Gut microbiota as a target to limit toxic effects of traditional Chinese medicine: Implications for therapy.

Traditional Chinese medicines (TCMs) are medicines that are widely used in oriental countries under the guidance of ancient Chinese medicinal philosophies. With thousands of years of experiences in fighting against diseases, TCMs are gaining increasing importance in the world. Although the efficacy of TCMs is well recognized in clinic, the toxicity of TCMs has become a serious issue around the world in recent years. In general, the toxicity of TCMs is caused by the toxic medicinal compounds and contaminants in TCMs such as pesticides, herbicides, and heavy metals. Recent studies have demonstrated that gut microbiota can interact with TCMs and thus influence the toxicity of TCMs. However, there is no focused review on gut microbiota and the toxicity of TCMs. Here, we summarized the influences of the gut microbiota on the toxicity of medicinal compounds in TCMs and the corresponding mechanisms were offered. Then, we discussed the relationships between gut microbiota and the TCM contaminants. In addition, we discussed the methods of manipulating gut microbiota to reduce the toxicity of TCMs. At the end of this review, the perspectives on gut microbiota and the toxicity of TCMs were also discussed.

Feng W ，Liu J ，Huang L ，Tan Y ，Peng C ... -  《-》

Traditional Chinese medicines differentially modulate the gut microbiota based on their nature (Yao-Xing).

Property theory is a unique principle guiding traditional Chinese medicine (TCM) that classifies various TCMs into four natures (hot, warm, cool, and cold) to reflect their medical actions on the human body. Despite successful application for thousands of years, characterizing the nature of medical TCMs by modern physiological indicators remains a challenge. In this study, we investigated the potential relationship between the nature of TCMs and their modulation of the gut microbiota. We selected twelve TCMs with hot, warm, cool, or cold natures that possess antidiarrheal effects. Their aqueous extracts were orally administered to C57BL/6 mice at a clinical dose for 4 weeks. The gut microbiota was measured by 16S rRNA-based metagenomics, and the correlation between microbial composition/function and TCM nature was analyzed. Antidiarrheal TCMs with different natures showed distinct impacts on the gut microbiota. Hot-natured TCMs had no influence on the gut microbiota, warm-natured TCMs had a moderate influence, cool-natured TCMs had a strong influence, and cold-natured TCMs substantially changed the structure of the gut microbial community. The abundance of Anaerotruncus, Tyzzerella and Ruminiclostridium steadily increased, while that of Ruminococcaceae_UCG-010, Parasutterella and Bifidobacterium continuously decreased as the herbal nature turned from cold to hot. Microbiome functional prediction for Cluster of Orthologous Groups (COG) of proteins and Kyoto Encyclopedia of Genes and Genomes (KEGG) categories showed that colder TCMs imposed a stronger influence on microbial functional repertoires. Specifically, the abundance of ABC transporters, key bacterial proteins involved in nutrient absorption and drug resistance, was gradually decreased by colder TCMs. Our results demonstrated that the nature of TCMs could be reflected by their modulation of gut microbes. Cold TCMs may exert their antidiarrheal effects, at least partially, by modulating the gut microbiota, while hot TCMs may alleviate dysentery in other ways.

Zhang X ，Yang Y ，Zhang F ，Yu J ，Sun W ，Wang R ，Wu C ... -  《-》

Therapeutic mechanisms of traditional Chinese medicine to improve metabolic diseases via the gut microbiota.

Metabolic diseases such as obesity, type 2 diabetes mellitus, and hyperlipidemia are associated with the dysfunction of gut microbiota. Traditional Chinese medicines (TCMs) have shown considerable effects in the treatment of metabolic disorders by regulating the gut microbiota. However, the underlying mechanisms are unclear. Studies have shown that TCMs significantly affect glucose and lipid metabolism by modulating the gut microbiota, particularly mucin-degrading bacteria, bacteria with anti-inflammatory properties, lipopolysaccharide- and short-chain fatty acid (SCFA)-producing bacteria, and bacteria with bile-salt hydrolase activity. In this review, we explored potential mechanisms by which TCM improved metabolic disorders via regulating gut microbiota composition and functional structure. In particular, we focused on the protection of the intestinal barrier function, modulation of metabolic endotoxemia and inflammatory responses, regulation of the effects of SCFAs, modulation of the gut-brain axis, and regulation of bile acid metabolism and tryptophan metabolism as therapeutic mechanisms of TCMs in metabolic diseases.

Zhang HY ，Tian JX ，Lian FM ，Li M ，Liu WK ，Zhen Z ，Liao JQ ，Tong XL ... -  《-》

The interactions between gut microbiota and bioactive ingredients of traditional Chinese medicines: A review.

In recent years, the interaction between the bioactive ingredients of traditional Chinese medicine (TCM) and gut microbiota has been a focus of many studies. When TCM enters the digestive tract, some bioactive ingredients are not absorbed into the gut well thus leading to low bioavailability. Ingredients of TCM are metabolised, or biotransformed by gut microbiota, thereby producing new bioactive molecules, and promote medicine absorption into the circulation. At the same time, the ingredients of TCM effect the composition and structure of gut microbiota, thereby influencing the remote function of diseased organs / tissues through the systemic action of the gut microbiota. In this review, we summarise the gut microbiota-mediated metabolism of flavonoids, alkaloids, terpenoids, saponins, polysaccharides, phenylpropanoids, and organic acids, along with a discussion on the metabolites formed and the biotransformation pathways involving various enzymes. We also highlight the importance of bioactive ingredients of TCM in regulating gut microbiota.

Gong X ，Li X ，Bo A ，Shi RY ，Li QY ，Lei LJ ，Zhang L ，Li MH ... -  《-》

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.

Yang Y ，Su W ，Zang C ，Tan Y ，Zhang Y ，Zhou Z ，Lu W ，Wu S ，Zhang X ，Wu C ... -  《-》