Effects of the antibiotic rifaximin on cortical functional connectivity are mediated through insular cortex

Abstract

It is well-known that antibiotics affect commensal gut bacteria; however, only recently evidence accumulated that gut microbiota (GM) can influence the central nervous system functions. Preclinical animal studies have repeatedly highlighted the effects of antibiotics on brain activity; however, translational studies in humans are still missing. Here, we present a randomized, double-blind, placebo-controlled study investigating the effects of 7 days intake of Rifaximin (non-absorbable antibiotic) on functional brain connectivity (fc) using magnetoencephalography. Sixteen healthy volunteers were tested before and after the treatment, during resting state (rs), and during a social stressor paradigm (Cyberball game—CBG), designed to elicit feelings of exclusion. Results confirm the hypothesis of an involvement of the insular cortex as a common node of different functional networks, thus suggesting its potential role as a central mediator of cortical fc alterations, following modifications of GM. Also, the Rifaximin group displayed lower connectivity in slow and fast beta bands (15 and 25 Hz) during rest, and higher connectivity in theta (7 Hz) during the inclusion condition of the CBG, compared with controls. Altogether these results indicate a modulation of Rifaximin on frequency-specific functional connectivity that could involve cognitive flexibility and memory processing.

The Effect of Long-Term or Repeated Use of Antibiotics in Children and Adolescents on Cognitive Impairment in Middle-Aged and Older Person(s) Adults: A Cohort Study

“…In humans, some antibiotics, cefepime, can cross the blood-brain barrier, leading to changes in mental state, loss of consciousness, myoclonus and insanity ( Payne et al, 2017 ). fMRI study also shows that antibiotic influences insular cortex functional connectivity that could involve cognitive flexibility and memory processing ( Sometti et al, 2021 ).…”

Non-alcoholic fatty liver disease in irritable bowel syndrome: More than a coincidence?

“…Rifaximin is also often used to treat SIBO[ 64 ], a condition which has been shown to affect cognitive function in a subset of patients who present with brain fog[ 65 ]. Interestingly, treatment with Rifaximin has recently been shown in brain imaging studies to alter neuronal connectivity and increase cognitive flexibility through its effect on the gut microbiome particularly in beta and theta frequencies with a particular focus on the insular cortex, a region known to be affected in patients with IBS[ 66 ]. Furthermore, Rifaximin has an immunomodulatory action counteracting the pro-inflammatory response seen in gut microbiota dysbiosis[ 67 ].…”

“…Specifically in patients with biopsy proven NASH, Rifaximin has also been shown to reduce insulin resistance, inflammation and NAFLD fat scores[ 68 ]. Therefore, the effects of Rifaximin are multifactorial including reduced endotoxemia, modulation of inflammatory cytokines, and intestinal permeability as well as changing functional brain connectivity[ 62 , 66 ].…”