ARTICLE: Gut Microbiome Metagenomic Sequencing Reveals Distinct Profiles in Participants with AKI and CKD from the KPMP
AUTHORS: Noel, Sanjeev; White, James Robert; Patel, Shishir Kumar; Menez, Steven; Raj, Dominic S.; Parikh, Chirag R; Rabb, Hamid
JOURNAL: Journal of the American Society of Nephrology 35(10S):10.1681/ASN.2024k2n81acd, October 2024. | DOI: 10.1681/ASN.2024k2n81acd
Abstract
Background: Previous experimental studies using 16S RNA sequencing demonstrated distinct gut microbial changes following acute kidney injury (AKI) in mice and dysbiosis in chronic kidney disease (CKD) patients. Metagenomic whole genome sequencing (mWGS) has several advantages over 16S, including the ability to identify bacteria, fungi and viruses plus provide functional information. We applied mWGS to KPMP stool samples from AKI and CKD participants for species level identification and functional pathway analysis.
Methods: mWGS on AKI (n=7) and CKD (n=70) stool was performed to achieve >25 million reads/sample. Metagenomic data of healthy controls (n=94) from 4 published studies was downloaded from the NCBI Sequence Read Archive. Kraken2 and Metaphlan3 were used for taxonomic assignment and HUMAnN3 for functional annotation. Unsupervised clustering was performed using pheatmap, and comparisons between groups were computed with the non-parametric Mann-Whitney U test.
Results: Kraken2 analysis showed a decline in the percent mean abundance of Ruminococcus bicirculans in AKI (1.82) compared to CKD (6.47; p=0.07) and healthy individuals (2.42; p=0.01). Furthermore, genus Chryseobacterium declined in AKI (0.05) compared to CKD (0.07; p=0.05) and healthy individuals (0.20). Conversely, Gordonibacter pamelaeae increased in AKI (0.07) compared to healthy individuals (0.03) but was less abundant compared to CKD (0.30; p=0.05). Metaphlan3 identified 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. Gemmiger formicilis was significantly reduced in AKI (0.01) compared to CKD (0.51; p=0.06) and healthy (0.26; p=0.001) individuals. HUMAnN3 analysis showed significant correlation between amino acid metabolism and Clostridium asparagiforme in AKI compare to CKD and healthy individuals.
Conclusion: These preliminary results demonstrate distinct microbiota profile during an episode of AKI compared to CKD and healthy individuals. Future studies with larger sample sizes are needed to confirm these findings and highlight the pathophysiologic significance of these changes.
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