Gut Dysbiosis and Plasma Trimethylamine Oxide Are Associated with Subclinical Coronary Atherosclerosis in Obese Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease

<b>Background/Objectives</b>: Gut microbiota has been implicated in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular disease (CVD). This study aimed to identify associations between gut dysbiosis and MASLD, regarding body mass index (BMI) and subclinical coronary atherosclerosis (SCA). <b>Methods</b>: We conducted a cross-sectional study of 202 patients with MASLD who had no previous history of CVD. The severity of MASLD was evaluated using a magnetic resonance imaging-based method, and SCA was measured by assessing coronary artery calcification (CAC). Gut microbiota was assessed in fecal specimens using sequencing targeting the V4 region of the <i>16S rRNA</i> gene. <b>Results</b>: Our results demonstrated that gut microbial profiles between low- and high-BMI groups (<30 vs. ≥30 kg/m²) differed significantly in beta-diversity, but not in alpha-diversity indices. At the genus level, we identified <i>Megamonas</i>, <i>Sutterella</i>, <i>Catenibacterium</i>, and <i>Odoribacter</i>, enriched in the high BMI group. Compared to the low CAC group (<100 AU), MASLD patients with high CAC scores (≥100 AU) exhibited enrichment in <i>Ruminococcus gnavus</i>, <i>Bacteroides</i>, and <i>Lachnoclostridium</i>, along with depletion of several short-chain fatty acid (SCFA)-producing bacteria, such as <i>Faecalibacterium</i>. Multivariate analysis demonstrated that older age, the presence of diabetes, high BMI, fibrosis stage F3-F4, and high plasma trimethylamine oxide (TMAO) levels were independently associated with a high CAC score in patients with MASLD. <b>Conclusions</b>: These data indicated that gut dysbiosis and related metabolites, in association with advanced liver disease, were potential contributors to the progression of SCA in obese patients with MASLD.