To Örebro University

The human intestinal microbiota has a major impact on host physiology and might play an important role in several diseases. Therapeutic interventions aimed at modifying the gut microbiota might exert their effects locally as well as systemically, for example via the gut-brain axis, a bidirectional communication system.

The overall aim of this thesis was to investigate potential modes of action via which modifications of the gut microbiota might influence health and disease. Paper I shows that faecal microbiota transfer could improve gastrointestinal symptoms in a subset of patients with collagenous colitis– a chronic low-grade inflammation of the large intestine. Papers II – IV describe the effects of an oral probiotic intervention on different aspects of the gut-brain axis in young, healthy adults. Paper II shows that brainactivity and functional connectivity during negative emotional stimuli were altered after probiotic intervention without major effects on the gut microbiota composition itself. Paper III shows that brain response patterns to an acute stressor were altered, whereas cortisol stress response, autonomic nervous system function and cognitive performance were not affected by the probiotic intervention. Paper IV describes the effect of the probiotic intervention on mental health in daily life. Amongst others, altered resting state brain function, slight improvements in depression symptoms and sleep quality were observed. Furthermore, serum levels of serotonin were slightly altered, indicating a potential mechanism of how probiotics might affect brain function. Paper V is an in vitro study that aimed to further elucidate a potential mechanism behind the microbiota-gut-brain axis. The short-chain fatty acid butyrate, an important microbial metabolite, rescued the disturbed uptake of the serotonin precursor tryptophan into fibroblasts mimicking cells of the nervous system.

This thesis provides insights into whether and how gut microbiota modifications could improve health by affecting the gut-brain axis. Uncovering the underlying mechanisms might facilitate the development of personalised medicine.