A butyrate-rich diet improves redox status and fibrin lysis in Behçet's syndrome patients

Introduction: Behçet’s syndrome (BS) is a systemic vasculitis of unknown etiology characterized as a multisystemic immune-inflammatory disorder affecting vessels of all sizes and frequently complicated by thrombosis. Systemic redox imbalance and heightened neutrophil activation in BS patients are believed to contribute to impaired coagulation. Our group have already demonstrated an altered fibrinogen structure and reduced fibrin susceptibility to plasmin-induced lysis in BS patients, primarily due to increased reactive oxygen species (ROS) production by neutrophils. This supports the idea that BS serves as a model for inflammation-driven thrombosis. Moreover, BS has been associated with a peculiar dysbiosis in the gut microbial ecosystem, represented by a depletion in the Clostridium cluster, involved in short-chain fatty acid (SCFA) production. Among SCFAs, patients show a decrease in the production of butyrate, which exerts anti-inflammatory and trophic activity.

Methods: To explore the relationship between butyrate, blood redox balance, and cardiovascular risk, we examined the effects of a 3-month butyrate-enriched diet in 30 bariatric surgery (BS) patients. Participants were randomly divided into two groups: 15 received oral butyrate supplementation (2.4 g/day), while 15 followed a lacto-ovo-vegetarian diet rich in insulin and resistant starch, which enhance butyrate production through fermentation. At baseline (T0) and after the intervention (T3), we assessed leukocyte intracellular ROS production, plasma malondialdehyde (MDA) levels as a marker of lipid peroxidation, and plasma total antioxidant capacity (TAC). Additionally, we evaluated fibrin susceptibility to plasmin-induced lysis using purified fibrinogen fractions.

Results: Both butyrate-enriched interventions led to significant reductions in leukocyte ROS production and plasma lipid peroxidation, alongside an increase in plasma total antioxidant capacity. Importantly, fibrin susceptibility to plasmin-induced lysis showed marked improvement in both groups at T3 compared to T0.

Conclusions: Our findings suggest that a butyrate-enriched diet enhances blood redox balance and promotes fibrin degradation, highlighting its potential role in cardiovascular disease prevention.