Colonic targeting of gut hormone modulators GLP-1 and PYY

Short-chain fatty acids (SCFA) are the natural ligands for receptors on specialised cells (L-cells) in the colonic epithelium which bind to free fatty acid receptors to stimulate the release of GLP-1 and PYY. We have shown in published work that the SCFA propionate stimulates GLP-1 and PYY in human studies to attenuate energy intake, improve metabolic health and preserve lean body mass during weight loss.

Inulin propionate ester is a formulation that delivers g quantities of propionate to the colon. This novel food ingredient can be produced at scale at food grade and has recently been granted a favourable opinion on safety by the European Food Safety Authority.

In the context of pharmacological GLP-1a use, dietary strategies that stimulate GLP-1 (and other anorectic gut hormones) are required to facilitate long-term weight loss maintenance else populations are bound to life-long pharmacotherapy, where the long-term health impacts are yet unknown. Nutritional targeting of appetite regulating circuits is an attractive solution to long-term weight maintenance for both prevention of weight gain and maintenance of a healthy weight after weight loss.

We have published several first-in-human studies using IPE together with under-pinning mechanistic work to describe the appetite regulating effects of IPE. However, further work is required to optimise the efficacy across different age groups (where appetite and drivers of food intake change with age), different demographics within our populations and to formulate products that have optimum use profiles.

One essential next step where we would like to partner is to examine the potential for IPE regulate weight post GLP-1a use. There is an urgent unmet need for patients coming off GLP-1a therapy where current evidence shows almost all will regain all weight loss withing two years. The potential for IPE to attenuate or even prevent this inexorable weight regain trajectory is unknown atthe present time.