Rifamixin may modulate the neural signature of social stress via our gut microbiota in healthy volunteers

Our gut microbiota may be involved in mediating interactions between the enteric nervous system and central nervous system (CNS) through the gut-brain axis. The impact of commensal gut microbes on CNS functions have been studied mostly in mice. As such, the antibiotic-induced CNS consequences of manipulating humans’ gut microbiota are still unknown.

A new double-blinded randomized study led by our research group from University Hospital Tübingen in collaboration with the International Max Planck Research School for Cognitive and Systems Neuroscience, also based in Tübingen (Germany), and within the European Training Network NeuroGUT, has found that rifaximin—a poorly absorbable antibiotic acting mainly in the gut —may exhibit stress-reducing effects by modulating our gut microbiota in a way similar to probiotics.

In the pilot study, 16 healthy normoweight volunteers (median 27 years; 9 males) received either rifaximin (600 mg/day) or a placebo for 7 days. The brain activity of participants was measured using magnetoencephalography (MEG) during a rest period and during a social stressor (Cyberball game) (review article) that induced feelings of exclusion, both before and after the antibiotic intervention. Participants’ health status was also surveyed by the 36-item short-form health survey and their acute level of distress was assessed by the self-report measures of the Need Threat Scale (NTS), Mood questionnaire (MQ) and the subjective “exclusion perception” (SEP).

MEG showed brain regions had significantly higher neural activations during the exclusion compared to the inclusion condition, which confirmed the stressful effect of the Cyberball game. This is the first study that has found how social exclusion may lead to larger neural oscillatory activities in various frequency bands in the brain.

Compared with the placebo group, rifaximin treatment led to a significantly higher increase of “emotional well-being”, measured by the SF-36 item survey. This suggests rifaximin may play a beneficial role in improving mental health by relieving stress. This finding deserves further research to explore which mechanisms are involved in the improvement of wellbeing due to rifaximin.

During resting state, rifaximin significantly increased the frontal and cingulate neural activities, and this was not correlated to the participants’ health status. Regarding rifaximin’s effect on the subjects’ neural response to the Cyberball game, a decrease in both prefrontal and cingulate neural activities was found compared with inclusion in the intervention group. A significant correlation between the exclusion perception score and neural changes was also detected, but only in the rifaximin group. The neural changes only observed in the intervention group show rifaximin’s effects on CNS function in healthy volunteers. Taking into account that this is a poorly absorbable drug, the suggestion is that the observed neural effects are brought about by affecting the gut microbiota. CNS effects may result from subsequent either metabolic, immune, or endocrine consequences.

To sum up, rifamixin may be beneficial in relieving stress, both in resting conditions and in stressful situations. Contrary to common belief, these preliminary results suggest that antibiotics could exhibit stress-reducing effects similar to the reported positive effects of probiotics on both gut and brain functions.



Wang H, Braun C, Enck P. Effects of rifaximin on central responses to social stress—a pilot experiment. Neurotherapeutics. 2018; doi: 10.1007/s13311-018-0627-2.

Wang H, Braun C, Enck P. How the brain reacts to social stress (exclusion) – A scoping review. Neurosci Biobehav Rev. 2017; 80:80-8. doi: 10.1016/j.neubiorev.2017.05.012.

Paul Enck
Paul Enck
Prof. Dr. Paul Enck, Director of Research, Dept. of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Germany. His main interests are gut functions in health and disease, including functional and inflammatory bowel disorders, the role of the gut microbiota, regulation of eating and food intake and its disorders, of nausea, vomiting and motion sickness, and the psychophysiology and neurobiology of the placebo response, with specific emphasis on age and gender contributions. He has published more than 170 original data paper in scientific, peer-reviewed journals, and more than 250 book chapters and review articles. He is board member/treasurer of the European Society of Neurogastroenterology and Motility and of the German Society of Neurogastroenterology and Motility, and has served as reviewer for many international journals and grant agencies.