A dysbiotic microbiome promotes head and neck squamous cell carcinoma.

A dysbiotic microbiome promotes head and neck squamous cell carcinoma.
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DOI:
10.1038/s41388-021-02137-1
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发表时间:
2022-03
期刊:
影响因子:
8
通讯作者:
Lu SL
Lu SL
中科院分区:
医学1区
文献类型:
--
作者:
Frank DN;Qiu Y;Cao Y;Zhang S;Lu L;Kofonow JM;Robertson CE;Liu Y;Wang H;Levens CL;Kuhn KA;Song J;Ramakrishnan VR;Lu SL

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最近的研究报告了人类头颈部鳞状细胞癌(HNSCC)中的口腔微生物群和肿瘤驻留细菌。我们的目的是确定和验证口腔微生物签名初治HNSCC患者与健康对照组相比。我们证实了早期的报道,乳酸杆菌的相对丰度。和奈瑟氏菌属(Neisseria spp.)在人HNSCC中分别升高和降低。同时,我们通过在诱导的HNSCC小鼠模型(4-硝基喹啉1-氧化物,4 NQO)中抗生素消耗微生物群和在无菌原位小鼠模型中重建肿瘤相关微生物群来检查HNSCC中微生物群的疾病改善作用。我们证明,微生物群的消耗延迟了口腔肿瘤的发生,而来自口腔癌小鼠的微生物群转移加速了肿瘤的发生。乳杆菌属的富集在鼠HNSCC中也观察到,并且在鼠和人肿瘤中都记录了芳烃受体的活化。总之,我们的研究结果支持了生态失调促进HNSCC发展的假设。
Recent studies have reported dysbiotic oral microbiota and tumor-resident bacteria in human head and neck squamous cell carcinoma (HNSCC). We aimed to identify and validate oral microbial signatures in treatment-naïve HNSCC patients compared with healthy control subjects. We confirm earlier reports that the relative abundances of Lactobacillus spp. and Neisseria spp. are elevated and diminished, respectively, in human HNSCC. In parallel, we examined the disease-modifying effects of microbiota in HNSCC, through both antibiotic depletion of microbiota in an induced HNSCC mouse model (4-Nitroquinoline 1-oxide, 4NQO) and reconstitution of tumor-associated microbiota in a germ-free orthotopic mouse model. We demonstrate that depletion of microbiota delays oral tumorigenesis, while microbiota transfer from mice with oral cancer accelerates tumorigenesis. Enrichment of Lactobacillus spp. was also observed in murine HNSCC, and activation of the aryl-hydrocarbon receptor was documented in both murine and human tumors. Together, our findings support the hypothesis that dysbiosis promotes HNSCC development.
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