Understanding the “individual drug reaction” from the perspective of the interaction between probiotics and lovastatin in vitro and in vivo

Background The existence of the gut microbiota produces an “individual drug reaction.” As members of the intestinal microbiota, probiotics, although they have prebiotic functions, may accelerate the degradation of drugs, thereby affecting drug efficacy. Lovastatin is one of the well-recognized lipid-lowering drugs. Its main action site is the liver. Therefore, if it is degraded in advance by gastrointestinal probiotics, its efficacy may be reduced. Results Here, we designed a two-stage experiment in vitro and in vivo to explore the degradation of lovastatin by probiotics. In vitro, the degradation of lovastatin by 83 strains of Lactiplantibacillus plantarum and the “star strain” Lacticaseibacillus paracasei strain Shirota was investigated by high-performance liquid chromatography (HPLC). The results showed that probiotics could degrade lovastatin to varying degrees. Subsequently, we selected Lactiplantibacillus plantarum A5 (16.87%) with the strongest ability to degrade lovastatin, Lactiplantibacillus plantarum C3 (4.61%) with the weakest ability to degrade lovastatin and Lacticaseibacillus paracasei strain Shirota (17.6%) as representative probiotics for in vivo experiments. In vivo, the therapeutic effect of lovastatin combined with probiotics on golden hamsters with mixed hyperlipidemia was evaluated by measuring blood indicators, intestinal microbiota metagenomic sequencing, and the liver transcriptome. The results showed that the intake of probiotics did not affect the efficacy of lovastatin and could slow the inflammatory reaction of the liver. Conclusions The supplementation of probiotics produced beneficial metabolites in the intestine by promoting beneficial microbes. Intestinal metabolites affected the expression of the liver genes through the gut-liver axis, increased the relative content of the essential amino acids, and finally improved the liver inflammatory response of the host. This study aims to reveal the impact of probiotics on the human body from a unique perspective, suggesting the impact of taking probiotics while taking drugs. -yAebddubv-jsx3W7b_Hvz Video Abstract