Gastrointestinal chemosensation: chemosensory cells in the alimentary tract

Abstract

Sensing potentially beneficial or harmful constituents in the luminal content by specialized cells in the gastrointestinal mucosa is an essential prerequisite for governing digestive processes, initiating protective responses and regulating food intake. Until recently, it was poorly understood how the gastrointestinal tract senses and responds to nutrients and non-nutrients in the diet; however, the enormous progress in unraveling the molecular machinery underlying the responsiveness of gustatory cells in the lingual taste buds to these compounds has been an important starting point for studying intestinal chemosensation. Currently, the field of nutrient sensing in the gastrointestinal tract is evolving rapidly and is benefiting from the deorphanization of previously unliganded G-protein-coupled receptors which respond to important nutrients, such as protein degradation products and free fatty acids as well as from the FACS-assisted isolation of distinct cell populations. This review focuses on mechanisms and principles underlying the chemosensory responsiveness of the alimentary tract. It describes the cell types which might potentially contribute to chemosensation within the gut: cells that can operate as specialized sensors and transducers for luminal factors and which communicate information from the gut lumen by releasing paracrine or endocrine acting messenger molecules. Furthermore, it addresses the current knowledge regarding the expression and localization of molecular elements that may be part of the chemosensory machinery which render some of the mucosal cells responsive to constituents of the luminal content, concentrating on candidate receptors and transporters for sensing nutrients.

Long-lived intestinal tuft cells serve as colon cancer–initiating cells

“…However, previous reports have suggested that tuft cells are often found in close proximity to neurons (14,18,39), and our collaborators have demonstrated that functional innervation regulates epithelial homeostasis and response to injury (52). Indeed, we found that DCLK1 + cells were sustained when organoids were cocultured with neurons and therefore represent, to the best of our knowledge, the first cell type that cannot be generated in organoid cultures in the absence of nonepithelial niche signals.…”

“…These results suggested that nonepithelial signals might be critical for tuft cell maintenance and longevity in organoid cultures. Given that previous reports suggested an association between epithelial tuft cells and neuronal structures (14,18,39), we hypothesized that neuronal input might support tuft cell survival in colonic, intestinal, and gastric organoid cultures. To test this hypothesis, we established a coculture system of primary neurons isolated from the spinal cord (40) To test whether functional innervation was associated with tuft cell survival in vivo, we examined paired biopsies from intestinal transplant patients (n = 2) and found that while the transplanted graft (which was extrinsically denervated) lacked DCLK1 + cells, the endogenous intestine (which was normally innervated) had a normal complement of DCLK1 + cells (Supplemental Figure .…”

Berberine induces GLP-1 secretion through activation of bitter taste receptor pathways

“…These receptors are also expressed in gastrointestinal tract [3,4], where they play important roles in nutrient assimilation and endocrine responses [5,6]. Recently, several studies focused on the connection between the activation of gut-expressed taste receptor and the hormonal secretion [7,8]. Glucagon-like peptide-1 (GLP-1), an incretin hormone which augments the release of insulin, is secreted in a taste receptor-dependent manner by enteroendocrine L cells [9].…”

GPR40 and GPR120 fatty acid sensors are critical for postoral but not oral mediation of fat preferences in the mouse

“…and inhibits the release of the feeding-stimulatory gut hormone ghrelin (3,19). Consequently, deletion of gut fatty acid sensors would be expected to reduce the satiating response to fat, and this has been documented in CD36 KO mice (27,28).…”