Curli Carrier Burden: a quantitative trait-level microbiome index for amyloidogenic bacterial signals in Parkinsons disease gut metagenomes

Abstract

BackgroundParkinsons disease (PD) gut metagenomic studies have repeatedly reported disease-associated shifts in microbial taxa, genes, and pathways. However, the field still lacks transparent trait-level indices that summarize biologically coherent microbial exposures. Curli fibres are extracellular bacterial amyloids produced by several Enterobacteriaceae and related taxa, and they provide a plausible microbiological bridge between gut microbial ecology, epithelial/immune interfaces, and alpha-synuclein-centered gut-brain-axis hypotheses. We introduced Curli Carrier Burden (CCB), a mathematically explicit, taxon-informed index that estimates the aggregate abundance of curated curli-carrier bacterial taxa in processed metagenomic profiles. MethodsA curated curli-carrier candidate panel was converted into an evidence-weighted taxon set. For sample s, CCB was defined as [Formula], where ais is the processed relative abundance of matched curli-carrier taxon i and wi is an evidence weight reflecting curli-carrier confidence. We evaluated CCB in five main PD gut metagenomic evidence streams: Wallen 2022, Integrated-US, Mao Central China, Romano non-Wallen, and DuruIC 2024. Results were interpreted cohort-wise rather than as a formal meta-analysis. ResultsThe CCB framework generated a reproducible sample-level microbial trait variable and enabled cohort-wise comparison of amyloidogenic bacterial burden. Wallen showed discovery-stage PD-associated elevation (724 samples; 31 matched curli taxa; Mann-Whitney p = 0.0020). Integrated-US provided supportive independent evidence (244 samples; 18 matched taxa; p = 0.0079). Mao Central China and DuruIC 2024 showed the same PD-greater-than-control direction by mean and median CCB, although their individual comparisons were not nominally significant. Romano non-Wallen provided a large multi-study analysis (600 samples; 29 matched curli-associated mOTUs taxa), with higher PD mean and median CCB in pooled analysis (p = 0.0036, Cliffs{delta} = 0.137) and cohort-sensitive behavior under study-stratified permutation (p = 0.1974). Additional processed-cohort checks indicated that CCB interpretability depends on taxonomic representation and matched curli-candidate coverage, reinforcing the value of explicit compatibility reporting. ConclusionsCCB is a novel, extensible, microbiology-informed index for quantifying amyloidogenic curli-carrier bacterial burden in processed gut metagenomic profiles. The current results support CCB as a useful exploratory trait-level variable for PD microbiome research and provide a principled route toward future raw-read, csg-operon, strain-resolved, and phenotype-aware studies of the curli-vagal PD axis.