OC 32.4 - Gut microbiome composition and intestinal immunity in antiphospholipid syndrome patients versus healthy controls

Background: An increasing body of research indicates a role of the gut microbiome in the etiology of auto-immunity and antiphospholipid syndrome (APS). A specific gut commensal, Roseburia intestinalis, expresses peptides that mimic the main epitopes in APS auto-antigen beta-2-glycoprotein-1 and is able to elicit the syndrome in APS-prone mice. As evidenced by antibiotics experiments, the phenotype in APS mouse models is gut microbiome dependent.

Aims: To compare gut microbiota composition of APS patients to healthy controls

Methods: Samples were selected from our biobank of patients with APS, the majority with an obstetric phenotype, and healthy controls were recruited alongside the APS patients from the same geographic region. For the current study we selected patients with beta-2-glycoprotein-1 antibodies and excluded subjects with recent use of antibiotics or proton pump inhibitors. To determine differences in the gut microbiome we performed fecal shotgun metagenomics. Microbiome composition was assessed using Shannon Index and Bray-curtis dissimilarity and general taxonomic abundance, all corrected for multiple testing. We measured fecal short chain fatty acids (SCFA) by high-performance liquid chromatography because of their role in intestinal immunity, and calprotectin levels as a marker for intestinal inflammation.

Results: We included 15 patients and 16 controls, all female. Both alpha and beta gut microbiota diversity did not differ between APS patients and healthy controls [Figure 1]. R. intestinalis was not more abundant in APS patients, nor did we find other differentially abundant taxa. There were also no differences in fecal calprotectin levels between APS patients and controls, nor in SCFA [Table 1].

Conclusion(s): We found no differences in gut microbiota composition, intestinal inflammation and SCFA levels in APS patients compared to healthy controls. The reported effects of the gut microbiome on APS are likely mediated by other mechanisms than overabundance, SCFA production or local inflammation.