The function of the gut depends on both neurons that are integral to function of the organ and that signal changes in function to the brain. Bile acids are molecules synthesised in the liver for the purpose of facilitating fat digestion. However, they may also act as signalling molecules that communicate with the host regarding changes in the gut lumen. However, it is unknown if bile acids are transported across the gut barrier to directly activate gut neurons, or if they use an intermediary signalling cell. A good candidate for a cellular transducer undertaking that role is the glucagon-like peptide 1 (GLP-1) – secreting L-cell, which is embedded in the epithelium and expresses bile acid receptors.
GLP-1 is released from gut L-cells following food intake. This hormone enhances glucose-stimulated insulin secretion and is therefore important in energy metabolism. However, studies have detected GLP-1 and GLP-1 receptors on neurons embedded within the layers of the gut, where it increases excitation of these neurons causing increased colonic contraction. In patients with Irritable Bowel Syndrome, a functional bowel disorder characterized by altered bowel habit and abdominal pain, GLP-1 lowers muscular spasms and provides pain relief. The study involves screening bile acids to observe their effects on the enteric neurons and investigating L-cells as a signalling intermediary. Calcium imaging will be used to monitor neuronal excitability in the presence of bile acids and to determine if epithelial L-cells are involved in the cross-barrier communication.
