Effects of probiotics on central nervous system functions in humans

Abstract

Gut microbiota plays an important role in the gut-brain axis. Symbiosis of the gut microbiota maintains the physiological integrity of the host so as to ensure the normal functions of the gut and the brain. Probiotics have beneficial effects on both, physical and mental health, when administered in adequate amount. Thus, probiotics are considered as “psychobiotics”, for their effects on central nervous system functions such as stress-related mental disorders and memory abilities, through the gut-brain axis. However, the efficacy of the probiotics on these central functions was in need to be systematically summarized. While there is a host of animal studies on microbiota, it has not yet been studied much how and where in the brain of humans they unfold their effects. Furthermore, antibiotics, having effects on commensal gut bacteria by eliminating and inhibiting them, have so far not been studied for their role in affecting brain functions. In the current thesis, I performed two literature reviews and two experimental studies on central effects of pro- and antibiotics. The first review systematically analyzed previous research studying the effects of probiotics on central nervous system functions in both, animals and humans. The review concluded the most efficient probiotic interventions and evaluated the possibility of translating preclinical studies to clinical trials. In the second review, we aimed to evaluate the feasibility of a socio-psychological paradigm (Cyberball game) to be used in the following experimental studies with neuroimaging methods and manipulations of the GM. We examined the current neuroimaging literature employing the Cyberball game to induce social stress and feelings of exclusion. The review was intended to generate a framework describing neural processes during the stress. Following the results of the two reviews, we conducted two clinical trials, to investigate effects of antibiotic rifaximin and probiotic Bifidobacterium longum 1714 on neural activations during resting state and during the Cyberball game by using magnetoencephalography. In both studies, the stress induced by the Cyberball game enhanced oscillatory brain activity in different areas and in different frequency bands. Both, rifaximin and probiotics had effects on specific neural oscillatory activities in response to the social stress – rifaximin improved subjects’ relaxation status by reducing frontal and cingulate beta-1 band power, and B.longum 1714 enhanced emotion regulation process by increasing frontal and cingulate theta and alpha bands power. In addition, during the resting state, rifaximin favored individuals’ relaxation status by increasing frontal alpha band power, and B.longum 1714 increased subject’s arousal state by increasing theta band power in frontal and cingulate cortex and reducing the beta-3 band power in hippocampus and temporal cortex. Rifaximin and B.longum 1714, both showed neural effects on the stress response through an “eubiotic” effect, which refers to a healthy balance of the micro-flora in the gastrointestinal tract. Our results provide evidence for gut microbiota alerting CNS functions. Both, reviews and experimental work give clues for further studies targeting the underlying mechanisms of interaction between gut microbiota and CNS function using neuroimaging in patients with psychiatric disorders or gastrointestinal diseases.