Safety and efficacy assessment of fecal microbiota transplantation as an adjunctive treatment for IgA nephropathy: an exploratory clinical trial

Abstract

To assess the safety and efficacy of fecal microbiota transplantation (FMT) as an adjunctive therapeutic intervention for IgA nephropathy (IgAN). Fifteen patients with IgA nephropathy were recruited based on inclusion and exclusion criteria and underwent FMT using enteric microbial capsules. Clinical indicators, intestinal microbiota and metabolomic profiles, as well as changes in serum immune cells and cytokines, were monitored before and after FMT. No severe adverse reactions were observed in the subjects. After FMT, there was a reduction in the 24-h urinary protein quantification in subjects. The relative abundances of Phocaeicola_vulgatus, Bacteroides_uniformis, Prevotella_copri, Phocaeicola_dorei, Bacteroides_ovatus, Bacteroides_xylanisolvens, Parabacteroides _distasonis, Bifidobacterium_pseudocatenulatum, Bacteroides_sp._HF-162, and Bifidobacterium_longum changed after FMT. In terms of intestinal metabolites, the levels of acylcarnitine18:0 (ACar.18:0), cotinine, N-arachidonoyl-L-serine, phosphatidylcholine (PC. (18:3e/22:6)), serotonin, and fumagillin showed significant changes. Flow cytometry analysis showed the absolute count of plasma B cells decreased in subjects, and this change correlated with alterations in the intestinal microbiota and metabolites. This study preliminarily evaluates the safety and efficacy of FMT in patients with IgAN. No significant adverse reactions were observed, and the administration of FMT alongside ACEI/ARB therapy was effective in reducing urinary protein levels in patients with IgAN, a process that may be associated with B-cell immunity.

Keywords: Clinical trial; Fecal microbiota transplantation; Gut microbiota and metabolites; IgA nephropathy; Immune function.

Fig. 1

Quantitative changes in urinary protein 24 h before and After FMT. (A) Show the changes in 24-h urinary protein quantification for the 15 participants in the study, (B) shows the changes in urinary protein quantification for the remaining 13 participants after excluding two patients with acute upper respiratory infections. pre refers to before the FMT, after refers to immediately after FMT, 1 month refers to one month after FMT, and 3 month refers to 3 months after FMT.

Fig. 2

The relative abundance of the top 10 strains before and after FMT transplantation. before refers to before the FMT, 1 month refers to one month after FMT, and 3month refers to 3 months after FMT.

Fig. 3

Differential metabolite expression before and after FMT transplantation. before refers to before the FMT, 1month refers to one month after FMT, and 3month refers to three months after FMT.