Sharma Prateek, Jain Tejeshwar, Sorgen Ali, Iyer Srikanth, Tarique Mohammad, Roy Pooja, Kurtom Saba, Sethi Vrishketan, Bava Ejas P, Gutierrez-Garcia A K, Vaish Utpreksha, Suresh Dhanisha Sulekha, Sahay Preeti, Edwards Dujon, Afghani Jumana, Putluri Satwikreddy, Reddy Karthik Reddy Kami, Amara Chandra Sekhar, Kamal Abu Hena Mustafa, Fodor Anthony, Dudeja Vikas
Department of Surgery, University of Alabama, Birmingham, AL 35233, USA.
Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC 28223, USA.
iScience. 2025 Feb 11;28(3):112002. doi: 10.1016/j.isci.2025.112002. eCollection 2025 Mar 21.
Cigarette smoke exposure (CSE) increases the risk for a plethora of cancers. Recent evidence indicates that the gut microbiome can influence cancer progression by immune system modulation. Since CSE alters the gut microbiome, we hypothesized that the gut microbiome serves as a causative link between smoking and cancer growth. Through a combination of syngeneic animal models and fecal microbiota transplantation studies, we established an essential role for smoke-induced dysbiosis in cancer growth. 16s rRNA sequencing and liquid chromatography-mass spectrometry indicated a unique CSE-associated microbial and metabolomic signature. Immunophenotyping of tumor specimens and experiments in Rag1-KO and CD8-KO demonstrated that smoke-induced tumor growth requires functional adaptive immunity. Finally, utilizing gut microbial ablation strategies with broad- and narrow-spectrum antibiotics, we demonstrated the reversal of phenotypic effects of CSE. Our study provides evidence for gut microbiome as an actionable target to mitigate CSE-induced tumor promotion.
接触香烟烟雾（CSE）会增加患多种癌症的风险。最近的证据表明，肠道微生物群可通过调节免疫系统来影响癌症进展。由于CSE会改变肠道微生物群，我们推测肠道微生物群是吸烟与癌症生长之间的因果联系。通过同基因动物模型和粪便微生物群移植研究相结合，我们确定了烟雾诱导的生态失调在癌症生长中的重要作用。16s rRNA测序和液相色谱-质谱分析表明存在独特的与CSE相关的微生物和代谢组学特征。肿瘤标本的免疫表型分析以及在Rag1基因敲除和CD8基因敲除小鼠中的实验表明，烟雾诱导的肿瘤生长需要功能性适应性免疫。最后，利用广谱和窄谱抗生素的肠道微生物消除策略，我们证明了CSE表型效应的逆转。我们的研究为肠道微生物群作为减轻CSE诱导的肿瘤促进作用的可操作靶点提供了证据。
