Sensing of luminal contents and downstream modulation of GI function

The luminal environment is rich in macronutrients coming from our diet and resident microbial populations including their metabolites. Together, they have the capacity to modulate unique cell surface receptors, known as G-protein coupled receptors (GPCRs). Along the entire length of the gut epithelium, enteroendocrine cells express GPCRs to interact with luminal contents, such as GPR93 and the calcium sensing receptor to sense proteins, FFA2 and GPR84 to sense fatty acids, and SGLT1 and T1R to sense carbohydrates. Nutrient-receptor interaction causes the release of hormonal stores such as glucagon-like peptide 1, peptide YY, and cholecystokinin, which further regulate gut function. Existing data show the role of luminal components and microbial fermentation products on gut function. However, there is a lack of understanding in the mechanistic interactions between diet-derived luminal components and microbial products and nutrient-sensing receptors and downstream gastrointestinal modulation. This review summarizes current knowledge on various luminal components and describes in detail the range of nutrients and metabolites and their interaction with nutrient receptors in the gut epithelium and the emerging impact on immune cells.