![Sample our Medicine, Dentistry, Nursing & Allied Health journals, sign in here to start your FREE access for 14 days]({"type":"image" , "src" : "/sda/5944/TOC-Subject-Sample-2021-Medicine-Dentistry-Nursing-Allied-Health.jpg"})
ABSTRACT
Emerging evidence has revealed the novel role of gut microbiota in the development of cancer. The characteristics of function and composition in the gut microbiota of patients with breast cancer patients has been reported, however the detailed causation between gut microbiota and breast cancer remains uncertain. In the present study, 16S rRNA sequencing revealed that Prevotella, particularly the dominant species Prevotella copri, is significantly enriched and prevalent in gut microbiota of breast cancer patients. Prior-oral administration of P. copri could promote breast cancer growth in specific pathogen-free mice and germ-free mice, accompanied with sharp reduction of indole-3-pyruvic acid (IPyA). Mechanistically, the present of excessive P. copri consumed a large amount of tryptophan (Trp), thus hampering the physiological accumulation of IPyA in the host. Our results revealed that IPyA is an intrinsic anti-cancer reagent in the host at physiological level. Briefly, IPyA directly suppressed the transcription of UHRF1, following by the declined UHRF1 and PP2A C in nucleus, thus inhibiting the phosphorylation of AMPK, which is just opposite to the cancer promoting effect of P. copri. Therefore, the exhaustion of IPyA by excessive P. copri strengthens the UHRF1-mediated negative control to inactivated the energy-controlling AMPK signaling pathway to promote tumor growth, which was indicated by the alternation in pattern of protein expression and DNA methylation. Our findings, for the first time, highlighted P. copri as a risk factor for the progression of breast cancer.
Acknowledgments
We would like to acknowledge and thank Prof. Liwu Fu (Sun Yat-sen University Cancer Center) for the help in manuscript drafting and editing, and thank Prof. Wang Sheng (Beijing Institute of Technology) for the help in cell and bacterial culture.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Author contributions
Conceptualization: JYS, QJC, CLX. Methodology: JYS, XJL, YZX, QJC, CLX. Investigation: JYS, XJL, DL, CMY, SML, XHC, XJY, BTP, RX, LPR, YFZ. Funding acquisition: JYS, QJC, CLX. Project administration: YZX, QJC, CLX. Supervision: YZX, QJC, CLX. Writing – original draft: JYS, XJL, DL, YZX. Writing – review & editing: JYS, XJL, DL, CLX.
Availability of data and materials
All data generated during the current study are included in this article and its supplementary information files, and they are available from the corresponding authors upon reasonable request. The sequences generated and analyzed in this study were uploaded to the NCBI Sequence Read Archive (SRA) data repository, with project numbers PRJNA887717 (microbiota raw sequencing data) and PRJNA890318 (DNA methylation raw sequencing data).
Ethics approval and consent to participate
The enrollment of participants and sample collection was approved by the Ethics Committee of the Guangdong Provincial Hospital of Chinese Medicine (Guangzhou, China, Ethics Approval number: ZF2018–179). Consent for participation was obtained when the patients were enrolled.
All animal experiments were approved by Guangdong Institute of Microbiology Laboratory Animal Ethics Committee (permission number: GT-IACUC201910121) according to the Guidelines for the Care and Use of Laboratory Animals published by the United States National Institutes of Health (NIH Publication, revised 2011).
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2024.2347757