Abstract
Gut microbiota dysbiosis induced by antibiotics is strongly connected with health concerns. Studying the mechanisms underlying antibiotic-induced gut microbiota dysbiosis could help to identify effective drugs and prevent many serious diseases. In this study, in rats with antibiotic-induced gut microbiota dysbiosis treated with total alkaloids of Corydalis saxicola Bunting (TACS), urinary and fecal biochemical changes and cecum microbial diversity were investigated using 16S rRNA gene sequencing analysis and untargeted metabolomics. The microbial diversity results showed that 10 genera were disturbed by the antibiotic treatment, and two of them were obviously restored by TACS. The untargeted metabolomics analysis identified 34 potential biomarkers in urine and feces that may be the metabolites that are most related to the mechanisms underlying antibiotic-induced gut microbiota dysbiosis and the therapeutic effects of TACS treatment. The biomarkers were involved in six metabolic pathways, comprising pathways related to branched-chain amino acid (BCAA), bile acid, arginine and proline, purine, aromatic amino acid, and amino sugar and nucleotide sugar metabolism. Notably, there was a strong correlation between these metabolic pathways and two gut microbiota genera (g__Blautia and g__Intestinibacter). The correlation analysis suggested that TACS might synergistically affect four of these metabolic pathways (BCAA, bile acid, arginine and proline, and purine metabolism), thereby modulating gut microbiota dysbiosis. Furthermore, we performed a molecular docking analysis involving simulating high-precision docking and using molecular pathway maps to illuminate the way that ligands (the five main alkaloid components of TACS) act on a complex molecular network, using CYP27A1 (a key enzyme in the bile acid synthesis pathway) as the target protein. This study provides a comprehensive overview of the intervening effects of TACS on the host metabolic phenotype and gut microbiome in rats with gut microbiota dysbiosis, and it presents new insights for the discovery of effective drugs and the best therapeutic approaches.
Highlights
Millions of microorganisms that live in human organs have commensal relationships with humans
G__Blautia was completely restored to the control level by therapeutic drug used (TACS), while there was incomplete restoration of g__Clostridium_sensu_stricto_1, g__Hungatella, and g__Intestinibacter. These results indicated that gut microbiota dysbiosis at the operational taxonomic units (OTUs) level and genus level could be caused by antibiotic administration, and this kind of dysbiosis can be modulated by TACS treatment
The results indicated that antibiotic administration induced significant metabolic changes in the urine and that these changes could be modulated by TACS treatment
Summary
Millions of microorganisms that live in human organs have commensal relationships with humans. The microorganisms that inhabit the gastrointestinal tract are called gut microbiota, which are a key factor in host health and confer an extended metabolic capacity on the host (Swann et al, 2011). Gut microbiota dysbiosis is strongly associated with several serious health concerns including obesity, type 2 diabetes, and non-alcoholic fatty liver disease (Cox and Blaser, 2013; Mahana et al, 2016). Studies have shown that disease- or drug-related gut microbiota dysbiosis can be regulated by natural medicinal herbs, such as Chai-Hu-Shu-Gan-San and cloudberry (Yu et al, 2017; Carrera-Quintanar et al, 2018). Investigation of the protective effects of Chinese traditional medicines against gut microbiota dysbiosis will broaden the search for effective therapeutic drugs
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