Parkinson's disease - a multisystem disorder 

Parkinson's disease is a common neurodegenerative disorder characterised by a loss of neurons and associated reduced dopamine levels. This leads to characteristic motor symptoms such as tremors, muscle rigidity and balance problems. However, it's now recognized that Parkinson's is a multisystem disease that can include a variety of non-motor symptoms in addition to the motor symptoms.^1,2

Gut microbiome in Parkinson's disease

Studies have shown that there are significant differences in the gut microbiomes of people with Parkinson's disease compared to healthy individuals.^1–4 These include changes in overall community composition (also known as “beta diversity”), and an enrichment of certain types of bacteria such as Lactobacillus, Akkermansia and Bifidobacterium, and a reduction of others, such as Faecalibacterium and the family Lachnospiraceae.^1,2,4 Functional differences related to gut microbes have also been detected, for example increased levels of certain microbial metabolites such as methionine and cysteinylglycine.³

Cognitive impairment, Parkinson's & microbes

Cognitive impairment is frequently observed in people with Parkinson's disease, with severity ranging from mild cognitive impairment to Parkinson's disease dementia. Such symptoms can worsen treatment outcomes and negatively impact the quality of life. Due to the established link between gut microbes and Parkinson’s disease, the question arises whether there might also be microbial differences between people with Parkinson's who are cognitively impaired and those who are not. Before our study, only one other research group had investigated this question. They were able to detect differences in microbial diversity and in the amounts of several different kinds of bacteria related to the presence of mild cognitive impairment.⁵

Can the results be replicated?

We conducted our study to find out if the past results could be replicated in a different, geographically distinct cohort. We compared individuals representing three groups: 58 with Parkinson's disease and mild cognitive impairment, 60 with Parkinson's without cognitive impairment, and 90 cognitively normal control subjects.

We detected differences in microbial diversity between controls and the two Parkinson’s disease groups, in line with past research, but we did not see any when comparing the two Parkinson’s groups — with and without cognitive impairment — which contradicts the results of the previous study. A similar pattern emerged when we considered the amounts of specific microbes: there were many differences between the control subjects and either of the two Parkinson’s groups, but very few between the individuals with and without mild cognitive impairment. Out of them, the one that intrigued us the most was the lack of Akkermansia muciniphila in individuals with mild cognitive impairment, since this bacterium is typically more abundant in people with Parkinson's disease compared to control subjects^1–4. However, Akkermansia was not on the list of altered microbes from the previous study⁵, nor were any of the other bacteria that our comparisons suggested as potentially different in relation to cognitive impairment.

Implications

As expected, we were able to see overall gut microbiome differences between people with Parkinson's and control subjects. However, we barely saw any differences between people with Parkinson's who have mild cognitive impairment and those who do not. In other words, we could not replicate the findings of the previous study, which makes it less clear whether there is a microbial signature for Parkinson’s disease with mild cognitive impairment or not. Only additional research can definitively answer this question.

References

1. Romano, S. et al. Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation. Npj Park. Dis. 7, 1–13 (2021).
2. Heintz-Buschart, A. et al. The nasal and gut microbiome in Parkinson’s disease and idiopathic rapid eye movement sleep behavior disorder. Mov. Disord. 33, 88–98 (2018).
3. Baldini, F. et al. Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions. BMC Biol. 18, 62 (2020).
4. Kleine Bardenhorst, S. et al. Gut microbiota dysbiosis in Parkinson disease: A systematic review and pooled analysis. Eur. J. Neurol. 30, 3581–3594 (2023).
5. Ren, T. et al. Gut microbiota altered in mild cognitive impairment compared with normal cognition in sporadic Parkinson’s disease. Front. Neurol. 11, (2020).