Gut microbiota from colorectal cancer patients enhances the progression of intestinal adenoma in Apcmin/+ mice

Abstract

BackgroundAccumulating evidence points to a close relationship between gut dysbiosis and colorectal cancer (CRC). As >90% of CRC develop from adenoma, we aimed to investigate the crucial role of imbalanced gut microbiota on the progression of intestinal adenoma.MethodsThe Apcmin/+ mice gavage with phosphate-buffered saline (PBS), feces from healthy controls or CRC patients after antibiotic cocktails. The intestinal tissues were isolated for histopathology, western blotting, and RNA-seq. The microbiota of feces and short-chain fatty acids (SCFAs) were analysed by 16S rDNA Amplicon Sequencing and gas chromatography.FindingsThe Apcmin/+mice gavaged by feces from CRC patients had more intestinal tumours compared with those fed with feces from healthy controls or PBS. Administration of feces from CRC patients increased tumour proliferation and decreased apoptosis in tumour cells, accompanied by impairment of gut barrier function and up-regulation the pro-inflammatory cytokines profile. The up-regulated the expression of β-catenin and cyclinD1 further indicating the activation of Wnt signalling pathway. The abundance of pathogenic bacteria was increased after FMT, while producing SCFAs bacteria and SCFAs production were decreased.InterpretationGut microbiota of CRC patients disrupted intestinal barrier, induced low-grade inflammation and dysbiosis. The altered gut microbiota enhanced the progression of intestinal adenomas in Apcmin/+mice, suggesting that a new strategy to target gut microbiota against CRC could be noted.FundThe study was supported by the , , and .

Faecal microbiota transplantation, a promising way to treat colorectal cancer

“…This pathway is classified into canonical ( β-catenin dependent) and non-canonical ( β-catenin independent) [9] . Consistent with Li and colleagues' results [3] , Jiang and colleagues [10] also showed that the canonical Wnt pathway played an essential role in different stages of tumour development.…”

“…This process can not only provide energy for the microbiota but also result in the release of short-chain fatty acids (SCFAs), including butyrate, which could be used for metabolic needs by the colonocytes, maintain mucosal integrity, and suppress inflammation and carcinogenesis [6] . Analysing the faecal supernatant of patients with colorectal cancer, Li and colleagues [3] found that the relative abundance of Roseburia spp and Clostridium spp was lower than that in the faecal supernatant of healthy patients, consistent with Wang and colleagues' findings [7] , whereas the relative abundance of Akkermansia spp and Ruminococcus spp was higher, consistent with Weir and colleagues' results [8] . Similarly, the number of pathogenic bacteria increased after FMT, whereas the number of bacteria secreting SCFAs (such as Ruminococcus spp, Roseburia spp, and Clostridium cluster XlVa spp) and the production of SCFAs in the caecum decreased, which could be one of the reasons for the destruction of intestinal mucosal barrier and the occurrence of chronic inflammation in Apc min/ + mice after transplantation.…”

“…In EBioMedicine , Li and colleagues [3] showed that faecal microbiota transplantation (FMT) with faeces of patients with colorectal cancer accelerates the progression of adenoma to adenocarcinoma could cause chronic inflammation and disturb the ecological balance of the mice's gut microbiota. This study is of great importance because, although a previous study [4] showed that gavage of faecal samples from patients with colorectal cancer promoted the intestinal carcinogenesis in both germ-free and control mice, the effect of gut microbiota on Apc min/ + mice had not been investigated.…”

“…To further understand the molecular mechanisms induced by FMT, Li and colleagues [3] conducted further tests and showed that the gut microbiota from patients with colorectal cancer could activate the Wnt signaling pathway. This pathway is classified into canonical ( β-catenin dependent) and non-canonical ( β-catenin independent) [9] .…”

Rubidium chloride modulated the fecal microbiota community in mice

“…The increase in abundance Clostridium XlVa could alleviate the pathogenesis of depression and cancers. Clostridium XlVa was signi cantly lower in CRC patients [77]. Clostridium XIVa was overrepresented in healthy control subjects [36,82].…”