Unique and overlapping behavioral effects of isoform-specific NRXN1 deletions.

Colorectal cancer (CRC) is the third most common cancer worldwide, accounting for approximately 10% of all cancer cases. It is also the second leading cause of cancer-related deaths worldwide. In recent years, the incidence of cancer has tended to increase among those under 50 years of age, which poses a grave threat to human life and health. CRC generally evolves from precancerous lesions such as those seen in colorectal adenoma (CRA) patients. The pathogenesis of CRC is complex and involves genetic, environmental, lifestyle and immunological factors. Recent research has focused on the role of the intestinal microbiota in CRC pathogenesis. The gut microbiota plays crucial roles in maintaining intestinal health. Dysbiosis of the gut microbiota has been associated with CRC development. Studies have shown that putatively procarcinogenic microbial members, including , , , and , have relatively high relative abundances in CRC patients, whereas those of so-called protective genera, including , , and , are reduced. In this context, has attracted substantial interest because it participates in the mechanism of CRC through promotion of the proliferation and migration of CRC cells, recruitment of infiltrating immune cells, and its effect on the balance of the intestinal microbiota. Additionally, some microorganisms, including enteropathogenic with a “” gene island, can cause CRC by damaging DNA. Metabolites of the intestinal microbiota also play a role in CRC development: bile acids can promote CRC growth by suppressing CD8 + T-cell effector functions; formate, a metabolite produced by , promotes CRC development. Moreover, the immune system plays pivotal roles in CRC pathogenesis, maintaining homeostasis and defending against pathogens. Immune dysregulation can trigger chronic inflammation, increasing the risk of CRC. Inflammation is a well-established driver of colorectal carcinogenesis. Bacterially induced inflammation has also been shown to be positively correlated with CRC. can generate a proinflammatory environment conducive to colorectal neoplasia progression by activating the NF-κB pathway and driving myeloid cell infiltration in tumors in mice. Enterotoxigenic can activate the STAT3 signaling pathway in mice, leading to the secretion of large amounts of IL-1, which significantly induces colitis and CRC. However, the role of crosstalk between the gut microbiome and the host, which shapes the tumor immune environment and modulates the microbiota, remains largely unexplored.