Small Intestinal Bacterial Overgrowth in Metabolic Dysfunction-Associated Steatotic Liver Disease: Prevalence, Subtypes, and Risk Factors Across Disease Spectrum and Comorbidity Profiles

Background: Small intestinal bacterial overgrowth (SIBO) has been implicated in the pathogenesis of MASLD; however, large-scale clinical data characterizing prevalence patterns, phenotypic subtypes, and disease-specific associations remain limited. Methods: This cross-sectional study enrolled 2549 MASLD patients with gastrointestinal symptoms undergoing lactulose methane–hydrogen breath testing and transient elastography. Univariate and multivariable analysis identified independent risk factors for SIBO. We also explore the distribution of SIBO subtypes and their associations with comorbidity profiles across the MASLD spectrum. Results: The overall prevalence of SIBO was 66.3%, escalating from 65.9% in MASL to 72.8% in at-risk MASH and 78.9% in cirrhosis, alongside a notable enrichment of the intestinal methanogen overgrowth (IMO) phenotype. Multivariable analysis identified advanced fibrosis (stage F4; OR = 1.75, 95% CI: 1.03–2.96), gastroesophageal reflux disease (GERD; OR = 1.66, 95% CI: 1.22–2.28), and coronary artery disease (CAD; OR = 1.80, 95% CI: 1.06–3.06) as independent predictors of SIBO. Additionally, elevated ALT (OR = 1.01, 95% CI: 1.01–1.13) showed a modest association with SIBO. Subtype analysis revealed that IMO was associated with GERD, alcohol consumption, CAD, and obesity, while a history of cholecystectomy and elevated triglycerides were linked to early-phase hydrogen peaks. Conclusions: SIBO is highly prevalent among patients with MASLD, with its prevalence and phenotypic subtype distribution being closely associated with disease severity. The identification of fibrosis-specific risk factors and subtype–clinical associations suggest consideration of SIBO assessment in advanced MASLD, particularly in patients with cardiometabolic or gastrointestinal comorbidities.