School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA.
Department of Microbiology, Immunology and Genetics, University of North Texas Health Sciences Center, Fort Worth, TX 76107, USA.
Nutrients. 2021 Oct 19;13(10):3656. doi: 10.3390/nu13103656.
Triple-negative breast cancer (TNBC) is an aggressive, molecularly heterogeneous subtype of breast cancer. Obesity is associated with increased incidence and worse prognosis in TNBC through various potential mechanisms. Recent evidence suggests that the gut microbiome plays a central role in the progression of cancer, and that imbalances or dysbiosis in the population of commensal microbiota can lead to inflammation and contribute to tumor progression. Obesity is characterized by low-grade inflammation, and gut dysbiosis is associated with obesity, chronic inflammation, and failure of cancer immunotherapy. However, the debate on what constitutes a "healthy" gut microbiome is ongoing, and the connection among the gut microbiome, obesity, and TNBC has not yet been addressed. This study aims to characterize the role of obesity in modulating the gut microbiome in a syngeneic mouse model of TNBC. 16S rRNA sequencing and metagenomic analyses were performed to analyze and annotate genus and taxonomic profiles. Our results suggest that obesity decreases alpha diversity in the gut microbiome. Metagenomic analysis revealed that obesity was the only significant factor explaining the similarity of the bacterial communities according to their taxonomic profiles. In contrast to the analysis of taxonomic profiles, the analysis of variation of functional profiles suggested that obesity status, tumor presence, and the obesity-tumor interaction were significant in explaining the variation of profiles, with obesity having the strongest correlation. The presence of tumor modified the profiles to a greater extent in obese than in lean animals. Further research is warranted to understand the impact of the gut microbiome on TNBC progression and immunotherapy.
三阴性乳腺癌（TNBC）是一种侵袭性的、分子异质性的乳腺癌亚型。肥胖通过多种潜在机制与 TNBC 的发病率增加和预后恶化相关。最近的证据表明，肠道微生物组在癌症的进展中起着核心作用，共生微生物群落的失衡或失调会导致炎症，并促进肿瘤进展。肥胖的特点是低度炎症，肠道菌群失调与肥胖、慢性炎症和癌症免疫治疗失败有关。然而，关于什么构成“健康”的肠道微生物组的争论仍在继续，肠道微生物组、肥胖和 TNBC 之间的联系尚未得到解决。本研究旨在表征肥胖在调节 TNBC 同源小鼠模型中肠道微生物组中的作用。进行了 16S rRNA 测序和宏基因组分析，以分析和注释属和分类群谱。我们的结果表明，肥胖会降低肠道微生物组的 alpha 多样性。宏基因组分析表明，肥胖是唯一能够根据细菌分类群谱解释细菌群落相似性的显著因素。与分类群谱分析相比，功能谱变异分析表明，肥胖状况、肿瘤存在以及肥胖-肿瘤相互作用在解释谱的变异方面是显著的，其中肥胖的相关性最强。肿瘤的存在使肥胖动物的肠道微生物组发生了更大的改变。需要进一步研究以了解肠道微生物组对 TNBC 进展和免疫治疗的影响。
