A study from Inner Mongolia Agricultural University, published in Engineering, investigates the interactions between the probiotic Lacticaseibacillus paracasei Zhang (LCZ) and the cholesterol-lowering drug lovastatin. The findings indicate that low doses of LCZ significantly boost lovastatin's effectiveness, while higher doses may increase the drug's toxicity.
In vitro experiments revealed that LCZ converts lovastatin into its active form, lovastatin hydroxy acid, suggesting a potential enhancement of the drug's efficacy. In vivo tests on hyperlipidemic Syrian golden hamsters confirmed that a combination of low-dose lovastatin (2.5 mg/kg) with LCZ significantly reduced body weight and blood lipid levels without causing liver, kidney, or muscle damage. This combination was more effective than lovastatin alone, indicating improved absorption facilitated by the probiotic. However, higher lovastatin doses (10 and 20 mg/kg) combined with LCZ led to increased mortality rates, suggesting toxic blood levels. All animal experiments adhered to the ethical guidelines of Inner Mongolia Agricultural University (IACUC-20220007).
Analyses of gut microbiota and their metabolites showed that LCZ alters the gut environment, promoting lovastatin solubility and absorption. This explains the enhanced efficacy at low doses. At higher doses, however, increased absorption led to toxic effects. Furthermore, gene expression analysis in the liver indicated an upregulation of genes involved in bile acid and drug metabolism, supporting the amplified effect.
The study highlights the need for precise dosing when combining probiotics and medications. While low LCZ doses optimize lovastatin efficacy, higher doses require caution due to toxicity risks. The findings contribute to the field of pharmacomicrobiomics and emphasize the importance of personalized approaches in medicine to balance benefits and risks.
Background: Lovastatin, a statin, is used to treat hyperlipidemia but can cause side effects such as muscle damage or liver strain. Probiotics like LCZ are increasingly being explored to enhance drug efficacy by modulating gut flora. The study (DOI: 10.1016/j.eng.2025.04.017) provides a foundation for further clinical research to validate the safety and effectiveness of such combination therapies in humans.
