在过去的十年中,肠道微生物组研究急剧增加,包括肾脏健康和疾病。使用正向和反向微生物组方法,该领域正在从仅仅显示关联的实验转向因果关系,利用无菌动物等工具,用抗生素治疗,和粪便微生物移植。然而,我们仍然看到发现和翻译之间的差距需要解决,以便患者可以从基于微生物组的治疗中受益。在这份指导文件中,我们讨论了影响动物和临床研究评估肾功能的肠道微生物组的关键考虑因素,许多经常被忽视的,导致假阳性结果。对于动物研究,这些包括供应商,适应环境,基线微生物群及其正常化,同窝和队列/笼子效应,饮食,性别差异,年龄,昼夜节律差异,抗生素和甜味剂,和使用的模型。临床研究有一些独特的考虑因素,其中包括采样,肠道运输时间,饮食记录,药物,和肾脏表型。我们提供关于抽样的最佳实践指导,storage,DNA提取,和微生物DNA测序方法(16SrRNA和鸟枪宏基因组)。最后,我们讨论后续分析,包括可用的工具,指标、和他们的解释,以及微生物组领域面临的关键挑战。通过标准化研究设计,方法和报告,我们将加速从发现到转化的研究结果,并产生可能改善肾脏健康的新的基于微生物组的疗法.
Gut microbiome research has increased dramatically in the last decade, including in renal health and disease. The field is moving from experiments showing mere association to causation using both forward and reverse microbiome approaches, leveraging tools such as germ-free animals, treatment with antibiotics, and fecal microbiota transplantations. However, we are still seeing a gap between discovery and translation that needs to be addressed, so that patients can benefit from microbiome-based therapies. In this
guideline paper, we discuss the key considerations that affect the gut microbiome of animals and clinical studies assessing renal function, many of which are often overlooked, resulting in false-positive results. For animal studies, these include suppliers, acclimatization, baseline microbiota and its normalization, littermates and cohort/cage effects, diet, sex differences, age, circadian differences, antibiotics and sweeteners, and models used. Clinical studies have some unique considerations, which include sampling, gut transit time, dietary records, medication, and renal phenotypes. We provide best-practice guidance on sampling, storage, DNA extraction, and methods for microbial DNA sequencing (both 16S rRNA and shotgun metagenome). Finally, we discuss follow-up analyses, including tools available, metrics, and their interpretation, and the key challenges ahead in the microbiome field. By standardizing study designs, methods, and reporting, we will accelerate the findings from discovery to translation and result in new microbiome-based therapies that may improve renal health.