Inflammatory bowel disease (IBD) is a chronic relapsing disease of the gastrointestinal tract; Crohn’s disease and ulcerative colitis are common forms of IBD. Although the etiology of IBD remains unclear, it is thought to involve complex interactions between multiple genetic factors, altered gut microbiota, inappropriate host immune responses, and environmental factors. Traditionally, IBD has been most common in individuals of Western European ancestry. Most of the more than 200 genes with variants associated with an increased risk of IBD also include a membrane receptor with immune function, NOD2. Both mouse and human studies have shown that intake of a Western diet, characterized by high fat and sugar content, influences the pathogenesis of IBD.
Some experimental data suggest that food taste receptors (TARs) have a potential role in conditioning this risk of Crohn’s appearing based on the genetic terrain conditioned by food style. Taste receptors comprise two families of membrane receptors: type 1 taste receptor (T1R) and type 2 taste receptor. The T1R family perceives sweet (TAS1R2, TAS1R3) and umami (TAS1R1, TAS1R3) stimuli , while the receptor of the type 2 taste family perceives bitter stimuli. TARs regulate the release of intestinal peptide hormones, including glucagon-like peptide 1 (GLP-1). GLP-1, secreted by entero-endocrine cells, potentiates glucose-induced insulin response, promotes beta-cell survival, slows gastric emptying, and regulates energy expenditure.
In addition to the mouth, taste receptors are also expressed in certain organs and in the intestinal mucosa. To the knowledge of scientists, there are no data on the role of TAR responses to endogenous dietary ligands. Given the immense diversity of non-microbial signals (nutrients and non-nutrient chemicals) that stimulate immune responses at the intestinal barrier site, intestinal TARs, which are directly activated by food ligands, may modulate intestinal immunity and inflammation. intestinal mucosa. That’s why scientists developed a mouse model of severe intestinal inflammation triggered by a long-term Western dietary pattern to evaluate the influence of this dietary style on intestinal inflammation and study the mechanisms by which it affects the development of IBD.
Researchers hypothesized that direct nutrient-induced modulation of the intestinal taste receptor TAS1R3 is critical for the regulation of intestinal inflammation. They conducted experiments in molecular biology, gene transcription and histological-cellular study. They thus found that a combination of glucose, fructose and palmitate in the diet regulates the expression of pro-inflammatory cytokines and chemokines via the activation of TAS1R3. Instead, these glucose, fructose, and palmitate-induced increases in IL-8 and TNF-ɑ secretion was inhibited by knockdown of TAS1R3. Consistently, pretreatment of NCI-H716 cells with lactisole, a TAS1R3 antagonist, significantly inhibited GLP-1 synthesis and secretion induced by the three combined nutrients, as well as related cytokine synthesis.
With a mouse model genetically programmed to have low expression of the TAS1R3 receptor, the researchers were able to see that the mice were quite protected against the predisposing effects of the Western diet on the risk of Crohn’s inflammatory bowel disease. Gene expression in these mice also changed in favor of increased cell protection: the activities of the transcription factor NF-kB and mTOR1 cell signaling pathway were impaired, while PPAR-gamma (protector) cell receptor was increased . PPAR-gamma is expressed at high levels in the intestinal tract and its activation inhibits the production of numerous inflammatory cytokines, through its action on kinases and transcription factors, including NF-κB and AP-1.
Interestingly, the mRNA and protein expression of PPAR-gamma continuously increased after TAS1R3 suppression, regardless of the nutritional condition of the animals. Finally, the altered presence of TAS1R3 also causes alterations in the composition of the intestinal microbiota. Transgenic mice overexpressing the TAS1R3 receptor and fed a Western diet had more Proteobacteria, Prevotellacee and Enterobacteriaceae, all pathogenic microorganisms that are increased in Crohn’s disease. In contrast, the receptor-deficient mice had more intestinal bacteria of the phylum Firmicutes: TAS1R3 deficiency significantly improved the relative abundance of Faecalibacterium, Lachnospira, Ruminococcus, Butyricicoccus, Butyrivibrio e Roseburia.
All of these species, by the way, are recognized by experts to be lacking in IBD and to be protective of the intestinal mucosa. With this information, the scientists concluded that the long-term adoption of a Western diet “prepares” the biological and molecular terrain of IBD, also favoring the expansion of pathogens related to these forms of chronic colitis.
- By Dr. Gianfrancesco Cormaci, PhD; specialist in Clinical Biochemistry.
Scientific publications
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