Increasing Comparability and Utility of Gut Microbiome Studies in Parkinson's Disease: A Systematic Review

Abstract

Gut microbiota have been studied in relation to the pathophysiology of Parkinson's disease (PD) due to the early gastrointestinal symptomatology and presence of alpha-synuclein pathology in the enteric nervous system, hypothesized to ascend via the vagal nerve to the central nervous system. Accordingly, sixteen human case-control studies have published gut microbiome composition changes in PD and reported over 100 differentially abundant taxa covering all taxonomic levels from phylum to genus or species, depending on methodology. While certain findings were replicated across several studies, various contradictory findings were reported. Here, differences in methodologies and the presence of possible confounders in the study populations are assessed for their potential to confound the results of gut microbiome studies in PD. Gut microbiome studies in PD exhibited considerable variability with respect to the study population, sample transport conditions, laboratory protocols and sequencing, bioinformatics pipelines, and biostatistical methods. To move from the current heterogeneous dataset towards clinically relevant biomarkers and the identification of putative therapeutic targets, recommendations are derived from the limitations of the available studies to increase the future comparability of microbiome studies in PD. In addition, integration of currently available data on the gut microbiome in PD is proposed to identify robust gut microbiome profiles in PD. Furthermore, expansion of the current dataset with atypical parkinsonism cohorts, prodromal and treatment-naïve de novo PD subjects, measurements of fecal microbial concentrations and multi-omics assessments are required to provide clinically relevant biomarkers and reveal therapeutic targets within the gut microbiome of PD.

Keywords: Parkinson disease; case-control studies; gut microbiome; systematic review.

Fig.1

Overview of screening procedure to identify case-control gut microbiome studies in Parkinson’s disease.

Fig.2

Differences in study populations and methodologies between gut microbiome studies in Parkinson’s disease (PD). (a) Study populations differed in age and sex distributions, sample size, geographical background, and the extent to which gastrointestinal confounders of gut microbiome composition were assessed. (b) Differences in PD subtypes, disease duration and PD medication regimen were linked to gut microbiome composition changes. (c) Sample collection procedures, transport conditions, DNA extraction, sequencing and the analytical and bio-informatics pipelines are known technical confounders of gut microbiome composition studies and differed across gut microbiome studies in PD. TD, tremor dominant subtype; AR/PIGD, akinetic rigid and/or postural instability and gait disorders subtypes; HC, healthy controls.