Lymphatic vessels are crucial for fluid absorption and the transport of peripheral immune cells to lymph nodes. However, in the small intestine, the lymphatic fluid is rich in diet-derived lipids incorporated into chylomicrons and gut-specific immune cells. Thus, intestinal lymphatic vessels have evolved to handle these unique cargoes and are critical for systemic dietary lipid delivery and metabolism. This Review covers mechanisms of lipid absorption from epithelial cells to the lymphatics as well as unique features of the gut microenvironment that affect these functions. Moreover, we discuss details of the intestinal lymphatics in gut immune cell trafficking and insights into the role of inter-organ communication. Lastly, we highlight the particularities of fat absorption that can be harnessed for efficient lipid-soluble drug distribution for novel therapies, including the ability of chylomicron-associated drugs to bypass first-pass liver metabolism for systemic delivery. In all, this Review will help to promote an understanding of intestinal lymphatic–systemic interactions to guide future research directions.

淋巴管对于液体吸收和外周免疫细胞向淋巴结的运输至关重要。然而，在小肠中，淋巴液富含饮食衍生的脂质，这些脂质掺入乳糜微粒和肠道特异性免疫细胞中。因此，肠道淋巴管已经进化到可以处理这些独特的货物，并且对全身膳食脂质输送和代谢至关重要。本综述涵盖了脂质从上皮细胞吸收到淋巴管的机制，以及影响这些功能的肠道微环境的独特特征。此外，我们讨论了肠道免疫细胞运输中肠道淋巴管的细节，并深入了解了器官间通讯的作用。最后，我们强调了脂肪吸收的特殊性，这些特性可用于新疗法的脂溶性药物的有效分布，包括乳糜微粒相关药物绕过首过肝脏代谢进行全身递送的能力。总而言之，本综述将有助于促进对肠道淋巴-系统相互作用的理解，以指导未来的研究方向。