Department of Pulmonary Medicine, Affiliated Hospital of Northwest University, Xi'an Peoples' Hospital, Xi'an, China.
Department of Pulmonary and Critical Care of Medicine, The First Affiliated Hospital of Fourth Military Medical University, Xi'an, China.
Microbiol Spectr. 2024 Nov 5;12(11):e0071924. doi: 10.1128/spectrum.00719-24. Epub 2024 Oct 4.
Lung cancer accounts for the large majority of cancer incidence and mortality worldwide for decades. The dysbiotic microbiome and its metabolite secretions in the gut have been regarded as the dominant biological factors in oncogenesis, development, and progression, adding probiotic components of which have come to be potential therapeutic regimes. However, there still exists little knowledge about whether probiotic microorganisms in lower airways inhibit lung cancer by lung microenvironment remodulation. In this study, we performed bioinformatics analysis from previous sequencing data and specific microbiome databases to identify the potent protective microbes in lower airways, followed by bacterial cultivation and morphological verifications . We found that was correlated closely with the anti-tumorous by-product acetic acid in lower respiratory tract. Additionally, the enrichment of this microorganism in the health, rather than in lung neoplasms from public data sets, further confirmed its protective activity in preserving pulmonary homeostasis. Colony cultivation of this strain and targeted metabolite analysis indicated that proliferation was weakened at 37°C but lasted longer than it did at the optimal temperature. And performing as a candidate origin of acetic acid, this strain was liable to inhibit the growth of lung cancer cells in time- and dose-dependent approaches which was validated by colony formation assays. These results suggested that functions as a candidate probiotic in lower airways to restrict lung cancer cell growth by releasing protective molecules, indicating a potential preventive microbial strategy.IMPORTANCEVarious types of microorganisms in lower respiratory tracts protect local homeostasis against oncogenesis. Although extensive efforts engaged in gut microbiome-mediated pulmonary carcinogenesis, emerging evidence suggested the crucial role of microbial metabolites from respiratory tracts in modulating carcinogenesis-related host inflammation and DNA damage in lung cancer, which was still not fully understood in lower respiratory tract microbes and its metabolite-mediated microecological environment homeostasis in preventing or alleviating lung cancer. In this study, we analyzed the lower respiratory tract microbiome and SCFAs expression among different lung segments from the same participants, further identifying that was correlated closely with anti-tumorous by-product, acetate acid in lower respiratory tract by multi-omics analysis. And previous experiments showed this strain could inhibit the growth of lung cancer cells . These findings indicated that in lower respiratory tracts might perform as a candidate probiotic against lung carcinogenesis by releasing protective factor acetate, which further presented a promising diagnostic and interventional approach in clinical settings of lung cancer.
几十年来,肺癌一直是全球癌症发病率和死亡率的主要原因。肠道中的失调微生物组及其代谢产物分泌被认为是致癌、发展和进展的主要生物学因素,添加益生菌成分已成为潜在的治疗方案。然而,关于下呼吸道中的益生菌微生物是否通过肺微环境重塑来抑制肺癌,人们的了解仍然很少。在这项研究中,我们从以前的测序数据和特定的微生物组数据库中进行了生物信息学分析,以确定下呼吸道中的有效保护微生物,然后进行细菌培养和形态学验证。我们发现,在呼吸道中与抗肿瘤副产物乙酸密切相关。此外,从公共数据集可知,这种微生物在下呼吸道健康中富集,而不是在肺部肿瘤中富集,这进一步证实了它在维持肺内平衡方面的保护作用。该菌株的集落培养和靶向代谢物分析表明,该菌株在 37°C 时增殖减弱,但持续时间比最适温度长。作为乙酸的候选来源,该菌株能够以时间和剂量依赖的方式抑制肺癌细胞的生长,这在集落形成试验中得到了验证。这些结果表明,在呼吸道中作为候选益生菌,通过释放保护性分子来限制肺癌细胞的生长,这表明了一种潜在的预防微生物策略。
下呼吸道中的各种类型的微生物可以保护局部内环境免受致癌作用的影响。尽管在肠道微生物组介导的肺癌发生中进行了广泛的研究,但新出现的证据表明,微生物代谢物从呼吸道在调节与肺癌相关的致癌相关宿主炎症和 DNA 损伤方面起着至关重要的作用,这在下呼吸道微生物及其代谢物介导的微生态环境平衡中仍然没有得到充分理解,以预防或减轻肺癌。在这项研究中,我们分析了来自同一参与者不同肺段的下呼吸道微生物组和 SCFAs 表达,通过多组学分析进一步确定,在呼吸道中与抗肿瘤副产物乙酸密切相关。以前的实验表明,这种菌株可以抑制肺癌细胞的生长。这些发现表明,下呼吸道中的可能通过释放保护性因子乙酸来作为一种候选益生菌,以对抗肺癌的发生,这进一步为肺癌的临床诊断和干预提供了一种有前途的方法。