Abstract
Objective To investigate whether axial spondyloarthritis (AxSpA) patients have an altered immunoglobulin A (IgA) response in the gut and oral microbial communities.
Methods We performed 16S rRNA gene (16S) sequencing on IgA positive (IgA+) and IgA negative (IgA−) fractions (IgA-SEQ) from feces (n=17 AxSpA; n=14 healthy) and saliva (n=17 AxSpA; n=12 healthy), as well as on IgA-unsorted fecal and salivary samples. PICRUSt2 was used to predict microbial metabolic potential in AxSpA patients and healthy controls (HCs).
Results IgA-SEQ revealed enrichment of several microbes in the fecal (Akkermansia, Ruminococcaceae, Lachnospira) and salivary (Prevotellaceae, Actinobacillus) microbiome in AxSpA patients as compared with HCs. Fecal microbiome from AxSpA patients showed a trend towards increased alpha diversity of the IgA+ fraction and decreased diversity in the IgA− fraction in comparison with HCs, while the salivary microbiome exhibits a significant decrease in alpha diversity in both IgA+ and IgA− fractions. Increased IgA coating of Clostridiales Family XIII correlated with disease severity. Inferred metagenomic analysis suggests perturbation of metabolites and metabolic pathways for inflammation (oxidative phosphorylation, glutathione metabolism) and metabolism (propanoate and butanoate metabolism) in AxSpA patients.
Conclusions Analyses of fecal and salivary microbes from AxSpA patients reveal distinct populations of immunoreactive microbes using novel IgA-SEQ approach, which were not captured by comparing their relative abundance with HCs. Predictive metagenomic analysis revealed perturbation of metabolites/metabolic pathways in AxSpA patients. Future studies on these immunoreactive microbes may lead to better understanding of the functional role of IgA in maintaining microbial structure and human health.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵♢ Co-First Authors
↵‡ Co-Senior Authors
↵§ Deceased
Support:This study was supported by NIH R01 EY029266 (JTR-PI), NIH P30 EY010572 (Casey Eye Institute), Research to Prevent Blindness (Casey Eye Institute), the Rheumatology Research Foundation, the Spondylitis Association of America (Jane Bruckel ECI Award to TG), NIH K01DK116706 (LK) and NIH National Library of Medicine Training Grant T15-LM007088 (JN). JTR receives support from the Grandmaison Fund for Autoimmunity Research, the Stan and Madelle Rosenfeld Family Trust, and the William and Mary Bauman Foundation.