The fire within: microbes inflame tumors.

The immune system and the microbiota mutually interact to maintain homeostasis in the intestine. However, components of the microbiota can alter this balance and promote chronic inflammation, promoting intestinal tumor development. We review recent advances in understanding the complex interactions between the microbiota and the innate and adaptive immune systems and discuss their potential to lead us in new directions for understanding cancer biology and treatment.

GMrepo v2: a curated human gut microbiome database with special focus on disease markers and cross-dataset comparison.

GMrepo (data repository for Gut Microbiota) is a database of curated and consistently annotated human gut metagenomes. Its main purposes are to increase the reusability and accessibility of human gut metagenomic data, and enable cross-project and phenotype comparisons. To achieve these goals, we performed manual curation on the meta-data and organized the datasets in a phenotype-centric manner. GMrepo v2 contains 353 projects and 71,642 runs/samples, which are significantly increased from the previous version. Among these runs/samples, 45,111 and 26,531 were obtained by 16S rRNA amplicon and whole-genome metagenomics sequencing, respectively. We also increased the number of phenotypes from 92 to 133. In addition, we introduced disease-marker identification and cross-project/phenotype comparison. We first identified disease markers between two phenotypes (e.g. health versus diseases) on a per-project basis for selected projects. We then compared the identified markers for each phenotype pair across datasets to facilitate the identification of consistent microbial markers across datasets. Finally, we provided a marker-centric view to allow users to check if a marker has different trends in different diseases. So far, GMrepo includes 592 marker taxa (350 species and 242 genera) for 47 phenotype pairs, identified from 83 selected projects. GMrepo v2 is freely available at: https://gmrepo.humangut.info.

Molecular profiling and identification of prognostic factors in Chinese patients with small bowel adenocarcinoma.

Small bowel adenocarcinoma (SBA) is a rare malignancy with a poor prognosis and limited treatment options. Despite prior studies, molecular characterization of this disease is not well defined, and little is known regarding Chinese SBA patients. In this study, we conducted multigene next-generation sequencing and 16S ribosomal RNA gene sequencing on samples from 76 Chinese patients with surgically resected primary SBA. Compared with colorectal cancer and Western SBA cohorts, a distinctive genomic profile was revealed in Chinese SBA cohorts. According to the levels of clinical actionability to targetable alterations stratified by OncoKB system, 75% of patients harbored targetable alterations, of which ERBB2, BRCA1/2, and C-KIT mutations were the most common targets of highest-level actionable alterations. In DNA mismatch repair-proficient (pMMR) patients, significant associations between high tumor mutational burden and specific genetic alterations were identified. Moreover, KRAS mutations/TP53 wild-type/nondisruptive mutations (KRASmut /TP53wt/non-dis ) were independently associated with an inferior recurrence-free survival (hazard ratio [HR] = 4.21, 95% confidence interval [CI] = 1.94-9.14, P < .001). The bacterial profile revealed Proteobacteia, Actinobacteria, Firmicutes, Bacteroidetes, Fusobacteria, and Cyanobacteria were the most common phyla in SBA. Furthermore, patients were clustered into three subgroups based on the relative abundance of bacterial phyla, and the distributions of the subgroups were significantly associated with the risk of recurrence stratified by TP53 and KRAS mutations. In conclusion, these findings provided a comprehensive molecular basis for understanding SBA, which will be of great significance in improving the treatment strategies and clinical management of this population.

High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity.

Several features common to a Western lifestyle, including obesity and low levels of physical activity, are known risk factors for gastrointestinal cancers. There is substantial evidence suggesting that diet markedly affects the composition of the intestinal microbiota. Moreover, there is now unequivocal evidence linking dysbiosis to cancer development. However, the mechanisms by which high-fat diet (HFD)-mediated changes in the microbial community affect the severity of tumorigenesis in the gut remain to be determined. Here we demonstrate that an HFD promotes tumour progression in the small intestine of genetically susceptible, K-ras(G12Dint), mice independently of obesity. HFD consumption, in conjunction with K-ras mutation, mediated a shift in the composition of the gut microbiota, and this shift was associated with a decrease in Paneth-cell-mediated antimicrobial host defence that compromised dendritic cell recruitment and MHC class II molecule presentation in the gut-associated lymphoid tissues. When butyrate was administered to HFD-fed K-ras(G12Dint) mice, dendritic cell recruitment in the gut-associated lymphoid tissues was normalized, and tumour progression was attenuated. Importantly, deficiency in MYD88, a signalling adaptor for pattern recognition receptors and Toll-like receptors, blocked tumour progression. The transfer of faecal samples from HFD-fed mice with intestinal tumours to healthy adult K-ras(G12Dint) mice was sufficient to transmit disease in the absence of an HFD. Furthermore, treatment with antibiotics completely blocked HFD-induced tumour progression, suggesting that distinct shifts in the microbiota have a pivotal role in aggravating disease. Collectively, these data underscore the importance of the reciprocal interaction between host and environmental factors in selecting a microbiota that favours carcinogenesis, and they suggest that tumorigenesis is transmissible among genetically predisposed individuals.

Detection of the Bacteroides fragilis toxin gene in sheep with and without small intestinal adenocarcinoma.

Aims: To determine if presence of the Bacteroides fragilis toxin (bft) gene, a molecular marker of colonic carriage of entertoxigenic Bacteroides fragilis (ETBF) in humans, was associated with a finding of small intestinal adenocarcinomas (SIA) in sheep in New Zealand. Methods: Samples of jejunal tissue were collected from the site of tumours and from grossly normal adjacent tissue in 20 sheep, in different consignments, diagnosed with SIA based on gross examination of viscera following slaughter. Two jejunal samples were also collected from a control sheep in the same consignment that had no gross evidence of SIA. A PCR assay was used to detect the presence of the bft gene in the samples. Results: Of the sheep with SIA, the bft gene was amplified from one or both samples from 7/20 (35%) sheep, and in sheep that had no gross evidence of SIA the bft gene was amplified from at least one sample in 11/20 (55%) sheep (RR 0.61; 95% CI = 0.30-1.25; p = 0.34). Of 11 positive samples analysed, ETBF subtype bft-1 was detected in one, bft-2 was detected in 10, and none were bft-3. Conclusions and Clinical Relevance: There was a high prevalence of detection of the bft gene in both SIA-affected and non-affected sheep, but there was no apparent association between carriage of ETBF, evidenced by detection of the bft gene, and the presence of SIA. ETBF are increasingly implicated in the aetiology of human colorectal cancer, raising the possibility that sheep may provide a zoonotic reservoir of this potentially carcinogenic bacterium. Abbreviation: Bft: Bacteroides fragilis toxin; ETBF: Enterotoxigenic Bacteroides fragilis; SIA: Small intestinal adenocarcinoma.

Transmission of a common intestinal neoplasm in zebrafish by cohabitation.

Intestinal neoplasms are common in zebrafish (Danio rerio) research facilities. These tumours are most often seen in older fish and are classified as small cell carcinomas or adenocarcinomas. Affected fish populations always contain subpopulations with preneoplastic lesions, characterized by epithelial hyperplasia or inflammation. Previous observations indicated that these tumours are unlikely caused by diet, water quality or genetic background, suggesting an infectious aetiology. We performed five transmission experiments by exposure of naïve fish to affected donor fish by cohabitation or exposure to tank effluent water. Intestinal lesions were observed in recipient fish in all exposure groups, including transmissions from previous recipient fish, and moribund fish exhibited a higher prevalence of neoplasms. We found a single 16S rRNA sequence, most similar to Mycoplasma penetrans, to be highly enriched in the donors and exposed recipients compared to unexposed control fish. We further tracked the presence of the Mycoplasma sp. using a targeted PCR test on individual dissected intestines or faeces or tank faeces. Original donor and exposed fish populations were positive for Mycoplasma, while corresponding unexposed control fish were negative. This study indicates an infectious aetiology for these transmissible tumours of zebrafish and suggests a possible candidate agent of a Mycoplasma species.

Helicobacter pylori genotypes determine risk of non-cardia gastric cancer and intestinal- or diffuse-type GC in Ardabil: A very high-risk area in Northwestern Iran.

Frequency of the Helicobacter pylori vacA gene polymorphism and its association with gastric cancer (GC) was assessed in Ardabil, a very high-risk area in Northwestern Iran. We determined the presence of the H. pylori 16S rDNA gene and the vacA s-, m-, i-, and d-region genotypes in DNA from fresh gastric biopsies. Patients with GC were classified based on both the anatomic site and the histopathologic type of tumor Of 135 patients, including 57 with non-atrophic gastritis (NAG) and 78 with GC, 103 were infected by H. pylori. The vacA i1 and d1 genotypes were significantly linked to an increased risk of GC, where both cardia (CGC) and non-cardia GC (NCGC) patients were entered into the analysis. The adjusted OR was 9.59 for i1 and 4.39 for d1. Furthermore, i1 was significantly linked to an increased risk of the intestinal-type adenocarcinoma (OR = 14.04) and d1 to the risk of the diffuse-type adenocarcinoma (OR = 7.71). The presence of the m1-type of vacA in combination with i1 or d1 further increased the risk of GC. When the analysis was restricted to NCGC, the adjusted OR for i1 and d1, was 37.52 and 7.17, respectively. No significant association was found between genotypes and the risk of GC in the cardia site of the stomach. It is proposed that the new types of H. pylori vacA, i1 and d1, might be important determinants of NCGC risk in Ardabil. The m1, not independently, but in combination might further define the risk of GC. i1and d1 might also predict the risk of the intestinal- and diffuse-type adenocarcinomas, respectively.

Intestinal Organoids: New Frontiers in the Study of Intestinal Disease and Physiology.

The development of sustainable intestinal organoid cell culture has emerged as a new modality for the study of intestinal function and cellular processes. Organoid culture is providing a new testbed for therapeutic research and development. Intestinal organoids, self-renewing 3-dimensional structures comprised intestinal stem cells and their differentiated epithelial progeny allow for more facile and robust exploration of cellular activity, cell organization and structure, genetic manipulation, and vastly more physiologic modeling of intestinal response to stimuli as compared to traditional 2-dimensional cell line cultures. Intestinal organoids are affecting a wide variety of research into gastrointestinal pathology. The purpose of this review is to discuss the current state-of-the-art and future effect of research using enteroids and colonoids (organoids grown from the small and large intestines, respectively).

Identification of Mucosa-Invading and Intravascular Bacteria in Feline Small Intestinal Lymphoma.

Persistent bacterial infections of the gastrointestinal mucosa are causally linked to gastric carcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma in people and laboratory animals. We examined the relationship of mucosa-associated bacteria to alimentary lymphoma in cats. Intestinal biopsies from 50 cats with alimentary lymphoma (small cell, n = 33; large cell, n = 17) and 38 controls without lymphoma (normal to minimal change on histopathology, n = 18; lymphocytic-plasmacytic enteritis, n = 20) were evaluated. The number and spatial distribution of bacteria (ie, in luminal cellular debris, villus-associated mucus, adherent to epithelium, mucosal invasion, intravascular, or serosal) were determined by fluorescence in situ hybridization with the eubacterial probe EUB-338. Mucosa-invasive bacteria were more frequently observed in cats with large cell lymphoma (82%, P ≤ .001) than in cats with small cell lymphoma (18%), normal to minimal change on histopathology, and lymphocytic-plasmacytic enteritis (3%). Intravascular bacteria were observed solely in large cell lymphoma (29%), and serosal colonization was more common in cats with large cell lymphoma (57%) than with small cell lymphoma (11%, P ≤ .01), normal to minimal change (8%, P ≤ .01), and lymphocytic-plasmacytic enteritis (6%, P ≤ .001). The high frequency of invasive bacteria within blood vessels and serosa of cats with large cell lymphoma may account for the sepsis-related complications associated with large cell lymphoma and inform clinical management. Further studies are required to determine the role of intramucosal bacteria in the etiopathogenesis of feline alimentary lymphoma.

Interactions between the colonic transcriptome, metabolome, and microbiome in mouse models of obesity-induced intestinal cancer.

Obesity is a significant risk factor for colorectal cancer (CRC); however, the relative contribution of high-fat (HF) consumption and excess adiposity remains unclear. It is becoming apparent that obesity perturbs both the intestinal microbiome and metabolome, and each has the potential to induce protumorigenic changes in the epithelial transcriptome. The physiological consequences and the degree to which these different biologic systems interact remain poorly defined. To understand the mechanisms by which obesity drives colonic tumorigenesis, we profiled the colonic epithelial transcriptome of HF-fed and genetically obese (DbDb) mice with a genetic predisposition to intestinal tumorigenesis (Apc(1638N)); 266 and 584 genes were differentially expressed in the colonic mucosa of HF and DbDb mice, respectively. These genes mapped to pathways involved in immune function, and cellular proliferation and cancer. Furthermore, Akt was central within the networks of interacting genes identified in both gene sets. Regression analyses of coexpressed genes with the abundance of bacterial taxa identified three taxa, previously correlated with tumor burden, to be significantly correlated with a gene module enriched for Akt-related genes. Similarly, regression of coexpressed genes with metabolites found that adenosine, which was negatively associated with inflammatory markers and tumor burden, was also correlated with a gene module enriched with Akt regulators. Our findings provide evidence that HF consumption and excess adiposity result in changes in the colonic transcriptome that, although distinct, both appear to converge on Akt signaling. Such changes could be mediated by alterations in the colonic microbiome and metabolome.

Akkermansia muciniphila and Helicobacter typhlonius modulate intestinal tumor development in mice.

Gastrointestinal tumor growth is thought to be promoted by gastrointestinal bacteria and their inflammatory products. We observed that intestine-specific conditional Apc mutant mice (FabplCre;Apc (15lox/+)) developed many more colorectal tumors under conventional than under pathogen-low housing conditions. Shotgun metagenomic sequencing plus quantitative PCR analysis of feces DNA revealed the presence of two bacterial species in conventional mice, absent from pathogen-low mice. One, Helicobacter typhlonius, has not been associated with cancer in man, nor in immune-competent mice. The other species, mucin-degrading Akkermansia muciniphila, is abundantly present in healthy humans, but reduced in patients with inflammatory gastrointestinal diseases and in obese and type 2 diabetic mice. Eradication of H.typhlonius in young conventional mice by antibiotics decreased the number of intestinal tumors. Additional presence of A.muciniphila prior to the antibiotic treatment reduced the tumor number even further. Colonization of pathogen-low FabplCre;Apc (15lox/+) mice with H.typhlonius or A.muciniphila increased the number of intestinal tumors, the thickness of the intestinal mucus layer and A.muciniphila colonization without H.typhlonius increased the density of mucin-producing goblet cells. However, dual colonization with H.typhlonius and A.muciniphila significantly reduced the number of intestinal tumors, the mucus layer thickness and goblet cell density to that of control mice. By global microbiota composition analysis, we found a positive association of A.muciniphila, and of H.typhlonius, and a negative association of unclassified Clostridiales with increased tumor burden. We conclude that A.muciniphila and H.typhlonius can modulate gut microbiota composition and intestinal tumor development in mice.

Association of COX2 gene hypomethylation with intestinal type gastric cancer in samples of patients from northern Brazil.

To verify the methylation status of THBS1, GPX3, and COX2 genes and to evaluate their association with Helicobacter pylori in gastric adenocarcinomas. Methylation-sensitive restriction enzyme PCR assay was performed in 16 diffuse type gastric cancer samples, 23 intestinal type, and 15 normal stomach tissue. The presence of H. pylori was performed by amplification of the fragment of the 16S rRNA. Statistical analyses were performed using Fisher's exact test. The hypermethylation of GPX3, THBS1, and COX2 occurred in 18 (n = 7), 5 (n = 2), and 36 % (n = 14) of gastric cancer samples, respectively, whereas in normal samples, it was found in 13, 7, and 67 %. The presence of H. pylori was detected in 67 % of gastric cancer samples and 67 % in normal gastric samples. The methylation of THBS1 and GPX3 was not significantly different between the types of tumors, normal sample, the presence of H. pylori, or clinicopathological variables studied (P > 0.05). However, the methylation status of the gene COX2 is significantly different between normal tissue and intestinal type gastric cancer (P = 0.02). Therefore, our results suggest that the methylation status of the gene COX2 is associated with the intestinal type of gastric cancer.

Microbial metabolite trimethylamine-N-oxide induces intestinal carcinogenesis through inhibiting farnesoid X receptor signaling.

PURPOSE: Microbial dysbiosis is considered as a hallmark of colorectal cancer (CRC). Trimethylamine-N-oxide (TMAO) as a gut microbiota-dependent metabolite has recently been implicated in CRC development. Nevertheless, evidence relating TMAO to intestinal carcinogenesis remains largely unexplored. Herein, we aimed to examine the crucial role of TMAO in CRC progression. METHODS: Apcmin/+ mice were treated with TMAO or sterile PBS for 14 weeks. Intestinal tissues were isolated to evaluate the effects of TMAO on the malignant transformation of intestinal adenoma. The gut microbiota of mouse feces was detected by 16S rRNA sequencing analysis. HCT-116 cells were used to provide further evidence of TMAO on the progression of CRC. RESULTS: TMAO administration increased tumor cell and stem cell proliferation, and decreased apoptosis, accompanied by DNA damage and gut barrier impairment. Gut microbiota analysis revealed that TMAO induced changes in the intestinal microbial community structure, manifested as reduced beneficial bacteria. Mechanistically, TMAO bound to farnesoid X receptor (FXR), thereby inhibiting the FXR-fibroblast growth factor 15 (FGF15) axis and activating the Wnt/ß-catenin signaling pathway, whereas the FXR agonist GW4064 could blunt TMAO-induced Wnt/ß-catenin pathway activation. CONCLUSION: The microbial metabolite TMAO can enhance intestinal carcinogenesis by inhibiting the FXR-FGF15 pathway.

Intestinal epithelial cells as mediators of the commensal-host immune crosstalk.

Commensal bacteria regulate the homeostasis of host effector immune cell subsets. The mechanisms involved in this commensal-host crosstalk are not well understood. Intestinal epithelial cells (IECs) not only create a physical barrier between the commensals and immune cells in host tissues, but also facilitate interactions between them. Perturbations of epithelial homeostasis or function lead to the development of intestinal disorders such as inflammatory bowel diseases (IBD) and intestinal cancer. IECs receive signals from commensals and produce effector immune molecules. IECs also affect the function of immune cells in the lamina propria. Here we discuss some of these properties of IECs that define them as innate immune cells. We focus on how IECs may integrate and transmit signals from individual commensal bacteria to mucosal innate and adaptive immune cells for the establishment of the unique mucosal immunological equilibrium.

Microbiota and innate immunity in intestinal inflammation and neoplasia.

PURPOSE OF REVIEW: This review focuses on recent advances and novel insights into the mechanistic events that may link commensal microbiota and host innate immunity in the pathophysiology of intestinal inflammation and neoplasia. Unanswered questions are discussed and future perspectives in the field are highlighted. RECENT FINDINGS: Commensal microbiota, host innate immunity, and genetics form a multidimensional network that controls homeostasis of the mucosal barrier in the intestine. Large-scale sequencing projects have begun to catalog the healthy human microbiome. Converging evidence suggests that alterations in the regulation of the complex host environment [e.g., dysbiosis and overgrowth of select commensal bacterial species, dietary factors, copresence of facultative pathogens (including viruses), and changes in mucus characteristics] may trigger aberrant innate immune signaling, thereby contributing to the development of intestinal inflammation and associated colon cancer in the susceptible individual. Genetically determined innate immune malfunction may create an inflammatory environment that promotes tumor progression (such as the TLR4-D299G mutation). SUMMARY: The next challenging steps to be taken are to decipher changes in the human microbiome (and virome) during well defined diseased states, and relate them to intestinal mucosal immune functions and host genotypes.

Synergy between bacterial infection and genetic predisposition in intestinal dysplasia.

Accumulating evidence suggests that hyperproliferating intestinal stem cells (SCs) and progenitors drive cancer initiation, maintenance, and metastasis. In addition, chronic inflammation and infection have been increasingly recognized for their roles in cancer. Nevertheless, the mechanisms by which bacterial infections can initiate SC-mediated tumorigenesis remain elusive. Using a Drosophila model of gut pathogenesis, we show that intestinal infection with Pseudomonas aeruginosa, a human opportunistic bacterial pathogen, activates the c-Jun N-terminal kinase (JNK) pathway, a hallmark of the host stress response. This, in turn, causes apoptosis of enterocytes, the largest class of differentiated intestinal cells, and promotes a dramatic proliferation of SCs and progenitors that serves as a homeostatic compensatory mechanism to replenish the apoptotic enterocytes. However, we find that this homeostatic mechanism can lead to massive over-proliferation of intestinal cells when infection occurs in animals with a latent oncogenic form of the Ras1 oncogene. The affected intestines develop excess layers of cells with altered apicobasal polarity reminiscent of dysplasia, suggesting that infection can directly synergize with the genetic background in predisposed individuals to initiate SC-mediated tumorigenesis. Our results provide a framework for the study of intestinal bacterial infections and their effects on undifferentiated and mature enteric epithelial cells in the initial stages of intestinal cancer. Assessment of progenitor cell responses to pathogenic intestinal bacteria could provide a measure of predisposition for apoptotic enterocyte-assisted intestinal dysplasias in humans.

The effects of aerobic exercise on the intestinal tumors and flora of the ApcMin/+ mouse.

INTRODUCTION: Intestinal tumor is one of the most common tumors that seriously threaten the health of residents all over the world. Studies suggest that the imbalance of intestinal flora is associated with tumorgenesis; meanwhile, long-term regular aerobic exercise can improve the occurrence and development of tumors. However, moderate aerobic exercise affecting the development of intestinal tumors and their related flora has not been explored. Thus, the purpose of our study is to explore the effects of aerobic exercise on intestinal tumor growth and flora changes in ApcMin/+ mice, and try to answer whether there is a correlation between them after exercise intervention. METHODS: In this study, 18 required ApcMin/+ mice were randomly divided into Model group (n = 6), Exercise group (n = 6), and Aspirin group (positive control, n = 6), while C57BL/6 J wild-type mice were used as the blank control group. Each group is given corresponding intervention. Weight monitoring, tumor counts, hematoxylin-eosin staining, TdT-mediated dUTP nick-end labeling (TUNEL) fluorescence assay, immunohistochemistry (IHC), fecal sampling and grouping, and bacterial 16S rDNA gene analysis were completed after 12 weeks' intervention for each group of mice. RESULTS: As a result, we were able to show significant improvements in mice' body weight changing rates (Exercise group 8.6% higher than Model control group), tumor numbers (Exercise group 4.33 ± 0.94 vs. Model control group 7.33 ± 2.49, Then put the slides into xylenewith tumor inhibition rate 40.93%), tumor pathological staging (Exercise group mainly low-grade tumorous adenomas vs. Model group mainly high-grade adenomas), and TUNEL staining (Exercise group 8.59% higher positive rate of apoptotic cells in tumors than Model group). The 16s rRNA sequencing analysis results showed that aerobic exercise could regulate the abundance of some genus (16/149, P < 0.01), and the number of intestinal tumors correlates with changes in the abundance of some bacteria in the intestinal flora (positive correlation with probiotics abundance and negative correlation with conditioned pathogens). DISCUSSION: Changes in flora abundance may be one of the reasons for aerobic exercise to reduce the number of intestinal tumors, probably mediated by cell apoptosis. Future studies should focus on the potential mechanism of aerobic exercise in preventing intestinal tumorgenesis, especially the molecular mechanism through intestinal flora. CONCLUSION: Aerobic exercise has a preventive effect on intestinal tumors in ApcMin/+ mice, and can regulate the abundance of intestinal flora.

Analysis of abnormal intestinal flora on risk of intestinal cancer and effect of heparin on formation of bacterial biofilm.

To study the effect of abnormal intestinal flora on the risk of colorectal cancer and the effect of heparin on the formation of bacterial biofilm, 50 patients with colorectal cancer and 50 healthy subjects were selected. The distribution and quantity of bacteria in feces, the levels of D-lactic acid and endotoxin in serum of the two groups were detected. Intestinal flora strains and biofilm growth were also detected in patients with colorectal cancer cultured in different heparin concentrations (0 mg/mL, 5 mg /mL, 10 mg/mL, and 20 mg/mL). The results showed that there was significant difference in the number of major strains of intestinal flora between healthy subjects and colorectal cancer patients before and after operation (P < 0.05). The serum D-lactic acid levels (1.41 ± 0.39, 6.38 ± 1.42 µg/mL) and endotoxin levels (0.62 ± 0.09, 0.80 ± 0.15 EU/mL) in the experimental group were higher than those in the control group (0.91 ± 0.52 µg/mL) (0.05 ± 0.02 EU/mL) before and after operation (P < 0.05). The amount of biofilm formation increased significantly with the increase of heparin concentration (P < 0.05). In summary, there was a close relationship between the occurrence of colorectal cancer and abnormal intestinal flora. Heparin may have a positive effect on regulating intestinal flora in patients with colorectal cancer, which provided certain reference value for the treatment of colorectal cancer.

Functions of Dendritic Cells and Its Association with Intestinal Diseases.

Dendritic cells (DCs), including conventional DCs (cDCs) and plasmacytoid DCs (pDCs), serve as the sentinel cells of the immune system and are responsible for presenting antigen information. Moreover, the role of DCs derived from monocytes (moDCs) in the development of inflammation has been emphasized. Several studies have shown that the function of DCs can be influenced by gut microbes including gut bacteria and viruses. Abnormal changes/reactions in intestinal DCs are potentially associated with diseases such as inflammatory bowel disease (IBD) and intestinal tumors, allowing DCs to be a new target for the treatment of these diseases. In this review, we summarized the physiological functions of DCs in the intestinal micro-environment, their regulatory relationship with intestinal microorganisms and their regulatory mechanism in intestinal diseases.