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Meta-Analysis
. 2021 Jul 30;12(4):1286-1304.
doi: 10.1093/advances/nmab010.

Gut Microbiota-Derived Trimethylamine N-Oxide and Kidney Function: A Systematic Review and Meta-Analysis

Yan Zeng  1   2   3 , Man Guo  1   2   3 , Xia Fang  1   2   3 , Fangyuan Teng  1   2   3   4 , Xiaozhen Tan  1   2   3 , Xinyue Li  1   2   3 , Mei Wang  1   2   3 , Yang Long  1   2   3   4 , Yong Xu  1   2   3
Affiliations
Meta-Analysis

Gut Microbiota-Derived Trimethylamine N-Oxide and Kidney Function: A Systematic Review and Meta-Analysis

Yan Zeng et al. Adv Nutr. .

Abstract

Elevated circulating trimethylamine N-oxide (TMAO) concentrations have been observed in patients with chronic kidney disease (CKD). We aimed to systematically estimate and quantify the association between TMAO concentrations and kidney function. The PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science databases were systematically searched from 1995 to 1 June, 2020, for clinical studies on circulating TMAO concentrations and kidney function indicators. We used R software to conduct meta-analyses of the extracted data. A cumulative meta-analysis was applied to test whether health status affected the pooled effect value. Meta-regression and subgroup analyses were performed to identify possible sources of heterogeneity. Ultimately, we included a total of 32 eligible clinical studies involving 42,062 participants. In meta-analyses of continuous-outcome variables, advanced CKD was associated with a 67.9 μmol/L (95% CI: 52.7, 83.2; P < 0.01) increase in TMAO concentration, and subjects with high concentrations of TMAO had a 12.9 mL/(min·1.73 m2) (95% CI: -16.6, -9.14; P < 0.01) decrease in glomerular filtration rate (GFR). In meta-analyses of the correlations, TMAO was strongly inversely correlated with GFR [Fisher's z-transformed correlation coefficient (ZCOR): -0.45; 95% CI: -0.58, -0.32; P < 0.01] and positively associated with the urine albumin-to-creatinine ratio (UACR; ZCOR: 0.26; 95% CI: 0.08, 0.43; P < 0.01), serum creatinine (sCr; ZCOR: 0.43; 95% CI: 0.28, 0.58; P < 0.01), urine albumin excretion rate (UAER; ZCOR: 0.06; 95% CI: 0.04, 0.09; P < 0.01), blood urea (ZCOR: 0.50; 95% CI: 0.29, 0.72; P < 0.01), blood uric acid (ZCOR: 0.32; 95% CI: 0.25, 0.38; P < 0.01), and serum cystatin C (CysC; ZCOR: 0.47, 95% CI: 0.44, 0.51; P < 0.01). This is the first systematic review and meta-analysis to reveal a negative association between circulating TMAO concentrations and kidney function.

Keywords: TMAO; chronic kidney disease; glomerular filtration rate; gut microbiome; kidney function; kidney impairment; meta-analysis; trimethylamine N-oxide.

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Figures

FIGURE 1
FIGURE 1
Flow chart of the literature search and study selection process.
FIGURE 2
FIGURE 2
Meta-analysis of the circulating TMAO concentrations in patients with advanced CKD compared with healthy subjects. CKD, chronic kidney disease; MD, mean difference; TMAO, trimethylamine N-oxide.
FIGURE 3
FIGURE 3
Subgroup analyses in meta-analysis of the circulating TMAO concentrations in patients with advanced CKD compared with healthy subjects. CKD, chronic kidney disease; MD, mean difference; TMAO, trimethylamine N-oxide.
FIGURE 4
FIGURE 4
Meta-analysis of the GFR in subjects with high concentrations of TMAO compared with subjects with low concentrations of TMAO. In this analysis, if the original study reported circulating TMAO concentrations as quartiles or tertiles, the high concentration of TMAO included the highest layer of TMAO concentration, and the other layers were classified into the low concentration of TMAO. High category: subjects with high concentrations of TMAO. Low category: subjects with low concentrations of TMAO. GFR, glomerular filtration rate; MD, mean difference; TMAO, trimethylamine N-oxide.
FIGURE 5
FIGURE 5
Subgroup analyses in meta-analysis of the GFR in subjects with high concentrations of TMAO compared with subjects with low concentrations of TMAO. In this analysis, if the original study reported circulating TMAO concentrations as quartiles or tertiles, the high concentration of TMAO included the highest layer of TMAO concentration, and the other layers were classified into the low concentration of TMAO. High category: subjects with high concentrations of TMAO. Low category: subjects with low concentrations of TMAO. CAG, coronary angiography; CKD, chronic kidney disease; CVD, cardiovascular disease; DM, diabetes mellitus; GFR, glomerular filtration rate; MD, mean difference; TMAO, trimethylamine N-oxide.
FIGURE 6
FIGURE 6
Meta-analysis of the correlations between circulating TMAO concentrations and GFR. CVD, cardiovascular disease; DM, diabetes mellitus; GFR, glomerular filtration rate; TMAO, trimethylamine N-oxide; ZCOR, Fisher's z-transformed correlation coefficient.
FIGURE 7
FIGURE 7
Subgroup analyses in meta-analysis of the correlations between circulating TMAO concentrations and GFR. CKD, chronic kidney disease; GFR, glomerular filtration rate; TMAO, trimethylamine N-oxide; ZCOR, Fisher's z-transformed correlation coefficient.
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