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 GIT 中的局部疾病，还影响各种全身性疾病。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。药物的选择性递送，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，已在口服疫苗、免疫耐受、炎症性肠病的治疗和其他全身性疾病（包括癌症）方面显示出有希望的结果。然而，GIT 的物理化学和生物屏障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，还可以选择性地将药物递送到 GIT 中的目标位点。在这篇综述中，我们讨论了 GIT 因子以及 GIT 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、免疫耐受和抗炎疗法方面的最新进展。我们还讨论了旨在加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医学的最新进展。最后，我们对口服纳米免疫疗法的未来方向发表了看法。