Background: Lung cancer is the leading cause of cancer-related mortality globally, with lung adenocarcinoma (LUAD) as the most common subtype. Dysbiotic intratumoral mycobiomes drive LUAD pathogenesis, andAspergillus sydowii(A. sydowii) acts as a key oncogenic fungal species. Ginseng polysaccharides (GPs), bioactive phytochemicals with immunomodulatory and oncostatic properties, counteract fungal infections and restore immunosurveillance in LUAD. Methods: Subcutaneous and orthotopic LUAD murine models were established by implanting Lewis lung carcinoma (LLC) cells. Subcutaneous tumors were infected intratumorally and orthotopic models via nasal inoculation. GPs (200 mg/kg/day) were orally administered to evaluate tumor growth. Metagenomic and targeted bile acid metabolomic profiling of fecal and tumor tissues was performed, with Spearman correlations analyzed using R packages. Results: GPs significantly inhibitedA. sydowii-induced tumor growth in both models. In subcutaneous tumors; GPs reduced volume (p< 0.05) and weight vs. infected controls. In orthotopic models, GPs decreased pathological nodules and lung weight, with micro-CT/H&E confirming attenuated hyperplasia. Metagenomics showed GPs restored gut homeostasis by enrichingLactobacillus/Muribaculum intestinaleand suppressing pro-inflammatoryAlistipes. Targeted metabolomics revealed reduced β-Hyodeoxycholic Acid (3β-HDCA), Chenodeoxycholic acid 24-acyl-b-D-glucuronide (CDCA-24G) and 3β-hydroxychol-5-en-24-oic acid (5-isoLCA) after GP treatment. Network analysis confirmed significant microbe–bile acid interactions. Conclusions: GPs exert antitumor effects againstA. sydowii-induced LUAD by modulating gut microbiota and bile acid metabolism. This identifies GPs as a promising therapy for mycobiome-influenced cancers, with dual targeting of fungal infection and metabolic reprogramming.
背景：肺癌是全球癌症相关死亡的主要原因，其中肺腺癌（LUAD）是最常见的亚型。肿瘤内菌群失调会驱动LUAD的发病机制，而聚多曲霉（A. sydowii）是关键致癌真菌。人参多糖（GPs）是具有免疫调节和抑癌特性的生物活性植物化学物质，可对抗真菌感染并恢复LUAD的免疫监视功能。方法：通过植入Lewis肺癌（LLC）细胞建立皮下和原位LUAD小鼠模型。皮下肿瘤通过瘤内感染，原位模型通过鼻腔接种感染。口服GPs（200 mg/kg/天）以评估肿瘤生长。对粪便和肿瘤组织进行宏基因组学和靶向胆汁酸代谢组学分析，并使用R包进行Spearman相关性分析。结果：GPs在两种模型中均显著抑制A. sydowii诱导的肿瘤生长。在皮下肿瘤中，GPs与感染对照组相比，显著减小了肿瘤体积（p<0.05）和重量。在原位模型中，GPs减少了病理结节和肺重量，微CT/H&E染色证实了增生减弱。宏基因组学显示，GPs通过富集乳酸杆菌/肠道鼠杆菌并抑制促炎性Alistipes，恢复了肠道稳态。靶向代谢组学显示，GP治疗后β-猪去氧胆酸（3β-HDCA）、鹅去氧胆酸24-酰基-β-D-葡萄糖醛酸苷（CDCA-24G）和3β-羟基-5-烯-24-酸（5-isoLCA）减少。网络分析证实了显著的微生物-胆汁酸相互作用。结论：GPs通过调节肠道菌群和胆汁酸代谢，对A. sydowii诱导的LUAD发挥抗肿瘤作用。这表明GPs是一种有前景的治疗真菌菌群影响癌症的疗法，具有双重靶向真菌感染和代谢重编程的作用。
肿瘤(癌症)患者之家