越来越多的证据表明肠道微生物组影响癌症的进展和治疗。我们最近在人类相关小鼠模型中表明，肠道微生物多样性和组成的渐进变化与烟草相关肺腺癌（LUAD）密切相关。此外，我们证明这些小鼠中抗菌蛋白 Lcn2 的缺失会加剧促肿瘤炎症表型，同时进一步减少微生物多样性。然而，肠道微生物组的改变如何影响 LUAD 的发展仍然知之甚少。在这里，我们利用粪便微生物群转移研究了肠道微生物组变化在 LUAD 发育中的作用，并描绘了 Lcn2 缺失引起的肠道微生物组变化促进 Alistipes 属促炎细菌增殖的途径，从而引发肠道炎症。这种炎症会全身传播，在肿瘤微环境中发挥免疫抑制作用，通过 IL-6 依赖性机制促进肿瘤生长，并抑制对免疫治疗的反应。我们发现肠道中 Alistipes 物种相对丰度较高的 LUAD 患者对新辅助免疫治疗的反应减弱，这证实了我们的临床前研究结果。这些见解揭示了微生物组诱导的炎症在 LUAD 中的作用，并为拦截和治疗提供了新的潜在靶标。

Accumulating evidence indicates that the gut microbiome influences cancer progression and therapy. We recently showed that progressive changes in gut microbial diversity and composition are closely associated with tobacco-associated lung adenocarcinoma (LUAD) in a human-relevant mouse model. Furthermore, we demonstrated that the loss of the antimicrobial protein Lcn2 in these mice, exacerbates pro-tumor inflammatory phenotypes while further reducing microbial diversity. Yet, how gut microbiome alterations impinge on LUAD development remains poorly understood. Here, we investigated the role of gut microbiome changes in LUAD development using fecal microbiota transfer and delineated a pathway by which gut microbiome alterations incurred by loss of Lcn2 fostered the proliferation of pro-inflammatory bacteria of the genus Alistipes, triggering gut inflammation. This inflammation propagated systemically, exerting immunosuppression within the tumor microenvironment, augmenting tumor growth through an IL-6-dependent mechanism and dampening response to immunotherapy. Corroborating our preclinical findings, we found that patients with LUAD with a higher relative abundance of Alistipes species in the gut showed diminished response to neoadjuvant immunotherapy. These insights reveal the role of microbiome-induced inflammation in LUAD and present new potential targets for interception and therapy.