Abstract
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. Several observations suggest that gut microbiota could be implicated in IgAN pathophysiology. Aiming at exploring whether microbiota modulation is able to influence disease outcome, we performed fecal microbiota transplantation (FMT) from healthy controls (HC-sbjs), non-progressor (NP-pts) and progressor (P-pts) IgAN patients to antibiotic-treated humanized IgAN mice (α1KI-CD89Tg), by oral gavage. FMT was able to modulate renal phenotype and inflammation. On one hand, the microbiota from P-pts was able to induce an increase of serum BAFF and galactose deficient-IgA1 levels and a decrease of CD89 cell surface expression on blood CD11b+ cells which was associated with soluble CD89 and IgA1 mesangial deposits. On the other hand, the microbiota from HC-sbjs was able to induce a reduction of albuminuria immediately after gavage, an increased cell surface expression of CD89 on blood CD11b+ cells and a decreased expression of KC chemokine in kidney. Higher serum BAFF levels were found in mice subjected to FMT from IgAN patients. The main bacterial phyla composition and volatile organic compounds profile significantly differed in mouse gut microbiota. Microbiota modulation by FMT influences IgAN phenotype opening new avenues for therapeutic approaches in IgAN.
Highlights
IgA nephropathy (IgAN) is the most common primary glomerulonephritis throughout most developed countries of the world [1] and it shows a progression to end-stage renal disease (ESRD) in approximately 15 to 25 percent of cases at 10 years [2]
We showed that microbiota depletion by antibiotic treatment prevent IgA nephropathy development in these mice [22], confirming that nephritogenic IgA is modulated by a microbiota gut-kidney axis [23]
CD89Tg mice keeping normal levels of serum IgA [22], here we investigated whether transplanting intestinal microbiota through fecal microbiota transplantation (FMT) procedures from healthy control subjects (HC-sbjs), NP-pts, and P-pts into antibiotic-treated humanized IgAN mouse model (a1KICD89Tg) leads to a different disease outcome
Summary
IgA nephropathy (IgAN) is the most common primary glomerulonephritis throughout most developed countries of the world [1] and it shows a progression to end-stage renal disease (ESRD) in approximately 15 to 25 percent of cases at 10 years [2]. Hallmark of the disease is the presence of mesangial deposition of polymeric IgA1 [3]. Decreased serum IgA1-sCD89 complexes have been shown to be associated with disease progression or recurrence after transplantation [7,8,9]. IgA1 complexes deposit in the glomerular mesangium, where they activate mesangial cells through IgA receptor, transferrin receptor 1 (TfR1) [10,11,12]
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