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

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.