Fecal metabonomics combined with 16S rRNA gene sequencing to analyze the changes of gut microbiota in mouse with 4T1 xenograft-breast cancer and the intervention effect of 8-O-acetylharpagide

Aim: Ajuga decumbens Thunb (ADT), a natural drug of the Labiatae family, has been demonstrated to have anti-tumor activity in previous studies, but its mechanism is still unknown and studies have shown that gut microbiota is associated with the development and progression of breast cancer (BC). We are now investigating the effects of 8-O-acetylharpagide (the main active component of ADT) on the gut microbiota and metabolomics of mouse with BC.Methods and Results: In the present study, an integrated approach based on 16S rRNA gene sequencing combined with UPLC-Q-TOF-MS-based metabolomics method was performed to assess the effects of 8-O-acetylharpagide on BC induced by 4T1 cells through the regulation of the relative abundances and biomarker candidates of gut microbiota.Conclusions: Our results preliminarily confirm that BC is closely related to metabolic and gut microbial dysbiosis, and that 8-O-acetylharpagide may exert anticancer effects by acting on the gut microbiota to ameliorate the metabolic disorder in BC mouse.Significance and Impact of Study: Our results will lay the foundation for further studies on the mechanism and course of action of 8-O-acetylharpagide against breast cancer and the use of gut microbiota as a drug target for the treatment of BC.