McKee Alastair M, Kirkup Benjamin M, Madgwick Matthew, Fowler Wesley J, Price Christopher A, Dreger Sally A, Ansorge Rebecca, Makin Kate A, Caim Shabhonam, Le Gall Gwenaelle, Paveley Jack, Leclaire Charlotte, Dalby Matthew, Alcon-Giner Cristina, Andrusaite Anna, Feng Tzu-Yu, Di Modica Martina, Triulzi Tiziana, Tagliabue Elda, Milling Simon W F, Weilbaecher Katherine N, Rutkowski Melanie R, Korcsmáros Tamás, Hall Lindsay J, Robinson Stephen D
Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK.
Earlham Institute, Norwich Research Park, Norwich, NR4 7UZ, UK.
iScience. 2021 Aug 20;24(9):103012. doi: 10.1016/j.isci.2021.103012. eCollection 2021 Sep 24.
The gut microbiota's function in regulating health has seen it linked to disease progression in several cancers. However, there is limited research detailing its influence in breast cancer (BrCa). This study found that antibiotic-induced perturbation of the gut microbiota significantly increases tumor progression in multiple BrCa mouse models. Metagenomics highlights the common loss of several bacterial species following antibiotic administration. One such bacteria, , rescued this increased tumor growth. Single-cell transcriptomics identified an increased number of cells with a stromal signature in tumors, and subsequent histology revealed an increased abundance of mast cells in the tumor stromal regions. We show that administration of a mast cell stabilizer, cromolyn, rescues increased tumor growth in antibiotic treated animals but has no influence on tumors from control cohorts. These findings highlight that BrCa-microbiota interactions are different from other cancers studied to date and suggest new research avenues for therapy development.
肠道微生物群在调节健康方面的功能已使其与多种癌症的疾病进展相关联。然而,详细阐述其在乳腺癌(BrCa)中影响的研究有限。本研究发现,抗生素诱导的肠道微生物群扰动在多个BrCa小鼠模型中显著加速肿瘤进展。宏基因组学突出了抗生素给药后几种细菌种类的共同缺失。其中一种细菌挽救了这种肿瘤生长增加的情况。单细胞转录组学确定肿瘤中具有基质特征的细胞数量增加,随后的组织学显示肿瘤基质区域肥大细胞丰度增加。我们表明,给予肥大细胞稳定剂色甘酸钠可挽救抗生素治疗动物中增加的肿瘤生长,但对对照组动物的肿瘤无影响。这些发现突出表明,BrCa与微生物群的相互作用不同于迄今为止研究的其他癌症,并为治疗开发提出了新的研究途径。