ENVIRONMENTAL MODULATION OF GUT-BRAIN AXIS SIGNALLING

The microbiota-gut-brain axis describes the dynamic communication between gastrointestinal microbes, visceral organs and the brain. Signals from the brain are essential to regulate digestive functions, while signals from microbes and host cells are able to influence mood, behaviour and neurobiology. Chronic stress is known to adversely interfere with this bidirectional communication, but the precise impact of beneficial environmental factors on microbiota-gut-brain axis signalling is currently unknown. To investigate the effects of beneficial environmental factors, we will use environmental enrichment (EE), a set of refined husbandry procedures known to improve laboratory animal housing and to beneficially modulate animal behaviour. Animals living in EE will be compared to standard laboratory housing conditions in terms of behaviour, gastrointestinal microbe composition, microbial metabolites, immune system activity and changes to neurobiology. To analyse the role of gastrointestinal microbes and metabolites in mediating the positive effects of EE, we will investigate the behaviour of mice without gastrointestinal microbes exposed to EE and the behaviour of standard-housed mice receiving microbes from EE mice. In addition, we will put a focus on immunological effects of EE. For this, we will use an animal model of experimental colitis and assess whether EE can positively modify disease course and/or prevent detrimental effects of colitis on the gastrointestinal tract, the brain and behaviour. We will use a number of behavioural tests to assess the effects of the experimental interventions on brain functions such as anxiety, cognition, social and depressive-like behaviour. These readouts will be complemented with sequencing experiments, metabolite profiling, immune cell characterizations and gene/protein expression analysis. The project is the first of its kind to investigate the role of gastrointestinal microbiota and immune cells as potential mediators translating positive environmental stimulation in the form of EE into beneficial neurobiological effects. It has the potential to unravel novel biological pathways, bacterial signatures and signalling molecules mediating these beneficial effects, which could be harnessed to develop novel therapeutic strategies mimicking beneficial environmental stimulation.