a human volunteer study. Int J Food Microbiol 2009;130:117-121.
9. Devos D, Lebouvier T, Lardeux B, et al. Colonic inflammation in Parkinson’s disease. Neurobiol Dis 2013;50:42-48.
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