College of Integrated Chinese and Western Medicine, Hebei Medical University, Shijiazhuang, 050017, China.
The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China.
Sci Rep. 2024 Jun 4;14(1):12827. doi: 10.1038/s41598-024-63774-6.
Gut microbiota plays a crucial role in gastrointestinal tumors. Additionally, gut microbes influence the progression of esophageal cancer. However, the major bacterial genera that affect the invasion and metastasis of esophageal cancer remain unknown, and the underlying mechanisms remain unclear. Here, we investigated the gut flora and metabolites of patients with esophageal squamous cell carcinoma and found abundant Bacteroides and increased secretion and entry of the surface antigen lipopolysaccharide (LPS) into the blood, causing inflammatory changes in the body. We confirmed these results in a mouse model of 4NQO-induced esophageal carcinoma in situ and further identified epithelial-mesenchymal transition (EMT) occurrence and TLR4/Myd88/NF-κB pathway activation in mouse esophageal tumors. Additionally, in vitro experiments revealed that LPS from Bacteroides fragile promoted esophageal cancer cell proliferation, migration, and invasion, and induced EMT by activating the TLR4/Myd88/NF-κB pathway. These results reveal that Bacteroides are closely associated with esophageal cancer progression through a higher inflammatory response level and signaling pathway activation that are both common to inflammation and tumors induced by LPS, providing a new biological target for esophageal cancer prevention or treatment.
肠道微生物在胃肠道肿瘤中起着至关重要的作用。此外，肠道微生物也影响食管癌的进展。然而，影响食管癌侵袭和转移的主要细菌属仍不清楚，其潜在机制也不清楚。在这里，我们研究了食管鳞状细胞癌患者的肠道菌群和代谢物，发现丰富的拟杆菌属和表面抗原脂多糖（LPS）进入血液的分泌和进入增加，导致机体炎症变化。我们在 4NQO 诱导的原位食管癌小鼠模型中证实了这些结果，并进一步鉴定了上皮-间充质转化（EMT）的发生和 TLR4/Myd88/NF-κB 通路在小鼠食管肿瘤中的激活。此外，体外实验表明脆弱拟杆菌的 LPS 通过激活 TLR4/Myd88/NF-κB 通路促进食管癌细胞的增殖、迁移和侵袭，并诱导 EMT。这些结果表明，拟杆菌通过更高的炎症反应水平和信号通路激活与食管癌的进展密切相关，这些炎症反应水平和信号通路激活与 LPS 诱导的炎症和肿瘤具有共同性，为食管癌的预防或治疗提供了一个新的生物学靶点。
