In vitro triple coculture with gut microbiota from spondyloarthritis patients is characterized by inter-individual differences in inflammatory responses

Abstract

Abstract Spondyloarthritis is a group of chronic inflammatory diseases that primarily affects axial or peripheral joints and is frequently associated with inflammation at non-articular sites. The disease is multifactorial, involving genetics, immunity and environmental factors, including the gut microbiota. In vivo, microbiome contributions are difficult to assess due to the multifactorial disease complexity. In a proof-of-concept approach, we therefore used a triple coculture model of immune-like, goblet and epithelial cells to investigate whether we could detect a differential impact from spondyloarthritis- vs. healthy-derived gut microbiota on host cell response. Despite their phylogenetic resemblance, flow cytometry-based phenotypic clustering revealed human-derived gut microbiota from healthy origin to cluster together and apart from spondyloarthritis donors. At host level, mucus production was higher upon exposure to healthy microbiota. Pro-inflammatory cytokine responses displayed more inter-individual variability in spondyloarthritis than in healthy donors. Interestingly, the high dominance in the initial sample of one patient of Prevotella, a genus previously linked to spondyloarthritis, resulted in the most differential host response upon 16 h host-microbe coincubation. While future research should further focus on inter-individual variability by using gut microbiota from a large cohort of patients, this study underscores the importance of the gut microbiota during the SpA disease course.