Associations between gut microbial families and brain myelin in a human cohort

Abstract

AbstractBackgroundWe previously reported brain myelin (Dean et al, 2017) and gut microbial composition alterations (Vogt et al, 2017) in Alzheimer’s disease (AD). Prior animal studies suggest that myelin is impacted by experimentally altered gut microbiota (Keogh et al, 2021), suggesting that gut microbiota may be linked to brain myelination. However, little is yet known about the human gut microbiome and myelin alterations in the context of AD. Here, we examined the gut‐brain association in humans using biomarker and neuroimaging data.MethodAmyloid positive (n=27) and negative (n=91) participants from the Wisconsin Alzheimer’s Disease Research Center and the Wisconsin Registry for Alzheimer’s Prevention were included based on completion of one MPnRAGE (Kecskemeti et al., 2018) scan and donation of one stool sample. Myelin was assessed using MPnRAGE‐derived quantitative R1 and myelin content in 9 white matter tracts were examined as primary outcomes (Table). Intestinal microbiota composition was characterized using 16S rRNA sequencing of fecal samples. QIIME2 was used to denoise and classify features. Phyloseq was used to filter rare taxa, compute relative abundances, and agglomerate at the family taxonomic rank, resulting in 35 microbial families used as primary predictors. Multiple regression was used to test associations between each microbial family and regional myelin content. Benjamini‐Hochberg false discovery rate (FDR) adjustment was applied post‐regression; results were considered significant at q<.05.ResultMicrobial family Turicibacteraceae was positively associated with myelin indexed by R1 (Figure) in the forceps minor (b=.014, q=.037) and uncinate fasciculus (b=.011, q=.028). Across all white matter tracts, higher age was associated with lower R1. Interestingly, there was a significant Paraprevotellaceae‐by‐amyloid effect in the superior longitudinal fasciculus (b= ‐.017, p =.031) and Clostridiaceae‐by‐amyloid effect in the forceps major (b=.002, p=.037) though neither interaction survived FDR correction.ConclusionIn both the uncinate fasciculus and forceps minor, higher levels of Turicibacteraceae were associated with greater myelin content. Turicibacteraceae were previously identified as less abundant among individuals with AD; the current study’s microbial associations with large white matter tracts that are altered in AD warrants further study. Future studies will test additional metrics of AD pathology to clarify gut microbe and brain relationships.