Probing gut-brain links in Alzheimer's disease with rifaximin.

Journal Article (Journal Article)

Gut-microbiome-inflammation interactions have been linked to neurodegeneration in Alzheimer's disease (AD) and other disorders. We hypothesized that treatment with rifaximin, a minimally absorbed gut-specific antibiotic, may modify the neurodegenerative process by changing gut flora and reducing neurotoxic microbial drivers of inflammation. In a pilot, open-label trial, we treated 10 subjects with mild to moderate probable AD dementia (Mini-Mental Status Examination (MMSE) = 17 ± 3) with rifaximin for 3 months. Treatment was associated with a significant reduction in serum neurofilament-light levels (P < .004) and a significant increase in fecal phylum Firmicutes microbiota. Serum phosphorylated tau (pTau)181 and glial fibrillary acidic protein (GFAP) levels were reduced (effect sizes of -0.41 and -0.48, respectively) but did not reach statistical significance. In addition, there was a nonsignificant downward trend in serum cytokine interleukin (IL)-6 and IL-13 levels. Cognition was unchanged. Increases in stool Erysipelatoclostridium were correlated significantly with reductions in serum pTau181 and serum GFAP. Insights from this pilot trial are being used to design a larger placebo-controlled clinical trial to determine if specific microbial flora/products underlie neurodegeneration, and whether rifaximin is clinically efficacious as a therapeutic.

Full Text

Duke Authors

Cited Authors

  • Suhocki, PV; Ronald, JS; Diehl, AME; Murdoch, DM; Doraiswamy, PM

Published Date

  • 2022

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • e12225 -

PubMed ID

  • 35128026

Pubmed Central ID

  • PMC8804600

Electronic International Standard Serial Number (EISSN)

  • 2352-8737

Digital Object Identifier (DOI)

  • 10.1002/trc2.12225

Language

  • eng

Conference Location

  • United States