Wang Xianmei, Chen Hang, Yang Meng, Huang Minshan, Zhang Dan, Li Mingke, Wang Hui, Zhou Qingqing, Lu Lihong, Li Yu, Yu Jiangkun, Ma Lanqing
Yunnan Institute of Digestive Disease, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, School of Life Sciences, Yunnan University, Kunming, Yunnan, China.
Front Microbiol. 2025 Apr 16;16:1556056. doi: 10.3389/fmicb.2025.1556056. eCollection 2025.
Colorectal adenomas (CRA) are the primary precancerous lesions leading to colorectal cancer (CRC). Early detection and intervention of CRA can significantly reduce the incidence of CRC. We investigated the relationships between the gut microbiome and the expression levels of PD-L1, IL-6, and IFN-γ at different CRA stages.
Participants were divided into normal, non-advanced adenoma (NAA), and advanced adenoma (AA) groups. PD-L1 expression in collected tissues was analyzed via immunohistochemistry (IHC) and Western blotting. Serum IL-6 and IFN-γ levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA). 16S rRNA gene sequencing was used to examine gut microbiota changes, with correlation analysis to assess microbial influences on CRA progression.
The main differences in bacterial composition among the three groups were found within the Firmicutes and Bacteroidetes phyla. In the normal vs. NAA comparison, were more abundant in the normal group, while was enriched in the NAA group. For the normal vs. AA comparison, the normal group was enriched with , whereas was more abundant in the AA group. In the NAA vs. AA comparison, the NAA group exhibited higher levels of relative to the AA group. are positively correlated with PD-L1 protein levels progressively increase with CRA advancement. Additionally, were negatively associated with IFN-γ, while were positively associated with IL-6.
This study highlights the dynamic alterations in gut microbiota composition and their potential influence on the regulation of inflammatory cytokines and PD-L1 expression during CRA progression. The enrichment of protective taxa, such as and , in the normal group emphasizes their potential role in mitigating adenoma progression. Dietary modulation to promote the proliferation of these beneficial bacteria could serve as a promising strategy to improve colorectal health. Future research should further explore the specific relationships between dietary components, gut microbiota, and metabolic pathways, and assess the effects of dietary interventions on gut health.
结直肠腺瘤（CRA）是导致结直肠癌（CRC）的主要癌前病变。CRA的早期检测和干预可显著降低CRC的发病率。我们研究了不同CRA阶段肠道微生物群与PD-L1、IL-6和IFN-γ表达水平之间的关系。
将参与者分为正常组、非进展性腺瘤（NAA）组和进展性腺瘤（AA）组。通过免疫组织化学（IHC）和蛋白质免疫印迹法分析收集组织中PD-L1的表达。采用酶联免疫吸附测定（ELISA）测量血清IL-6和IFN-γ水平。使用16S rRNA基因测序检查肠道微生物群的变化，并进行相关性分析以评估微生物对CRA进展的影响。
三组之间细菌组成的主要差异存在于厚壁菌门和拟杆菌门中。在正常组与NAA组的比较中，正常组中 更丰富，而 在NAA组中富集。在正常组与AA组的比较中，正常组中 富集，而 在AA组中更丰富。在NAA组与AA组的比较中，相对于AA组，NAA组 的水平更高。 与 呈正相关，PD-L1蛋白水平随着CRA进展而逐渐升高。此外， 与IFN-γ呈负相关，而 与IL-6呈正相关。
本研究强调了肠道微生物群组成的动态变化及其在CRA进展过程中对炎性细胞因子调节和PD-L1表达的潜在影响。正常组中保护性分类群如 和 的富集强调了它们在减轻腺瘤进展中的潜在作用。通过饮食调节促进这些有益细菌的增殖可能是改善结直肠健康的一种有前景的策略。未来的研究应进一步探索饮食成分、肠道微生物群和代谢途径之间的具体关系，并评估饮食干预对肠道健康的影响。
