Objective: Quantify total microbial load in the gut microbiome of people with Parkinson’s disease (PD) and compare the absolute abundance of bacterial taxa between PD and non-PD. Additionally, to correlate differentially abundant taxa with immune transcriptomic profiles.

Background: Previous studies have identified differences in the relative abundance of bacterial taxa between PD and non-PD. However, relative abundance measures are inherently proportional, meaning that an increase in one taxon leads to a perceived decrease in others, even if their absolute concentrations remain unchanged. This hinders the ability to accurately quantify microbial dysbiosis and its potential mechanistic role in disease pathology. To address this gap, we measure total microbial load and absolute abundance differences in bacterial taxa between PD and non-PD. 96% of non-PD controls share a household with a PD participant, helping to disentangle the influence of the environment from the effects of disease. By integrating these novel data with peripheral blood mononuclear cell (PBMC) RNA sequencing, we aim to define a distinct microbial signature of PD and correlate this with immune transcriptomic profiles.

Method: Participants (n=112 PD, n=83 non-PD) provided blood and stool samples and completed a lifestyle questionnaire. DNA was extracted using Qiagen QIAamp PowerFecal Pro DNA kit. ddPCR quantification of 16S rRNA gene was performed. We applied cell type deconvolution to bulk PBMC RNA-seq data to infer immune cell proportions and estimate cell-type-specific gene expression profiles, similar to scRNA-seq, in PD and non-PD samples.

Results: The total microbial load is decreased in PD compared to non-PD, as measured by total 16S rRNA copies per dry gram of stool (p<.005). In addition, the comparison of differential absolute abundance analyses with published differential relative abundance yielded both complementary and contradictory insights, underscoring the limitations of relying solely on relative abundance data. Analysis of PBMC RNA sequencing is in process at time of writing.

Conclusion: Absolute abundance offers a more precise and biologically meaningful representation of microbiome alterations in PD.  By integrating these data with PBMC RNA sequencing, we can identify microbiome-immune interactions that may underlie disease mechanisms.

Total microbial load

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MDS Abstracts - https://www.mdsabstracts.org/abstract/advancements-in-microbiome-research-total-microbial-load-differential-absolute-abundance-and-correlations-with-immune-transcriptomics/