Gut microbial families associate with brain volume in cognitively unimpaired aging adults

Background The gut microbiome may be a potential modifiable risk factor for Alzheimer’s disease (AD). Studies have identified gut microbial associations with amyloid and tau pathology, however the microbiome’s preclinical relationship with neurodegeneration measures including brain gray matter (GM), white matter (WM), and total brain (TBV) volumes require further examination. For this study, we hypothesized that higher relative abundances of Ruminococcaceae, Prevotellaceae, Pasteurellaceae, Enterobacteriaceae, and Bifidobacteriacea would be associated with higher GM, WM, and TBV given prior differences in a smaller AD cohort. Method 157 cognitively unimpaired participants from the Wisconsin Alzheimer’s Disease Research Center and Wisconsin Registry for Alzheimer’s Prevention provided fecal samples and underwent T1‐weighted neuroimaging. The sample was enriched for participants with preclinical AD and APOE e4 carriage. CAT12 (SPM12) was used to process images and quantify brain volumes. 16S rRNA V4 fecal bacteria sequencing was performed using published methods. Taxa were denoised, classified, and agglomerated at the family taxonomic rank. Multiple regressions tested the associations of each bacterial family with GM and WM individually, and with total volume (GM and WM volumes summed). Covariates included age and total intracranial volume. Result Analyses focused on relationships with the afore‐mentioned families even though several others were observed in the sample. Prevotellaceae showed significant positive associations with all three brain volume measures. Pasteurellaceae showed negative correlations with GM and TBV, and no significant association with WM. Enterobacteriaceae showed a significant negative association with TBV but no significant associations with other measures of brain volume. Ruminococcaceae and Bifidobacteriaceae had no significance with all measures of brain volume. Conclusion Greater abundance of Prevotellaceae was associated with larger volumes. Prevotellaceae are known to be diminished in Parkinson’s disease, and produce short chain fatty acids which maintain intestinal barrier integrity. Higher Enterobacteriaceae was associated with lower total volume, consistent with prior studies showing Enterobacteriaceaeare elevated in AD. Higher Pasteurellaceae was associated with smaller TBV; some bacteria in the family Pasteurellaceae are pathogenic and are associated with disease, possibly explaining this association. Ruminococcaceae and B