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 adenomas (CRA) are the primary precancerous lesions leading to colorectal cancer (CRC). Early detection and intervention of CRA can significantly reduce the incidence of CRC. We investigated the relationships between the gut microbiome and the expression levels of PD-L1, IL-6, and IFN-γ at different CRA stages.

Participants were divided into normal, non-advanced adenoma (NAA), and advanced adenoma (AA) groups. PD-L1 expression in collected tissues was analyzed via immunohistochemistry (IHC) and Western blotting. Serum IL-6 and IFN-γ levels were measured using Enzyme-Linked Immunosorbent Assay (ELISA). 16S rRNA gene sequencing was used to examine gut microbiota changes, with correlation analysis to assess microbial influences on CRA progression.

The main differences in bacterial composition among the three groups were found within the Firmicutes and Bacteroidetes phyla. In the normal vs. NAA comparison, Clostridium sensu stricto, Faecalimonas, Gemmiger, and Ruminococcus were more abundant in the normal group, while Solobacterium was enriched in the NAA group. For the normal vs. AA comparison, the normal group was enriched with Anaerostipes, Blautia, Clostridium sensu stricto, Intestinibacter, Phocaeicola, and Turicibacter, whereas Solobacterium was more abundant in the AA group. In the NAA vs. AA comparison, the NAA group exhibited higher levels of Blautia, Faecalimonas, and Turicibacter relative to the AA group. Anaerostipes and Blautia are positively correlated with taurine and hypotaurine metabolism, propanoate metabolism, and zeatin biosynthesis. PD-L1 protein levels progressively increase with CRA advancement. Additionally, Faecalimonas, and Solobacterium were negatively associated with IFN-γ, while Gemmiger, and Anaerostipes were positively associated with IL-6.

This study highlights the dynamic alterations in gut microbiota composition and their potential influence on the regulation of inflammatory cytokines and PD-L1 expression during CRA progression. The enrichment of protective taxa, such as Anaerostipes and Blautia, in the normal group emphasizes their potential role in mitigating adenoma progression. Dietary modulation to promote the proliferation of these beneficial bacteria could serve as a promising strategy to improve colorectal health. Future research should further explore the specific relationships between dietary components, gut microbiota, and metabolic pathways, and assess the effects of dietary interventions on gut health.

Colorectal cancer (CRC) is one of the most prevalent forms of cancer globally. The human gut microbiome plays an important role in the development of CRC and serves as a biomarker for early detection and treatment. This research effort focuses on the identification of potential taxonomic biomarkers of CRC using a grouping-based feature selection method. Additionally, this study investigates the effect of incorporating biological domain knowledge into the feature selection process while identifying CRC-associated microorganisms. Conventional feature selection techniques often fail to leverage existing biological knowledge during metagenomic data analysis. To address this gap, we propose taxonomy-based Grouping Scoring Modeling (G-S-M) method that integrates biological domain knowledge into feature grouping and selection. In this study, using metagenomic data related to CRC, classification is performed at three taxonomic levels (genus, family and order). The MetaPhlAn tool is employed to determine the relative abundance values of species in each sample. Comparative performance analyses involve six feature selection methods and four classification algorithms. When experimented on two CRC associated metagenomics datasets, the highest performance metric, yielding an AUC of 0.90, is observed at the genus taxonomic level. At this level, 7 out of top 10 groups (Parvimonas, Peptostreptococcus, Fusobacterium, Gemella, Streptococcus, Porphyromonas and Solobacterium) were commonly identified for both datasets. Moreover, the identified microorganisms at genus, family, and order levels are thoroughly discussed via refering to CRC-related metagenomic literature. This study not only contributes to our understanding of CRC development, but also highlights the applicability of taxonomy-based G-S-M method in tackling various diseases.

Experimental research has uncovered lipocalin 2 (LCN2) as a novel biomarker implicated in the modulation of intestinal inflammation, metabolic homeostasis, and colon carcinogenesis. However, evidence from human research has been scant. We, therefore, explored the association of pre-diagnostic circulating LCN2 concentrations with incident colorectal cancer (CRC) in a nested case-control study within the in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. LCN2 was measured in 1267 incident CRC cases matched to 1267 controls using incidence density sampling. Conditional logistic regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) according to tumor subsite and sex. Weighted Cox proportional hazard regression was used to explore associations by adiposity status. In multivariable-adjusted analyses, the IRR [95% CI] per doubling in LCN2 concentration was 1.16 [0.98-1.37] for CRC overall, 1.26 [1.00-1.59] for colon cancer, and 1.08 [0.85-1.38] for rectal cancer. The association for colon cancer was more pronounced in women (IRR [95% CI], 1.66 [1.20-2.30]) and for proximal colon cancer (IRR [95% CI], 1.96 [1.15-3.34]), whereas no association was seen in men and distal colon cancer. The association for colon cancer was positive in individuals with high waist circumference (hazard ratio [95% CI], 1.69 [1.52-1.88]) and inverse in individuals with low waist circumference (hazard ratio [95% CI], 0.86 [0.76-0.98], P interaction<0.01). Overall, these data suggest that pre-diagnostic LCN2 concentrations were positively associated with colon cancer, particularly occurring in the proximal colon, in women and among individuals with abdominal adiposity.

This study aims to determine whether gender is a factor in the interplay between the human intestinal flora and colorectal cancer (CRC), ultimately providing new evidence for the clinical prediction and management of CRC in different genders. In this study, we included 186 untreated CRC patients, and classified them into two groups based on pathological staging: Groups Ⅰ-Ⅱ and Groups Ⅲ-Ⅳ, with male and female groups within each group. We collected preoperative fecal samples from these patients and performed 16S rRNA gene sequencing to analyze their intestinal flora. In the CRC Stages I-II cohort, the gut microbiota of the female group exhibited greater diversity and abundance compared to the male group, with a total of 13 gut microbiota demonstrating significant disparities. Notably, s__Parabacteroides gordonii, s__Bacteroides faecis, and s__Bacteroides nordii were found to be more prevalent in the female group relative to the male group. Within the CRC Stages III-IV cohort, 51 gut microbiota exhibited significant differences between the genders. In the immunocyte composition of fecal samples from patients with CRC, a higher proportion of naive B cells is observed in the male group as compared to the female group. In female CRC patients within the CRC Stages III-IV cohort, Actinomyces exhibited a significant negative correlation with activated dendritic cells, CD4+ memory T cells, and eosinophils. In male CRC patients within the CRC Stages III-IV cohort, Actinomyces demonstrated a significant positive correlation with naive B cells and a significant positive correlation with immune activation genes TNFRSF25 and TMIGD2. In female CRC patients within the CRC Stages III-IV cohort, Actinomyces showed a significant negative correlation with activated dendritic cells, CD4+ memory T cells, and eosinophils, and a significant positive correlation with immune activation genes TNFSF13B, LTA, KLRK1, and CXCL12. In the CRC Stages I-II group, the female group's intestinal flora is more diverse and richer than the male group. In the CRC Stages III-IV group, there are a total of 51 different intestinal flora in both the male and female groups. We also found that Actinomyces affects the occurrence and development of CRC in the male and female groups through different pathways. The results show that the intestinal flora differs between male and female CRC patients and is closely associated with cancer development.

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.

Colorectal cancer (CRC) is the third most common malignancy globally and the second leading cause of cancer-related mortality. Its development is a multifactorial and multistage process influenced by a dynamic interplay between gut microbiota, environmental factors, and fatty acid metabolism. Dysbiosis of intestinal microbiota and abnormalities in microbiota-associated metabolites have been implicated in colorectal carcinogenesis, highlighting the pivotal role of microbial and metabolic interactions. Fatty acid metabolism serves as a critical nexus linking dietary patterns with gut microbial activity, significantly impacting intestinal health. In CRC patients, reduced levels of short-chain fatty acids (SCFAs) and SCFA-producing bacteria have been consistently observed. Supplementation with SCFA-producing probiotics has demonstrated tumor-suppressive effects, while therapeutic strategies aimed at modulating SCFA levels have shown potential in enhancing the efficacy of radiation therapy and immunotherapy in both preclinical and clinical settings. This review explores the intricate relationship between gut microbiota, fatty acid metabolism, and CRC, offering insights into the underlying mechanisms and their potential translational applications. Understanding this interplay could pave the way for novel diagnostic, therapeutic, and preventive strategies in the management of CRC.

Gut microbiota is associated with endometrial cancer (EC); however, the causal relationship remains unexplored. This study attempted to explore the relationship between gut microbiota and EC using Mendelian randomization (MR) methods.

In this two-sample MR analysis, we used MiBioGen's gut microbiota data as the exposure and three datasets from European populations with EC as the outcome. The EC datasets included general EC, endometrioid histology, and non-endometrioid histology. Single nucleotide polymorphism (SNP) was used as the instrumental variable. Inverse variance weighted (IVW), multiplicative random effects IVW (MRE-IVW), Maximum likelihood (ML), MR Egger, MR-PRESSO, and the weighted median were used to perform MR analysis. Sensitivity analysis was conducted to assess the reliability of the results.

In this MR analysis of three EC datasets, specific gut microbiota were identified as potentially associated with different pathological types of EC. For general EC (ID: ebi-a-GCST006464), Family.Acidaminococcaceae (OR = 1.23, 95%CI: 1.02-1.48) and genus.Butyrivibrio (OR = 1.08, 95%CI: 1.01-1.16) were identified as risk factors, while genus.Ruminococcaceae UCG014 (OR = 0.82, 95%CI: 0.69-0.98) and genus.Turicibacter (OR = 0.84, 95%CI: 0.73-0.97) appeared to have protective effects. For endometrioid histology EC (ID: ebi-a-GCST006465), Family.Acidaminococcaceae (OR = 1.27, 95%CI: 1.01-1.59) and genus.Butyrivibrio (OR = 1.10, 95%CI: 1.01-1.19) were identified as risk factors, while several microbiota, including Family.Lactobacillaceae, genus.Coprococcus3, genus.Dorea, genus.Flavonifractor, genus.Lactobacillus, genus.Paraprevotella, and genus.Turicibacter, were identified as protective factors. For non-endometrioid histology EC (ID: ebi-a-GCST006466), Family.Rhodospirillaceae (OR = 1.41, 95%CI: 1.01-1.96) and genus.Peptococcus (OR = 1.43, 95%CI: 1.07-1.91) were identified as risk factors, while no significant protective factors were identified.

This two-sample MR study has identified gut microbiota with potential causal relationships with EC, varying by pathological type. These findings provide new insights into the pathogenesis of EC and suggest directions for future research on diagnosis and treatment strategies.

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.

Breast cancer (BC) is one of the most diagnosed cancers in women. Based on histological characteristics, they are classified as non-invasive, or in situ (tumors located within the milk ducts or milk lobules) and invasive. BC may develop from in situ carcinomas over time. Determining prognosis and predicting response to treatment are essential tools to manage this disease and reduce its incidence and mortality, as well as to promote personalized therapy for patients. However, over half of the cases are not associated with known risk factors. In addition, some patients develop resistance to treatment and relapse. Therefore, it is necessary to identify new biomarkers and treatment strategies that improve existing therapies. In this regard, the role of the microbiome is being researched as it could play a role in carcinogenesis and the efficacy of BC therapies. This review aims to describe specific microbiome patterns associated with BC. For this, a literature search was carried out in PubMed database using the MeSH terms "Breast Neoplasms" and "Gastrointestinal Microbiome", including 29 publications. Most of the studies have focused on characterizing the gut or breast tissue microbiome of the patients. Likewise, studies in animal models and in vitro that investigated the impact of gut microbiota (GM) on BC treatments and the effects of the microbiome on tumor cells were included. Based on the results of the included articles, BC could be associated with an imbalance in the GM. This imbalance varied depending on molecular type, stage and grade of cancer, menopause, menarche, body mass index, and physical activity. However, a specific microbial profile could not be identified as a biomarker. On the other hand, some studies suggest that the GM may influence the efficacy of BC therapies. In addition, some microorganisms and bacterial metabolites could improve the effects of therapies or influence tumor development.

As a key component of tumor microenvironment, the microbiota has gradually played a key role in cancer research. Particularly in colorectal cancer, the specific population of microbiota within the tumor shows a strong association with the tumor type. Although the existence and potential role of microbiota in tumors have been recognized, the specific associations between the microbiota and tumor tissue and the mechanism of action still need to be further explored. This paper reviews the discovery, origin, and emerging role of the intratumor microbiota in the immune microenvironment and systematically outlines the oncogenic and metastasis-promoting strategies of the intratumor microbiota. Moreover, it comprehensively and holistically evaluates therapeutic strategies and prognostic performance on the basis of the intratumor microbiota, with the goal of providing strong support for future research and clinical practice.

The high diversity and complexity of the eukaryotic transcriptome make it difficult to effectively detect specific transcripts of interest. Current targeted RNA sequencing methods often require complex pre-sequencing enrichment steps, which can compromise the comprehensive characterization of the entire transcriptome. Here we describe programmable full-length isoform transcriptome sequencing (PROFIT-seq), a method that enriches target transcripts while maintaining unbiased quantification of the whole transcriptome. PROFIT-seq employs combinatorial reverse transcription to capture polyadenylated, non-polyadenylated and circular RNAs, coupled with a programmable control system that selectively enriches target transcripts during sequencing. This approach achieves over 3-fold increase in effective data yield and reduces the time required for detecting specific pathogens or key mutations by 75%. We applied PROFIT-seq to study colorectal polyp development, revealing the intricate relationship between host immune responses and bacterial infection. PROFIT-seq offers a powerful tool for accurate and efficient sequencing of target transcripts while preserving overall transcriptome quantification, with broad applications in clinical diagnostics and targeted enrichment scenarios.

The aim of this study is to systematically examine and compare the characteristics distinguishing colorectal adenomatous polyps from normal mucosal intestinal microbiota.

A total of 30 specimens were obtained from patients diagnosed with colorectal adenomatous polyps (adenoma group) who underwent endoscopic removal at Wenzhou People's Hospital between September 2021 and November 2021. Concurrently, 30 normal mucosal specimens were collected from patients without adenomatous polyps (control group). Subsequently, microbiome total DNA extraction was carried out, followed by PCR amplification targeting the V3-V4 region of the 16S rDNA. High-throughput sequencing was conducted using the Illumina MiSeq platform. Subsequent to sequencing, bioinformatics analysis was used to assess the diversity, composition, and functional aspects of the intestinal microbiota in both study groups.

A notable dissimilarity in the microbiota structure was identified, specifically within the transverse colon, between these two groups ( P  < 0.05). Species composition analysis revealed that Escherichia , Fusobacterium , and Bacteroides were predominant bacteria in both groups, with Escherichia and Enterobacter displaying significant differences at the genera level between the control group and the adenoma group ( P  < 0.05). Correlation analysis and functional prediction demonstrated substantial disparities in interactions among dominant intestinal microbial genera within patients from both groups. Additionally, it was discovered that the intestinal microbiomes in patients in the adenoma group exhibited a significantly higher pathogenic potential.

Upon conducting a comprehensive analysis, it was discerned that the microbiota present in the transverse colon of the control group exhibited distinctive characteristics that may contribute to the maintenance of intestinal health.

We have previously demonstrated an association between increased abundance of Phascolarctobacterium and colorectal cancer (CRC) and adenomas in two independent Norwegian cohorts. Here we seek to verify our previous findings using new cohorts and methods. In addition, we characterize lifestyle and sex specificity, the functional potential of the Phascolarctobacterium species, and their interaction with other microbial species. We analyze Phascolarctobacterium with 16S rRNA sequencing, shotgun metagenome sequencing, and species-specific qPCR, using 2350 samples from three Norwegian cohorts-CRCAhus, NORCCAP, and CRCbiome-and a large publicly available data set, curatedMetagenomicData. Using metagenome-assembled genomes from the CRCbiome study, we explore the genomic characteristics and functional potential of the Phascolarctobacterium pangenome. Three species of Phascolarctobacterium associated with adenoma/CRC were consistently detected by qPCR and sequencing. Positive associations with adenomas/CRC were verified for Phascolarctobacterium succinatutens and negative associations were shown for Phascolarctobacterium faecium and adenoma in curatedMetagenomicData. Men show a higher prevalence of P. succinatutens across cohorts. Co-occurrence among Phascolarctobacterium species was low (<6%). Each of the three species shows distinct microbial composition and forms distinct correlation networks with other bacterial taxa, although Dialister invisus was negatively correlated to all investigated Phascolarctobacterium species. Pangenome analyses showed P. succinatutens to be enriched for genes related to porphyrin metabolism and degradation of complex carbohydrates, whereas glycoside hydrolase enzyme 3 was specific to P. faecium.IMPORTANCEUntil now Phascolarctobacterium has been going under the radar as a CRC-associated genus despite having been noted, but overseen, as such for over a decade. We found not just one, but two species of Phascolarctobacterium to be associated with CRC-Phascolarctobacterium succinatutens was more abundant in adenoma/CRC, while Phascolarctobacterium faecium was less abundant in adenoma. Each of them represents distinct communities, constituted by specific microbial partners and metabolic capacities-and they rarely occur together in the same patients. We have verified that P. succinatutens is increased in adenoma and CRC and this species should be recognized among the most important CRC-associated bacteria.

Colorectal cancer (CRC) is influenced by perturbations in the colonic microbiota, characterized by an imbalance favoring pathogenic bacteria over beneficial ones. This dysbiosis contributes to CRC initiation and progression through mechanisms such as carcinogenic metabolite production, inflammation induction, DNA damage, and oncogenic signaling activation. Understanding the role of external factors in shaping the colonic microbiota is crucial for mitigating CRC progression. This study aims to elucidate the gut microbiome's role in CRC progression by analyzing paired tumor and mucosal tissue samples obtained from the colon walls of 17 patients. Through sequencing of the V3-V4 region of the 16S rRNA gene, we characterized the tumor microbiome and assessed its association with clinical variables. Our findings revealed a significant reduction in alpha diversity within tumor samples compared to paired colon biopsy samples, indicating a less diverse microbial environment within the tumor microenvironment. While both tissues exhibited dominance of similar bacterial phyla, their relative abundances varied, suggesting potential colon-specific effects. Fusobacteriota enrichment, notably in the right colon, may be linked to MLH1 deficiency. Taxonomy analysis identified diverse bacterial genera, with some primarily associated with the colon wall and others unique to this region. Conversely, several genera were exclusively expressed in tumor tissue. Functional biomarker analysis identified three key genes with differential abundance between tumor microenvironment and colon tissue, indicating distinct metabolic activities. Functional biomarker analysis revealed three key genes with differential abundance: K11076 (putrescine transport system) and K10535 (nitrification) were enriched in the tumor microenvironment, while K11329 (SasA-RpaAB circadian timing mediator) dominated colon tissue. Metabolic pathway analysis linked seven metabolic pathways to the microbiome. Collectively, these findings highlight significant gut microbiome alterations in CRC and strongly suggest that long-term dysbiosis profoundly impacts CRC progression.

The intricate interplay between the gut microbiome and colorectal cancer (CRC) presents novel avenues for early diagnosis and prognosis, crucial for improving patient outcomes. This comprehensive review synthesizes current findings on the gut microbiome's contribution to CRC pathogenesis, highlighting its potential as a biomarker for non-invasive CRC screening strategies. We explore the mechanisms through which the microbiome influences CRC, including its roles in inflammation, metabolism, and immune response modulation. Furthermore, we assess the viability of microbial signatures as predictive tools for CRC prognosis, offering insights into personalized treatment approaches. Our analysis underscores the necessity for advanced metagenomic studies to elucidate the complex microbiome-CRC nexus, aiming to refine diagnostic accuracy and prognostic assessment in clinical settings. This review propels forward the understanding of the microbiome's diagnostic and prognostic capabilities, paving the way for microbiome-based interventions in CRC management.

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death worldwide. In recent years, the impact of the gut microbiota on the development of CRC has become clear. The gut microbiota is the community of microorganisms living in the gut symbiotic relationship with the host. These microorganisms contribute to the development of CRC through various mechanisms that are not yet fully understood. Increasing scientific evidence suggests that metabolites produced by the gut microbiota may influence CRC development by exerting protective and deleterious effects. This article reviews the metabolites produced by the gut microbiota, which are derived from the intake of complex carbohydrates, proteins, dairy products, and phytochemicals from plant foods and are associated with a reduced risk of CRC. These metabolites include short-chain fatty acids (SCFAs), indole and its derivatives, conjugated linoleic acid (CLA) and polyphenols. Each metabolite, its association with CRC risk, the possible mechanisms by which they exert anti-tumour functions and their relationship with the gut microbiota are described. In addition, other gut microbiota-derived metabolites that are gaining importance for their role as CRC suppressors are included.

Colorectal cancer (CRC) is a common cancer that causes millions of deaths worldwide each year. At present, numerous studies have confirmed that intestinal microbes play a crucial role in the process of CRC. Additionally, studies have shown that CRC can be divided into several consensus molecular subtypes (CMS) based on tumor gene expression, and CRC microbiomes have been reported related to CMS. However, most previous studies on intestinal microbiome of CRC have only compared patients with healthy controls, without classifying of CRC patients based on intestinal microbial composition.

In this study, a CRC cohort including 339 CRC samples and 333 healthy controls was selected as the discovery set, and the CRC samples were divided into two subgroups (234 Subgroup1 and 105 Subgroup2) using PAM clustering algorithm based on the intestinal microbial composition. We found that not only the microbial diversity was significantly different (Shannon index, p-value < 0.05), but also 129 shared genera altered (p-value < 0.05) between the two CRC subgroups, including several marker genera in CRC, such as Fusobacterium and Bacteroides. A random forest algorithm was used to construct diagnostic models, which showed significantly higher efficiency when the CRC samples were divided into subgroups. Then an independent cohort including 187 CRC samples (divided into 153 Subgroup1 and 34 Subgroup2) and 123 healthy controls was chosen to validate the models, and confirmed the results.

These results indicate that the divided CRC subgroups can improve the efficiency of disease diagnosis, with various microbial composition in the subgroups.

Previous research has demonstrated an association between gut microbiota and immune status with the development of several diseases. However, whether these factors contribute to polyps remains unclear. This study aims to use Mendelian randomization (MR) to investigate the causal relationship between gut microbiota and 4 types of polyps (nasal, gallbladder, colon, and gastric polyps), as well as to analyze the mediating role of immune traits.

This study utilized large-scale GWAS meta-analyses of gut microbiota (MiBioGen Consortium), 731 immune traits, and 4 types of polyps (one from the FinnGen Consortium and three from the NBDC Human Database). Univariate MR with the inverse variance weighted (IVW) estimation method was employed as the primary analytical approach. A two-step MR analysis was performed to identify potential mediating immune traits. Additionally, multivariable MR approach based on Bayesian model averaging (MR-BMA) was employed to further prioritize gut microbiota and immune traits associated with polyp development.

Based on IVW method in univariate MR analysis, we identified 39 gut microbial taxa and 135 immune traits significantly causally associated with at least one type of polyp. For nasal polyps, 13 microbial taxa and 61 immune traits were causally associated. After false discovery rate (FDR) correction, CD3 on Central Memory CD8+ T cells and CD3 on CD4 regulatory T cells remained significant. MR-BMA identified 4 gut microbial taxa and 4 immune traits as high priority. For gallbladder polyps, 9 microbial taxa and 30 immune traits were causally associated. MR-BMA identified 8 microbial taxa and 6 immune traits as higher importance. For colon polyps, 6 microbial taxa and 21 immune traits were causally associated. MR-BMA identified 4 microbial taxa and 3 immune traits as higher importance. For gastric polyps, 12 microbial taxa and 33 immune traits were causally associated. Actinobacteria remained significant after FDR correction, and MR-BMA identified 7 gut microbial taxa and 6 immune traits as high priority. We identified 16 causal pathways with mediator directions consistent with the direction of gut microbiome-polyp association. Of these, 6 pathways were associated with the mechanism of nasal polyps, 1 with gallbladder polyps, 2 with colon polyps, and 7 with gastric polyps.

Our findings shed light on the causal relationships between gut microbiota, immune traits, and polyp development, underscoring the crucial roles of gut microbiota and immune status in polypogenesis. Furthermore, these findings suggest potential applications in polyp prevention, early screening, and the development of effective strategies to reduce polyp risk.

Globally, colorectal cancer (CRC) is a leading cause of cancer-related mortality. Dietary habits, inflammation, hereditary characteristics, and gut microbiota are some of its causes. The gut microbiota, a diverse population of bacteria living in the digestive system, has an impact on a variety of parameters, including inflammation, DNA damage, and immune response. The gut microbiome has a significant role in colon cancer susceptibility. Many studies have highlighted dysbiosis, an imbalance in the gut microbiota's makeup, as a major factor in colon cancer susceptibility. Dysbiosis has the potential to produce toxic metabolites and pro-inflammatory substances, which can hasten the growth of tumours. The ability of the gut microbiota to affect the host's immune system can also influence whether cancer develops or not. By better comprehending these complex interactions between colon cancer predisposition and gut flora, new preventive and therapeutic techniques might be developed. Targeting the gut microbiome with dietary modifications, probiotics, or faecal microbiota transplantation may offer cutting-edge approaches to reducing the risk of colon cancer and improving patient outcomes. The complex connection between the makeup of the gut microbiota and the emergence of colorectal cancer is explored in this narrative review.

Gut bacteria are related to colorectal cancer (CRC) and its clinicopathologic characteristics.

To develop gut bacterial subtypes and explore potential microbial targets for CRC.

Stool samples from 914 volunteers (376 CRCs, 363 advanced adenomas, and 175 normal controls) were included for 16S rRNA sequencing. Unsupervised learning was used to generate gut microbial subtypes. Gut bacterial community composition and clustering effects were plotted. Differences of gut bacterial abundance were analyzed. Then, the association of CRC-associated bacteria with subtypes and the association of gut bacteria with clinical information were assessed. The CatBoost models based on gut differential bacteria were constructed to identify the diseases including CRC and advanced adenoma (AA).

Four gut microbial subtypes (A, B, C, D) were finally obtained via unsupervised learning. The characteristic bacteria of each subtype were Escherichia-Shigella in subtype A, Streptococcus in subtype B, Blautia in subtype C, and Bacteroides in subtype D. Clinical information (e.g., free fatty acids and total cholesterol) and CRC pathological information (e.g., tumor depth) varied among gut microbial subtypes. Bacilli, Lactobacillales, etc., were positively correlated with subtype B. Positive correlation of Blautia, Lachnospiraceae, etc., with subtype C and negative correlation of Coriobacteriia, Coriobacteriales, etc., with subtype D were found. Finally, the predictive ability of CatBoost models for CRC identification was improved based on gut microbial subtypes.

Gut microbial subtypes provide characteristic gut bacteria and are expected to contribute to the diagnosis of CRC.

Colorectal polyps, which are characterized by a high recurrence rate, represent preneoplastic conditions of the intestine. Due to unclear mechanisms of pathogenesis, first-line therapies for non-hereditary recurrent colorectal polyps are limited to endoscopic resection. Although recent studies suggest a mechanistic link between intestinal dysbiosis and polyps, the exact compositions and roles of bacteria in the mucosa around the lesions, rather than feces, remain unsettled.

To clarify the composition and diversity of bacteria in the mucosa surrounding or 10 cm distal to recurrent intestinal polyps.

Mucosal samples were collected from four patients consistently with adenomatous polyps (Ade), seven consistently with non-Ade (Pol), ten with current Pol but previous Ade, and six healthy individuals, and bacterial patterns were evaluated by 16S rDNA sequencing. Linear discriminant analysis and Student's t-tests were used to identify the genus-level bacteria differences between groups with different colorectal polyp phenotypes. Pearson's correlation coefficients were used to evaluate the correlation between intestinal bacteria at the genus level and clinical indicators.

The results confirmed a decreased level of probiotics and an enrichment of pathogenic bacteria in patients with all types of polyps compared to healthy individuals. These changes were not restricted to the mucosa within 0.5 cm adjacent to the polyps, but also existed in histologically normal tissue 10 cm distal from the lesions. Significant differences in bacterial diversity were observed in the mucosa from individuals with normal conditions, Pol, and Ade. Increased abundance of Gram-negative bacteria, including Klebsiella, Plesiomonas, and Cronobacter, was observed in Pol group and Ade group, suggesting that resistance to antibiotics may be one risk factor for bacterium-related harmful environment. Meanwhile, age and gender were linked to bacteria changes, indicating the potential involvement of sex hormones.

These preliminary results support intestinal dysbiosis as an important risk factor for recurrent polyps, especially adenoma. Targeting specific pathogenic bacteria may attenuate the recurrence of polyps.

The gut microbiota has been recognized as an important determinant in the initiation and progression of colorectal cancer (CRC), with recent studies shining light on the molecular mechanisms that may contribute to the interactions between microbes and the CRC microenvironment. Despite the increasing wealth of associations being established in the field, proving causality remains challenging. Obstacles include the high variability of the microbiome and its context, both across individuals and across time. Additionally, there is a lack of large and representative cohort studies with long-term follow-up and/or appropriate sampling methods for studying the mucosal microbiome. Finally, most studies focus on CRC, whereas interactions between host and bacteria in early events in carcinogenesis remain elusive, reinforced by the heterogeneity of CRC development. Here, we discuss these current most prominent obstacles, the recent developments, and research needs.

We aimed to identify plasma and urinary metabolites related to colorectal cancer (CRC) risk and elucidate their mediator role in the associations between modifiable risk factors and CRC.

Metabolite quantitative trait loci were derived from 2 published metabolomics genome-wide association studies, and summary-level data were extracted for 651 plasma metabolites and 208 urinary metabolites. Genetic associations with CRC were obtained from a large-scale genome-wide association study meta-analysis (100 204 cases, 154 587 controls) and the FinnGen cohort (4957 cases, 304 197 controls). Mendelian randomization and colocalization analyses were performed to evaluate the causal roles of metabolites in CRC. Druggability evaluation was employed to prioritize potential therapeutic targets. Multivariable Mendelian randomization and mediation estimation were conducted to elucidate the mediating effects of metabolites on the associations between modifiable risk factors and CRC.

The study identified 30 plasma metabolites and 4 urinary metabolites for CRC. Plasma sphingomyelin and urinary lactose, which were positively associated with CRC risk, could be modulated by drug interventions (ie, olipudase alfa, tilactase). Thirteen modifiable risk factors were associated with 9 metabolites, and 8 of these modifiable risk factors were associated with CRC risk. These 9 metabolites mediated the effect of modifiable risk factors (Actinobacteria, body mass index, waist to hip ratio, fasting insulin, smoking initiation) on CRC.

This study identified key metabolite biomarkers associated with CRC and elucidated their mediator roles in the associations between modifiable risk factors and CRC. These findings provide new insights into the etiology and potential therapeutic targets for CRC and the etiological pathways of modifiable environmental factors with CRC.

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.

Monoacylglycerol acyltransferase-2 (MOGAT2), encodes MOGAT enzyme in the re-synthesis of triacylglycerol and protects from metabolism disorders. While, its precise involvement in colorectal cancer (CRC) progression remains inadequately understood. Our study demonstrated that knockout of Mogat2 in Apcmin/+ mice expedited intestinal tumor growth and progression, indicating that Mogat2 plays a tumor-suppressing role in CRC. Mechanically, Mogat2 deletion resulted in a significant alter the gut microbiota, while Fecal Microbiota Transplantation (FMT) experiments demonstrated that the gut microbiota in Mogat2 deleted mice promoted tumor growth. Furthermore, we identified Mogat2 as a functional regulator suppressing CRC cell proliferation and tumor growth by inhibiting the NF-κB signaling pathway in vivo. Collectively, these results provide novel insights into the protective double roles of Mogat2, inhibiting of NF-κB pathway and keeping gut microbiota homeostasis in colorectal cancer, which may help the development of novel cancer treatments for CRC.

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies in the world. With the rapid pace of life and changes in diet structure, the incidence and mortality of CRC increase year by year posing a serious threat to human health. As the most complex and largest microecosystem in the human body, intestinal microecology is closely related to CRC. It is an important factor that affects and participates in the occurrence and development of CRC. Advances in next-generation sequencing technology and metagenomics have provided new insights into the ecology of gut microbes. It also helps to link intestinal flora with CRC, and the relationship between intestinal flora and CRC can be continuously understood from different levels. This paper summarizes the relationship between intestinal flora and CRC and its potential role in the diagnosis of CRC providing evidence for early screening and treatment of CRC.

Tongue coating microbiota has aroused particular interest in profiling oral and digestive system cancers. However, little is known on the relationship between tongue coating microbiome and colorectal cancer (CRC).

Metagenomic shotgun sequencing was performed on tongue coating samples collected from 30 patients with CRC, 30 patients with colorectal polyps (CP), and 30 healthy controls (HC). We further validated the potential of the tongue coating microbiota to predict the CRC by a random forest model.

We found a greater species diversity in CRC samples, and the nucleoside and nucleotide biosynthesis pathway was more apparent in the CRC group. Importantly, various species across participants jointly shaped three distinguishable fur types.The tongue coating microbiome profiling data gave an area under the receiver operating characteristic curve (AUC) of 0.915 in discriminating CRC patients from control participants; species such as Atopobium rimae, Streptococcus sanguinis, and Prevotella oris aided differentiation of CRC patients from healthy participants.

These results elucidate the use of tongue coating microbiome in CRC patients firstly, and the fur-types observed contribute to a better understanding of the microbial community in human. Furthermore, the tongue coating microbiota-based biomarkers provide a valuable reference for CRC prediction and diagnosis.

The gut microbiota has been significantly associated with differentiated thyroid cancer (DTC). However, the causal relationship between the gut microbiota and DTC remains unexplored.

Genome-wide association study (GWAS) summary databases were utilized to select exposures and outcomes. The Mendelian randomization (MR) method was employed to investigate the causal relationship between the gut microbiota and DTC. A sensitivity analysis was performed to assess the reliability of the findings.

Four bacterial traits were associated with the risk of DTC: Class Mollicutes [odds ratio (OR) = 10.953, 95% confidence interval (95% CI): 2.333-51.428, p = 0.002], Phylum Tenericutes (OR = 10.953, 95% CI: 2.333-51.428, p = 0.002), Genus Eggerthella (OR = 3.219, 95% CI: 1.033-10.024, p = 0.044), and Order Rhodospirillales (OR = 2.829, 95% CI: 1.096-7.299, p = 0.032). The large 95% CI range for the Class Mollicutes and the Phylum Tenericutes may be attributed to the small sample size. Additionally, four other bacterial traits were negatively associated with DTC: Genus Eubacterium fissicatena group (OR = 0.381, 95% CI: 0.148-0.979, p = 0.045), Genus Lachnospiraceae UCG008 (OR = 0.317, 95% CI: 0.125-0.801, p = 0.015), Genus Christensenellaceae R-7 group (OR = 0.134, 95% CI: 0.020-0.886, p = 0.037), and Genus Escherichia Shigella (OR = 0.170, 95% CI: 0.037-0.769, p = 0.021).

These findings contribute to our understanding of the pathological mechanisms underlying DTC and provide novel insights for the clinical treatment of DTC.

Crohn's disease (CD) entails intricate interactions with gut microbiome diversity, richness, and composition. The relationship between CD and gut microbiome is not clearly understood and has not been previously characterized in Saudi Arabia. We performed statistical analysis about various factors influencing CD activity and microbiota dysbiosis, including diagnosis, treatment, and its impact on their quality of life as well as high-throughput metagenomic V3-V4 16S rRNA encoding gene hypervariable region of a total of eighty patients with CD, both in its active and inactive state with healthy controls. The results were correlated with the demographic and lifestyle information, which the participants provided via a questionnaire. α-diversity measures indicated lower bacterial diversity and richness in the active and inactive CD groups compared to the control group. Greater dysbiosis was observed in the active CD patients compared to the inactive form of the disease, showed by a reduction in microbial diversity. Specific pathogenic bacteria such as Filifactor, Peptoniphilus, and Sellimonas were identified as characteristic of CD groups. In contrast, anti-inflammatory bacteria like Defluviitalea, Papillibacter, and Petroclostridium were associated with the control group. Among the various factors influencing disease activity and microbiota dysbiosis, smoking emerged as the most significant, with reduced α-diversity and richness for the smokers in all groups, and proinflammatory Fusobacteria was more present (p<0.05). Opposite to the control group, microbial diversity and richness were lower in CD participants of older age compared to younger ones, and male CD participants showed less diversity compared to women participants from the same groups. Our results describe the first report on the relationship between microbiota and Crohn's disease progress in Saudi Arabia, which may provide a theoretical basis for the application of therapeutic methods to regulate gut microbes in CD.

An expanding corpus of research robustly substantiates the complex interrelation between gut microbiota and the onset, progression, and metastasis of colorectal cancer. Investigations in both animal models and human subjects have consistently underscored the role of gut bacteria in a variety of metabolic activities, driven by dietary intake. These activities include amino acid metabolism, carbohydrate fermentation, and the generation and regulation of bile acids. These metabolic derivatives, in turn, have been identified as significant contributors to the progression of colorectal cancer. This thorough review meticulously explores the dynamic interaction between gut bacteria and metabolites derived from the breakdown of amino acids, fatty acid metabolism, and bile acid synthesis. Notably, bile acids have been recognized for their potential carcinogenic properties, which may expedite tumor development. Extensive research has revealed a reciprocal influence of gut microbiota on the intricate spectrum of colorectal cancer pathologies. Furthermore, strategies to modulate gut microbiota, such as dietary modifications or probiotic supplementation, may offer promising avenues for both the prevention and adjunctive treatment of colorectal cancer. Nevertheless, additional research is imperative to corroborate these findings and enhance our comprehension of the underlying mechanisms in colorectal cancer development.

Colorectal cancer (CRC), one of the most common malignancies in the world, urgently requires more treatment strategies. Although there has been much research on probiotics, limited research has been done in treating cancer. The purpose of this study was to investigate the role of Bifidobacterium longum (B. longum) in the prevention and treatment of CRC. Through Cell Counting Kit-8 and Colony Formation Assays, 8 h and a B. longum count of 1 × 108 CFU/ml were chosen as the best cocultivation conditions with CRC cells. The role of B. longum in inhibiting the progression of CRC cells was verified by a series of functional and immunofluorescence assays. For instance, in vivo assays have verified that B. longum could alleviate CRC progression. In addition, according to the results of in vivo assays and clinical statistical analysis, B. longum could reduce diarrhea symptoms. Mechanistically, by 16S and RNA sequencing, it was found that B. longum could affect the development of CRC by regulating the composition of gut microbes and enhancing immune function. The B. longum might inhibit the occurrence and development of CRC and relieve diarrhea symptoms by regulating intestinal microbes and immune function.

The gut microbiome maintains the mucus membrane barrier's integrity, and it is modulated by the host's immune system.

To detect the effect of microbiota modulation using probiotics, prebiotics, symbiotics, and natural changes on colorectal cancers (CRCs).

A PubMed search was conducted to retrieve the original and in vivo articles published in English language from 2010 until 2021 containing the following keywords: 1) CRCs, 2) CRCs treatment (i.e. surgical, chemotherapy, radiotherapy and/or immunotherapy), and 3) microbiota probiotic(s), prebiotic(s), symbiotic(s), dysbiosis and/or nutritional treatment. A total of 198 PubMed records/articles were initially identified. 108 articles were excluded at the initial screening, and another 29 articles were excluded after reviewing the abstracts, and finally 61 studies were analysed for this systematic review.

The gut microbiota metabolites and (SCFAs) short-chain fatty acids (i.e. acetate and butyrate) have a protective effect against CRCs. SCFAs reduce the inflammatory cytokines, inhibit colonocyte proliferation, and promote malignant cell apoptosis. Butyrate maintains the integrity of the mucus membrane barrier and reduces intestinal mucosal inflammation. Reduced butyric acid level and increased inflammatory cytokines were observed after reduced Bacteroides fragilis and Bacteroides vulgatus species in the colon. Akkermansia muciniphila bacterium decreased in patients with CRCs.

Prebiotics (i.e. inulin and resistant starch, SCFAs producers) and consumption of unprocessed plant products are useful for developing and maintaining healthy gut microbiota. The pro-, pre- and/or symbiotics may be useful when carefully selected for CRC patients, to restore beneficial gut microbiota and support treatment efficacy.