Metagenomic profiling reveals dominance of gram-positive bacteria in the gut microbiome shifts associated with immunoglobulin A vasculitis (Henoch–Schönlein Purpura)

Abstract

Objectives: Immunoglobulin A vasculitis (IgAV), previously known as Henoch–Schönlein purpura, is the most common vasculitis that has a classical skin manifestation of palpable purpuric rash. Factors pertinent to IgAV remain inadequately understood. Here, we aimed to examine the gut microbiome shifts associated with IgAV and its recovery. Methods: Stool samples were collected from 10 children with IgAV (6–14 years old) before and after a multi-drug therapy, along with 9 age-matched healthy children. The samples were subjected to metagenomic analyses to investigate the taxonomic and functional shifts of the gut microbiome. Results: The analyses revealed that compared with healthy controls, treatment-naïve patients exhibited substantial taxonomic and functional alterations of gut microbiota, including 104 IgAV-depleted species and 7 IgAV-elevated species (FDR < 0.05). After treatment, the IgAV patients displayed a partial restoration of the microbiota shifts, as the relative abundances of some biomarkers (e.g. 9 genera and 22 species) became comparable (FDR > 0.1) between the patients and healthy controls. The treatment-responsive features included Weissella, Faecalibacterium prausnitzii and Bifidobacterium pseudocatenulatum and three components of a putative glutamine transport system. Importantly, gram-positive bacteria accounted for over 85% of the numbers and total relative abundance of the species that were associated with IgAV and responsive to the treatment. In addition, of the 122 IgAV-depleted bacterial genes, 82 were mainly contributed by gram-positive bacteria and 12 by gram-negative bacteria. Conclusions: Gram-positive bacteria are the main drivers underlying the gut microbiome shifts of IgAV, which may assist rational management of the disease.