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

Abstract

BackgroundImmunoglobulin 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.MethodsThirty-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.ResultsIn 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.ConclusionThe 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.

Bibliometric Analysis of the Relationship between Gut Microbiota and Chronic Kidney Disease from 2001–2022

“…These findings highlight the increasing research attention directed toward the functional role of the gut microbiota in CKD in recent years. [37,38]…”

“…These findings highlight the increasing research attention directed toward the functional role of the gut microbiota in CKD in recent years. [37,38] We comprehensively analyzed the contributions of countries, institutions, and journals to research associated with gut microbiota and CKD. While China and the USA emerged as leading contributors to publications and citations, Western countries, including Italy, Japan, Australia, Germany, and France, demonstrated prominence in academic areas regarding influence.…”

Immunomodulatory Effect of Isocaloric Diets with Different Protein Contents on Young Adult Sprague Dawley Rats

“…IL-8 is important in local inflammation, and excess immune responses can increase its secretion, leading to inflammatory cell aggregation and oxidative stress [ 26 ]. TGF-β and TNF-α are essential for suppressing immune responses and are highly expressed in patients with autoimmune diseases and cancer [ 27 ], indicating that the increase in proinflammatory substances in the colonic mucosa of rats fed 50% CP diet may be linked to autoimmune disorders.…”

Lanthanum hydroxide protects kidney through gut microbiota in a rat model of chronic kidney disease

“…The intestinal mucosal barrier can prevent harmful microorganisms and toxic metabolites from entering the blood 18 . In patients that have chronic kidney disease, their mucosal barrier is destroyed 19 . Vaziri et al.…”