The gastrointestinal tract (GIT), in particular, the small intestine, plays a significant role in food digestion, fluid and electrolyte transport, drug absorption and metabolism, and nutrient uptake. As the longest portion of the GIT, the small intestine also plays a vital role in protecting the host against pathogenic or opportunistic microbial invasion. However, establishing polarized intestinal tissue models in vitro that reflect the architecture and physiology of the gut has been a challenge for decades and the lack of translational models that predict human responses has impeded research in the drug absorption, metabolism, and drug-induced gastrointestinal toxicity space. Often, animals fail to recapitulate human physiology and do not predict human outcomes. Also, certain human pathogens are species specific and do not infect other hosts. Concerns such as variability of results, a low throughput format, and ethical considerations further complicate the use of animals for predicting the safety and efficacy xenobiotics in humans. These limitations necessitate the development of in vitro 3D human intestinal tissue models that recapitulate in vivo–like microenvironment and provide more physiologically relevant cellular responses so that they can better predict the safety and efficacy of pharmaceuticals and toxicants. Over the past decade, much progress has been made in the development of in vitro intestinal models (organoids and 3D-organotypic tissues) using either inducible pluripotent or adult stem cells. Among the models, the MatTek’s intestinal tissue model (EpiIntestinal™ Ashland, MA) has been used extensively by the pharmaceutical industry to study drug permeation, metabolism, drug-induced GI toxicity, pathogen infections, inflammation, wound healing, and as a predictive model for a clinical adverse outcome (diarrhea) to pharmaceutical drugs. In this paper, our review will focus on the potential of in vitro small intestinal tissues as preclinical research tool and as alternative to the use of animals.

胃肠道 (GIT)，尤其是小肠，在食物消化、体液和电解质运输、药物吸收和代谢以及营养吸收方面发挥着重要作用。作为 GIT 最长的部分，小肠在保护宿主免受致病性或机会性微生物入侵方面也起着至关重要的作用。然而，几十年来，建立反映肠道结构和生理学的极化肠道组织模型一直是一个挑战，并且缺乏预测人类反应的转化模型阻碍了药物吸收、代谢和药物诱导的胃肠道毒性的研究。空间。通常，动物无法概括人类生理学，也无法预测人类结果。此外，某些人类病原体是物种特异性的，不会感染其他宿主。结果的可变性、低通量格式和伦理考虑等问题进一步使使用动物预测人类外源性物质的安全性和有效性变得复杂。这些限制需要开发体外 3D 人体肠道组织模型，该模型重现体内微环境并提供更多生理相关的细胞反应，以便更好地预测药物和毒物的安全性和有效性。在过去十年中，使用诱导型多能干细胞或成体干细胞在体外肠道模型（类器官和 3D 器官型组织）的开发方面取得了很大进展。在这些模型中，MatTek 的肠道组织模型 (EpiIntestinal™ Ashland, MA) 已被制药行业广泛用于研究药物渗透、代谢、药物诱导的胃肠道毒性、病原体感染、炎症、伤口愈合，以及作为药物临床不良结果（腹泻）的预测模型。在本文中，我们的综述将重点关注体外小肠组织作为临床前研究工具和替代动物使用的潜力。