Study data published in Gastroenterology delineate the effects of immunoglobin A (IgA) deficiency and IgA-autoantibody status on the gut microbiome. In a paired lifestyle-balanced study conducted in Sweden, the gut microbiota of patients with IgA deficiency (IgAD) was enriched for multiple factors associated with pro-inflammatory and disease-related processes. This association appeared more pronounced in patients with IgA-specific autoreactive antibodies. 

While IgAD is associated with increased risk for recurrent mucosal infections, its precise effect on the microbiota remains unclear. To elucidate the effects of IgAD on the composition and functional capacity of the gut microbiome, investigators performed a paired study of individuals living in Stockholm, Sweden.

Patients with IgAD (serum IgA <0.07 g/L) and IgA-sufficient controls were invited to participate. Controls were selected from the households of patients with IgAD to account for lifestyle and environment. Patients and controls provided fecal samples and serum blood samples at a single study visit. Fecal samples were used for metagenomic analyses of gut composition while blood samples were tested for the presence of IgA- autoantibodies. Paired Wilcoxon-Rank tests were used to quantify differences between patients and controls.


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Data were available from 50 patients with IgAD and 50 matched household controls. Additionally, fecal samples from 32 additional patients with IgAD were used to supplement the dataset. Overall, 23 patients with IgAD were also positive for IgA-autoreactive antibodies.

In paired analyses, patients with IgAD had significantly lower species richness (P =.018) and species diversity (P =.012) compared with IgA-sufficient controls. A total of 6 bacterial species were found to be more abundant in the IgAD group compared with the IgA-sufficient group, many of which are associated with gut dysregulation and pathologies.

Escherichia coli (E. coli) was enriched 26.5-fold in IgAD. The IgAD microbiota was also enriched for bacterial genes encoding many “pathogen-related functions”, including antimicrobial resistance, virulence factors, and Type III and VI secretion systems. These functional alterations were more prominent in patients with both IgAD and IgA-specific autoreactive antibodies. E. coli appeared to be the driving species behind many functional differences between IgAD and IgA-sufficient microbiomes.

Per this cross-sectional analysis, the microbiota of patients with IgAD is enriched with bacterial species with known pro-inflammatory effects. This relationship appeared to be particularly pronounced in patients with both IgAD and IgA-specific autoantibodies. Study limitations include the small sample size and cross-sectional design. Further research in a longitudinal cohort is necessary to further explore microbiome changes in IgAD.  

“[Our] findings indicate a link between systemic autoimmunity and gut microbiota functionality and highlights that IgAD subjects with anti-IgA autoantibodies will benefit from close follow-ups in the clinic to monitor potential progression into other disease states,” investigators wrote.

Reference

Moll JM, Myers PN, Zhang C, et al. Gut microbiota perturbation in IgA deficiency is influenced by IgA-autoantibody status. Gastroenterol. Published online March 1, 2021. doi: 10.1053/j.gastro.2021.02.053