optimizing anti-il17 antibody therapy by associating fiber supplementation to correct treatment-aggravated gut dysbiosis in axial spondyloarthritis - respond-il17

Conditions: Axial Spondyloarthritis

Summary: fiber is the main source of energy for colonic bacteria and its consumption favorably modifies the composition of the microbiota in only a few days. their fermentation in the colon releases short-chain fatty acids (scfas). clostridiales contain many strains producing scfas. these scfas can restore the intestinal barrier and promote certain anti-inflammatory cells, including regulatory t cells (tregs), which are essential to the mechanisms in tolerance of the self. fibers could therefore correct the intestinal abnormalities present in patients with axial spondyloarthritis (axspa) and aggravated by anti-il-17 drugs and thus improve the therapeutic response to these treatments. the hypothesis is that dietary fiber will correct the dysbiosis in axspa patients and increase the release of scfas, which favorably modulate the immune response and improve axspa.

axial spondyloarthritis (axspa) is the second most common chronic inflammatory rheumatic disease, which develops preferentially in young subjects and results in a significant impairment of quality of life, particularly due to painful symptoms. the importance of the digestive system has long been recognized, since this disease is considered to be part of a larger group of diseases including crohn's disease and ulcerative colitis because of their frequent association in the same patient, and because leaky gut disorders and alterations of the intestinal microbiota (dysbiosis) have been described in these patients. these abnormalities may stimulate the immune system and therefore be involved in inflammatory processes (especially th17). the available treatments are based on non-steroidal anti-inflammatory drugs, and in the event of failure or intolerance, biomedicines targeting tnf can be used. therapeutic monoclonal antibodies against il-17 have recently enriched the therapeutic arsenal. although most anti-tnf agents have a beneficial effect on the rheumatologic and digestive aspects of these diseases, anti-il-17 agents are not expected to be effective in inflammatory bowel diseases. indeed, a deleterious role of anti-il-17 on the intestinal microbiota has even been demonstrated, which could result in a reduction of the systemic anti-inflammatory effect expected from these molecules, and consequently of the clinical benefit felt by the patient. in fact, anti-il-17s lead to a significant decrease in clostridiales, bacteria that participate in intestinal homeostasis. fiber is the main source of energy for colonic bacteria and its consumption favorably modifies the composition of the microbiota in just a few days. their fermentation in the colon releases short-chain fatty acids (scfas). clostridiales contain many strains producing scfas. these scfas can restore the intestinal barrier and promote certain anti-inflammatory cells, including regulatory t cells (tregs), which are essential to the mechanisms in tolerance of the self. fibers could therefore correct the intestinal abnormalities present in axspa patients and aggravated by anti-il-17 drugs and thus improve the therapeutic response to these treatments. the hypothesis is therefore that dietary fiber will correct the dysbiosis in axspa patients and increase the release of scfas, which favorably modulate the immune response and thus improve axspa.

Eligibility criteria:
inclusion criteria: * patients with spondyloarthritis meeting the asas criteria * patient considered by the treating rheumatologist for anti-il-17 biomedication * patients aged between 18 and 90 years of age * patients who are affiliated to a french social security system or beneficiaries of such a system * patients with no desire to become pregnant during the study period (effective contraception for women of childbearing age during the study period (surgical sterilization, hormonal contraceptives, barrier method, intrauterine device)) exclusion criteria: * lack of written informed consent after a time of reflection * patients participating in other therapeutic research or having participated in research for which the exclusion period has not ended * patient under court protection, guardianship or curatorship. * patient unable to give consent. * pregnant or breastfeeding woman * patients with digestive disorders for which a chronic inflammatory bowel disease has not been excluded * patients with fructose intolerance or glucose or galactose malabsorption * patients with known intolerance to inulin or maltodextrin

Keywords: dysbiosis short-chain fatty acids fiber microbiota