Interaction Between the Gut Microbiome, Genetic and Clinical Risk Factors for Metabolic Dysfunction‐Associated Steatotic Liver Disease (MASLD) in Patients with Type 2 Diabetes Mellitus from Different Geographical Regions of Argentina

Background: Local specific biomarkers for MASLD risk stratification are urgently needed in Argentina. Aim: To characterized the interaction of gut microbiome signatures, genetic and clinical risk factors for MASLD in diabetics from different regions of Argentina. Material Methods: We recruited 214 diabetics from different regions. Anthropometric, clinical, and lifestyle data were obtained from all participants, who also underwent abdominal ultrasound for MASLD diagnosis and oral swabbing. PNPLA3 gene was amplified by PCR from the swabs, and rs738409 genotype was determined by bidirectional sequencing. To profile the MASLD-associated microbiome, stool was collected from 170 participants. V4 16S rRNA gene sequencing was performed and reads were analysed using QIIME2 2024.10.1. R Studio 2022.12.0 was used for statistical analyses. Results: MASLD prevalence was 77.9%, with similar rates in all regions. FIB-4 scores <1.3 and >2.67 were detected in 55.3% and 7.4% of patients, respectively. Half of diabetics had PNPLA3-GG genotype, with the highest rates in Northwestern Argentina (64.9%; p=0.02 vs Buenos Aires). PNPLA3-GG genotype was an independent risk factor for FIB-4 score (p=0.0008), and a protective factor against HbA1c (p=0.004), fasting plasma glucose (p=0.008), and cholesterol levels (p=0.02). Marked regional differences were observed in microbiota diversity and composition in Argentina. After adjusting for geographical region, Negativibacillus genus was exclusively detected in diabetics with MASLD and GG carriers. Catenibacterium genus was related to FIB-4>2.67. Short-chain fatty acids-producing bacteria were linked to absence of MASLD. Conclusions: These specific signatures could be potentially useful as MASLD biomarkers for risk stratification in diabetics from Argentina.