Gut Dysbiosis and Intestinal Barrier Dysfunction Promotes IgA Nephropathy by Increasing the Production of Gd-IgA1

Yuyan Tang; Yifan Zhu; Haidong He; Yinshun Peng; Ping Hu; Jiajun Wu; Weiqian Sun; Ping Liu; Yong Xiao; Xudong Xu; Minggang Wei

doi:10.3389/fmed.2022.944027

Gut Dysbiosis and Intestinal Barrier Dysfunction Promotes IgA Nephropathy by Increasing the Production of Gd-IgA1

Front Med (Lausanne). 2022 Jul 7:9:944027. doi: 10.3389/fmed.2022.944027. eCollection 2022.

Authors

Yuyan Tang^{1

2}, Yifan Zhu², Haidong He², Yinshun Peng³, Ping Hu², Jiajun Wu², Weiqian Sun², Ping Liu², Yong Xiao⁴, Xudong Xu², Minggang Wei¹

Affiliations

¹ Department of Traditional Chinese Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
² Department of Nephrology, Minhang Hospital, Fudan University, Shanghai, China.
³ School of Public Health, Fudan University, Shanghai, China.
⁴ Department of Emergency, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Abstract

Background: Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerular disease in adults worldwide. Several studies have reported that galactose-deficient IgA1 (Gd-IgA1) is involved in the pathogenesis of IgAN.

Methods: Thirty-five patients with IgAN diagnosed with renal biopsy for the first time served as the experimental group, who were hospitalized in our department. Twenty normal healthy cases in the physical examination center of our hospital served as the control group. Then the levels of Gd-IgA1 in serum and urine, and intestinal mucosal barrier injury indexes [diamine oxidase (DAO), serum soluble intercellular adhesion molecule-1 (sICAM-1), D-lactate (D-LAC), and lipopolysaccharide (LPS)] and inflammatory factors [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)] in the serum samples were detected. Fecal samples were collected to detect intestinal microbiota using 16 s rDNA sequencing. Then, we assessed possible correlations among clinical and laboratory findings.

Results: In patients with IgAN, the levels of Gd-IgA1 both in the serum and urine were higher than that of the healthy control. Furthermore, urine Gd-IgA1 level was positively correlated with the serum creatinine level, 24 h urine protein, and M, S, and T parameters in the Oxford classification. ROC curve analysis showed that urine Gd-IgA1 has a greater diagnostic value (AUC = 0.9714, 95% CI, 0.932-1; P < 0.0001) for IgAN. The best cutoff value for urine Gd-IgA1 was 0.745 ng·l/ml·μmol (sensitivity, 94%; specificity, 95%). The intestinal mucosal barrier damage indexes (DAO, sICAM-1, D-LAC, and LPS) were increased in the patients with IgAN, which were positively correlated with Gd-IgA1 levels (P < 0.05) both in serum and urine. The levels of inflammatory factors in the patients with IgAN were increased. 16 s rDNA analysis showed that the intestinal microbiota in these patients was disordered compared to that observed in the healthy subjects. Actinobacteria, Bifidobacterium, Blautia, Bifidobacteriaceae, and Bifidobacteriales were decreased and Shigella was increased in IgAN. The decreased populations of these flora were negatively and significantly correlated with urine Gd-IgA1 and the levels of DAO, sICAM-1, D-LAC, and LPS.

Conclusion: The urine Gd-IgA1 levels may be a non-invasive biological marker for evaluating kidney injury in IgAN. Gut flora dysbiosis and intestinal barrier dysfunction may be involved in Gd-IgA1 expression.

Keywords: IgA nephropathy; intestinal microbiota; intestinal mucosal barrier; non-invasive biological marker; urine Gd-IgA1.