Despite extensive investigations into the microbiome and metabolome changes associated with colon polyps and colorectal cancer (CRC), the microbiome and metabolome profiles of individuals with colonic polyposis, including those with (Gene-pos) and without (Gene-neg) a known genetic driver, remain comparatively unexplored. Using colon biopsies, polyps, and stool from patients with Gene-pos adenomatous polyposis (N = 9), Gene-neg adenomatous polyposis (N = 18), and serrated polyposis syndrome (SPS, N = 11), we demonstrated through 16S rRNA sequencing that the mucosa-associated microbiota in individuals with colonic polyposis is representative of the microbiota associated with small polyps, and that both Gene-pos and SPS cohorts exhibit differential microbiota populations relative to Gene-neg polyposis cohorts. Furthermore, we used these differential microbiota taxa to perform linear discriminant analysis to differentiate Gene-neg subjects from Gene-pos and from SPS subjects with an accuracy of 89% and 93% respectively. Stool metabolites were quantified via 1H NMR, revealing an increase in alanine in SPS subjects relative to non-polyposis subjects, and Partial Least Squares Discriminant Analysis (PLS-DA) analysis indicated that the proportion of leucine to tyrosine in fecal samples may be predictive of SPS. Use of these microbial and metabolomic signatures may allow for better diagnostric and risk-stratification tools for colonic polyposis patients and their families as well as promote development of microbiome-targeted approaches for polyp prevention.

Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide, causing a serious threat to global health and social burden. Clostridioides difficile infection (CDI) is one of the most important nosocomial infections and has a higher incidence in cancerous population compared with non-cancerous cases. Different risk factors, including gut microbiota dysbiosis, extensive surgery, chemotherapy, prolonged hospitalization, and antimicrobial therapy, compromise host defenses against CDI and contribute to cancer patients' susceptibility to this infection. The emergence of CDI in patients with CRC creates conditions for therapy escalation and prolonged hospitalization, highlighting the need for correct and effective CDI management in these patients. Here, common risk factors associated with CDI in patients with CRC are discussed. In addition, different available techniques for the prevention, detection, and treatment of CDI with the lowest impact on gut microbiota diversity are summarized. This review aims to improve the understanding of the interplay between CDI and CRC and provide new insights into restoring and maintaining gut microbiota balance during CDI management in patients with CRC.

Diagnostic value of Methane and Hydrogen Breath Test (MHBT) combined with intestinal flora detection in colorectal polyp screening.

Retrospective inclusion of 196 patients who had completed MHBT with colonoscopy during the same period of time in the General Hospital of the People's Liberation Army (PLA), China, from January 2022 to December 2023, were divided into a control group (no polyps) and an observation group (with polyps, n = 109). A total of 196 patients who were examined were divided into control group (without polyps, n = 109) and observation group (with polyps, n = 87). Baseline data, intestinal barrier function (DAO, D-lac, LPS), tumor markers (AFP, CA19-9, CA-125, CEA), MHBT positivity rate and relative abundance of intestinal flora were analyzed in the two groups, and diagnostic efficacy was assessed by ROC curve.

The proportion of males (64.94 vs. 49.54%) and age (61.85 ± 12.38 vs. 52.47 ± 13.57 years) in the observation group were significantly higher than those in the control group (P < 0.05). After multifactorial correction, CH4 (OR = 2.32, P = 0.019) and H2 positivity (OR = 2.14, P = 0.027) remained significantly higher in the observation group. In the observation group, Bifidobacterium spp. (Bb, -15.91 ± 2.86 vs. -16.65 ± 2.13 in the control group, t = 2.075, P = 0.039), Lactobacillus spp. (Lb, -12.58 ± 3.67 vs. -15.87 ± 2.70, t = 6.988, P < 0.001), enterotoxin-producing Enterotoxin fragile mimics (ETBF, -6.02 ± 2.17 vs. 6.02 ± 2.17 vs. -6.69 ± 2.23, t = 2.122, P = 0.035), Clostridium nucleatum (Fn, -18.73 ± 2.88 vs. -21.28 ± 3.07, t = 5.984, P < 0.001) and anaerobic Streptococcus pepticus (Panaerobius, -16.23 ± 1.98 vs. - 20.30 ± 2.43, t = -2.916, P < 0.001) were significantly higher than the relative quantitative values of the control group. ROC analysis showed that the AUC for diagnosing colorectal polyps with CH4, H2 and the combined assay (CH4+H2) were 0.725, 0.640, and 0.768, respectively; and after combining the intestinal flora (Bb, Lb, Fn, etc.) AUC was elevated to 0.831, with a sensitivity of 79.27% and a specificity of 82.90%.

HBT provides a non-invasive strategy for colorectal polyp screening by capturing CH4/H2 metabolic gases with intestinal flora characteristics. Combining flora markers significantly improves diagnostic efficacy, suggesting its translational potential in optimizing screening pathways. Future exploration of the mechanisms of flora-metabolic gas dynamic interactions and individualized threshold setting is warranted.

Cancer has long been associated with genetic and environmental factors, but recent studies reveal the important role of gut microbiota in its initiation and progression. Around 13% of cancers are linked to infectious agents, highlighting the need to identify the specific microorganisms involved. Gut microbiota can either promote or inhibit cancer growth by influencing oncogenic signaling pathways and altering immune responses. Dysbiosis can lead to cancer, while certain probiotics and their metabolites may help reestablish micro-ecological balance and improve anti-tumor immune responses. Research into targeted approaches that enhance therapy with probiotics is promising. However, the effects of probiotics in humans are complex and not yet fully understood. Additionally, methods to counteract harmful bacteria are still in development. Early clinical trials also indicate that modifying gut microbiota may help manage side effects of cancer treatments. Ongoing research is crucial to understand better how gut microbiota can be used to improve cancer prevention and treatment outcomes.

Colorectal cancer (CRC), the third most common cancer globally, is linked to gut microbiota imbalances. This study explores the association between gut microbiota composition and CRC, focusing on the therapeutic potential of probiotic-derived cell-free supernatants (CFSs). 50 participants, including 25 CRC patients and 25 healthy controls, were recruited and assessed for the relative abundance of six targeted gut bacterial species, including three probiotic strains (Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, and Bifidobacteriumbreve) and three non-probiotic bacteria (Enterococcus faecalis, Streptococcus bovis, and Porphyromonas gingivalis), using absolute quantification real-time PCR (qRT-PCR). Additionally, the in vitro studies investigated the anti-inflammatory effects of CFSs extracted from cultured L. acidophilus, L. rhamnosus, and B. breve, both individually and as a combined cocktail. The results showed that CRC patients exhibited significant increases in non-probiotic bacteria alongside reductions in the beneficial probiotics. Moreover, while the CFSs from all three probiotics exhibited anti-inflammatory properties, the combined CFS cocktail demonstrated the most pronounced effect, significantly downregulating pro-inflammatory cytokines IL-6 and TNF-α in HT-29 colon epithelial cells. These findings emphasize microbial imbalances as potential biomarkers for early CRC detection and underscore the therapeutic promise of probiotic-derived CFSs, presenting innovative, non-invasive strategies for managing CRC-associated inflammation.

Colorectal cancer etiology is multifactorial and influenced by colonic environmental exposures leading to the accumulation of genetic lesions in precancerous polyps. There is growing recognition for a role of the gut microbiome in colorectal cancer progression, but the structure of the gut mucosal microbiome in the early stages of polyp growth is limited. The aim of this study was to characterize the gut mucosal microbiome from patients with low-grade conventional bowel neoplasia compared to symptomatic but polyp-free patients.

In this case-control study conducted at a tertiary referral hospital, 148 symptomatic patients undergoing colonoscopy were prospectively recruited. Mucosal biopsies adjacent to low-grade dysplasia (LGD) adenomatous polyps were used for 16S rRNA gene amplicon sequencing to define bacterial taxonomies relative to polyp-free controls.

Minimal differences in gut mucosa community diversity measures were observed between participants with or without LGD adenomas. After correcting for clinical covariates, patients with adenomas in the proximal colon revealed elevated amplicons from Parabacteroides distasonis, Bacteroides uniformis, and unassigned Lachnospiraceae spp. Bacteroides/Phocaeicola massiliensis was the only microbe consistently found to be decreased in the gut mucosa of LGD adenoma patients compared with controls. Participants with LGD polyps in the distal colon showed more amplicons from Howardella sp. and Blautia faecicola.

This study identified microbial candidates in the colonic mucosa that are associated with adenomatous LGD bowel neoplasia as an early step in the colorectal carcinogenesis pathway.

The association between the oral pathogen Porphyromonas gingivalis (PG) and the gut microbiota in colorectal cancer (CRC) patients has been explored with inconsistent results. This study aims to systematically assess this potential association.

A systematic review was conducted across three databases (Pubmed, Embase and Web of Science) from inception up to January 2023 and updated until November 2024. Inclusion criteria were observational studies examining PG in the microbiota of adults with CRC compared to healthy controls. Exclusion criteria were studies without control group of healthy individuals, other designs or without full-text access. Two reviewers independently selected and extracted data following a pre-registered protocol. Disagreements were resolved by consensus or with a third reviewer. Risk of bias (RoB) was assessed using the Newcastle-Ottawa Scale (NOS). Results were summarized with a flow diagram, tables, and narrative descriptions. Meta-analysis was not feasible, so Fisher's method for combining p-values and the sign test were used as alternative integration methods.

Finally, 18 studies, with 23 analysis units were included, providing a total sample of 4,373 participants (48.0% cases and 52.0%controls), 38.2% men and 61.8% women, with a similar distribution among cases and controls. The mean (SD) age of cases was 63.3 (4.382) years old and 57.0 (7.753) years for controls. Most of the studies analyzed the presence of PG in feces (70.0%) collected before colonoscopy (55.0%) and were classified with good quality (70.0%) in the RoB assessment. Results suggested an effect (Fisher's test, p = .000006) with some evidence towards a positive association of PG in CRC patients compared to healthy controls (Sign test, p = .039).

Results of the systematic review suggest that PG is associated with the microbiota of CRC patients. Lack of information to calculate the effect size prevented the performance of a meta-analysis. Future research should aim for standardized protocols and statistical approaches.

No funding was received for this work.

The research protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 2023 (registration number: CRD42023399382).

Colorectal cancer (CRC), an emerging public health concern, is one of the leading causes of cancer morbidity and mortality worldwide. An increasing body of evidence shows that dysfunction in metabolic reprogramming is a crucial characteristic of CRC progression. Specifically, metabolic reprogramming abnormalities in glucose, glutamine and lipid metabolism provide the tumour with energy and nutrients to support its rapid cell proliferation and survival. More recently, microRNAs (miRNAs) appear to be involved in the pathogenesis of CRC, including regulatory roles in energy metabolism. In addition, it has been revealed that dysbiosis in CRC might play a key role in impairing the host metabolic reprogramming processes, and while the exact interactions remain unclear, the link may lie with miRNAs. Hence, the aims of the current review include first, to delineate the metabolic reprogramming abnormalities in CRC; second, to explain how miRNAs mediate the aberrant regulations of CRC metabolic pathways; third, linking miRNAs with metabolic abnormalities and dysbiosis in CRC and finally, to discuss the roles of miRNAs as potential biomarkers.

Colorectal polyps serve as the primary precursors for colorectal cancer. A close relationship has been observed between colorectal polyps and gut microbiota. However, the composition and role of the microbiome associated with tubular adenoma are not well understood. In this study, we prospectively evaluated alterations in gut microbiota among patients with colorectal polyps. A total of 60 subjects were enrolled in this study, including 30 patients with colorectal polyps (CP group) and 30 healthy controls (control group). The 16S rRNA sequencing was employed to characterize the gut microbiome in fecal samples. The results revealed that the beta diversity of the gut microbiota in the CP group significantly differs from that of the control group (p = 0.001). At the phylum level, the relative abundance of Bacteroides, Fusobacteria, and Proteobacteria was higher in the CP group compared to the control group (p < 0.05), whereas the relative abundance of Actinobacteria was higher in the control group in comparison to the CP group (p < 0.05). At the genus level, the abundance of Bacteroides increased in the CP group (p < 0.05), while Bifidobacterium declined in the CP group (p < 0.05). At the species level, the abundance of Clostridium perfringens, unidentified_Bacteroides, unidentified_Dorea, Escherichia coli, Clostridium ramosum, and Ruminococcus gnavus was higher (p < 0.05), whereas the abundance of Bifidobacterium adolescentis, unclassified_Bifidobacterium, Bifidobacterium longum, Faecalibacterium prausnitzii, and unidentified_Bifidobacterium is lower in CP group compared to the control group (p < 0.05). There was a structural imbalance in the composition of intestinal colonization flora for CP patients, characterized by a decrease in beneficial bacteria and an increase in harmful bacteria. Escherichia, Shigella, and Bacteroides may serve as promising biomarkers for early detection of colorectal polyps.

The dysregulation of intestinal microbiota has been implicated in the pathogenesis of colorectal cancer (CRC). However, the utilization of intestinal microbiota for identify the lesions in different procedures in CRC screening populations remains limited.

A total of 529 high-risk individuals who underwent CRC screening were included, comprising 13 advanced adenomas (Aade), 5 CRC, 59 non-advanced adenomas (Nade), 129 colon polyps (Pol), 99 cases of colorectal inflammatory disease (Inf), and 224 normal controls (Nor). 16S rRNA gene sequencing was used to profile the intestinal microbiota communities. The Gut Microbiota Health Index (GMHI) and average variation degree (AVD) were employed to assess the health status of the different groups.

Our findings revealed that the Nor group exhibited significantly higher GMHIs and the lowest AVD compared to the four Lesion groups. The model incorporating 13 bacterial genera demonstrated optimal efficacy in distinguishing CRC and Aade from Nor, with an area under the curve (AUC) of 0.81 and a 95% confidence interval (CI) of 0.72 to 0.89. Specifically, the 55 bacterial genera combination model exhibited superior performance in differentiating CRC from Nor (AUC 0.98; 95% CI, 0.96-1), the 25 bacterial genera combination showed superior performance in distinguishing Aade from Nor (AUC 0.95). Additionally, the 27 bacterial genera combination demonstrated superior efficacy in differentiating Nade from Nor (AUC 0.82). The 13 bacterial genera combination exhibited optimal performance in distinguishing Inf from Nor (AUC 0.71).

Our study has identified specific microbial biomarkers that can differentiate between colorectal lesions and healthy individuals. The intestinal microbiota markers identified may serve as valuable tools in community-based CRC screening programs.

Colorectal cancer (CRC) involves uncontrolled cell growth in the colon and rectum. This study aims to explore the prevalence of key pathogenic bacteria and their role in the progression of CRC, focusing on microbial dysbiosis. This study analyzed 52 stool and tissue samples through polymerase chain reaction (PCR), real-time PCR, and bioinformatics to identify associations between pathogenic bacteria and CRC progression. PCR results revealed a significant association between the Bacteroides fragilis toxin (bft) gene and CRC progression (P = 0.001, r = 0.570). Furthermore, Real-time PCR showed significant differences in the frequency of pks+Escherichia coli in CRC stages 1 (P = 0.03), 2 (P = 0.004), and 3 (P = 0.0002) compared to the control group. Additionally, the frequency of Fusobacterium nucleatum in stage 3 CRC patients was significantly higher than in the control group (P = 0.004) and stage 1 patients (P = 0.01). Furthermore, Streptococcus gallolyticus showed similar significant differences in stage 3 patients (P = 0.004). Bioinformatics analyses using KEGG, Reactome, STRING, and dbSNP highlighted bacteria's roles in colorectal carcinogenesis, emphasizing the need for early identification and management in CRC treatment and prevention strategies. Finally, due to the limitations of the study, the use of more advanced methods and the validation of results through more reliable techniques are essential for future research.

Colorectal cancer (CRC) is the second most common cause of cancer-related deaths globally. The gut microbiota, along with adenomatous polyps (AP), has emerged as a plausible contributor to CRC progression. This study aimed to scrutinize the impact of the FadA antigen derived from Fusobacterium nucleatum on the expression levels of the ANXA2 ceRNA network and assess its relevance to CRC advancement.

The functions of ANXA2 and LINC00460 in CRC have been partially clarified. According to our previous study to identify shared MicroRNA-Interaction-Targets (MITs) between ANXA2 and LINC00460, TargetScanHuman (V7.2) and miRDB databases have been used respectively. The Bioinformatics and Evolutionary Genomics web tool was employed to intersect the sets of shared microRNAs and their common targets. Then, the ANXA2 ceRNA network was constructed. Subsequently, the mRNA, miRNA, and lncRNA expression levels were examined in intestinal biopsy specimens from 30 healthy controls, 30 Adenoma patients, and 30 cases of CRC stage I using qRT-PCR.

Elevated expression levels of FadA, ANXA2, hsa-let-7a-2, and LINC00460 were observed in CRC specimens, followed by AP cases, in comparison to samples from normal individuals. Application of the Spearman test revealed a strong and significant correlation between FadA and LINC00460 (rS = 0.9311, p < 0.0001). Also, the functional analysis of ANXA2 revealed its impact on CRC progression through JAK-STAT and Hippo signaling pathways.

FadA appears to potentiate CRC progression by inducing the upregulation of LINC00460, consequently leading to the hyperexpression of ANXA2 through the ceRNA network.

The current understanding of colorectal carcinogenesis is based on the adenoma-carcinoma sequence, where genetics, intestinal microbiota changes and local immunity shifts seem to play the key roles. Despite the emerging evidence of dysbiotic intestinal state and immune-cell infiltration changes in patients with colorectal adenocarcinoma, early and advanced adenoma as precursors of colorectal cancer, and carcinoma in situ as the following progression, are rather less studied. The newly colon-site adapted AI-based analysis of immune infiltrates is able to predict long-term outcomes of colon carcinoma. Though it could also facilitate the pathologic evaluation of precancerous lesion's potential to progress. Therefore, the purpose of this prospective cohort study (MIMICA-1) is, firstly, to identify the intestinal microbiota and immune infiltration patterns around the normal bowel tissue, early and advanced adenoma, carcinoma in situ, and adenocarcinoma, and secondly, to analyze the immune - microbiome interplay along the steps of conventional colorectal tumorigenesis.

This study aims to prospectively recruit 40 patients (10 per group) with confirmed colorectal dysplasia undergoing endoscopic polypectomy, endoscopic mucosal resection for colorectal small (≤1cm), and large (>1cm) adenoma or carcinoma in situ, or biopsy and subsequent colon resection for invasive colorectal cancer, and 10 healthy patients undergoing screening colonoscopy. Stool samples will be collected prior to bowel preparation for the analysis of fecal (luminal) microbiota composition. Biopsy specimens will be taken from the terminal ileum, right colon, left colon, and a pathological lesion in the colon (if present) to assess mucosa-associated microbiota composition and intestinal immunity response. DNA will be extracted from all samples and sequenced using the Illumina MiSeq platform. Unifrac and Bray-Curtis methods will be used to assess microbial diversity. The intestinal immune system response will be examined using digital image analysis where primarily immunohistochemistry procedures for CD3, CD8, CD20 and CD68 immune cell markers will be performed. Thereafter, the count, density and distribution of immunocompetent cells in epithelial and stromal tissue compartments will be evaluated using AI-based platform. The interaction between the microbial shifts and intestinal immune system response in adenoma-carcinoma sequence and the healthy patients will be examined. In addition, fecal samples will be explored for gut microbiota's composition, comparing fecal- and tissue-derived bacterial patterns in healthy gut and along the adenoma-carcinoma sequence.

We hypothesize that changes within the human gut microbiota led to detectable alterations of the local immune response and correlate with the progression from normal mucosa to colorectal adenoma and invasive carcinoma. It is expectable to find more severe gut immune infiltration at dysplasia site, though analyzing invasive colorectal cancer we expect to detect broader mucosa-associated and luminal microbiota changes with subsequent local immune response at near-lesion site and possibly throughout the entire colon. We believe that specific compositional differences detected around premalignant colorectal lesions are critically important for its primary role in initiation and acceleration of colorectal carcinogenesis. Thus, these microbial patterns could potentially supplement fecal immunohistochemical tests for the early non-invasive detection of colorectal adenoma. Moreover, AI-based analysis of immune infiltrates could become additional diagnostic and prognostic tool in precancerous lesions prior to the development of colorectal cancer.

The study is registered at the Australian New Zealand Clinical Trials Registry (ACTRN12624000976583) https://www.anzctr.org.au/.

16S rRNA gene sequencing is commonly used for identification and quantitation of microorganisms in complex biological mixtures, such as the human gut microbiome. The 16S rRNA gene is an excellent target gene for sequencing DNA in a heterogenous sample, as it is a highly conserved part of the transcriptional machinery. Universal PCR primers are used to amplify the conserved regions of 16S. Thus, it is possible to amplify the gene in a wide range of different microorganisms from a single sample. As the 16S rRNA gene consists of both conserved and variable regions, sequencing of the variable regions can be used to differentiate between different bacterial species.

Fecal immunochemical test (FIT) followed by colonoscopy in positive cases is commonly used for population-based colorectal cancer screening. However, specificity of FIT for colorectal cancer is not ideal and has poor performance for advanced adenoma detection. Fecal Fusobacterium nucleatum (Fn) detection has been proposed as a potential noninvasive biomarker for colorectal cancer and advanced adenoma detection. We aimed to evaluate the diagnostic performance of Fn detection using droplet digital PCR (ddPCR) in FIT samples from individuals enrolled in a colorectal cancer screening program with colorectal adenoma or cancer. We evaluated Fn presence in DNA isolated from FIT leftover material of 300 participants in a colorectal cancer screening program using ddPCR. The Fn DNA amount was classified as Fn-low/negative and Fn-high, and the association with patients' clinicopathological features and accuracy measurements was calculated. Fn-high levels were more prevalent in FIT-positive (47.2%, n = 34 of 72) than FIT-negative samples (28.9%, n = 66 of 228; P < 0.04). Among FIT-positive samples, high Fn levels were significantly more frequent in patients with cancer (CA, n = 8) when compared to normal (NT, n = 16; P = 0.02), non-advanced adenomas (NAA, n = 36; P = 0.01), and advanced adenomas (AA, n = 12; P = 0.01). Performance analysis of Fn in FIT-positive samples for colorectal cancer detection yielded an AUC of 0.8203 [confidence interval (CI), 0.6464-0.9942], with high sensitivity (100%) and specificity of 50%. Concluding, we showed the feasibility of detecting Fn in FIT leftovers using the ultrasensitive ddPCR technique. Furthermore, we highlighted the potential use of Fn levels in fecal samples to ameliorate colorectal cancer detection. Prevention Relevance: Fusobacterium nucleatum detection by droplet digital PCR could prioritize the selection of fecal immunochemical test-positive individuals who might benefit the most from the colonoscopy procedure.

Colorectal polyps that develop via the conventional adenoma-carcinoma sequence [e.g., tubular adenoma (TA)] often progress to malignancy and are closely associated with changes in the composition of the gut microbiome. There is limited research concerning the microbial functions and gut microbiomes associated with colorectal polyps that arise through the serrated polyp pathway, such as hyperplastic polyps (HP). Exploration of microbiome alterations associated with HP and TA would improve the understanding of mechanisms by which specific microbes and their metabolic pathways contribute to colorectal carcinogenesis.

To investigate gut microbiome signatures, microbial associations, and microbial functions in HP and TA patients.

Full-length 16S rRNA sequencing was used to characterize the gut microbiome in stool samples from control participants without polyps [control group (CT), n = 40], patients with HP (n = 52), and patients with TA (n = 60). Significant differences in gut microbiome composition and functional mechanisms were identified between the CT group and patients with HP or TA. Analytical techniques in this study included differential abundance analysis, co-occurrence network analysis, and differential pathway analysis.

Colorectal cancer (CRC)-associated bacteria, including Streptococcus gallolyticus (S. gallolyticus), Bacteroides fragilis, and Clostridium symbiosum, were identified as characteristic microbial species in TA patients. Mediterraneibacter gnavus, associated with dysbiosis and gastrointestinal diseases, was significantly differentially abundant in the HP and TA groups. Functional pathway analysis revealed that HP patients exhibited enrichment in the sulfur oxidation pathway exclusively, whereas TA patients showed dominance in pathways related to secondary metabolite biosynthesis (e.g., mevalonate); S. gallolyticus was a major contributor. Co-occurrence network and dynamic network analyses revealed co-occurrence of dysbiosis-associated bacteria in HP patients, whereas TA patients exhibited co-occurrence of CRC-associated bacteria. Furthermore, the co-occurrence of SCFA-producing bacteria was lower in TA patients than HP patients.

This study revealed distinct gut microbiome signatures associated with pathways of colorectal polyp development, providing insights concerning the roles of microbial species, functional pathways, and microbial interactions in colorectal carcinogenesis.

Colorectal cancer (CRC) arises from complex interactions between host and environment, which include the gut and tissue microbiome. It is hypothesized that epigenetic regulation by gut microbiota is a fundamental interface by which commensal microbes dynamically influence intestinal biology. The aim of this study is to explore the interplay between gut and tissue microbiota and host DNA methylation in CRC.

Metagenomic sequencing of fecal samples was performed on matched CRC patients (n = 18) and healthy controls (n = 18). Additionally, tissue microbiome was profiled with 16S rRNA gene sequencing on tumor (n = 24) and tumor-adjacent normal (n = 24) tissues of CRC patients, while host DNA methylation was assessed through whole-genome bisulfite sequencing (WGBS) in a subset of 13 individuals.

Our analysis revealed substantial alterations in the DNA methylome of CRC tissues compared to adjacent normal tissues. An extensive meta-analysis, incorporating publicly available and in-house data, identified significant shifts in microbial-derived methyl donor-related pathways between tumor and adjacent normal tissues. Of note, we observed a pronounced enrichment of microbial-associated CpGs within the promoter regions of genes in adjacent normal tissues, a phenomenon notably absent in tumor tissues. Furthermore, we established consistent and recurring associations between methylation patterns of tumor-related genes and specific bacterial taxa.

This study emphasizes the pivotal role of the gut microbiota and pathogenic bacteria in dynamically shaping DNA methylation patterns, impacting physiological homeostasis, and contributing to CRC tumorigenesis. These findings provide valuable insights into the intricate host-environment interactions in CRC development and offer potential avenues for therapeutic interventions in this disease.

Colorectal cancer (CRC) is a common malignant tumor that occurs in the colon. Gut microbiota is a complex ecosystem that plays an important role in the pathogenesis of CRC. Our previous studies showed that the soluble dietary fiber of foxtail millet (FMB-SDF) exhibited significant antitumor activity in vitro. The present study evaluated the anticancer potential of FMB-SDF in the azoxymethane (AOM)- and dextran sodium sulfate (DSS)-induced mouse CRC models. The results showed that FMB-SDF could significantly alleviate colon cancer symptoms in mice. Further, we found that FMB-SDF consumption significantly altered gut microbiota diversity and the overall structure and regulated the abundance of some microorganisms in CRC mice. Meanwhile, KEGG pathway enrichment showed that FMB-SDF can also alleviate the occurrence of colon cancer in mice by regulating certain cancer-related signaling pathways. In conclusion, our findings may provide a novel approach for the prevention and biotherapy of CRC.

Pancreatic cancer (PC) ranks as the seventh leading cause of cancer-related deaths, with approximately 500,000 new cases reported in 2020. Existing strategies for early PC detection primarily target individuals at high risk of developing the disease. Nevertheless, there is a pressing need to identify innovative clinical approaches and personalized treatments for effective PC management. This study aimed to explore the dysbiosis signature of the fecal microbiota in PC and potential distinctions between its Intraductal papillary mucinous neoplasm (IPMN) and pancreatic ductal adenocarcinoma (PDAC) phenotypes, which could carry diagnostic significance. The study enrolled 33 participants, including 22 diagnosed with PDAC, 11 with IPMN, and 24 healthy controls. Fecal samples were collected and subjected to microbial diversity analysis across various taxonomic levels. The findings revealed elevated abundances of Firmicutes and Proteobacteria in PC patients, whereas healthy controls exhibited higher proportions of Bacteroidota. Both LEfSe and Random Forest analyses indicated the microbiome's potential to effectively distinguish between PC and healthy control samples but fell short of differentiating between IPMN and PDAC samples. These results contribute to the current understanding of this challenging cancer type and highlight the applications of microbiome research. In essence, the study provides clear evidence of the gut microbiome's capability to serve as a biomarker for PC detection, emphasizing the steps required for further differentiation among its diverse phenotypes.

Colorectal cancer (CRC) poses a significant healthcare challenge, accounting for nearly 6.1% of global cancer cases. Early detection, facilitated by population screening utilizing innovative biomarkers, is pivotal for mitigating CRC incidence. This study aims to scrutinize the fecal and salivary microbiomes of CRC-positive individuals (CPs) in comparison to CRC-negative counterparts (CNs) to enhance early CRC diagnosis through microbial biomarkers.

A total of 80 oral and stool samples were collected from Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, encompassing both CPs and CNs undergoing screening. Microbial profiling was conducted using 16S rRNA sequencing assays, employing the Nextera XT Index Kit on an Illumina NovaSeq platform.

Distinct microbial profiles were observed in saliva and stool samples of CPs, diverging significantly from those of CNs at various taxonomic levels, including phylum, family, and species. Saliva samples from CPs exhibited abundance of Calothrix parietina, Granulicatella adiacens, Rothia dentocariosa, and Rothia mucilaginosa, absent in CNs. Additionally, Lachnospiraceae and Prevotellaceae were markedly higher in CPs' feces, while the Fusobacteria phylum was significantly elevated in CPs' saliva. Conversely, the non-pathogenic bacterium Akkermansia muciniphila exhibited a significant decrease in CPs' fecal samples compared to CNs.

Through meticulous selection of saliva and stool microbes based on Mean Decrease GINI values and employing logistic regression for saliva and support vector machine models for stool, we successfully developed a microbiota test with heightened sensitivity and specificity for early CRC detection.

Background: Colorectal cancer is the second cause of cancer mortality and the third most commonly diagnosed cancer worldwide. Current data available implicate epigenetic modulations in colorectal cancer development. The health of the large bowel is impacted by gut microbiome dysbiosis, which may lead to colon and rectum cancers. The release of microbial metabolites and toxins by these microbiotas has been shown to activate epigenetic processes leading to colorectal cancer development. Increased consumption of a 'Westernized diet' and certain lifestyle factors such as excessive consumption of alcohol have been associated with colorectal cancer.Purpose: In this review, we seek to examine current knowledge on the involvement of gut microbiota, dietary factors, and alcohol consumption in colorectal cancer development through epigenetic modulations.Methods: A review of several published articles focusing on the mechanism of how changes in the gut microbiome, diet, and excessive alcohol consumption contribute to colorectal cancer development and the potential of using these factors as biomarkers for colorectal cancer diagnosis.Conclusions: This review presents scientific findings that provide a hopeful future for manipulating gut microbiome, diet, and alcohol consumption in colorectal cancer patients' management and care.

Serrated lesions are histologically heterogeneous, and detection can be challenging as these lesions have subtle features that may be missed by endoscopy. Furthermore, while approximately 30% of colorectal cancers (CRCs) arise from serrated lesions, only 8-10% of invasive serrated CRCs exhibit serrated morphology at presentation, suggesting potential loss of apparent characteristics with increased malignancy. Thus, understanding the genetic basis driving serrated CRC initiation and progression is critical to improve diagnosis and identify therapeutic biomarkers and targets to guide disease management. This review discusses the preclinical models of serrated CRCs reported to date and how these systems have been used to provide mechanistic insights into tumor initiation, progression, and novel treatment targets.

Colorectal cancer (CRC) is one of the most diagnosed cancers worldwide, with a high incidence and mortality rate when diagnosed late. Currently, the methods used in healthcare to diagnose CRC are the fecal occult blood test, flexible sigmoidoscopy, and colonoscopy. However, the lack of sensitivity and specificity and low population adherence are driving the need to implement other technologies that can identify biomarkers that not only help with early CRC detection but allow for the selection of more personalized treatment options. In this regard, the implementation of omics technologies, which can screen large pools of biological molecules, coupled with molecular validation, stands out as a promising tool for the discovery of new biomarkers from biopsied tissues or body fluids. This review delves into the current state of the art in the identification of novel CRC biomarkers that can distinguish cancerous tissue, specifically from fecal samples, as this could be the least invasive approach.

Colorectal cancer (CRC) is one of the primary causes of cancer-associated deaths worldwide, and growing evidence shows that alteration in the gut microbiota may be a contributing factor to the development and progression of the disease. This study investigates the correlation between CRC and specific intestinal microbiota abundance, including Firmicutes, Lactobacillus, Enterococcus, Clostridium, and Bifidobacterium.

In this study, 100 CRC samples and adjacent normal tissues were obtained from Iranian patients. Afterward, we assessed the abundance of the mentioned bacteria in matched tumor and normal tissue samples from 100 CRC patients, by TaqMan quantitative real-time polymerase chain reaction (qPCR).

Most of the patients (55 %) had grade II cancer (moderately differentiated), followed by grade III (poorly Differentiated) in 19 %, and the distribution of the tumor location was 65 % in the colon and 35 % in the rectum. Our research showed a substantial difference in the relative abundance of specific bacteria in tumors and healthy tissues. To this end, four genera of bacteria, including Bifidobacterium, Lactobacillus, Clostridium, and Firmicutes, exhibited statistically significant reductions in tumor tissues compared to adjacent normal tissue (p < 0.05). Conversely, Enterococcus demonstrated a statistically significant increase in tumor tissue samples (p < 0.05). Noteworthy, statistical analysis revealed a significant relationship between Enterococcus and prior cancer (p < 0.05).

These findings provide significant insight into the complex association between the gut microbiota and CRC and may pave the way for future research on novel screening methods, preventive measures, and therapeutic strategies targeting the gut microbiota in CRC patients.

Numerous studies have correlated dysbiosis in stool microbiota with colorectal cancer (CRC); however, fewer studies have investigated the mucosal microbiome in pre-cancerous bowel polyps. The short-read sequencing of variable regions in the 16S rRNA gene has commonly been used to infer bacterial taxonomy, and this has led, in part, to inconsistent findings between studies. Here, we examined mucosal microbiota from patients who presented with one or more polyps, compared to patients with no polyps, at the time of colonoscopy. We evaluated the results obtained using both short-read and PacBio long-read 16S rRNA sequencing. Neither sequencing technology identified significant differences in microbial diversity measures between patients with or without bowel polyps. Differential abundance measures showed that amplicon sequence variants (ASVs) associated with Ruminococcus gnavus and Escherichia coli were elevated in mucosa from polyp patients, while ASVs associated with Parabacteroides merdae, Veillonella nakazawae, and Sutterella wadsworthensis were relatively decreased. Only R. gnavus was consistently identified using both sequencing technologies as being altered between patients with polyps compared to patients without polyps, suggesting differences in technologies and bioinformatics processing impact study findings. Several of the differentially abundant bacteria identified using either sequencing technology are associated with inflammatory bowel diseases despite these patients being excluded from the current study, which suggests that early bowel neoplasia may be associated with a local inflammatory niche.

In recent years, several studies have suggested a strong association of microorganisms with several human cancers. Two periodontopathogenic species in particular have been mentioned frequently: Fusobacterium nucleatum (F. nucleatum) and Porphyromonas gingivalis. Chronic periodontal disease has been reported to be a risk factor for oral squamous cell carcinoma (OSCC), colorectal cancer (CRC) and pancreatic cancer. F. nucleatum is a Gram-negative anaerobic bacterium that lives in the oral cavity, urogenital, intestinal and upper digestive tract. It plays a significant role as a co-aggregation factor, with almost all bacterial species that participate in oral plaque formation acting as a bridge between early and late colonizers. F. nucleatum, gives an important inflammatory contribution to tumorigenesis progression and is associated with epithelial-derived malignancies, such as OSCC and CRC. F. nucleatum produces an adhesion protein, FadA, which binds to VE-cadherin on endothelial cells and to E-cadherins on epithelial cells. The last binding activates oncogenic pathways, such as Wnt/βcatenin, in oral and colorectal carcinogenesis. F. nucleatum also affects immune response because its Fap2 protein interacts with an immune receptor named TIGIT present on some T cells and natural killer cells inhibiting immune cells activities. Morover, F. nucleatum release outer membrane vesicles (OMVs), which induce the production of proinflammatory cytokines and initiating inflammation. F. nucleatum migrates from the oral cavity and reaches the colon hematogenously but it is not known if in the bloodstream it reaches the CRC as free, erythrocyte-bound bacteria or in OMV. F. nucleatum abundance in CRC tissue has been inversely correlated with overall survival (OS). The prevention and treatment of periodontal disease through the improvement of oral hygiene should be included in cancer prevention protocols. FadA virulence factors may also serve as novel targets for therapeutic intervention of oral and colorectal cancer.

Colorectal cancer (CRC) is one of the most common cancers all over the world, and dysbiosis in the gut microbiota may play a role in colorectal carcinogenesis. Bacteroides fragilis can lead to tumorigenesis by changing signaling pathways, including the WNT/β-catenin pathway. Therefore, in the present study, we investigated the correlation between the enterotoxigenic B. fragilis amount and the expression of signaling pathway genes involved in CRC.

B. fragilis was determined in 30 tumors and adjacent healthy tissues by the qPCR method. Next, the relationship between enterotoxigenic B. fragilis and the expression of signaling pathway genes, including CCND1, TP53, BCL2, BAX, WNT, TCF, AXIN, APC, and CTNNB1 was investigated. Additionally, possible correlations between clinicopathological features of the tumor samples and the abundance of B. fragilis were analyzed.

The results showed that B. fragilis was detected in 100% of tumor samples and 86% of healthy tissues. Additionally, enterotoxigenic B. fragilis colonized 47% of all samples, and bft-1 toxin was the most frequently found isotype among the samples. The analysis showed that the high level of B. fragilis has a significant relationship with the high expression of AXIN, CTNNB1, and BCL2 genes. On the other hand, our results did not show any possible correlation between this bacterium and the clinicopathological features of the tumor sample.

B. fragilis had a higher abundance in the tumor samples than in healthy tissues, and this bacterium may lead to CRC by making changes in cellular signaling pathways and genes. Therefore, to better understand the physiological effects of B. fragilis on the inflammatory response and CRC, future research should focus on dissecting the molecular mechanisms by which this bacterium regulates cellular signaling pathways.

Digestive system diseases have evolved into a growing global burden without sufficient therapeutic measures. Lactobacillus reuteri (L. reuteri) is considered as a new potential economical therapy for its probiotic effects in the gastrointestinal system. We have provided an overview of the researches supporting various L. reuteri strains' application in treating common digestive system diseases, including infantile colic, diarrhea, constipation, functional abdominal pain, Helicobacter pylori infection, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases.

The summarized literature in this review was derived from databases including PubMed, Web of Science, and Google Scholar.

The therapeutic effects of L. reuteri in digestive system diseases may depend on various direct and indirect mechanisms, including metabolite production as well as modulation of the intestinal microbiome, preservation of the gut barrier function, and regulation of the host immune system. These actions are largely strain-specific and depend on the activation or inhibition of various certain signal pathways. It is well evidenced that L. reuteri can be effective both as a prophylactic measure and as a preferred therapy for infantile colic, and it can also be recommended as an adjuvant strategy to diarrhea, constipation, Helicobacter pylori infection in therapeutic settings. While preclinical studies have shown the probiotic potential of L. reuteri in the management of functional abdominal pain, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases, its application in these disease settings still needs further study.

This review focuses on the probiotic effects of L. reuteri on gut homeostasis via certain signaling pathways, and emphasizes the importance of these probiotics as a prospective treatment against several digestive system diseases.

Colorectal cancer (CRC) is the most common cancer of the digestive system with high mortality and morbidity rates. Gut microbiota is found in the intestines, especially the colorectum, and has structured crosstalk interactions with the host that affect several physiological processes. The gut microbiota include CRC-promoting bacterial species, such as Fusobacterium nucleatum, Escherichia coli, and Bacteroides fragilis, and CRC-protecting bacterial species, such as Clostridium butyricum, Streptococcus thermophilus, and Lacticaseibacillus paracasei, which along with other microorganisms, such as viruses and fungi, play critical roles in the development of CRC. Different bacterial features are identified in patients with early-onset CRC, combined with different patterns between fecal and intratumoral microbiota. The gut microbiota may be beneficial in the diagnosis and treatment of CRC; some bacteria may serve as biomarkers while others as regulators of chemotherapy and immunotherapy. Furthermore, metabolites produced by the gut microbiota play essential roles in the crosstalk with CRC cells. Harmful metabolites include some primary bile acids and short-chain fatty acids, whereas others, including ursodeoxycholic acid and butyrate, are beneficial and impede tumor development and progression. This review focuses on the gut microbiota and its metabolites, and their potential roles in the development, diagnosis, and treatment of CRC.

While colorectal polyps are not cancerous, some types of polyps, known as adenomas, can develop into colorectal cancer over time. Polyps can often be found and removed by colonoscopy; however, this is an invasive and expensive test. Thus, there is a need for new methods of screening patients at high risk of developing polyps.

To identify a potential association between colorectal polyps and small intestine bacteria overgrowth (SIBO) or other relevant factors in a patient cohort with lactulose breath test (LBT) results.

A total of 382 patients who had received an LBT were classified into polyp and non-polyp groups that were confirmed by colonoscopy and pathology. SIBO was diagnosed by measuring LBT-derived hydrogen (H) and methane (M) levels according to 2017 North American Consensus recommendations. Logistic regression was used to assess the ability of LBT to predict colorectal polyps. Intestinal barrier function damage (IBFD) was determined by blood assays.

H and M levels revealed that the prevalence of SIBO was significantly higher in the polyp group than in the non-polyp group (41% vs 23%, P < 0.01; 71% vs 59%, P < 0.05, respectively). Within 90 min of lactulose ingestion, the peak H values in the adenomatous and inflammatory/hyperplastic polyp patients were significantly higher than those in the non-polyp group (P < 0.01, and P = 0.03, respectively). In 227 patients with SIBO defined by combining H and M values, the rate of IBFD determined by blood lipopolysaccharide levels was significantly higher among patients with polyps than those without (15% vs 5%, P < 0.05). In regression analysis with age and gender adjustment, colorectal polyps were most accurately predicted with models using M peak values or combined H and M values limited by North American Consensus recommendations for SIBO. These models had a sensitivity of ≥ 0.67, a specificity of ≥ 0.64, and an accuracy of ≥ 0.66.

The current study made key associations among colorectal polyps, SIBO, and IBFD and demonstrated that LBT has moderate potential as an alternative noninvasive screening tool for colorectal polyps.

The role of the human gut microbiome in colorectal cancer (CRC) is unclear as most studies on the topic are unable to discern correlation from causation. We apply two-sample Mendelian randomization (MR) to estimate the causal relationship between the gut microbiome and CRC. We used summary-level data from independent genome-wide association studies to estimate the causal effect of 14 microbial traits (n = 3890 individuals) on overall CRC (55,168 cases, 65,160 controls) and site-specific CRC risk, conducting several sensitivity analyses to understand the nature of results. Initial MR analysis suggested that a higher abundance of Bifidobacterium and presence of an unclassified group of bacteria within the Bacteroidales order in the gut increased overall and site-specific CRC risk. However, sensitivity analyses suggested that instruments used to estimate relationships were likely complex and involved in many potential horizontal pleiotropic pathways, demonstrating that caution is needed when interpreting MR analyses with gut microbiome exposures. In assessing reverse causality, we did not find strong evidence that CRC causally affected these microbial traits. Whilst our study initially identified potential causal roles for two microbial traits in CRC, importantly, further exploration of these relationships highlighted that these were unlikely to reflect causality.

Alterations in gut microbiota play a pivotal role in the adenoma-carcinoma sequence. However, there is still a notable lack of the correct implementation of tissue and fecal sampling in the setting of human gut microbiota examination. This study aimed to review the literature and to consolidate the current evidence on the use of mucosa and a stool-based matrix investigating human gut microbiota changes in precancerous colorectal lesions. A systematic review of papers from 2012 until November 2022 published on the PubMed and Web of Science databases was conducted. The majority of the included studies have significantly associated gut microbial dysbiosis with premalignant polyps in the colorectum. Although methodological differences hampered the precise fecal and tissue-derived dysbiosis comparison, the analysis revealed several common characteristics in stool-based and fecal-derived gut microbiota structures in patients with colorectal polyps: simple or advanced adenomas, serrated lesions, and carcinomas in situ. The mucosal samples considered were more relevant for the evaluation of microbiota's pathophysiological involvement in CR carcinogenesis, while non-invasive stool sampling could be beneficial for early CRC detection strategies in the future. Further studies are required to identify and validate mucosa-associated and luminal colorectal microbial patterns and their role in CRC carcinogenesis, as well as in the clinical setting of human microbiota studies.

Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. Once limited to older populations, the incidence of CRC in patients under the age of 50 years is increasing and the etiology for this is uncertain. One hypothesis lies on the impact of the intestinal microbiome. The intestinal microbiome, composed primarily of bacteria but also viruses, fungi, and archaea, has been shown to regulate CRC development and progression both in vitro and in vivo. In this review, the role and intersection of the bacterial microbiome in various stages of clinical CRC development and management are discussed beginning with CRC screening. Various mechanisms whereby the microbiome has been shown to modulate CRC development including the influence of diet on the microbiome, bacterial-induced injury to the colonic epithelium, bacterial-produced toxins, and alteration of normal cancer immunosurveillance by the microbiome are discussed. Finally, the influence of microbiome on the response of CRC to treatment is discussed while highlighting ongoing clinical trials. The complexities of the microbiome and its role in CRC development and progression have become apparent and will require ongoing commitment to translate laboratory findings into meaningful clinical results that will aid more than 150,000 patients that develop CRC every year.

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 (P < 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 (P < 0.05). Based on the LEfSe analysis, the abundances of Bacteroides, Prevotella-2 and Agathobacter were higher, whereas the abundances of Haemophilus, Escherichia_Shigella, Fusobacterium and Streptococcus 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 Fusobacterium was significantly higher in the normal colorectal mucosa than in faeces. Moreover, there was no significant difference in the abundance of Fusobacterium 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 Fusobacterium 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, Fusobacterium may be a normal colonizer in colonic mucosa, and an abnormal increase of Fusobacterium 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 a common cancer with an increasing incidence worldwide. The implementation of a mass screening program has been proven effective in reducing the global burden of CRC, but its effectiveness is not ideal and some metabolic derangements and lifestyle factors were reported to be attributable for such a deficit. Implementing positive lifestyle intervention as primary prevention therefore becomes critical because colorectal carcinogenesis can be promoted by several lifestyle factors, such as a lack of physical activity. Herein, we review the current evidence on the association and possible mechanisms between physical activity and CRC carcinogenesis. In addition, since CRC prevention heavily relies on resection of precancerous polyps and subsequent surveillance by colonoscopy, this review will also explore the impact of physical activity on populations with different colorectal polyp risks and its potential adjunct role in altering surveillance outcomes.

The microbiome has been implicated in the initiation and progression of colorectal cancer (CRC) in cross-sectional studies. However, there is a lack of studies using prospectively collected samples.

From the Norwegian Colorectal Cancer Prevention (NORCCAP) trial, we analyzed 144 archived fecal samples from participants who were diagnosed with CRC or high-risk adenoma (HRA) at screening and from participants who remained cancer-free during 17 years of follow-up. We performed 16S rRNA sequencing of all the samples and metagenome sequencing on a subset of 47 samples. Differences in taxonomy and gene content between outcome groups were assessed for alpha and beta diversity and differential abundance.

Diversity and composition analyses showed no significant differences between CRC, HRA, and healthy controls. Phascolarctobacterium succinatutens was more abundant in CRC compared with healthy controls in both the 16S and metagenome data. The abundance of Bifidobacterium and Lachnospiraceae spp. was associated with time to CRC diagnosis.

Using a longitudinal study design, we identified three taxa as being potentially associated with CRC. These should be the focus of further studies of microbial changes occurring prior to CRC diagnosis.