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Parkinson’s disease (PD) is one of the most prevalent neurodegenerative diseases with pathological hallmarks including the formation of Lewy bodies, which occur in the caudal brainstem and then in most cases, progress through the upper brainstem and limbic regions [1]. This localisation in the brain is why PD is classified as a neurodegenerative disease; however, symptoms also manifest in the gut. Up to 80% of PD patients report gastrointestinal symptoms including constipation, with some of these reports even pre-dating the onset of neurological symptoms by 10 to 20 years [2]. Scientists have proposed that this body-type PD subtype is caused by abnormal α-synuclein aggregation in enteric neurons and that pathology spreads to the brain, with damage to noradrenergic nuclei in the locus coeruleus [2]. In addition, those with PD show an abundance of certain inflammatory markers in the gut, including IL-1β, CXCL8, C-reactive protein, and calprotectin [2]. There is also an increased permeability in the gut, with studies showing high levels of barrier dysfunction markers, for example, zonulin [2]. Dysfunctional epithelial barrier function is seen in gut-derived diseases such as inflammatory bowel disease (IBD), so it is perhaps unsurprising that epidemiology studies have shown an association between PD and IBD, with IBD patients more likely to develop PD in later life [2].
To investigate this link further, Krueger et al. analysed the gut microbiome of PD and IBD patients for potential microbial links that may lend itself to symptom onset and disease progression [2]. They used several metagenomic analysis methods to compare their own data as well as publicly available data sets, for example, they used HUMAnN3.5 to evaluate taxonomic differences as well as the ability of the microbes to perform different biological functions based on genes by mapping gene families [2]. Across both PD and IBD data sets, there were depletions in short-chain fatty acid (SCFA)-producing bacteria including Faecalibacterium prausnitzii, Anaerostipes hadrus and Roseburia intestinalis [2]. Similarly, reduction in butyrate-producing bacteria in IBD patients could impact host immunity and cause a predisposition to systemic inflammation which subsequently is causing downstream neuroinflammation and a higher risk of PD [2]. It is likely that there are mechanistic similarities between PD and IBD with regards to the gut microbiome, and this could be a potential therapeutic target for treatment [2]. With the rise of probiotic and live biotherapeutic research, supplementation of SCFA-producing bacteria could be an avenue to explore with regards to treatment, as this kind of supplementation is showing promising results in current scientific research.
Whilst in terms of classification, PD will most likely always be regarded as a neurodegenerative disease, it is important not to forget the significant gastrointestinal link. Further research into the disease-microbiome link in PD and gastrointestinal diseases such as IBD is vital for therapeutic potential, and it is hoped that scientists continue to explore the gut microbiome as this could be the solution to revolutionary PD and IBD treatments.
References
- Tolosa E, Garrido A, Scholz SW, Poewe W. Challenges in the diagnosis of Parkinson’s disease. Lancet Neurol. 2021 May;20(5):385–97.
- Krueger M, Boles J, Simon Z, Alvarez S, et al. Comparative analysis of Parkinson’s and inflammatory bowel disease gut microbiomes reveals shared butyrate-producing bacteria depletion. Nature. 2025;11(50).
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