Research progress on the metabolism of glycosides by gut microbiota
Glycosides are a class of compounds formed by connecting sugars or sugar derivatives with aglycones through the carbon atom at the sugar end, and are widely present in traditional Chinese medicine. Glycoside compounds have a wide variety of glycoside types, and any compound with hydroxyl, carboxyl, amino, or thiol groups in its structure can become a glycoside. In addition, glycoside compounds have one or more sugar groups in their structure, high polarity, low lipid solubility, and low membrane permeability, resulting in generally low oral bioavailability. However, glycoside drugs have shown good therapeutic effects in clinical treatment. The phenomenon of low bioavailability but good therapeutic effect of glycoside drugs has aroused great interest among researchers.

Research suggests that after entering the body, glycoside compounds are converted into secondary glycosides or aglycones with low polarity and high lipid solubility by microorganisms and enzymes secreted in the intestine. The aglycones are absorbed and metabolized by phase I and phase II drug metabolizing enzymes in the intestinal epithelium and liver, and are excreted through urine and bile or returned to the intestine through the hepatointestinal circulation. Subsequently, some residual aglycones and/or metabolic derivatives enter the vascular circulation. And the metabolites of glycoside compounds in the intestine mostly exhibit better biological activity than their parent compounds. Therefore, the metabolism of glycoside compounds by gut microbiota is a prerequisite for their pharmacological effects. This article will review the metabolism of glycoside compounds by gut microbiota and its significance.

 

 

Glycoside compounds are often used as “prodrugs”, and their intestinal metabolites often exhibit diverse pharmacological activities. The metabolism of glycoside compounds by gut microbiota has always been a focus of drug research, and the development of technology has provided powerful tools for research. Liquid chromatography-mass spectrometry technology can detect the intestinal metabolites of glycoside compounds, and microbial culture technology and high-throughput sequencing technology can be used to explore the interaction between glycoside compounds and gut microbiota, which helps establish a network of “glycoside bacteria enzyme metabolite” relationships. However, compared to the vast number of gut microbiota and metabolic enzymes, we know very little about the specific microbial strains, genes, and enzymes responsible for glycoside metabolism. In addition, existing research mainly focuses on the metabolism of glycosides by gut microbiota in normal organisms, while the characteristic metabolites produced in the intestines of diseased organisms can better reflect the material basis for the therapeutic effects of glycoside compounds. Therefore, by combining high-throughput sequencing technology with microbial culture technology, and combining in vivo metabolism with in vitro incubation, comparing the specific products produced by gut specific bacteria and their metabolic glycoside compounds between normal and diseased organisms, as well as between different diseased organisms, is more conducive to exploring specific pharmacological components and explaining the mechanism of therapeutic effects. On this basis, efficient metabolic strains/enzymes are screened, and microbial/enzyme conversion technology is used to transform glycoside compounds in vitro, which can provide a foundation for the research and development of new drugs.