ModulAtion of gut Microbiota through nutritional interventions in Behçet's syndrome pAtients: the MAMBA Study

Background and aims of the study: Behçet’s syndrome (BS) is a systemic inflammatory disorder characterized by a wide range of clinical manifestations with no gold-standard therapy. Although the pathogenesis of BS is currently unknown, gut microbiota (GM) is recognized to deeply influence the course of the disease. Recent evidence suggests that the GM in BS has low biodiversity with a significant depletion in butyrate production, one of the most representative short-chain fatty acids (SCFAs), contributing to the inflammatory state. The aim of the present project is to investigate whether a tailored dietary intervention could ameliorate the clinical manifestations and modulate the GM of BS patients. Patients and methods This is a randomized, open, cross-over study that involved BS patients, who were randomly assigned to one of three different isocaloric diets for 3 months: a lacto-ovo-vegetarian diet (VD), a Mediterranean diet (MD), or a Mediterranean diet supplemented with butyrate (MD-Bt). Anthropometric measurements, body composition, blood, and fecal samples were obtained from each participant at the beginning and the end of each intervention phase. The primary outcomes were the change from baseline of the BS gastrointestinal and systemic symptoms. Changes from baseline in antioxidant profile and in GM composition were considered as secondary outcomes. Results A cohort of 38 patients were analysed. Following the three nutritional interventions, a reduction in clinical BS activity was detected, though without statistical significance. Also, a remarkable improvement in gastrointestinal symptoms was observed in all three groups. Of major note, VD allowed to significantly reduce the daily glucocorticoids dosage, with a significant reduction in the proportion of patients receiving steroids. A significant improvement in the redox status was detected after VD and MD+Bt interventions, both in terms of ROS production, plasma lipid peroxidation, and total antioxidant capacity, while no effect of MD was observed. On the other hand, these 3-month butyrate-enriched diets did not affect GM composition. Conclusion A long-term supportive treatment based on dietary and lifestyle issues, might be able to improve the patients’ wellbeing, to allow steroid spare, and to reduce the oxidative stress sustaining BS-related thrombotic events. This could have a high impact on BS-related morbidity and mortality, considering the high cardiovascular risk in chronic inflammatory conditions such as BS.