Hagihara Mao, Kato Hideo, Yamashita Makoto, Shibata Yuichi, Umemura Takumi, Mori Takeshi, Hirai Jun, Asai Nobuhiro, Mori Nobuaki, Mikamo Hiroshige
Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University, Nagakute, 480-1195, Japan.
Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute, 480-1195, Japan.
Heliyon. 2023 Dec 9;10(1):e23509. doi: 10.1016/j.heliyon.2023.e23509. eCollection 2024 Jan 15.
Despite advances in medical technology, lung cancer still has one of the highest mortality rates among all malignancies. Therefore, efforts must be made to understand the precise mechanisms underlying lung cancer development. In this study, we conducted lung and gut microbiome analyses and a comprehensive lipid metabolome analysis of host tissues to assess their correlation. Alternations in the lung microbiome due to lung cancer, such as a significantly decreased abundance of and , were observed compared to a mock group. However, mice with lung cancer had significantly lower relative abundances of and and higher relative abundances of and in the gut microbiome. The activations of retinol, fatty acid metabolism, and linoleic acid metabolism metabolic pathways in the lung and gut microbiomes was inversely correlated. Additionally, changes occurred in lipid metabolites not only in the lungs but also in the blood, small intestine, and colon. Compared to the mock group, mice with lung cancer showed that the levels of adrenic, palmitic, stearic, and oleic (a ω-9 polyunsaturated fatty acid) acids increased in the lungs. Conversely, these metabolites consistently decreased in the blood (serum) and colon. Leukotriene B4 and prostaglandin E2 exacerbate lung cancer, and were upregulated in the lungs of the mice with lung cancer. However, isohumulone, a peroxisome proliferator-activated receptor gamma activator, and resolvin (an ω-3 polyunsaturated fatty acid) both have anti-cancer effects, and were upregulated in the small intestine and colon. Our multi-omics data revealed that shifts in the microbiome and metabolome occur during the development of lung cancer and are of possible clinical importance. These results reveal one of the gut-lung axis mechanisms related to lung cancer and provide insights into potential new targets for lung cancer treatment and prophylaxis.
尽管医学技术取得了进步，但肺癌仍是所有恶性肿瘤中死亡率最高的疾病之一。因此，必须努力了解肺癌发生的确切机制。在本研究中，我们对肺和肠道微生物群进行了分析，并对宿主组织进行了全面的脂质代谢组分析，以评估它们之间的相关性。与假手术组相比，观察到肺癌导致的肺微生物群变化，如 和 的丰度显著降低。然而，肺癌小鼠肠道微生物群中 和 的相对丰度显著降低，而 和 的相对丰度较高。肺和肠道微生物群中视黄醇、脂肪酸代谢和亚油酸代谢途径的激活呈负相关。此外，脂质代谢产物不仅在肺中发生变化，在血液、小肠和结肠中也发生了变化。与假手术组相比，肺癌小鼠肺中肾上腺酸、棕榈酸、硬脂酸和油酸（一种ω-9多不饱和脂肪酸）的水平升高。相反，这些代谢产物在血液（血清）和结肠中持续降低。白三烯B4和前列腺素E2会加重肺癌，在肺癌小鼠的肺中上调。然而，异胡薄荷酮（一种过氧化物酶体增殖物激活受体γ激活剂）和消退素（一种ω-3多不饱和脂肪酸）都具有抗癌作用，在小肠和结肠中上调。我们的多组学数据表明，微生物群和代谢组的变化发生在肺癌发展过程中，可能具有临床重要性。这些结果揭示了与肺癌相关的肠-肺轴机制之一，并为肺癌治疗和预防的潜在新靶点提供了见解。
