Traditional Chinese medicines (TCMs) with varied meridians (Gui-Jing) differentially alleviate the adverse impact of Coptis chinensis on gut microbiota

The meridian (GuiJing) theory is a unique theory of traditional Chinese medicine (TCM) which has been guiding the clinical practice of TCM for thousands of years, but physiological foundation of TCM's meridian remains to be clarified. Recent investigations have marked gut microbiota as a key mediator for the pharmacological effects of various TCMs. However, most studies focus on the response of gut microbes to a single drug or formula, the interactive effects of different drugs on gut microbiota are scarcely investigated.In this work, we evaluated the co-regulatory effects of different TCMs on gut microbiota when they were individually combined with Coptis chinensis (HL), and assessed the relationship between gut microbiota and the GuiJing of TCMs.Normal C57BL/6 mice were gavaged with HL extract for 14 days to disrupt the gut microbial community. Simultaneously, animals were treated with different TCMs which all possess antimicrobial activity but belong to different meridians. The gut microbiota was analyzed by full-length 16S rRNA gene amplicon sequencing to get a thorough bacterial profile at the species level.Administration of HL dramatically disrupted the gut microbiota and decreased the alpha diversity. Co-administration of different TCMs alleviated the adverse impact of HL on gut microbiota in a meridian-dependent manner. TCMs belonging to Shaoyin meridian moderately shifted the gut microbiota, while TCMs belonging to Taiyin and especially Jueyin meridians remarkably recovered the gut microbial community to the normal status. Decreased Firmicutes (Clostridia and Bacilli) and Actinobacteria (Bifidobacteriales) and increased Proteobacteria (Enterobacteriaceae) were main features of HL-induced gut dysbiosis. TCMs belonging to Shaoyin, Taiyin and Jueyin meridians gradually reversed the abundance of these bacteria to their normal levels. Simultaneously, the promoting effect of HL on beneficial bacteria such as Akkermansia muciniphila and Blautia coccoides was substantially preserved when co-administration of these TCMs, suggesting that co-treatment with these TCMs may reduce the toxicity of HL without deteriorating its beneficial effects.Combination of special TCMs may alleviate the adverse effect of HL on gut microbiota while preserving its beneficial actions. Gut microbiota may be a potential biological indicator of the meridian of TCMs.