Preprint
From mouth to colon: a framework for engineering food matrices to engage the satiety cascade and endogenous GLP-1 signalling
ChemRxiv, Vol.23 June 2026
American Chemical Society
2026
Abstract
Glucagon-like peptide-1 (GLP-1) receptor agonists have produced the largest pharmacological reductions in body weight yet achieved. Their success is most usefully interpreted not as the discovery of a new target but as validation of an endogenous pathway the gut already possesses, and of appetite regulation as a tractable physiological target. Yet food engages appetite control weakly and inconsistently, and pharmacotherapy alone cannot meet the global burden of metabolic disease. This Perspective argues that satiety is not a single signal but a spatially and temporally distributed cascade—oro-sensory and cephalic at the mouth, volumetric at the stomach, nutrient chemosensing at the duodenum, direct enteroendocrine sensing at the ileum, and fermentative signalling in the colon—and that the food matrix is the common variable that governs engagement at each station. Food processing acts on precisely this architecture, weakening engagement station by station: a softened matrix shortens oral exposure and accelerates eating; lowered viscosity speeds gastric emptying; raised digestibility diverts substrate from the distal small intestine and colon, where the food-responsive L-cell populations and fermentative capacity reside. Recent human work shows that engineering a single structural lever—intact plant cells that carry starch past proximal digestion—elevates and sustains GLP-1 and PYY. This single-station result is interpreted here as evidence supporting the plausibility of a broader and largely unattempted programme: designing real, multi-component food matrices that engage multiple components of the satiety cascade across the gastrointestinal tract rather than acting predominantly at a single site. Drawing on an integrated body of in vivo evidence, the analysis treats structural digestibility as a measurable candidate variable with the potential to predict relationships among matrix architecture, ileal escape, intestinal transit, the colonic site of fermentation, and food intake. It sets out what must be established—structural characterisation as standard practice, model systems that preserve the food-to-signal chain, and fermentation phenotype as a determinant of individual response—to make multi-site, food-based appetite engineering clinically actionable.
Details
- Title
- From mouth to colon: a framework for engineering food matrices to engage the satiety cascade and endogenous GLP-1 signalling
- Authors
- Vishal Ratanpaul (Corresponding Author) - University of the Sunshine Coast
- Publication details
- ChemRxiv, Vol.23 June 2026
- Publisher
- American Chemical Society
- Date published
- 2026
- DOI
- 10.26434/chemrxiv.15005120/v1
- Organisation Unit
- School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 991252398902621
- Output Type
- Preprint
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