Table 1_Enhancement of oxaliplatin efficacy and amelioration of intestinal epithelial damage by Lactobacillus rhamnosus GG through modulation of gut microbiota.xlsx

BackgroundNon-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide, necessitating extensive research into effective treatment strategies. Despite advancements in targeted therapies and immunotherapies, traditional chemotherapy remains the primary treatment modality for most patients. Here, we explored the synergy between Lactobacillus rhamnosus GG (LGG), a probiotic, and the chemotherapeutic drug oxaliplatin (Oxp) in enhancing NSCLC treatment outcomes.
MethodsWe utilized a BALB/c nude mouse subcutaneous tumor model to assess the therapeutic impacts of LGG and Oxp. Mice were randomized into five groups: negative control, model control, Oxp, LGG, and LGG + Oxp treatment groups. The main outcomes assessed included tumor weight and volume, histopathological changes, and gene expression via qRT-PCR. The gut microbiota composition was examined by 16s rRNA gene sequencing.
ResultsThe combined treatment of LGG and Oxp significantly reduced tumor weight and volume, and improved tumor-associated pathological changes compared to the model group. The LGG treatment also alleviated Oxp-induced intestinal damage and inflammation, maintaining intestinal barrier integrity. The combined treatment modulated genes linked to intestinal barrier function and inflammation, upregulated Occludin and Mucin2, and downregulating Tnf-α and Il-1β in colon tissues. Gut microbiota analysis showed notable shifts following treatment. Specifically, the Oxp group exhibited a decrease in Clostridium_XlVa and an increase in Desulfovibrio, indicating a shift in microbial balance. The relative abundance of Lactobacillus increased significantly in the combined treatment group compared to the control, suggesting a potential probiotic effect. The combined treatment also restored some of the microbial communities, such as Bacteroidaceae resembles the Bacteroidetes, Bacteroidia, and Bacteroidales in the NC group, which were reduced by Oxp treatment alone.
ConclusionThe combined use of LGG and Oxp offers a promising therapeutic strategy for NSCLC, warranting further investigation into the interplay between probiotics, chemotherapy, and the gut microbiota.

研究背景：非小细胞肺癌（Non-small cell lung cancer, NSCLC）是全球范围内癌症相关死亡的首要诱因，亟需针对有效治疗策略开展深入研究。尽管靶向治疗与免疫治疗已取得诸多进展，但传统化疗仍是多数患者的主要治疗手段。本研究探讨了益生菌鼠李糖乳杆菌GG（Lactobacillus rhamnosus GG, LGG）与化疗药物奥沙利铂（oxaliplatin, Oxp）联用对非小细胞肺癌治疗效果的协同增强作用。
研究方法：本研究采用BALB/c裸鼠皮下移植瘤模型评估LGG与Oxp的治疗效果。将小鼠随机分为5组：阴性对照组、模型对照组、Oxp单药治疗组、LGG单药治疗组以及LGG联合Oxp治疗组。本次研究的主要评估指标包括瘤重、瘤体积、组织病理学变化，以及通过定量反转录聚合酶链反应（qRT-PCR）检测的基因表达水平。同时通过16S rRNA基因测序分析肠道菌群的组成结构。
研究结果：与模型对照组相比，LGG联合Oxp治疗可显著降低瘤重与瘤体积，并改善肿瘤相关病理损伤。单独使用LGG亦可缓解Oxp诱导的肠道损伤与炎症反应，维持肠道屏障的完整性。联合治疗可调控肠道屏障功能与炎症相关基因的表达：上调结肠组织中闭合蛋白（Occludin）和黏蛋白2（Mucin2）的表达水平，同时下调肿瘤坏死因子α（Tnf-α）与白细胞介素1β（Il-1β）的转录水平。肠道菌群分析显示，各治疗组均存在显著的菌群结构改变。具体而言，Oxp单药组中梭菌属XlVa群（Clostridium_XlVa）丰度降低，而脱硫弧菌属（Desulfovibrio）丰度升高，提示菌群平衡被打破。联合治疗组中乳杆菌属（Lactobacillus）的相对丰度较对照组显著升高，表明其潜在的益生功能。此外，联合治疗可恢复部分被Oxp单药治疗抑制的菌群类群，例如拟杆菌科（Bacteroidaceae）、拟杆菌门（Bacteroidetes）、拟杆菌纲（Bacteroidia）以及拟杆菌目（Bacteroidales），这些类群在Oxp单药处理后丰度显著降低。
研究结论：LGG与Oxp联合使用为非小细胞肺癌提供了一种极具前景的治疗策略，值得进一步探究益生菌、化疗与肠道菌群之间的相互作用机制。