PO.TB04.06 · 肿瘤生物学
转基因MUC13表达对肠道菌群和趋化因子谱的影响
Influence of transgenic MUC13 expression on gut microbiota and chemokine profile
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：MUC13是一种重要的癌蛋白，常在包括结直肠癌在内的癌症中过表达，并与更差的预后相关，尽管其确切作用尚未完全阐明。利用MUC13转基因小鼠模型，我们研究了MUC13过表达如何影响肠道微生物组以及可能影响癌症风险和治疗反应的细胞因子。
方法：从MUC13过表达转基因小鼠（MUC13Tg）和野生型小鼠中采集粪便样本。为评估粪便细菌群落，我们进行了DNA提取，随后在Illumina MiSeq平台上进行16S rRNA宏基因组测序。此外，通过IHC评估MUC13Tg和野生型小鼠的结肠组织，以确认MUC13的过表达。进而，分别使用趋化因子芯片对MUC13过表达小鼠和野生型小鼠的血清样本进行趋化因子谱分析。
结果：IHC证实转基因小鼠结肠中MUC13表达升高，这促使我们研究肠道和免疫环境的相关变化。16S rRNA测序显示肠道菌群出现明显变化，与野生型小鼠相比，Alistipes、Clostridium_XIVa、Oscillibacter和TM7增加（25→35%、1.6→11.6%、8.3→16.6%、2.5→6.6%），而Parabacteroides和Akkermansia减少（31.6→11.6%、15→3.3%）。这些微生物改变伴随着细胞因子变化，包括EGF、FGF21、CD93和Leptin升高，以及Angiopoietin-1、CD14、HGF和CCL17等细胞因子水平降低。总之，这些结果表明MUC13过表达不仅改变了肠道微生物组成，还改变了全身炎症信号传导。
结论：本研究提示MUC13过表达显著改变了小鼠的肠道微生物组和细胞因子表达谱。Firmicutes/Bacteroidetes比值升高、促炎物种富集以及有益菌受抑，共同表明肠道菌群失调和促肿瘤环境的形成。这些发现提示MUC13在塑造肠道微生物格局和影响免疫调节方面发挥关键作用，两者都是癌症发生的重要驱动因素。
查看英文原文 English abstract
Background: MUC13 is an important oncoprotein that is often overexpressed in cancers, including colorectal cancer, and is linked to worse outcomes, although its exact role is not fully understood. Using a MUC13 transgenic mouse model, we examined how MUC13 overexpression affects gut microbiome and cytokines that can influence cancer risk and treatment responses.
Methods: Fecal specimens were collected from MUC13-overexpressing transgenic mice (MUC13Tg) and wild-type mice. To assess the fecal bacterial communities, we performed DNA extraction followed by 16S rRNA metagenomic sequencing on the Illumina MiSeq platform. Additionally, colon tissues from MUC13Tg and wild-type mice were assessed by IHC to confirm the overexpression of MUC13. Furthermore, chemokine profiling analyses were performed using chemokines arrays in serum samples of MUC13-overexpressing mice and wild-type mice, respectively.
Results: IHC confirmed elevated MUC13 expression in the colon of transgenic mice, leading us to investigate associated changes in the gut and immune environment. 16S rRNA sequencing showed clear shifts in the gut microbiota, with increases in Alistipes, Clostridium_XIVa, Oscillibacter, and TM7 (25→35%, 1.6→11.6%, 8.3→16.6%, 2.5→6.6%) and decreases in Parabacteroides and Akkermansia (31.6→11.6%, 15→3.3%) compared with wild-type mice. These microbial alterations were accompanied by cytokine changes, including elevated EGF, FGF21, CD93, and Leptin, as well as reduced levels of cytokines such as Angiopoietin-1, CD14, HGF, and CCL17. Together, these results demonstrate that MUC13 overexpression not only shifts gut microbial composition but also modifies systemic inflammatory signaling.
Conclusion: This study suggests that MUC13 overexpression markedly alters the gut microbiome and cytokine expression profile in mice. The increased Firmicutes/Bacteroidetes ratio, enrichment of pro-inflammatory species, and repression of beneficial bacteria collectively indicate a shift toward gut dysbiosis and a pro-tumorigenic environment. These findings suggest that MUC13 plays a key role in shaping the gut microbial landscape and influencing immune modulation, both of which are important drivers of cancer development.
利益披露 Disclosure
S. Dhasmana, None..
A. Dhasmana, None..
S. Singh, None..
I. A. Perez, None..
S. Malik, None..
S. Khan, None..
M. M. Yallapu, None..
S. C. Chauhan, None.