eIF6 deficiency alleviates colorectal cancer by modulating the gut microbiota and related metabolites

eIF6 is overexpressed in multiple cancers. Previous work has showed that deficiency alters the gut microbiota. This study investigated the mechanism linking eIF6 deficiency, microbial dysbiosis, and colorectal cancer (CRC). eIF6 expression was assessed in human and mouse CRC samples. Functional assays were conducted in mice with AOM/DSS-induced CRC. Antibiotic treatment and faecal microbiota transplantation (FMT) were applied to evaluate microbiota-mediated effects. 16S rDNA sequencing and Dubosiella newyorkensis (D. newyorkensis) supplementation were used to identify key bacteria. Metabolites from the bacterial supernatant were analysed via targeted mass spectrometry. The effect of indole-3-carboxaldehyde (3-ICA) was tested in murine models. eIF6 expression was upregulated in CRC. Its deficiency reduced the tumour incidence and proliferation of tumours in mice and increased the abundance of beneficial bacteria such as Akkermansia and Dubosiella. FMT from eIF6 deficient mice and D. newyorkensis administration attenuated tumorigenesis and enhanced barrier function. 3-ICA, a metabolite of D. newyorkensis, also suppressed CRC progression. eIF6 deficiency exerts protective effects against CRC through the enrichment of D. newyorkensis and its metabolite 3-ICA, revealing a novel mechanism and potential therapeutic strategy for CRC.