Role of the Gut Microbiome in Modulating Interactions Between β-Lactam Antibiotics and Statins in Coronary Heart Disease

Clinical evidence suggests that the lipid-lowering efficacy of statins may be diminished by concurrent β-lactam administration in patients with coronary heart disease (CHD), yet the mechanisms driving this potential drug-drug interaction, particularly the role of gut microbiota as a mediator, remain undefined. To address this gap, we conducted a retrospective analysis of data from a tertiary hospital spanning 5 years, enrolling 436 CHD patients on statin therapy who had two hospital admissions within a 3-month window. Patients were stratified into β-lactam-treated and antibiotic-free cohorts to assess the correlation between β-lactam exposure and statin efficacy. Additionally, 16S ribosomal RNA gene sequencing was employed to characterize and compare gut microbiota profiles between CHD patients receiving combined rosuvastatin and β-lactam therapy versus those on rosuvastatin monotherapy. Our findings demonstrated that β-lactam exposure was associated with elevated low-density lipoprotein cholesterol and total cholesterol levels. Both rosuvastatin and β-lactams induced significant alterations in gut microbiota composition, with distinct shifts in bacterial taxa abundances: rosuvastatin increased the relative abundance of Faecalibacterium and Dysosmobacter, whereas β-lactams disrupted the abundance of Faecalibacterium, Roseburia, and Dysosmobacter. Collectively, these results indicate that concomitant β-lactam use impairs rosuvastatin efficacy in CHD patients, likely via perturbation of gut microbiota composition. Rosuvastatin may exert a portion of its cardioprotective effects through modulation of gut microbiota, and β-lactams may abrogate this benefit by depleting key bacterial taxa linked to statin-mediated lipid regulation. Notably, Dysosmobacter emerges as a potential mediating species in this interaction, supporting a microbiome-dependent mechanism underlying the reduced lipid-lowering efficacy of rosuvastatin during β-lactam co-administration.