Spondyloarthritis (SpA) encompasses several inflammatory rheumatic diseases that frequently harbor overt or subclinical intestinal inflammation. Dysbiosis, characterized by an overabundance of the Ruminococcus gnavus species, has recently been demonstrated in the intestinal microbiota of patients affected by SpA and correlates positively with disease activity. A thorough understanding of the microbiota-host interaction mechanisms in SpA is lacking due to the intrinsic limitations of standard cellular models. Organ-on-Chip systems have been recently developed thanks to the integration of nanotechnologies and microfluidics. The application of a laminar flux in two separate channels adjacent to a cell culture patch would allow the prolonged interaction between bacteria (including anaerobes) and patient-derived intestinal epithelium, closely mimicking interactions that occur in vivo.
The primary objective of this project is to set up a relevant microphysiological model of gut epithelium in SpA based on colon organoids and Gut-on-Chip technology. Furthermore, we aim to determine how different strains of Ruminococcus gnavus and other relevant members of the gut microbiota directly isolated from SpA patients or healthy controls interact with gut epithelial cells and modulate the inflammatory response in order to assess a possible causal link.
The main goals along the timeline are the following:
This project aims to create a reliable model for the study of the interactions between intestine and microbiota in patients with SpA. After validation, the far-reaching output of our project will provide some important advantages for patients suffering from SpA. First, this model will give the opportunity to experiment with new treatments, in particular those that can have an effect on the intestinal microbiota (such as antibiotics and probiotics), to understand if patients suffering from SpA can obtain an improvement in their condition. Second, it will allow the ex vivostudy of the sensitivity to the pharmacological treatments available, allowing to select the best treatment before administering it to the patient. These applications fall within the field of "tailored medicine". At the present stage, the project is based on the use of a microphysiological platform, and there are no clinical outcomes directly related to the patient. Thus, the patients were not involved in the experimental design. Biological samples will be used from adequately informed subjects who have explicitly given their consent, respecting all the regulations in force regarding the ethics of biomedical research, and approval by the local authorities has been obtained. Future clinical protocols based on the model developed in this project will certainly benefit from the full involvement of patient partners in the research team.