Bacteroides fragilis (BF) plays a critical role in developing and maintaining the mammalian immune system. We previously found that BF colonization could prevent inflammation and tumor formation in a germ-free (GF) colitis-associated colorectal cancer (CAC) mouse model. The role of Toll-like receptor 4 (TLR4) in CAC development has not been clearly elucidated in BF mono-colonized gnotobiotic mice. The wild-type (WT) and TLR4 knockout (T4K) germ-free mice were raised with or without BF colonization for 28 days (GF/WT, GF/T4K, BF/WT, and BF/T4K) and then CAC was induced under azoxymethane (AOM)/dextran sulfate sodium (DSS) administration. The results showed that tumor formation and tumor incidence were significantly inhibited in the BF/WT group compared to those observed in the GF/WT group. However, the tumor prevention effect was not observed in the BF/T4K group unlike in the BF/WT group. Moreover, the CAC histological severity of the BF/WT group was ameliorated, but more severe lesions were found in the GF/WT, GF/T4K, and BF/T4K groups. Immunohistochemistry showed decreased cell proliferation (PCNA, β-catenin) and inflammatory markers (iNOS) in the BF/WT group compared to those in the BF/T4K group. Taken together, BF mono-colonization of GF mice might prevent CAC via the TLR4 signal pathway.

脆弱拟杆菌(BF) 在哺乳动物免疫系统的发育和维持中发挥着关键作用。我们之前发现 BF 定植可以预防无菌 (GF) 结肠炎相关结直肠癌 (CAC) 小鼠模型中的炎症和肿瘤形成。 Toll 样受体 4 (TLR4) 在 BF 单菌定生小鼠 CAC 发育中的作用尚未明确阐明。将野生型 (WT) 和 TLR4 敲除 (T4K) 无菌小鼠在有或没有 BF 定植的情况下饲养 28 天（GF/WT、GF/T4K、BF/WT 和 BF/T4K），然后诱导 CAC氧化偶氮甲烷（AOM）/葡聚糖硫酸钠（DSS）给药。结果显示，与GF/WT组相比，BF/WT组的肿瘤形成和肿瘤发生率均受到显着抑制。然而，与BF/WT组不同，在BF/T4K组中没有观察到肿瘤预防效果。此外，BF/WT组的CAC组织学严重程度有所改善，但GF/WT、GF/T4K和BF/T4K组中发现更严重的病变。免疫组织化学显示，与 BF/T4K 组相比，BF/WT 组的细胞增殖（PCNA、β-catenin）和炎症标志物（iNOS）减少。总而言之，GF 小鼠的 BF 单一定植可能通过 TLR4 信号通路预防 CAC。