The gastrointestinal tract (GIT) affects not only local diseases in the GIT but also various systemic diseases. Factors that can affect the health and disease of both GIT and the human body include 1) the mucosal immune system composed of the gut-associated lymphoid tissues and the lamina propria, 2) the intestinal barrier composed of mucus and intestinal epithelium, and 3) the gut microbiota. Selective delivery of drugs, including antigens, immune-modulators, intestinal barrier enhancers, and gut-microbiome manipulators, has shown promising results for oral vaccines, immune tolerance, treatment of inflammatory bowel diseases, and other systemic diseases, including cancer. However, physicochemical and biological barriers of the GIT present significant challenges for successful translation. With the advances of novel nanomaterials, oral nanomedicine has emerged as an attractive option to not only overcome these barriers but also to selectively deliver drugs to the target sites in GIT. In this review, we discuss the GIT factors and physicochemical and biological barriers in the GIT. Furthermore, we present the recent progress of oral nanomedicine for oral vaccines, immune tolerance, and anti-inflammation therapies. We also discuss recent advances in oral nanomedicine designed to fortify the intestinal barrier functions and modulate the gut microbiota and microbial metabolites. Finally, we opine about the future directions of oral nano-immunotherapy.

胃肠道（GIT）不仅影响胃肠道的局部疾病，而且影响各种全身疾病。影响胃肠道和人体健康和疾病的因素包括1）由肠道相关淋巴组织和固有层组成的粘膜免疫系统，2）由粘液和肠上皮组成的肠道屏障，以及3）肠道微生物群。选择性递送药物，包括抗原、免疫调节剂、肠道屏障增强剂和肠道微生物组操纵剂，在口服疫苗、免疫耐受、炎症性肠病和包括癌症在内的其他全身性疾病的治疗方面已显示出有希望的结果。然而，胃肠道的物理化学和生物障碍对成功翻译提出了重大挑战。随着新型纳米材料的进步，口服纳米药物已成为一种有吸引力的选择，不仅可以克服这些障碍，而且可以选择性地将药物输送到胃肠道的目标部位。在这篇综述中，我们讨论了胃肠道因素以及胃肠道中的理化和生物屏障。此外，我们还介绍了口服纳米药物在口服疫苗、免疫耐受和抗炎治疗方面的最新进展。我们还讨论了旨在增强肠道屏障功能并调节肠道微生物群和微生物代谢物的口服纳米药物的最新进展。最后，我们对口服纳米免疫疗法的未来发展方向进行了展望。