肠道中表达的嗅觉受体及其功能
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1.北京生命科技研究院,郑州烟草研究院;2.北京生命科技研究院,郑州大学;3.北京生命科技研究院

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中国国家自然科学基金(No. 22578008)及北京生命科技研究院基金(No. 2024601QPID08, No. 2025600CC0210)


Olfactory Receptors Expressed in the Intestine and Their Functions
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1.Beijing Life Science Academy, Zhengzhou Tobacco Research Institute of CNTC;2.Beijing Life Science Academy, Zhengzhou University;3.Beijing Life Science Academy

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National Natural Science Foundation of China(No. 22578008)and Beijing Life Science Academy Foundation(No. 2024601QPID08, No. 2025600CC0210)

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    摘要:

    嗅觉受体(olfactory receptors,ORs)作为G蛋白偶联受体超家族中最大的亚群,在鼻腔嗅觉上皮原位表达,经气味分子激活后介导嗅觉感知,此外,嗅觉受体还在多种非嗅觉组织中异位表达,参与多种局部与全身生理调控。肠道是营养物质摄入与消化吸收的核心场所,拥有复杂的化学环境。肠道上的多种“化学感受器”共同作用构建起丰富的感应网络,在体内发挥重要的生理功能。嗅觉受体广泛表达于肠道不同部位与各类肠道细胞中,参与感知膳食成分、肠道菌群代谢产物及内源性小分子信号,并激活特定的细胞信号通路,调控肠道激素分泌、免疫稳态、代谢平衡及肿瘤细胞增殖等生理病理过程。因此肠道中的嗅觉受体可能成为连接气味分子与化学感应之间的桥梁,加深我们对食物如何在分子水平影响肠道生理功能的理解。基于此本文梳理了肠道中嗅觉受体的表达特征与配体分类,重点总结其在肠内分泌细胞中介导肠道激素分泌调控的分子机制,及其在肠道炎症调节、稳态维持及肿瘤发生发展中的作用,并探讨了通过解析膳食成分与特定嗅觉受体之间的配对关系,靶向嗅觉受体在代谢性疾病、炎症性肠病及肿瘤干预中的潜在价值。

    Abstract:

    Olfactory receptors (ORs) constitute the largest superfamily of G protein-coupled receptors (GPCRs). While they are classically defined by their expression in the nasal olfactory epithelium where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidney. The intestine, serving as the core site for nutrient digestion and absorption, possesses a highly complex chemical environment. To adapt to this environment, the gut utilizes a sophisticated network of "chemosensors" to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as critical functional components, acting as a molecular bridge that links environmental chemical cues—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened the understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Research indicates that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a diverse array of ligands, including exogenous dietary components, metabolic byproducts of the gut microbiota such as short-chain fatty acids, and endogenous small molecules such as azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to introduce the molecular mechanisms by which these receptors regulate the secretion of gut hormones. The activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as Glucagon-like peptide-1 (GLP-1), Peptide YY (PYY), and Serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility.Furthermore, the critical roles of ORs in immune regulation and pathology. It highlights evidence suggesting that specific ORs contribute to the maintenance of intestinal immune homeostasis, potentially offering protection against inflammation. In addition to their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation through the remodeling of the gut microbiome and metabolome. These findings collectively indicate that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and sustaining intestinal homeostasis. Additionally, the review explores the emerging significance of ORs in cancer. While often downregulated in tumor tissues compared to normal mucosa, the activation of specific ORs by specific ligands can inhibit tumor cell proliferation, and migration, and induce apoptosis through pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors such as OR7C1 may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut's sensory network, the review discusses the potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may become promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases and malignancies.

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杨沛雯,原梦梦,周颖,李鹏,齐桂红,杨颖,茅中一,周梦莎,毛小爽,谢剑平,杨伊楠,孙世豪.肠道中表达的嗅觉受体及其功能[J].生物化学与生物物理进展,,():

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  • 收稿日期:2025-07-09
  • 最后修改日期:2026-01-13
  • 录用日期:2026-01-16
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