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GUT MICROBIAL FAMILY BACTEROIDACEAE ASSOCIATES WITH MYELIN CONTENT ALTERATIONS IN MAJOR WHITE MATTER TRACTS IMPLICATED IN ALZHEIMER’S DISEASE PATHOPHYSIOLOGY
Abstract
Aims
Individuals with Alzheimer’s disease (AD) show alterations in gut microbial composition and brain myelin content. However, whether microbes and myelination are mechanistically linked is unknown. Prior murine studies demonstrate myelin is uniquely affected by experimentally altered gut microbiota, suggesting that microbial changes could lead to disturbances in myelination. Here, we tested this relationship in humans using neuroimaging and biomarker data from a cohort enriched for AD risk factors.
Methods
57 cognitively unimpaired amyloid-positive and -negative participants were recruited from the Wisconsin Alzheimer’s Disease Research Center. Quantitative myelin imaging measured brain myelin content in the forceps major, uncinate fasciculus, inferior fronto-occipital fasciculus, and cingulum. Stool samples were collected within 1.03±0.74 years of neuroimaging, and intestinal microbiota composition was characterized using 16S rRNA sequencing. QIIME2 was used to denoise (deblur) and classify features, and phyloseq (R) was used to filter rare taxa, compute relative abundances, agglomerate at the family taxonomic rank, and select microbial families Bacteroidaceae, Coriobacteriaceae, Alcaligenaceae, and Rikenellaceae. Multiple regression tested associations between microbial families and regional myelin content.
Results
Higher Bacteroidaceae relative abundance significantly associated with lower myelin content in the forceps major and inferior fronto-occipital fasciculus (Figure). There were no significant family-by-amyloid status interactions. Reported p-values are unadjusted for multiple comparisons.
Conclusions
For the first time in human subjects, we show that a gut microbial family is associated with myelin alterations. Future investigation will utilize mediation modeling to determine mechanistic linkages between microbes and myelin.