Evaluation of Defensins as Markers of Gut Microbiota Disturbances in Children with Obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD).

Until recently, it was believed that bacterial translocation occurs as a result of leaky gut syndrome or sepsis. To confirm or exclude the process of bacterial translocation, biomarkers can be used. One such biomarker is defensins, which indicate immune activity, as defensins are cationic peptides with antibacterial properties produced by intestinal epithelial cells. Also, fatty acid-binding proteins (I-FABP and L-FABP) can serve as useful serological markers for intestinal epithelial damage, indicating impaired intestinal permeability or organ damage, as high concentrations of them are found in tissues and low concentrations in blood serum. In the context of obesity, the integrity of the intestinal barrier, which can be disrupted by dietary fat, leads to increased intestinal permeability. Since bacterial translocation and microbiota contribute to obesity and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) associated with metabolic dysfunction, intestinal barrier markers can be used to study the role of the gut-liver axis. The aim of this study was to gain insight into the pathogenesis of MASLD and examine the impact of bacterial translocation markers and intestinal and hepatic fatty acid-binding proteins (I-FABP and L-FABP) in children with MASLD. : We examined 60 children with MASLD and overweight/obesity (MASLD was diagnosed based on increased liver echogenicity in ultrasound and elevated ALT activity), aged 14.5 years (range 8.5 to 15.8); 33 children with overweight/obesity without MASLD, aged 13.0 years (range 11.4 to 15.8); and 16 healthy controls aged 11.0 years (range 7.0 to 16.2). Defensin, I-FABP, and L-FABP levels were measured using commercial kits: ELISA kits (Drg Medtek) were used to assess α-5 and α-6 defensin concentrations (HBD5, HBD6). I-FABP and L-FABP concentrations were measured using commercial ELISA kits (Hycult Biotech Inc., Wayne, PA, USA). ANOVA analysis was used to compare results across the three study groups. : A significant difference was found for the following tests among children with MASLD, obesity, and healthy controls: defensin 6 (14.4 ng/mL vs. 6.13 ng/mL vs. 17.2 ng/mL, respectively), L-FABP (9168 pg/mL vs. 7954 pg/mL vs. 7620 pg/mL, respectively), and I-FABP (272 pg/mL vs. 321 pg/mL vs. 330 pg/mL, respectively). No differences were found in defensin 5 levels (median 567.2 pg/mL vs. 485.7 pg/mL vs. 601.8 pg/mL). No differences were observed in cholesterol levels (HDL, LDL) or triglyceride concentrations, as well as apolipoprotein levels. : Based on our study, it was concluded that inflammation and intestinal barrier damage lead to increased L-FABP levels, as it is released from enterocytes in response to oxidative stress or tissue damage. Defensin 6 may indirectly affect L-FABP through microbiota regulation and protection of the intestinal barrier. Defensin 6 also exerts antimicrobial activity and may accompany liver inflammation, with its increased concentration in comparison to obesity explained by the activation of defense mechanisms.