Gut microbiome is not associated with mild cognitive impairment in Parkinson’s disease Original paper

What was studied?

This study investigated whether the gut microbiome harbors a distinct microbial signature associated with mild cognitive impairment (MCI) in individuals with Parkinson’s disease (PD). Prior research has established significant differences in the gut microbiome between PD patients and healthy controls, but the question of whether specific gut microbiome changes are linked to cognitive decline within PD remained unresolved. Using fecal samples and 16S rRNA gene sequencing, the authors compared gut microbial diversity and composition across three groups: PD patients with MCI (PD-MCI), PD patients without cognitive impairment (PD-NC), and cognitively normal control subjects. The primary goal was to determine if MCI in PD is associated with unique microbiome alterations, beyond those observed in PD itself.

Who was studied?

The study analyzed data from 208 individuals after stringent exclusion criteria. The cohort comprised 58 people with PD-MCI, 60 with PD-NC, and 90 cognitively unimpaired controls, all drawn from the Luxembourg Parkinson’s Study (NCER-PD). Controls were age-matched and excluded if genetically related to PD subjects. Participants met the UK Parkinson’s Disease Society Brain Bank criteria for PD, and cognitive status was determined using Movement Disorder Society (MDS) taskforce criteria and the Montreal Cognitive Assessment (MoCA). Exclusions included subjects under 65 years (to address age imbalance), those with insufficient sequencing data, recent immunosuppressant or corticosteroid use, and incomplete clinical information. Clinical variables such as disease duration, constipation, medication use, and body mass index were recorded and adjusted for in the analysis.

Most important findings

The study found robust differences in gut microbial composition between PD patients (both PD-MCI and PD-NC) and controls, consistent with prior literature. PD groups had lower microbial diversity and distinct beta diversity compared to controls, with notable decreases in families such as Lachnospiraceae, Clostridiaceae, and Butyricicoccaceae, and increases in Enterobacteriaceae, Hungatella, and Methanobrevibacter. However, critically, no significant differences in overall microbiome diversity or community structure were observed between PD-MCI and PD-NC. In taxon-level analyses, only one out of three statistical tools (DESeq2) detected several taxa differing between PD-MCI and PD-NC, but these findings were not corroborated by the other methods and did not overlap with results from the only previous study on this topic. Among the few detected, Streptococcus was increased and Akkermansia muciniphila decreased in PD-MCI, but these were isolated results lacking replication. Thus, the data do not support the existence of a reproducible gut microbiome signature specific to MCI in PD.

Key implications

For clinicians and researchers, these findings indicate that while gut microbiome alterations are a hallmark of PD, there is currently no consistent or clinically actionable microbial signature distinguishing PD with MCI from cognitively intact PD. This suggests that gut microbiome-based biomarkers are unlikely to aid in the identification or risk stratification of MCI within PD populations at present. The absence of reproducible taxonomic differences, even in a larger and geographically distinct cohort, underscores the need for further research—potentially involving larger, multi-omic, or longitudinal designs—to clarify whether subtle or dynamic microbiome changes contribute to cognitive decline in PD. For clinical practice, gut microbiome profiles should not yet be used to inform the assessment of cognitive impairment in PD.

Citation

Aho VTE, Klee M, Landoulsi Z, et al; on behalf of the NCER-PD Consortium. Gut microbiome is not associated with mild cognitive impairment in Parkinson’s disease. npj Parkinson’s Disease. 2024;10:78. doi:10.1038/s41531-024-00687-1