Modulation of Gut Microbiota and Antibiotic Resistance Genes by Heat-Killed EF-2001 in High-Fat Diet-Induced Obesity Mice: A Shotgun Metagenomics Study.

The gut microbiome is vital in maintaining metabolic health, and dietary habits can significantly impact its composition. A high-fat diet (HFD) can disrupt gut microbial balance, contributing to obesity, insulin resistance, and fatty liver disease. This study explores the potential benefits of heat-killed EF-2001 (EF-2001) in restoring gut balance and improving metabolic health in HFD-fed mice (HFD-mice). HFD mice administered EF-2001 had 18% less body fat, 22% lower triglyceride levels, and significantly reduced liver enzyme markers, including aspartate aminotransferase (AST) by 28% and alanine aminotransferase (ALT) by 31%. Additionally, EF-2001 improved glucose metabolism, increasing glucose tolerance by 20% and insulin sensitivity by 15%, while reducing fat buildup in the liver by 24%, indicating protection against fatty liver disease. These changes correlated with better metabolic health and reduced inflammation. Our results show that EF-2001 supplementation helped counteract HFD-induced gut imbalances by increasing microbial diversity and supporting beneficial bacteria, such as and spp. Our findings highlight the potential of heat-killed EF-2001 as a promising strategy to restore gut balance and mitigate diet-related metabolic issues. Furthermore, analysis of antibiotic resistance genes (ARGs) revealed that HFD mice exhibited an increased abundance of multidrug resistance genes, particularly those associated with antibiotic efflux mechanisms, such as A, A, and A. Notably, EF-2001 supplementation mitigated this increase, reducing the relative abundance of the above ARGs and suggesting a protective role in limiting the spread of antibiotic resistance linked to dysbiosis. EF-2001 offers a compelling approach to managing obesity and metabolic disorders, paving the way for microbiome-based health interventions.