Effects of Rifaximin on Central Responses to Social Stress—a Pilot Experiment

Abstract

Probiotics that promote the gut microbiota have been reported to reduce stress responses, and improve memory and mood. Whether and how antibiotics that eliminate or inhibit pathogenic and commensal gut bacteria also affect central nervous system functions in humans is so far unknown. In a double-blinded randomized study, 16 healthy volunteers (27.00 ± 1.60 years; 9 males) received either rifaximin (600 mg/day) (a poorly absorbable antibiotic) or placebo for 7 days. Before and after the drug intervention, brain activities during rest and during a social stressor inducing feelings of exclusion (Cyberball game) were measured using magnetoencephalography. Social exclusion significantly affected (p < 0.001) mood and increased exclusion perception. Magnetoencephalography showed brain regions with higher activations during exclusion as compared to inclusion, in different frequency bands. Seven days of rifaximin increased prefrontal and right cingulate alpha power during resting state. Low beta power showed an interaction of intervention (rifaximin, placebo) × condition (inclusion, exclusion) during the Cyberball game in the bilateral prefrontal and left anterior cingulate cortex. Only in the rifaximin group, a decrease (p = 0.004) in power was seen comparing exclusion to inclusion; the reduced beta-1 power was negatively correlated with a change in the subjective exclusion perception score. Social stress affecting brain functioning in a specific manner is modulated by rifaximin. Contrary to our hypothesis that antibiotics have advert effects on mood, the antibiotic exhibited stress-reducing effects similar to reported effects of probiotics (supported by NeuroGUT, a EU 7th Framework Programme ITN no. 607652; ClinicalTrials.gov identifier number NCT02793193).

Bifidobacterium longum 1714™ Strain Modulates Brain Activity of Healthy Volunteers During Social Stress

“…Social exclusion produced differential neural oscillations in all frequency bands in various areas, such as frontal, temporal, and fusiform cortex. These results were similar to previous EEG and MEG studies, showing modulation of neural oscillations by social exclusion (14,15,17,21). Previously reported ACC activations were related to processing of negative emotions and event appraisal due to the social stress/exclusion, and PFC activation was related to emotional regulation (13,34–36).…”

“…The CBG was used to study the effects of social stress and exclusion as outlined previously by Wang et al (21). Briefly, during the CBG, participants were asked to play a virtual ball-tossing game with 2 other virtual players programmed.…”

The stress concept in gastroenterology: from Selye to today

“…However, it should be kept in mind that these experiments were frequently performed in germ-free animals colonized by single bacterial species, or complex microbiota transplanted from other animals, or “humanized” with fecal microbiota from healthy or diseased humans. Germ-free mice by themselves are questionable models for regular human gut ecology, and elimination or distortion of the gut microbiota by antibiotics is feasible only in animals, except with the locally acting antibiotic rifaximin that exerted stress-reducing effects in healthy volunteers 137 in a stress paradigm mimicking social isolation 138 .…”

Rifaximin Alters Intestinal Microbiota and Prevents Progression of Ankylosing Spondylitis in Mice

“…This special feature distinguishes rifaximin from other systemic antibiotics. Most studies up to now have focused on evaluating the effect of rifaximin on gut-liver axis or gut-brain axis (Ponziani, 2015; Wang et al, 2018). However, it is not clear whether orally administered rifaximin can prevent the development of AS by down-regulation of the inflammatory response triggered by gut microbes.…”