Abstract

Simple SummaryHigh-fat diet (HFD) is hypothesized to induce gut dysbiosis and promote colorectal cancer (CRC). However, the specific mechanisms involved require investigation. In this study, we established an animal model and utilized 16S sequencing to determine the effects of HFD on gut microbiota, as well as on the colon and liver. Furthermore, due to the abundance ofDesulfovibrio(DSV) in the faecal samples of HFD-fed rats and CRC hepatic metastasis patients, we also conducted a DSV gavage animal experiment to determine the role of DSV in CRC development. Our study confirmed that HFD could cause microbiota dysbiosis, especially DSV enrichment, and may promote CRC initiation and metastasis.AbstractObesity, metabolic changes, and intestinal microbiota disruption significantly affect tumorigenesis and metastasis in colorectal cancer (CRC). However, the relationships among these factors remain poorly understood. In this study, we found that a high-fat diet (HFD) promoted gut barrier dysfunction and inflammation in the colorectum and liver. We further investigated gut microbiota changes through 16S rRNA sequencing of faecal samples from HFD-fed rats and CRC hepatic metastasis patients and found an abundance ofDesulfovibrio(DSV). DSV could also induce barrier dysfunction in the colorectum and inflammation in the colorectum and liver, suggesting that it contributes to the formation of a microenvironment conducive to CRC tumorigenesis and metastasis. These findings highlight that HFD-induced microbiota dysbiosis, especially DSV abundance, could promote CRC initiation and metastasis.Keywords:colorectal cancer;liver metastasis;high-fat diet;microbiota dysbiosis;Desulfovibrio;tumour microenvironment