ABSTRACT

Our understanding of microorganisms residing within our gut and their roles in the host metabolism and immunity advanced greatly over the past 20 years. Currently, microbiome studies are shifting from association and correlation studies to studies demonstrating causality of identified microbiome signatures and identification of molecular mechanisms underlying these interactions. This transformation is crucial for the efficient translation into clinical application and development of targeted strategies to beneficially modulate the intestinal microbiota. As mechanistic studies are still quite challenging to perform in humans, the causal role of microbiota is frequently evaluated in animal models that need to be appropriately selected. Here, we provide a comprehensive overview on approaches that can be applied in addressing causality of host-microbe interactions in five major animal model organisms (Caenorhabditis elegans, Drosophila melanogaster, zebrafish, rodents, and pigs). We particularly focused on discussing methods available for studying the causality ranging from the usage of gut microbiota transfer, diverse models of metabolic and immune perturbations involving nutritional and chemical factors, gene modifications and surgically induced models, metabolite profiling up to culture-based approached. Furthermore, we addressed the impact of the gut morphology, physiology as well as diet on the microbiota composition in various models and resulting species specificities. Finally, we conclude this review with the discussion on models that can be applied to study the causal role of the gut microbiota in the context of metabolic syndrome and host immunity. We hope this review will facilitate important considerations for appropriate animal model selection.

摘要

在过去的 20 年里，我们对肠道内微生物及其在宿主新陈代谢和免疫中的作用的理解有了很大进步。目前，微生物组研究正在从关联和相关研究转向证明已鉴定微生物组特征的因果关系和确定这些相互作用背后的分子机制的研究。这种转变对于有效地转化为临床应用和开发有利于调节肠道微生物群的靶向策略至关重要。As mechanistic studies are still quite challenging to perform in humans, the causal role of microbiota is frequently evaluated in animal models that need to be appropriately selected. 这里，秀丽隐杆线虫，黑腹果蝇、斑马鱼、啮齿动物和猪）。我们特别专注于讨论可用于研究因果关系的方法，范围从肠道微生物群转移的使用、涉及营养和化学因素的代谢和免疫扰动的不同模型、基因修饰和手术诱导模型、代谢物分析到基于培养的方法。此外，我们还讨论了肠道形态、生理学和饮食对各种模型中微生物群组成的影响以及由此产生的物种特异性。最后，我们通过讨论可用于研究肠道微生物群在代谢综合征和宿主免疫背景下的因果作用的模型来结束这篇综述。我们希望这次审查将有助于适当的动物模型选择的重要考虑。