Electrophysiological investigations on the molecular mechanisms underlying gut-to-brain signalling evoked by colonic microbiota

Year of award: 2015

Grantholders

  • Dr Dervla O'Malley

    University College Cork

Project summary

Studies have demonstrated how altering the intestinal microbiome with commensal probiotics has beneficial effects both on gut function but more intriguingly, on central nervous system (CNS) function. This has led to the concept of the 'microbiota-gut-brain' signalling axis. Although the vagus nerve has been implicated, little is understood of the cellular and molecular events that 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.

We will 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.

This study will contribute significantly to our understanding of microbiota-gut-brain signalling and will support a larger grant application.