The concept of the ‘microbiota-gut-brain’ signalling axis has been proposed recently, with headlinegrabbing studies demonstrating how altering the intestinal microbiome with commensal probiotics has beneficial effects both on gut function but more intriguingly, on central nervous system (CNS) function. Although the vagus nerve has been implicated, little is understood of the cellular and molecular events which translate changes in external luminal bacteria to the enteric nervous or endocrine systems and on to the CNS. Neural, hormonal and immune factors are likely candidates. Indeed, we have previously demonstrated that activation of stress hormones in an environment of low-grade mucosal inflammation underlies the initiation, exacerbation and prolongation of bowel disorders. The studies proposed in this application aim to use electrophysiology to record vagal nerve firing from intact ex vivo colon sections exposed to various probiotics (GABA-, conjugated poly-unsaturated fatty acid- and exopolysaccharide-producing Lactobacillus strains). Underlying molecular mechanisms will be investigated using pharmacological and immune inhibitors of likely molecular mediators, such as toll like receptors, cytokines and gastrointestinal hormones. Mechanisms of microbiota-induced changes in CNS function are currently unexplained. The proposed study goals are logical and attainable, and will contribute significantly to our understanding of microbiota-gut-brain signalling to support a larger grant application.
