Abstract

Accumulating evidence suggests that the gut microbiota dysbiosis and their host metabolic phenotype alteration is an important factor in human disease development. A traditional Chinese herbal formula, Chaihu-Shu-Gan-San (CSGS), has been effectively used in the treatment of various gastrointestinal (GI) disorders. The present study was carried out to investigate whether CSGS modulates the host metabolic phenotype under the condition of gut microbiota dysbiosis. The metabonomics studies of biochemical changes in urine and feces of antibiotic-induced gut microbiota dysbiosis rats after treatment with CSGS were performed using UPLC-Q-TOF/MS. Partial least squares-discriminate analysis (PLS-DA) indicated that the CSGS treatment reduced the metabolic phenotype perturbation induced by antibiotic. In addition, there was a strong correlation between gut microbiota genera and urinary and fecal metabolites. Moreover, the correlation analysis and the metabolic pathway analysis (MetPA) identified that three key metabolic pathways including glycine, serine and threonine metabolism, nicotinate and nicotinamide metabolism, and bile acid metabolism were the most relevant pathways involved in antibiotic-induced gut microbiota dysbiosis. These findings provided a comprehensive understanding of the protective effects of CSGS on the host metabolic phenotype of the gut microbiota dysbiosis rats, and further as a new source for drug leads in gut microbiota-targeted disease management.

Highlights

  • It has been fully evidenced that the gut microbiota dysbiosis along with the metabolic phenotype alteration was associated with various diseases, such as obesity, diabetes and atherosclerosis

  • A combined 16S rRNA gene sequencing and UPLC-Q-TOF/MS-based metabonomics method was established to provide a comprehensive understanding of the protective effects of CSGS on the host metabolic phenotype of the gut microbiota dysbiosis rats

  • A combined 16S rRNA gene sequencing and urinary and fecal metabonomics method have been established to evaluate the protective effects of CSGS on the metabolic phenotype of the host on the antibiotic-induced gut microbiota dysbiosis rats

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Summary

Introduction

It has been fully evidenced that the gut microbiota dysbiosis along with the metabolic phenotype alteration was associated with various diseases, such as obesity, diabetes and atherosclerosis. Emerging evidence from patients with depressive disorders demonstrated that gut microbiota dysbiosis associated with the etiology and biological mechanisms of depression[15,16]. These observations highlight that the association of the antidepressant effects of CSGS might potentially work directly to regulate the dysbiosis of gut microbiota and abnormal host metabolic phenotype. A combined 16S rRNA gene sequencing and UPLC-Q-TOF/MS-based metabonomics method was established to provide a comprehensive understanding of the protective effects of CSGS on the host metabolic phenotype of the gut microbiota dysbiosis rats

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