Do you have the guts to be happy?: Role of the gut-brain axis and gut microbiota in human metabolism

Although the research field is growing, indicating an important role for the gut-brain axis in metabolic disorders, effect size of microbiota based treatments in human intervention trials are modest. However, it might be possible to enhance these effects by providing a combination of dietary precursors of specific metabolites together with certain bacterial strains. In this thesis we show the beneficial effect of lean donor fecal microbiota transplantation (FMT) on insulin sensitivity. The associated changes in plasma metabolites involved in GABA and serotonin metabolism imply their role as signalling molecules driving insulin sensitivity. Other plasma metabolites of interest are those associated with the changes we observed in human striatal dopamine transporter binding upon FMT and butyrate treatment. Their involvement in the SAMe cycle, an important pathway in neurotransmitter synthesis, together with changes found in bacterial strains and amount of sympathetic activity, provide the first evidence of the existence of a gut-brain axis in humans. Future adequately powered studies are needed to investigate whether providing the identified microbial strains and/or their metabolites can affect brain dopamine homeostasis, known to be associated with improved impulse control and appetite. The same applies to our discovery of a potential new biomarker for predicting early stages of insulin resistance, citrulline. Concerning the therapeutic potential of butyrate and butyrate-producing bacteria for metabolic disorders, it seems clear that oral supplementation of butyrate is not suitable for treatment of insulin resistance, while a living single bacterial strain like the butyrate producing A. soehngenii shows more promise.