Gut microbiome studies in CKD: opportunities, pitfalls and therapeutic potential

Interest in gut microbiome dysbiosis and its potential association with the development and progression of chronic kidney disease (CKD) has increased substantially in the past 6 years. In parallel, the microbiome field has matured considerably as the importance of host-related and environmental factors is increasingly recognized. Past research output in the context of CKD insufficiently considered the myriad confounding factors that are characteristic of the disease. Gut microbiota-derived metabolites remain an interesting therapeutic target to decrease uraemic (cardio)toxicity. However, future studies on the effect of dietary and biotic interventions will require harmonization of relevant readouts to enable an in-depth understanding of the underlying beneficial mechanisms. High-quality standards throughout the entire microbiome analysis workflow are also of utmost importance to obtain reliable and reproducible results. Importantly, investigating the relative composition and abundance of gut bacteria, and their potential association with plasma uraemic toxins levels is not sufficient. As in other fields, the time has come to move towards in-depth quantitative and functional exploration of the patient’s gut microbiome by relying on confounder-controlled quantitative microbial profiling, shotgun metagenomics and in vitro simulations of microorganism–microorganism and host–microorganism interactions. This step is crucial to enable the rational selection and monitoring of dietary and biotic intervention strategies that can be deployed as a personalized intervention in CKD. Gut microbiome studies have potential to provide novel therapeutic targets in chronic kidney disease. Here, the authors not only examine the current state of the field and discuss potential gut-related therapies for targeting uraemic metabolites, but also provide guidelines for improving microbiome study design, and data collection and analysis.