Gut Microbiota-Metabolite Alterations Associated with Early Metabolic Dysfunction and Hepatic Steatosis in Adolescents.

Background: Overweight, obesity, and metabolic dysfunction-associated fatty liver disease (MASLD) are increasingly prevalent in adolescents and are linked to alterations in the gut-liver axis. Gut microbiota may contribute to early metabolic disturbances preceding overt disease. Objective: To compare gut microbiota composition and fecal metabolite profiles, including short-chain fatty acids (SCFAs) and amino acids (AAs), between adolescents with overweight/obesity and normal-weight peers, and to evaluate differences associated with hepatic steatosis assessed by FibroScan-controlled attenuation parameter (CAP). Of 111 participants aged 13 to 17 years, 83 and 28 represented the study group with overweight or obesity and normal-weight control group, respectively. Hepatic steatosis consistent with MASLD was defined as CAP ≥250 dB/m. Gut microbiota was assessed by 16S ribosomal RNA (rRNA) sequencing and fecal metabolites by gas chromatography-mass spectrometry (GC-MS). Results: Adolescents with overweight/obesity showed impaired metabolic profiles compared with controls, while overall microbial α and β diversity did not differ between groups. Differences were observed in the relative abundance of several bacterial genera, including depletion of Lactobacillus. Fecal concentrations of most AAs were significantly elevated in the overweight/obesity group, whereas SCFA levels were unchanged. CAP-based stratification revealed that hepatic steatosis was associated with differences in richness-related α-diversity indices without β-diversity separation. Adolescents with fatty liver exhibited a distinct microbial signature involving low-abundance taxa and higher fecal acetate and butyrate levels. Conclusions: Adolescents with overweight/obesity and fatty liver display subtle but biologically relevant alterations in gut microbiota composition and fecal metabolite profiles despite preserved global microbial diversity. Early metabolic impairment appears to be associated with changes in specific bacterial taxa and AA metabolism rather than generalized dysbiosis.