Metagenomic Profiling of Gut Microbiota in Kidney Precision Medicine Project Participants With CKD and AKI

BACKGROUND: The gut microbiome plays an important role in human health and disease. Kidney Precision Medicine Project (KPMP) is a well-phenotyped, kidney biopsy-proven cohort of AKI and CKD patients. Comprehensive profiling of gut microbiota can uncover novel mechanistic, diagnostic, and therapeutic strategies for CKD and AKI patients. METHODS: We performed metagenomic whole genome sequencing (mWGS; > 25 million reads) on KPMP stool samples. mWGS data of healthy controls from 4 published studies was used. Kraken2 and MetaPhlAn3 were used for taxonomic assignment, and HUMAnN3 for functional annotation. RESULTS: Kraken2 analysis showed significantly higher abundance of Ruminococcus bicirculans in CKD (6.47) compared to AKI (1.82) and healthy individuals (2.42; p = 0.01). Furthermore, the abundance of Gordonibacter pamelaeae increased in CKD (0.30) compared to AKI (0.07; p = 0.05) and healthy individuals (0.03). The percent mean abundance of genus Chryseobacterium was slightly higher in CKD (0.07) compared to AKI (0.05; p = 0.05) but reduced compared to healthy individuals (0.20; p < 0.001). MetaPhlAn3 identified alterations in Gordonibacter, Bacteroides, and Faecalibacterium with a significant increase in Clostridium asparagiforme in AKI (11.68) compared to CKD (0.03; p = 0.06) and healthy (0.01; p = 0.001) individuals. Roseburia hominis, Roseburia intestinalis, Dorea longicatena, and Gemmiger formicilis were significantly reduced in AKI compared to CKD and healthy individuals. LDA/HUMAnN3 analysis showed a significant correlation between several metabolites and bacterial species in this KPMP population. CONCLUSION: Kidney biopsy-proven CKD and AKI patients show a distinct gut microbiota profile compared to healthy individuals. This high-quality dataset is a valuable resource for developing microbiome-based diagnostics and therapies for CKD and AKI.