Feasibility Study For Developing Total Alkaloids Of Corydalis Saxicola Bunting Into Gut Microbioecologics

Objective: To study the intervention of total alkaloids of Corydalis saxicola Bunting(TACS)on rats with antibiotics-induced gut microbiota dysbiosis and lay the foundation of developing as gut microbioecologics.Methods: A rat model of antibiotic-induced gut microbiota dysbiosis was employed to investigate the influences that antibiotics act on the gut microbiome and fecal metabolome.16 S r RNA gene sequencing technique coupled ultra-performance liquid chromatography-quadrupole time-of-flight /mass spectrometry(UPLC-Q-TOF/MS)-based metabolomics strategy was used to illuminate the intervention of TACS on the host co-metabolism and gut microbiota in rats with antibiotic-induced gut microbiota dysbiosis.Results: The results of microbial diversity analysis showed that 10 genera were disturbed by antibiotic,and two of them(g＿＿Blautia and g＿＿Intestinibacter)were obviously restored by TACS.The fecal metabolomics study identified 23 potential biomarkers that might be the most related to the effects of antibiotic and TACS treatment.The biomarkers were involved in six metabolic pathways including branched-chain amino acid(BCAA)metabolism,bile acid metabolism pathway,arginine and proline metabolism,purine metabolism,aromatic amino acid metabolism,and amino sugar and nucleotide sugar metabolism.Besides,there was a strong correlation between part of these metabolic pathways and two gut microbiota genera(g＿＿Blautia and g＿＿Intestinibacter),suggesting that TACS might synergistically affect three of these metabolic pathways(BCAA metabolism,bile acid metabolism and purine metabolism)to modulate gut microbiota dysbiosis.Furthermore,we performed molecular docking analysis to simulate and illuminate the way that ligands(the five main alkaloid components of TACS)bind with CYP27A1(the key enzyme in the bile acid synthesis).Conclusion:Results of this study showed that antibiotic treatment changed the gut microbial diversity and richness,and fecal metabolome of rats while TACS could intervene the down-regulated gut microbiome diversity and richness and disturbed fecal metabolic profile of rats with antibiotic-induced gut microbiota dysbiosis.Besides,in this study,the intervening mechanism of TACS might be act by the potential active components(berberine,palmatine and chelerythrine)through the CYP27A1 to regulate the abnormal disturbances of bile acid metabolism.This study presents scientific basis for developing TACS into a micriobioecologics.