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The human intestine retains a complex microbial ecosystem, which performs crucial functions that impact on host health. Several studies have indicated that intestinal dysbiosis may impact on the establishment of life-threatening intestinal diseases such as colorectal cancer. An adenomatous polyp is the result of abnormal tissue growth, which is benign but is considered to be associated with a high risk of developing colorectal cancer, based on its grade of dysplasia. Development of diagnostic tools that are based on surveying the gut microbiota and are aimed at early detection of colorectal cancer represent highly desirable target. For this purpose, we performed a pilot study in which we applied a metataxonomic analysis based on 16S rRNA gene sequencing approach to unveil the composition of microbial communities of intestinal polyps. Moreover, we performed a meta-analysis involving the reconstructed microbiota composition of adenomatous polyps and publicly available metagenomics datasets of colorectal cancer. These analyses allowed the identification of microbial taxa such as Faecalibacterium , Bacteroides and Romboutsia , which appear to be depleted in cancerogenic mucosa as well as in adenomatous polyps, thus representing novel microbial biomarkers associated with early tumor formation. Furthermore, an absolute quantification of Fusubacterium nucleatum in polyps further compounded the important role of this microorganism as a valuable putative microbial biomarker for early diagnosis of colorectal cancer.

This work has been funded by the research project grant IDI-20120896/7 from CDTI (Spanish Ministry of Economy, Industry and Competitiveness) and IDI/2018/000120 from Programa de Ayudas a Grupos de Investigación del Principado de Asturias. We thank Servicios Científco Técnicos from the University of Oviedo (Sequencing Unit, Statistical Analysis Unit), Animal Pathology Unit from the IUOPA (Instituto Universitario de Oncología del Principado de Asturias), and Biostatistics Unit from ISPA.

Recently, cyclomodulins have been identified in Escherichia coli ( E. coli ), which can induce dysplastic damage. This work aimed to determine the dysplastic activity of cyclomodulin-harboring E. coli isolated from CRC patients, obese and normal-weight subjects in a mouse model. Forty-two mice were pretreated with streptomycin, azoxymethane, and dextran sodium sulfate. Mice were infected with E. coli pks +  isolated from a CRC patient, with E. coli pks + cif +  isolated from obese or normal-weight subjects, or with E. coli HB101. The presence of cyclomodulin-harboring E. coli in the feces, weight loss, changes in fecal consistency, and the presence of blood in the feces were monitored and used to assess the disease activity index (DAI). After 62 days, the mice were sacrificed to evaluate the presence of intestinal polyps and dysplastic damage by histologic sections. Cyclomodulin-harboring E. coli colonized the mice; these mice exhibited weight loss and watery diarrhea, and isolated normal-weight E. coli had a higher DAI. Polyps were observed in mice infected with cyclomodulin-harboring E. coli in the ileum but to a greater extent in obese isolates. E. coli isolated from CRC showed more significant endothelial damage associated with dysplasia in the ileum in equal proportions from obese and normal-weight isolates. In conclusion, E. coli harboring cyclomodulins isolated from CRC, obesity, or normal weight can cause dysplastic damage in the ileum of mice and may be a risk factor for CRC development.

Background Mouse and human studies support the promise of dry beans to improve metabolic health and to lower cancer risk. In overweight/obese patients with a history of colorectal polyps or cancer, the Beans to Enrich the Gut microbiome vs. Obesity’s Negative Effects (BE GONE) trial will test whether and how an increase in the consumption of pre-cooked, canned dry beans within the context of usual diet and lifestyle can enhance the gut landscape to improve metabolic health and reduce cancer risk. Methods/design This randomized crossover trial is designed to characterize changes in (1) host markers spanning lipid metabolism, inflammation, and obesity-related cancer risk; (2) compositional and functional profiles of the fecal microbiome; and (3) host and microbial metabolites. With each subject serving as their own control, the trial will compare the participant’s usual diet with (intervention) and without (control) dry beans. Canned, pre-cooked dry beans are provided to participants and the usual diet continually assessed and monitored. Following a 4-week run-in and equilibration period, each participant provides a total of 5 fasting blood and 6 stool samples over a total period of 16 weeks. The intervention consists of a 2-week ramp-up of dry bean intake to 1 cup/d, which is then continued for an additional 6 weeks. Intra- and inter-individual outcomes are assessed across each crossover period with consideration of the joint or modifying effects of the usual diet and baseline microbiome. Discussion The BE GONE trial is evaluating a scalable dietary prevention strategy targeting the gut microbiome of high-risk patients to mitigate the metabolic and inflammatory effects of adiposity that influence colorectal cancer risk, recurrence, and survival. The overarching scientific goal is to further elucidate interactions between diet, the gut microbiome, and host metabolism. Improved understanding of the diet-microbiota interplay and effective means to target these relationships will be key to the future of clinical and public health approaches to cancer and other major diet- and obesity-related diseases. Trial registration This protocol is registered with the U.S. National Institutes of Health trial registry, ClinicalTrials.gov , under the identifier NCT02843425. First posted July 25, 2016; last verified January 25, 2019.

ObjectiveA signature that unifies the colorectal cancer (CRC) microbiota across multiple studies has not been identified. In addition to methodological variance, heterogeneity may be caused by both microbial and host response differences, which was addressed in this study.DesignWe prospectively studied the colonic microbiota and the expression of specific host response genes using faecal and mucosal samples (‘ON’ and ‘OFF’ the tumour, proximal and distal) from 59 patients undergoing surgery for CRC, 21 individuals with polyps and 56 healthy controls. Microbiota composition was determined by 16S rRNA amplicon sequencing; expression of host genes involved in CRC progression and immune response was quantified by real-time quantitative PCR.ResultsThe microbiota of patients with CRC differed from that of controls, but alterations were not restricted to the cancerous tissue. Differences between distal and proximal cancers were detected and faecal microbiota only partially reflected mucosal microbiota in CRC. Patients with CRC can be stratified based on higher level structures of mucosal-associated bacterial co-abundance groups (CAGs) that resemble the previously formulated concept of enterotypes. Of these, Bacteroidetes Cluster 1 and Firmicutes Cluster 1 were in decreased abundance in CRC mucosa, whereas Bacteroidetes Cluster 2, Firmicutes Cluster 2, Pathogen Cluster and Prevotella Cluster showed increased abundance in CRC mucosa. CRC-associated CAGs were differentially correlated with the expression of host immunoinflammatory response genes.ConclusionsCRC-associated microbiota profiles differ from those in healthy subjects and are linked with distinct mucosal gene-expression profiles. Compositional alterations in the microbiota are not restricted to cancerous tissue and differ between distal and proximal cancers.

Familial adenomatous polyposis (FAP) causes benign polyps along the colon. If left untreated, FAP leads to a high incidence of colon cancer. To understand how polyps influence tumor formation, Dejea et al. examined the colonic mucosa of FAP patients. They discovered biofilms containing the carcinogenic versions of the bacterial species Escherichia coli and Bacteroides fragilis . Colon tissue from FAP patients exhibited greater expression of two bacterial genes that produce secreted oncotoxins. Studies in mice showed that specific bacteria could work together to induce colon inflammation and tumor formation. Science , this issue p. 592 Bacterial biofilms are linked to colon cancer. Individuals with sporadic colorectal cancer (CRC) frequently harbor abnormalities in the composition of the gut microbiome; however, the microbiota associated with precancerous lesions in hereditary CRC remains largely unknown. We studied colonic mucosa of patients with familial adenomatous polyposis (FAP), who develop benign precursor lesions (polyps) early in life. We identified patchy bacterial biofilms composed predominately of Escherichia coli and Bacteroides fragilis . Genes for colibactin ( clbB ) and Bacteroides fragilis toxin ( bft ), encoding secreted oncotoxins, were highly enriched in FAP patients’ colonic mucosa compared to healthy individuals. Tumor-prone mice cocolonized with E. coli (expressing colibactin), and enterotoxigenic B. fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacterial strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.

Colorectal polyps are the most common precursors of colorectal cancer (CRC). The close relationship has been observed between colorectal polyps and gut microbiota. However, gut microbiota signatures among sampling sites in patients with colorectal polyps and healthy adults remain elusive. To learn about gut microbiota signatures in tissues of the colorectal polyp and normal colorectal mucosa, and faeces. We performed 16S rRNA gene sequencing and bioinformatic analysis for the microbiota in the normal colorectal mucosa, the colorectal polyps and faeces of adults with colorectal polyps (n = 24) and in faeces and normal mucosa of healthy adults (n = 16) in this preliminary trial. The Ace and Chao indexes were higher in the normal colorectal mucosa and polyp tissues compared to faecal samples ( < 0.05). The composition of microbiota based on PCoA and ANOSIM analysis showed the significant differences only between faeces and tissues of the normal mucosa and polyp ( < 0.05). Based on the LEfSe analysis, the abundances of , and were higher, whereas the abundances of , and were lower in faeces both in patients with colorectal polyp and healthy individuals, compared with those in the normal mucosa in two groups or polyp tissues. In healthy individuals, the abundance of was significantly higher in the normal colorectal mucosa than in faeces. Moreover, there was no significant difference in the abundance of between the normal colorectal mucosa and polyps in patients with colorectal polyps, but it was significantly higher in the mucosa and polyps than in faeces. Remarkably, the abundance of in the normal colorectal mucosa was significantly higher in healthy individuals than in the polyp group. The microbial structure in faeces differs from that in tissues of polyp and normal mucusa. Additionally, may be a normal colonizer in colonic mucosa, and an abnormal increase of detected in faeces may be related with the injury of the colorectal mucosa. The difference of the faecal microbiota and mucosal microbiota should be carefully considered in studies on gut microbiota in patients with colorectal lesions.

Colorectal cancer (CRC) is the fourth most common cancer and the third leading cause of cancer-related mortality worldwide, with incidence rising among younger populations. The significant clinical and economic burden highlights the need for minimally invasive technologies capable of detecting pre-malignant and early-stage disease. Although liquid biopsy approaches have advanced, they have not achieved sufficient performance for clinical adoption when compared with colonoscopy, the current diagnostic gold standard. CRC is a mucosal pathology, yet current diagnostic methods have not leveraged mucosal biology. Here we demonstrate the clinical utility of rectal mucus specimens, collected using a minimally invasive device in an outpatient setting, without bowel preparation. Through a hologenomic approach integrating host and microbial genomics, we identify genetic and epigenetic aberrations and perturbations in microbial communities that drive the detection of adenomatous polyps and CRC in rectal mucus. Hologenomic integration enables superior stratification of CRC by disease site and stage compared with single-omics methods. In summary, we demonstrate the clinical utility of rectal mucus sampling combined with hologenomic analysis as a translatable prospective tool for diagnostic application. Colorectal cancer is often diagnosed at later stages, leading to poor prognosis. Here, the authors utilise analysis of rectal mucus specimens using host and microbial analysis to detect cancer lesions.

Emerging evidence suggests that tissue-resident microbiota (TRM) is associated with tumor biology; however, their distribution and compositional characteristics across different colorectal tissue types remain incompletely defined. Here, we conducted a comprehensive cross-sectional analysis of TRM distribution and abundance across 1134 clinical specimens, including normal mucosa, precancerous polyps, and colorectal cancer (CRC) tissues. Our results reveal distinct microbial profiles among these diagnostic groups, with consistent differences in community composition between normal, polyps, and CRC samples. Integrative analyses further identified microbial signatures capable of distinguishing tissue categories and reflected differences in the local tumor microenvironment. In contrast, intratumoral microbiota composition showed subtle variation across established tumor stages and was not associated with clinical outcomes. These findings define diagnostic group-associated patterns of TRM in colorectal tissues and establish a foundation for future mechanistic investigations into the biological roles of TRM in colorectal cancer. Colorectal cancer has been associated with changes in tissue-resident microbiota. Here, the authors characterize a cross-sectional delineation of microbiota changes across normal, polyp, and colorectal cancer tissues.