2nd Edition of International Obesity and Metabolism Conference 2026

Abstract

Lean metabolic dysfunction associated steatotic liver disease (Lean MASLD) is increasingly recognized as a distinct phenotype with clinical and metabolic characteristics that differ from non lean MASLD. However, the relationship between small intestinal bacterial overgrowth (SIBO) and Lean MASLD remains incompletely understood.

A total of 350 participants were classified as normal controls, lean MASLD, or non lean MASLD. MASLD was defined by CT confirmed steatosis and cardiometabolic criteria. SIBO and breath test gas patterns were assessed using standardized lactulose hydrogen methane breath tests. Clinical characteristics, metabolic parameters, and liver related biomarkers were compared across groups, with subgroup analyses according to MASLD phenotype, steatosis severity, SIBO subtype, and sex. Associations between SIBO and MASLD were evaluated using sequentially adjusted regression models. Gut microbial composition and fecal metabolic profiles were explored using 16S rRNA sequencing and untargeted metabolomics.

Compared with non lean MASLD, lean MASLD exhibited a distinct metabolic profile characterized by more pronounced alterations in lipid related indices. The prevalence of SIBO and the distribution of hydrogen and methane positive breath test patterns differed across MASLD phenotypes. In adjusted logistic regression analyses, breath test positivity was inversely associated with MASLD overall, with evidence of heterogeneity by BMI category and sex. Microbiome analyses demonstrated relative enrichment of Bacteroides, Enterobacter, and Fusobacteria related taxa in lean MASLD compared with non lean MASLD. Furthermore, SIBO associated lean MASLD showed enrichment of Bacteroidetes related lineages, whereas SIBO associated non lean MASLD was characterized by increased abundance of Bacteroidaceae, Clostridium cluster XIVa, Burkholderiales, and Sutterella.

Lean MASLD is associated with distinct metabolic characteristics, breath test gas profiles, and gut microbial signatures. Breath test positivity was inversely associated with MASLD, while methane positivity varied across phenotypes. These findings highlight potential gut liver axis differences in Lean MASLD and provide candidate microbial signatures for future investigation.