eIF6 deficiency alleviates colorectal cancer through maintaining the intestinal barrier and homeostasis of gut microbiota

In this study, we demonstrate the mitigating effect of eIF6 deficiency on the progression of CRC in an AOM/DSS-induced mouse model, elucidating how eIF6 deficiency directly alleviates CRC progression through its impact on the gut microbiota. We observe that eIF6 deficiency promotes colonic epithelial regeneration, maintains intestinal barrier integrity, and suppresses tumor proliferation in CRC mice. The eIF6 deficiency-modulated gut microbiota directly contributes to alleviating CRC progression. Furthermore, eIF6 deficiency-dependent <i>Dubosiella newyorkensis</i> reduces monocyte aggregation, inhibits the MAPK and NF-κB carcinogenic pro-inflammatory pathways, thereby attenuating CRC progression. These findings confirm the pivotal role of the gut microbiota in mediating the alleviation of CRC progression of eIF6 deficiency.

本研究在氧化偶氮甲烷/葡聚糖硫酸钠（AOM/DSS）诱导的小鼠模型中，证实了eIF6缺失对结直肠癌（CRC）进展的缓解作用，并阐明了eIF6缺失通过调控肠道菌群直接延缓CRC进展的具体机制。本研究观察到，在CRC模型小鼠体内，eIF6缺失可促进结肠上皮再生、维持肠道屏障完整性，并抑制肿瘤增殖。eIF6缺失所调控的肠道菌群可直接介导CRC进展的缓解。此外，依赖eIF6缺失的纽约杜波西氏菌（*Dubosiella newyorkensis*）可减少单核细胞聚集，抑制丝裂原活化蛋白激酶（MAPK）与核因子κB（NF-κB）这两条致癌促炎通路，进而延缓CRC进展。上述研究结果证实，肠道菌群在介导eIF6缺失缓解CRC进展的过程中发挥关键作用。