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P157 Microbiome Analysis Reveals That Ralstonia is Responsible for Decreased Renal Function in Patients with Ulcerative Colitis

Kim, J.M.(1,2,3);Rim, J.H.(3,4);Kim, D.H.(1,2);Kim, H.Y.(3);Choi, S.K.(5);Kim, D.Y.(3,4);Choi, Y.J.(3);Yu, S.(3);Gee, H.Y.(3);Cheon, J.H.(1,2);

(1)Yonsei University College Of Medicine, Department of Internal Medicine And Institute Of Gastroenterology, Seoul, Korea- Republic Of;(2)Yonsei University College Of Medicine, Department of Severance Biomedical Science Institute, Seoul, Korea- Republic Of;(3)Yonsei University College Of Medicine, Department of Pharmacology- Graduate School Of Medical Science- Brain Korea 21 Project, Seoul, Korea- Republic Of;(4)Yonsei University Graduate School Of Medicine, Department of Medicine- Physician-Scientist Program, Seoul, Korea- Republic Of;(5)Hanyang University erica, Department of Applied Mathematics, Ansan, Korea- Republic Of

Background

Inflammatory bowel diseases (IBDs), such as ulcerative colitis (UC), are characterized by a disturbance of the normal gut microbiota and contribute to the development of chronic kidney disease (CKD). The incidence of CKD is higher in individuals with UC, but the causal link is unknown. Therefore, we investigated the role of gut microbiota in decreasing renal function in patients with UC

Methods

We performed 16S ribosomal DNA sequencing using ileocecal mucosal samples from nine individuals with UC and CKD (UC+CKD), 29 individuals with UC only, and 12 healthy controls. We also analyzed the operational taxonomic units, microbial diversity, and correlation with renal function. Co-culture assay using kidney organoids and Caco-2 cells was performed.
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Figure 1. The taxonomic composition of the gut microbiota of the study population and comparison of the 10 most abundant genera and species in the UC + CKD, UC, and control groups.

Results

Bacterial species diversity was significantly decreased in the UC+CKD group compared to that in the other groups based on Shannon and inverse Simpson indexes. At the genus level, Ralstonia had significantly greater abundance in the UC+CKD and UC groups compared to the control group. At the species level, unclassified Ralstonia species and Citrobacter portucalensis showed higher abundance in the UC+CKD group compared to the other groups. The relative abundance of Ralstonia showed a negative correlation with the estimated glomerular filtration rate (eGFR), but a positive correlation with the serum uric acid level. Ralstonia pickettii represented a negative correlation with eGFR, and induced damaging changes to kidney organoids in co-culture assay.


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Figure 2. The correlation between the relative abundance of Ralstonia with renal function (indicated by eGFR) and serum uric acid level. Effects of Ralstonia pickettii on Caco‐2 cells and kidney organoids. (A) mRNA expression of pro‐inflammatory cytokine genes in Caco‐2 cells treated with and without Ralstonia pickettii, reflecting the inflammation seen in ulcerative colitis.

Conclusion

Gut microbial community profiles of the UC+CKD group are different from those of the UC group. Furthermore, Ralstonia pickettii contributes in decreasing renal function in patients with UC.

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