Department of Biomedical Engineering, The University of Texas at Austin, 107 W. Dean Keeton St. BME 4.202C, Austin, TX, 78712, USA.
College of Natural Sciences, The University of Texas at Austin, Austin, TX, 78712, USA.
Stem Cell Rev Rep. 2017 Jun;13(3):321-334. doi: 10.1007/s12015-017-9739-z.
The human gut microbiome performs prodigious physiological functions such as production of microbial metabolites, modulation of nutrient digestion and drug metabolism, control of immune system, and prevention of infection. Paradoxically, gut microbiome can also negatively orchestrate the host responses in diseases or chronic disorders, suggesting that the regulated and balanced host-gut microbiome crosstalk is a salient prerequisite in gastrointestinal physiology. To understand the pathophysiological role of host-microbiome crosstalk, it is critical to recreate in vivo relevant models of the host-gut microbiome ecosystem in human. However, controlling the multi-species microbial communities and their uncontrolled growth has remained a notable technical challenge. Furthermore, conventional two-dimensional (2D) or 3D culture systems do not recapitulate multicellular microarchitectures, mechanical dynamics, and tissue-specific functions. Here, we review recent advances and current pitfalls of in vitro and ex vivo models that display human GI functions. We also discuss how the disruptive technologies such as 3D organoids or a human organ-on-a-chip microphysiological system can contribute to better emulate host-gut microbiome crosstalks in health and disease. Finally, the medical and pharmaceutical significance of the gut microbiome-based personalized interventions is underlined as a future perspective.
人类肠道微生物组执行着巨大的生理功能，如微生物代谢产物的产生、营养物质消化和药物代谢的调节、免疫系统的控制以及感染的预防。矛盾的是，肠道微生物组也可以在疾病或慢性疾病中对宿主反应进行负面调节，这表明调节和平衡的宿主-肠道微生物组相互作用是胃肠道生理学的一个显著前提。为了理解宿主-微生物组相互作用的病理生理学作用，关键是要在人类中重建体内相关的宿主-肠道微生物组生态系统模型。然而，控制多物种微生物群落及其不受控制的生长仍然是一个显著的技术挑战。此外，传统的二维（2D）或三维（3D）培养系统不能再现细胞外基质的多细胞微结构、力学动态和组织特异性功能。在这里，我们综述了展示人类胃肠道功能的体外和离体模型的最新进展和当前的困境。我们还讨论了 3D 类器官或人类器官芯片微生理系统等颠覆性技术如何有助于更好地模拟健康和疾病中的宿主-肠道微生物组相互作用。最后，强调了基于肠道微生物组的个性化干预在医学和制药方面的意义，这是未来的一个研究方向。
