Dataset Information

Daiokanzoto (Da-Huang-Gan-Cao-Tang) is an effective laxative in gut microbiota associated with constipation.

ABSTRACT: Interindividual differences affect the purgative activities of sennoside A (SA) and Daiokanzoto (Da-Huang-Gan-Cao-Tang, DKT). In this study, we manipulated gut microbiota in mice to establish laxative responders and non-responders by feeding them a high-carbohydrate, a high-fat or a high-fibre diet. To assess the relationship between laxatives and gut microbiota, we monitored the gut microbiota before and after administering laxatives. Twenty mice per diet were divided into four groups of five mice to evaluate purgative activities of four laxative preparations, DKT, SA, SA plus rhein 8-O-?-D-glucopyranoside (SA?+?RG), and SA plus liquiritin (SA?+?LQ). Gut microbiota changes were monitored by next-generation sequencing of 16?S rRNA gene amplicons. In high-carbohydrate and high-fat diet-fed mice, DKT exerted a significantly higher purgative activity than SA alone, and RG contributed to this activity. DKT and SA?+?RG administration increased the Enterobacteriaceae content of gut microbiota, which was associated with an increased purgative activity. In contrast, DKT activity was significantly suppressed by high-fibre diet. Hence, diet-induced differences in gut microbiota determined the effect of DKT, which is interesting, considering that Oriental medicines are formulated for a specific functional state or "pattern". These results demonstrated that the purgative activity of anthranoid laxatives is susceptible to diet-induced alterations in gut microbiota.

SUBMITTER: Takayama K

PROVIDER: S-EPMC6405880 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Daiokanzoto (Da-Huang-Gan-Cao-Tang) is an effective laxative in gut microbiota associated with constipation.

Takayama Kento K Takahara Chiho C Tabuchi Norihiko N Okamura Nobuyuki N

Scientific reports 20190307 1

Interindividual differences affect the purgative activities of sennoside A (SA) and Daiokanzoto (Da-Huang-Gan-Cao-Tang, DKT). In this study, we manipulated gut microbiota in mice to establish laxative responders and non-responders by feeding them a high-carbohydrate, a high-fat or a high-fibre diet. To assess the relationship between laxatives and gut microbiota, we monitored the gut microbiota before and after administering laxatives. Twenty mice per diet were divided into four groups of five m ...[more]

PMID: 30846728

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Project description:Cholestasis is characterized by bile acid (BA) circulation disorders, which is usually related to damage of hepatocyte barrier function. Currently, patients with cholestasis face several obstacles in seeking diagnosis and therapy. Da-Huang-Xiao-Shi decoction (DHXSD) is an ancient classic formula that has been used clinically for cholestasis treatment. Nevertheless, the underlying biological activities and therapeutic mechanisms remain unclear. In this study, an alpha-naphthylisothiocyanate (ANIT)-induced cholestasis rat model was established to examine the anticholestatic effects of DHXSD using histopathological and molecular analyses. Transcriptomic analysis combined with 16S rRNA gene sequencing analysis was systematically applied to study the mechanism of action of DHXSD. Simultaneously, the effect of DHXSD on gut microbiota, short-chain fatty acids (SCFAs), and intestinal barrier function were evaluated based on the ANIT-induced cholestasis model in rats. The results showed that DHXSD effectively attenuated ANIT-induced cholestasis by reducing liver function indicators (alanine transaminase [ALT], P < 0.05; alkaline phosphatase [ALP], P < 0.05; total bile acid [TBA], P < 0.01; γ-glutamyl transpeptidase [GGT], P < 0.001) and levels of hepatotoxicity-related enzymes (P < 0.05), thus improving the recovery of histopathological injuries, and regulating levels of inflammatory cytokines (P < 0.05). In addition, 16S rRNA gene sequencing analysis combined with intestinal barrier function analysis revealed that the DHXSD significantly ameliorated ANIT-induced gut microbiota dysbiosis. Significantly altered genes in the model and treatment groups were screened using transcriptomic analysis. Sixty-eight genes and four microbial genera were simultaneously altered with opposing trends in variation after ANIT and DHXSD treatments. We built a framework for predicting targets and host-microbe interaction mechanisms, as well as identifying alternative treatment for cholestasis, which should be validated further for clinical application. In conclusion, DHXSD appears to be a promising agent for protection against liver injury. IMPORTANCE Cholestasis is a serious manifestation of liver diseases resulting in liver injury, fibrosis, and liver failure with limited therapies. To date, only ursodeoxycholic acid (UDCA) has been approved by the U.S. Food and Drug Administration for the treatment of cholestasis. However, approximately one-third of patients with cholestasis are unresponsive to UDCA. Therefore, it is urgent to search for appropriate therapeutic agents for restoring stoppage status of the bile components to treat cholestasis. In this study, we investigated how the microbiome and transcriptome data sets correlated with each other to clarify the role of microbiome alterations in host metabolism. In combination, this research offers potential molecular biomarkers that should be validated for more accurate diagnosis of cholestasis and the clinical utilisation of gut microbiota as a target for treatment.

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Dataset Information

Daiokanzoto (Da-Huang-Gan-Cao-Tang) is an effective laxative in gut microbiota associated with constipation.

Publications

Daiokanzoto (Da-Huang-Gan-Cao-Tang) is an effective laxative in gut microbiota associated with constipation.

Similar Datasets

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