Alterations of the Human Gut Microbiome in Chronic Kidney Disease

Abstract

Gut microbiota make up the largest microecosystem in the human body and are closely related to chronic metabolic diseases. Herein, 520 fecal samples are collected from different regions of China, the gut microbiome in chronic kidney disease (CKD) is characterized, and CKD classifiers based on microbial markers are constructed. Compared with healthy controls (HC, n = 210), gut microbial diversity is significantly decreased in CKD (n = 110), and the microbial community is remarkably distinguished from HC. Genera Klebsiella and Enterobacteriaceae are enriched, while Blautia and Roseburia are reduced in CKD. Fifty predicted microbial functions including tryptophan and phenylalanine metabolisms increase, while 36 functions including arginine and proline metabolisms decrease in CKD. Notably, five optimal microbial markers are identified using the random forest model. The area under the curve (AUC) reaches 0.9887 in the discovery cohort and 0.9512 in the validation cohort (49 CKD vs 63 HC). Importantly, the AUC reaches 0.8986 in the extra diagnosis cohort from Hangzhou. Moreover, Thalassospira and Akkermansia are increased with CKD progression. Thirteen operational taxonomy units are correlated with six clinical indicators of CKD. In conclusion, this study comprehensively characterizes gut microbiome in non-dialysis CKD and demonstrates the potential of microbial markers as non-invasive diagnostic tools for CKD in different regions of China.

Specific alterations in gut microbiota in patients with chronic kidney disease: an updated systematic review

“…Twelve (12/25) studies analyzed the relatively distinct taxa at the phylum level ( Table S6 ), of which two studies (2/10) focused on ESRD [ 24 , 25 ]. Six (6/10) and three (3/10) studies demonstrated that Proteobacteria [ 24 , 25 , 27–29 , 33 ] and Fusobacteria [ 18 , 27 , 34 ] were more abundant, while two (2/10) studies [ 18 , 29 ] showed that the abundance of Synergistetes in patients with CKD was less than that in controls. The abundance of Firmicutes , Bacteroidetes , and Actinobacteria in patients with CKD was inconsistent when compared to controls.…”

“…Of 12 studies, 10 studies were conducted in China, and two (2/10) studies focused on ESRD. Five (5/8), two (2/8), and two (2/8) studies demonstrated that Proteobacteria [ 20 , 27–29 , 33 ], Fusobacteria [ 18 , 27 ], and Bacteroidetes [ 17 , 33 ] were more abundant, while four (4/8) and two (2/8) studies revealed that Firmicutes [ 17 , 27 , 28 , 33 ] and Synergistetes [ 18 , 29 ] were less abundant in Chinese CKD patients compared with healthy controls, respectively. However, the two studies conducted in the US [ 34 ] and Italy [ 19 ] did not identify any taxa with the same alteration in CKD patients.…”

“…In the ESRD subgroup, two (2/4) studies observed that Deltaproteobacteria [ 22 , 24 ], Alphaproteobacteria [ 23 , 25 ], and Bacilli [ 23 , 25 ] were more abundant in ESRD patients than in healthy controls. All the four studies focused on CKD were conducted in China, of which two (2/4) studies observed that Actinobacteria [ 27 , 30 ], Gammaproteobacteria [ 27 , 33 ], and Fusobacteria [ 17 , 27 ] were more abundant while Verrucomicrobiae [ 27 , 30 ] and Betaproteobacteria [ 27 , 30 ] were less abundant in CKD patients than in healthy controls, respectively.…”

“…Two studies (2/3) reported an increased abundance of Desulfovibrionales [ 22 , 24 ] in ESRD patients compared with healthy controls. Three (3/6) and two (2/6) studies showed increased abundance of Enterobacteriales [ 27 , 28 , 33 ] and Fusobacteriales [ 17 , 27 ] in CKD patients compared with healthy controls, respectively; three (3/6), three (3/6), and two (2/6) studies reported decreased abundance of Clostridiales [ 17 , 27 , 28 ], Burkholderiales [ 27 , 28 , 30 ], and Verrucomicrobiales [ 27 , 30 ] in CKD patients compared with healthy controls. Additionally, Desulfovibrionales [ 27 ] was also enriched in a study focused on CKD.…”

“…Fourteen (14/25) studies documented the relatively distinct taxa at the family level ( Table S9 ), of which five studies [ 21 , 23–25 , 28 ] focused on ESRD. Five (5/9) and two (2/9) studies showed that Enterococcaceae [ 18 , 19 , 27 , 28 , 33 ] and Fusobacteriaceae [ 17 , 27 ] were more abundant in patients with CKD than in healthy controls, respectively. Four (4/9) studies showed that Prevotellaceae [ 19 , 20 , 28 , 33 ] and Lachnospiraceae [ 27 , 28 , 32 , 33 ] were less abundant in patients with CKD than in healthy controls, respectively.…”