如今，人们已经认识到肠道菌群可以间接影响癌症易感性或进展。然而，在乳腺癌中，瘤内微生物是寄生、共生，还是仅仅是旁观者，目前还不完全清楚。通过调节线粒体和其他代谢通路，微生物代谢产物在宿主和微生物的相互作用中发挥着关键作用。而肿瘤驻留微生物群落与癌症代谢之间的关系仍是一个未知之数。我们从公共数据集中检索到1085名乳腺癌患者的标准化肿瘤内微生物丰度数据和32个单细胞RNA测序样本。我们使用基因集变异分析来评估乳腺癌样本的各种代谢活动。此外，我们应用剪刀方法从单细胞数据中识别与微生物相关的细胞亚群。然后，我们进行了全面的生物信息学分析，探索了乳腺癌中宿主和微生物之间的关联。我们发现，乳腺癌细胞的代谢状态非常具有可塑性，一些微生物属与癌症代谢活动显著相关。基于微生物丰度和肿瘤代谢数据，我们确定了两个不同的簇。不同细胞类型之间存在代谢通路的失调。代谢相关的微生物评分被计算用来预测乳腺癌患者的总生存率。此外，特定属的微生物丰度与基因突变相关，可能是由于微生物介导的突变。浸润性免疫细胞组成，包括调节性T细胞和活化NK细胞，与代谢相关的肿瘤内微生物显著相关，如Mantel测试分析所示。此外，乳腺代谢相关微生物与T细胞排斥和免疫治疗反应有关。总的来说，这项探索性研究揭示了代谢相关微生物在乳腺癌患者中的潜在作用。通过进一步研究宿主和肿瘤内微生物细胞中的代谢失调，新的治疗方法将得到实现。版权所有 ©2023陈、杨、郭、苏、盛和吴。

Nowadays, it has been recognized that gut microbiome can indirectly modulate cancer susceptibility or progression. However, whether intratumor microbes are parasitic, symbiotic, or merely bystanders in breast cancer is not fully understood. Microbial metabolite plays a pivotal role in the interaction of host and microbe via regulating mitochondrial and other metabolic pathways. And the relationship between tumor-resident microbiota and cancer metabolism remains an open question.1085 breast cancer patients with normalized intratumor microbial abundance data and 32 single-cell RNA sequencing samples were retrieved from public datasets. We used the gene set variation analysis to evaluate the various metabolic activities of breast cancer samples. Furthermore, we applied Scissor method to identify microbe-associated cell subpopulations from single-cell data. Then, we conducted comprehensive bioinformatic analyses to explore the association between host and microbe in breast cancer.Here, we found that the metabolic status of breast cancer cells was highly plastic, and some microbial genera were significantly correlated with cancer metabolic activity. We identified two distinct clusters based on microbial abundance and tumor metabolism data. And dysregulation of the metabolic pathway was observed among different cell types. Metabolism-related microbial scores were calculated to predict overall survival in patients with breast cancer. Furthermore, the microbial abundance of the specific genus was associated with gene mutation due to possible microbe-mediated mutagenesis. The infiltrating immune cell compositions, including regulatory T cells and activated NK cells, were significantly associated with the metabolism-related intratumor microbes, as indicated in the Mantel test analysis. Moreover, the mammary metabolism-related microbes were related to T cell exclusion and response to immunotherapy.Overall, the exploratory study shed light on the potential role of the metabolism-related microbiome in breast cancer patients. And the novel treatment will be realized by further investigating the metabolic disturbance in host and intratumor microbial cells.Copyright © 2023 Chen, Yang, Guo, Su, Sheng and Wu.