Endotoxin Markers Are Elevated in Adolescents With Obesity With and Without Metabolic Dysfunction‐Associated Steatotic Liver Disease

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease in paediatric patients. Adult and murine studies have suggested a role for endotoxin from gram-negative bacteria in the development of MASLD, but there is incomplete and conflicting evidence for its role in adolescents. PURPOSE: To determine if adolescents with biopsy-proven MASLD have elevated endotoxin activity and whether endotoxin markers are associated with liver histological features. METHODS: Serum endotoxin core antibodies (EndoCab IgG), lipopolysaccharide binding protein (LBP), soluble CD14 (sCD14) and C-reactive protein (CRP) were measured in adolescents with obesity and MASLD (n = 46), and control groups without MASLD with obesity (Ob, n = 28) or normal weight (NW, n = 34). RESULTS: Compared to the NW group, both the MASLD and Ob groups had higher EndoCab IgG (56%), LBP (33%) and CRP (11-fold), while sCD14 did not differ. LBP and CRP were positively correlated to trunk and total body fat (r = 0.45 and 0.64, respectively), and to one another (r = 0.42), all p < 0.001. None of the endotoxin markers varied between boys and girls, or with liver steatosis grade or fibrosis stage within the MASLD group. CONCLUSION: Serum markers of endotoxin activity and inflammation are increased in adolescents with obesity but are not further increased in patients with mild to moderate MASLD.