PMID- 35863004 OWN - NLM STAT- MEDLINE DCOM- 20220908 LR - 20221005 IS - 2165-0497 (Electronic) IS - 2165-0497 (Linking) VI - 10 IP - 4 DP - 2022 Aug 31 TI - Alterations of the Gut Microbiota in Patients with Diabetic Nephropathy. PG - e0032422 LID - 10.1128/spectrum.00324-22 [doi] LID - e00324-22 AB - Diabetic nephropathy (DN) is the primary cause of end-stage renal disease. Accumulating studies have implied a critical role for the gut microbiota in diabetes mellitus (DM) and DN. However, the precise roles and regulatory mechanisms of the gut microbiota in the pathogenesis of DN remain largely unclear. In this study, metagenomics sequencing was performed using fecal samples from healthy controls (CON) and type 2 diabetes mellitus (T2DM) patients with or without DN. Fresh fecal samples from 15 T2DM patients without DN, 15 DN patients, and 15 age-, gender-, and body mass index (BMI)-matched healthy controls were collected. The compositions and potential functions of the gut microbiota were estimated. Although no difference of gut microbiota alpha and beta diversity was observed between the CON, T2DM, and DN groups, the relative abundances of butyrate-producing bacteria (Clostridium, Eubacterium, and Roseburia intestinalis) and potential probiotics (Lachnospira and Intestinibacter) were significantly reduced in T2DM and DN patients. Besides, Bacteroides stercoris was significantly enriched in fecal samples from patients with DN. Moreover, Clostridium sp. 26_22 was negatively associated with serum creatinine (P < 0.05). DN patients could be accurately distinguished from CON by Clostridium sp. CAG_768 (area under the curve [AUC] = 0.941), Bacteroides propionicifaciens (AUC = 0.905), and Clostridium sp. CAG_715 (AUC = 0.908). DN patients could be accurately distinguished from T2DM patients by Pseudomonadales, Fusobacterium varium, and Prevotella sp. MSX73 (AUC = 0.889). Regarding the potential bacterial functions of the gut microbiota, the citrate cycle, base excision repair, histidine metabolism, lipoic acid metabolism, and bile acid biosynthesis were enriched in DN patients, while selenium metabolism and branched-chain amino acid biosynthesis were decreased in DN patients. IMPORTANCE Gut microbiota imbalance is found in fecal samples from DN patients, in which Roseburia intestinalis is significantly decreased, while Bacteroides stercoris is increased. There is a significant correlation between gut microbiota imbalance and clinical indexes related to lipid metabolism, glucose metabolism, and renal function. The gut microbiota may be predictive factors for the development and progression of DN, although further studies are warranted to illustrate their regulatory mechanisms. FAU - Zhang, Lili AU - Zhang L AUID- ORCID: 0000-0002-4616-2529 AD - Department of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, China. FAU - Wang, Zhisheng AU - Wang Z AD - Department of Neurosurgery, Sunshine Union Hospital, Weifang, China. FAU - Zhang, Xiaona AU - Zhang X AD - Department of Endocrinology, The First Affiliated Hospital of Weifang Medical University, Weifang, China. FAU - Zhao, Lu AU - Zhao L AD - Department of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, China. AD - Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China. FAU - Chu, Jinjin AU - Chu J AD - Department of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, China. FAU - Li, Haibo AU - Li H AD - Department of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, China. FAU - Sun, Wenchang AU - Sun W AD - Department of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, China. FAU - Yang, Chunjuan AU - Yang C AD - Department of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, China. AD - Department of Rheumatology, The First Affiliated Hospital of Weifang Medical University, Weifang, China. FAU - Wang, Hui AU - Wang H AD - Department of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, China. FAU - Dai, Wenqing AU - Dai W AD - Department of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, China. FAU - Yan, Shushan AU - Yan S AD - Department of General Surgery, The Affiliated Hospital of Weifang Medical University, Weifang, China. FAU - Chen, Xiaohua AU - Chen X AD - Department of Nuclear Medicine, The First Affiliated Hospital of Weifang Medical University, Weifang, China. FAU - Xu, Donghua AU - Xu D AUID- ORCID: 0000-0002-9146-7858 AD - Department of Central Laboratory, The First Affiliated Hospital of Weifang Medical University, Weifang, China. AD - Department of Rheumatology, The First Affiliated Hospital of Weifang Medical University, Weifang, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220714 PL - United States TA - Microbiol Spectr JT - Microbiology spectrum JID - 101634614 RN - Bacteroides stercoris RN - Roseburia intestinalis SB - IM MH - Bacteroides MH - Clostridiales MH - *Diabetes Mellitus, Type 2/microbiology MH - *Diabetic Nephropathies/microbiology/pathology MH - *Gastrointestinal Microbiome MH - Humans PMC - PMC9430528 OTO - NOTNLM OT - composition OT - diabetic nephropathy OT - function OT - gut microbiota OT - metagenomics COIS- The authors declare no conflict of interest. EDAT- 2022/07/22 06:00 MHDA- 2022/09/09 06:00 PMCR- 2022/07/14 CRDT- 2022/07/21 16:49 PHST- 2022/07/22 06:00 [pubmed] PHST- 2022/09/09 06:00 [medline] PHST- 2022/07/21 16:49 [entrez] PHST- 2022/07/14 00:00 [pmc-release] AID - 00324-22 [pii] AID - spectrum.00324-22 [pii] AID - 10.1128/spectrum.00324-22 [doi] PST - ppublish SO - Microbiol Spectr. 2022 Aug 31;10(4):e0032422. doi: 10.1128/spectrum.00324-22. Epub 2022 Jul 14.