Probing Gut-Brain Links in Alzheimer’s Disease with Rifaximin

This is the authors' abstract. We don't add key points for this paper.

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 (MMSE = 17 ± 3) with rifaximin for 3 months. Treatment was associated with a significant reduction in serum neurofilament-light levels (p <0.004) and a significant increase in fecal phylum Firmicutes microbiota. Serum pTau181 and GFAP levels were reduced (effect sizes of -0.41 and -0.48 respectively) but did not reach significance. There was also a non-significant downward trend in serum cytokine IL-6 and IL-13 levels. Increases in stool Erysipelatoclostridium were correlated significantly with reductions in serum pTau 181 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. Research in Context Systematic Review PubMed reviews showed emerging evidence for gut-microbiome-inflammation links in Alzheimer’s disease (AD). Interpretation Our pilot study revealed that rifaximin, a minimally absorbed, gut-specific antibiotic, reduced surrogate markers of neurodegeneration while increasing, potentially beneficial, microbiota in phylum Firmicutes. These data provide initial support to the hypothesis that microbiome related products may play a role in neurodegenerative disorders. Future Directions We plan to conduct additional human and pre-clinical studies to confirm these findings and determine the potential of rifaximin as a therapeutic for AD.