Predictive Power of Gut Microbiome in the Clinical or Pathological Diagnosis of Diabetic Kidney Disease

Abstract

Background: Diabetic kidney disease (DKD) is characterized by increasing incidence, deficient diagnostic methods and poor prognosis. Methods: Using 16S ribosomal RNA (rRNA) technique, we characterized the microbial community in patients with clinically or pathologically diagnosed DKD. Findings: Differences among groups included expanded opportunistic pathogens, sulfate-reducing bacteria and mucin-degrading bacteria and depleted bacteria producing short-chain fatty acids (SCFA) levels. Eleven microbiota-targeted markers could separate the DKD group (clinically diagnosed; n =120) from the HCDM group (DM =92, HC = 140) with an area under the curve (AUC) of 88.12% . We analyzed an independent cohort of 60 DKDs and 116 HCDMs (DM = 46, Con = 70) to assess the diagnostic efficiency, with an AUC of 79.75%. The predicted functional category referring lipid metabolism was increased in DKD, and metabolism of tyrosine, phenylalanine and tryptophan was increased in DM. DKD-enriched microbial markers were positively correlated with serum creatinine and 24h-proteinuria. We performed the same analysis on 22 biopsy-proved DKD (also named diabetic nephropathy, DN) and 22 membranous nephropathy (MN). Differences in gut microbiome were identified by linear discriminant analysis, and the relative abundance of nine genera could be used to differentiate DN from MN (AUC = 77.69%). Interpretation: The gut microbiome was associated with DKD/DN. Microbiota-associated biomarkers represent a new diagnostic test for DKD that distinguishes it from MN. Funding: The National Natural Science Foundation of China; Science and Technology Innovation Team of Henan; Foundation for Leading Personnel of Central Plains of China; National Key Research and Development Program of China. Declaration of Interests: The authors have declared that no competing interest exists. Ethics Approval Statement: Our study followed the Helsinki declaration. The Institutional Review Board of the First Affiliated Hospital of Zhengzhou University approved all protocols (2019-KY-361). All participants had the right to information about the study and signed a written informed consent before sample collection.