BackgroundIncreasing evidence has supported the link of intestinal Fusobacterium nucleatum infection to colorectal cancer (CRC). However, the value of F. nucleatum as a biomarker in CRC detection has not been fully defined. In order to reduce the random error and bias of individual research, this meta-analysis aimed to evaluate the diagnostic performance of intestinal F. nucleatum in CRC patients and provide evidence-based data to clinical practice.

MethodsAn article search was performed from PubMed, Embase, Cochrane Library, and Web of Science databases up to December 2017, using the following key words: "Fusobacterium nucleatum", "Fusobacterium spp.", "Fn", "colorectal cancer(s)", "colorectal carcinoma(s)", "colorectal neoplasm(s)", and "colorectal tumor(s)". Articles on relationships between F. nucleatum and CRC were selected according to the preestablished inclusion and exclusion criteria. This meta-analysis was performed using STATA 12.0 software, which included mapping of forest plots, heterogeneity tests, meta-regression, subgroup analysis, sensitivity analysis, and publication bias. The sensitivity, specificity, positive likelihood ratio (LR), negative LR, diagnostic odds ratio (DOR), and their corresponding 95% confidence interval (CI) of each eligible study were summarized.

ResultsFinally, data for 1198 participants (629 CRC and 569 healthy controls) in 10 controlled studies from seven articles were included. The summary receiver operator characteristic curve was mapped. The diagnostic performance of intestinal F. nucleatum infection on CRC was as follows: the area under the curve: 0.86 (95% CI: 0.83-0.89), the pooled sensitivity: 0.81 (95% CI: 0.64-0.91), specificity: 0.77 (95% CI: 0.59-0.89), and DOR: 14.00 (95% CI: 9.00-22.00).

ConclusionIntestinal F. nucleatum is a valuable marker for CRC diagnosis.

Colonic Neoplasms ; microbiology ; Colorectal Neoplasms ; microbiology ; Fusobacterium nucleatum ; physiology ; Humans ; Intestines ; microbiology ; pathology

Accumulating evidence suggests that intestinal bacteria play an important role in the pathogenesis of colorectal cancer (CRC). Due to the complexity of the intestinal microbiome, identification of the specific causative microbial agents in CRC remains challenging, and the search for the causative microbial agents is intense. However, whether bacteria or their products can induce inflammation that results in tumorigenesis or directly causes CRC in humans is still not clear. This review will mainly focus on the progress of bacterial infection and CRC, and introduce the microbial contribution to the hallmarks of cancer. This article uses Salmonella and its chronic infection as an example to investigate a single pathogen and its role in the development of CRC, based on laboratory and epidemiological evidence. The bacterial infection leads to an altered intestinal microbiome. The review also discusses the dysfunction of the microbiome and the mechanism of host-microbial interactions, for example, bacterial virulence factors, key signaling pathways in the host, and microbial post-translational modifications in the tumorigenesis. Colonic carcinogenesis involves a progressive accumulation of mutations in a genetically susceptible host leading to cellular autonomy. Moving forward, more human data are needed to confirm the direct roles of bacterial infection in CRC development. Insights into the inhibiting infection will help to prevent cancer and develop strategies to restore the balance between host and microorganisms.
Bacterial Infections/complications* ; Carcinogenesis ; Colorectal Neoplasms/microbiology* ; Gastrointestinal Microbiome ; Humans

Colorectal cancer is a common carcinoma of gastrointestinal tract, and its incidence is associated with genetic mutations, environment as well as inflammation. Recent studies have shown that many microorganisms may have played an important role in pathogenesis of colorectal cancer. The common bacteria involved in colorectal cancer are Streptococcus bovis, Helicobacter pylori, Escherichia coli, Bacteroides, and Fusobacterium, etc. The common viruses are Polyomavirus, Epstein Barr virus, Cytomegalovirus and Human papillomavirus, etc. The detailed mechanism of these microorganisms in the pathogenesis of colorectal cancer is unclear, and there are no reports on specific pathogenic microorganisms which cause the disease directly. The direction of future researches will focus on metagenome, metatranscriptome, and metaproteome of microorganisms associated with the incidence of colorectal cancer.
Colorectal Neoplasms ; microbiology ; Helicobacter Infections ; Helicobacter pylori ; Herpesvirus 4, Human ; Humans ; Inflammation ; Papillomaviridae

OBJECTIVE: To investigate the changes in bacterial flora in fecal samples, at the tumor loci and in adjacent mucosa in patients with colorectal cancer (CRC). METHODS: We collected fecal samples from 13 patients with CRC and 20 healthy individuals and tumor and adjacent mucosa samples from 6 CRC patients. The differences in bacterial composition between the fecal and mucosa samples were analyzed with 16S rDNA sequencing and bioinformatics methods. We also detected the total number of bacteria in the feces using flow cytometry, isolated and identified the microorganisms in the fecal and mucosa samples using common bacterial culture media. We further tested the effects of 7 isolated bacterial strains on apoptosis of 3 CRC cell lines using lactate dehydrogenase detection kit. RESULTS: The bacterial α-diversity in the feces of healthy individuals and in adjacent mucosa of CRC patients was significantly higher than that in the feces and tumor mucosa in CRC patients (P < 0.05). Lactobacillaceae is a specific bacteria in the feces, while Escherichia, Enterococcus, and Fusobacterium are specific bacteria in tumor mucosa of CRC patients as compared with healthy individuals. Cell experiment with3 CRC cell lines showed that Bacteroides fragilis isolated from the tumor mucosa of CRC patients produced significant inhibitory effects on cell proliferation (P < 0.0001), while the isolated strain Fusobacterium nucleatum obviously promoted the proliferation of the cell lines (P < 0.001). CONCLUSION The bacterial flora in the feces, tumor mucosa and adjacent mucosa of CRC patients is significantly different from that in the feces of healthy individuals, and the fecal flora of CRC patients can not represent the specific flora of the tumor mucosa. Inhibition of F. nucleatum colonization in the tumor mucosa and promoting B. fragilis colonization may prove beneficial for CRC treatment.
Bacteria ; Colorectal Neoplasms/pathology* ; Feces/microbiology* ; Gastrointestinal Microbiome ; Humans ; Intestinal Mucosa

The human intestinal microbiota is a community of 10(13)-10(14) microorganisms that harbor in the intestine and normally participate in a symbiotic relationship with human. Technical and conceptual advances have enabled rapid progress in characterizing the taxonomic composition, metabolic capacity and immunomodulatory activity of the human intestinal microbiota. Their collective genome, defined as microbiome, is estimated to contain > or =150 times as many genes as 2.85 billion base pair human genome. The intestinal microbiota and its microbiome form a diverse and complex ecological community that profoundly impact intestinal homeostasis and disease states. It is becoming increasingly evident that the large and complex bacterial population of the large intestine plays an important role in colorectal carcinogenesis. Numerous studies show that gut immunity and inflammation have impact on the development of colorectal cancer. Additionally, bacteria have been linked to colorectal cancer by the production of toxic and genotoxic bacterial metabolite. In this review, we discuss the multifactorial role of intestinal microbiota in colorectal cancer and role for probiotics in the prevention of colorectal cancer.
Animals ; Bacteroides/metabolism ; Colorectal Neoplasms/immunology/*microbiology ; Fatty Acids, Nonesterified/metabolism ; Humans ; Hydrogen Sulfide/metabolism ; Intestinal Mucosa/immunology/microbiology ; Metagenome ; *Probiotics ; Reactive Oxygen Species/metabolism ; Toxins, Biological/metabolism

OBJECTIVETo compare the impact of traditional and fast bowel preparation on the changes of gut flora in the patients following colorectal resection.

METHODSSixty patients undergoing colorectal resection from March 2010 to March 2011 in the Nanfang Hospital were randomly divided into the control group(n=27, 3 days of bowel preparation) and the experimental group(n=33, 1 day of bowel preparation). Fresh feces were collected before bowel preparation and on the first defecation after surgery. The postoperative changes in gut flora and septic complications were observed.

RESULTSGut flora disturbance was found in both groups. The postoperative population of Bifidobacterium and Lactobacillus decreased significantly(P<0.05), and the decrease was more significant in the experimental group compared to the control group(P<0.05), while E.coli and Staphylococcus were much higher than the preoperative level(P<0.05), which was more significant in the control group. The incidence of postoperative infection was 9.1%(3/33) in the experimental group, which was significantly lower than 29.6%(8/27) in the control group(P<0.05).

CONCLUSIONFast bowel preparation is effective in reducing gut flora disturbance and the incidence of postoperative infection.

Colorectal Neoplasms ; microbiology ; surgery ; Digestive System Surgical Procedures ; Enema ; methods ; Feces ; microbiology ; Female ; Humans ; Male ; Microbiota ; Middle Aged ; Postoperative Period ; Preoperative Care ; Prospective Studies

OBJECTIVETo investigate the effect of perioperative application of intestinal probiotics to substitute oral intestinal antimicrobial agents on intestinal flora and immune function in surgical patients with colorectal cancer.

METHODSSixty patients with colorectal cancer undergoing elective laparoscopic radical surgery were randomized to receive preoperative bowel preparation using oral intestinal antimicrobial agents (n=20) or using oral intestinal probiotics (Jinshuangqi Tablets, 2.0 g, 3 times daily) since the fifth day before the operation and at 24 h after the operation for 7 consecutive days. Upon admission and 7 days after the operation, fecal samples and fasting peripheral venous blood were collected from the patients to examine the intestinal flora and serum levels of interleukin-2 (IL-2), IgA, IgG, and IgM, NK cell activity, T lymphocytes subsets CD3(+), CD4(+), CD8(+) and CD4(+)/CD8(+) ratio.

RESULTSAt 7 days after the operation, the patients receiving probiotics showed significantly increased counts of intestinal Bifidobacterium, Lactobacillus, and Enterococcus (P<0.05) and significantly lowered counts of Escherichia coli and Staphylococcus aureus (P<0.05). The serum levels of IL-2, IgA, IgG and IgM as well as CD4(+) cell percentage all increased significantly in probiotics group compared with those in patients with conventional intestinal preparation (P<0.05).

CONCLUSIONSPerioperative application of intestinal probiotics to replace preoperative oral intestinal antimicrobial agents can effectively correct intestinal flora imbalance and improve the immune function of surgical patients with colorectal cancer.

Aged ; Bifidobacterium ; Colorectal Neoplasms ; immunology ; microbiology ; Female ; Humans ; Intestines ; microbiology ; Intraoperative Period ; Male ; Middle Aged ; Premedication ; Probiotics ; therapeutic use ; Prospective Studies ; Single-Blind Method

BACKGROUND: Type 2 diabetes mellitus (T2DM) is an independent risk factor for colorectal cancer (CRC), and the patients with CRC and T2DM have worse survival. The human gut microbiota (GM) is linked to the development of CRC and T2DM, respectively. However, the GM characteristics in patients with CRC and T2DM remain unclear. METHODS: We performed fecal metagenomic and targeted metabolomics studies on 36 samples from CRC patients with T2DM (DCRC group, n = 12), CRC patients without diabetes (CRC group, n = 12), and healthy controls (Health group, n = 12). We analyzed the fecal microbiomes, characterized the composition and function based on the metagenomics of DCRC patients, and detected the short-chain fatty acids (SCFAs) and bile acids (BAs) levels in all fecal samples. Finally, we performed a correlation analysis of the differential bacteria and metabolites between different groups. RESULTS: Compared with the CRC group, LefSe analysis showed that there is a specific GM community in DCRC group, including an increased abundance of Eggerthella , Hungatella , Peptostreptococcus , and Parvimonas , and decreased Butyricicoccus , Lactobacillus , and Paraprevotella . The metabolomics analysis results revealed that the butyric acid level was lower but the deoxycholic acid and 12-keto-lithocholic acid levels were higher in the DCRC group than other groups ( P < 0.05). The correlation analysis showed that the dominant bacterial abundance in the DCRC group ( Parvimonas , Desulfurispora , Sebaldella , and Veillonellales , among others) was negatively correlated with butyric acid, hyodeoxycholic acid, ursodeoxycholic acid, glycochenodeoxycholic acid, chenodeoxycholic acid, cholic acid and glycocholate. However, the abundance of mostly inferior bacteria was positively correlated with these metabolic acid levels, including Faecalibacterium , Thermococci , and Cellulophaga . CONCLUSIONS Unique fecal microbiome signatures exist in CRC patients with T2DM compared to those with non-diabetic CRC. Alterations in GM composition and SCFAs and secondary BAs levels may promote CRC development.
Humans ; Gastrointestinal Microbiome/genetics* ; Diabetes Mellitus, Type 2 ; Microbiota ; Bacteria/genetics* ; Fatty Acids, Volatile ; Colorectal Neoplasms/metabolism* ; Butyrates ; Feces/microbiology*

OBJECTIVESTo investigate the feasibility and safety of one-day bowel preparation for colorectal surgery.

METHODSForty patients undergone colorectal surgery were divided randomly into the Control group and the Experimental group and received 3-day magnesium sulfate and 1-day sodium phosphate bowel preparations before the operation, respectively. The levels of hemoglobin, hematocrit, serum electrolytes, and anaerobe counts in the stool prior and post bowel preparation were examined. The general status, surgical complications, and structure of intestinal mucosa in the patients were observed after the operation.

RESULTSThere was no significant difference in the anastomoses healing, infectious complications, serum tests and intestinal mucosa structures between the two groups. Less diarrhea occurred prior and post the surgery in the experimental group, and they felt better with the bowel preparation. The anaerobe counts in stool were higher after the bowel preparation than before in both groups.

CONCLUSIONSOne-day bowel preparation with sodium phosphate is a safe and reliable method for colorectal surgery. The shortening of preparation time can reduce the degrees of uncomfortable feeling and disruptions of intestinal micro-ecology and barrier.

Colorectal Neoplasms ; surgery ; Enema ; Humans ; Intestinal Mucosa ; drug effects ; microbiology ; Magnesium Sulfate ; administration & dosage ; Middle Aged ; Phosphates ; administration & dosage ; Postoperative Complications ; Preoperative Care ; methods ; Prospective Studies

OBJECTIVETo investigate the effect of preoperative use of viable Bifidobacterium supplement on the intestinal flora, immune status, inflammatory response and prognosis of patients undergoing colorectal cancer resection.

METHODSSixty patients with colorectal cancer were randomized into treatment group (n=30) and control group (n=30). Patients in the treatment group received oral viable Bifidobacterium with routine enteral nutrition and patients in the control group received routine enteral nutrition alone. The intestinal flora of stool was analyzed and stool SIgA, serum IgG, IgM, IgA, IL-6, and C-reactive protein (CRP) were detected.

RESULTSPostoperative Bifidobacterium/E.coli (B/E) ratio in the treatment group decreased significantly as compared to the preoperative ratio (2.01+/-0.36 vs 26.53+/-4.22, P<0.05). However, the ratios remained above one. Both preoperative and postoperative B/E ratios in the control group (0.72+/-0.14, 0.02+/-0.06) were significantly lower than those in the treatment group (P<0.05). Indexes of immunity and inflammation were not significantly different between the two groups (P>0.05). At day 9 after operation, stool SIgA was higher in the treatment group, while serum IgG, IgM, IgA, IL-6, CRP in the treatment group were lower (P<0.05). Postoperative septic complications in the treatment group was less than that in the control group (P<0.05), but other complications and hospital stay were comparable.

CONCLUSIONSIn patients with colorectal cancer, supplementation of viable Bifidobacterium before surgery can improve bacterial dysbiosis and immunity, and can reconstruct the balance of intestinal flora, and reduce infection complication of surgery.

Adult ; Aged ; Aged, 80 and over ; Antibodies ; blood ; Bifidobacterium ; C-Reactive Protein ; analysis ; Colorectal Neoplasms ; immunology ; microbiology ; therapy ; Female ; Humans ; Inflammation ; Interleukin-6 ; blood ; Male ; Middle Aged ; Postoperative Period ; Probiotics ; therapeutic use