肠道菌群及其代谢产物 与结肠腺瘤性息肉相关性的研究进展

结肠癌(colorectal cancer,CRC)是常见的消化道恶性肿瘤,其发病率和病死率都极高。从结肠息肉发展到结肠癌一般需要10～15年,且大多遵循息肉-腺瘤-癌症的发展过程,结肠腺瘤性息肉(colorectal adenomatous polyps,CAP)被认为是结肠癌的癌前病变。有研究显示肠道菌群的改变与肠道腺瘤性息肉样变及癌症的发生发展有密切的相关性。根据肠道菌群在不同病理状态下的富集程度,可以进一步分析其与结肠病变之间的关系。本文就肠道菌群的构成,CAP患者粪便和腺瘤组织中肠道菌群富集的改变,以及肠道菌群代谢产物对CAP患者的影响等内容进行综述,为结肠腺瘤性息肉的早期诊断和治疗提供依据。     

Gut microbiota in patients after surgical treatment for colorectal cancer

Colorectal cancer (CRC) is a common disease worldwide that is strongly associated with the gut microbiota. However, little is known regarding the gut microbiota after surgical treatment. 16S rRNA gene sequencing was used to evaluate differences in gut microbiota among colorectal adenoma patients, CRC patients, CRC postoperative patients and healthy controls by comparing gut microbiota diversity, overall composition and taxonomic signature abundance. The gut microbiota of CRC patients, adenoma patients and healthy controls developed in accordance with the adenoma-carcinoma sequence, with impressive shifts in the gut microbiota before or during the development of CRC. The gut microbiota of postoperative patients and CRC patients differed significantly. Subdividing CRC postoperative patients according to the presence or absence of newly developed adenoma which based on the colonoscopy findings revealed that the gut microbiota of newly developed adenoma patients differed significantly from that of clean intestine patients and was more similar to the gut microbiota of carcinoma patients than to the gut microbiota of healthy controls. The alterations of the gut microbiota between the two groups of postoperative patients corresponded to CRC prognosis. More importantly, we used the different gut microbiota as biomarkers to distinguish postoperative patients with or without newly developed adenoma, achieving an AUC value of 0.72. These insights on the changes in the gut microbiota of CRC patients after surgical treatment may allow the use of the microbiota as non-invasive biomarkers for the diagnosis of newly developed adenomas and to help prevent cancer recurrence in postoperative patients.     

Faecal microbial biomarkers in early diagnosis of colorectal cancer

Colorectal cancer (CRC) is ranked as the second most common cause of cancer deaths and the third most common cancer globally. It has been described as a ‘silent disease’ which is often easily treatable if detected early—before progression to carcinoma. Colonoscopy, which is the gold standard for diagnosis is not only expensive but is also an invasive diagnostic procedure, thus, effective and non-invasive diagnostic methods are urgently needed. Unfortunately, the current methods are not sensitive and specific enough in detecting adenomas and early colorectal neoplasia, hampering treatment and consequently, survival rates. Studies have shown that imbalances in such a relationship which renders the gut microbiota in a dysbiotic state are implicated in the development of adenomas ultimately resulting in CRC. The differences found in the makeup and diversity of the gut microbiota of healthy individuals relative to CRC patients have in recent times gained attention as potential biomarkers in early non-invasive diagnosis of CRC, with promising sensitivity, specificity and even cost-effectiveness. This review summarizes recent studies in the application of these microbiota biomarkers in early CRC diagnosis, limitations encountered in the area of the faecal microbiota studies as biomarkers for CRC, and future research exploits that address these limitations.     

How the interplay among the tumor microenvironment and the gut microbiota influences the stemness of colorectal cancer cells

Colorectal cancer (CRC) remains the third most prevalent cancer disease and involves a multi-step process in which intestinal cells acquire malignant characteristics. It is well established that the appearance of distal metastasis in CRC patients is the cause of a poor prognosis and treatment failure. Nevertheless, in the last decades, CRC aggressiveness and progression have been attributed to a specific cell population called CRC stem cells (CCSC) with features like tumor initiation capacity, self-renewal capacity, and acquired multidrug resistance. Emerging data highlight the concept of this cell subtype as a plastic entity that has a dynamic status and can be originated from different types of cells through genetic and epigenetic changes. These alterations are modulated by complex and dynamic crosstalk with environmental factors by paracrine signaling. It is known that in the tumor niche, different cell types, structures, and biomolecules coexist and interact with cancer cells favoring cancer growth and development. Together, these components constitute the tumor microenvironment (TME). Most recently, researchers have also deepened the influence of the complex variety of microorganisms that inhabit the intestinal mucosa, collectively known as gut microbiota, on CRC. Both TME and microorganisms participate in inflammatory processes that can drive the initiation and evolution of CRC. Since in the last decade, crucial advances have been made concerning to the synergistic interaction among the TME and gut microorganisms that condition the identity of CCSC, the data exposed in this review could provide valuable insights into the biology of CRC and the development of new targeted therapies.     

Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis

Inflammatory bowel disease (IBD) is a multifactorial disease which arises as a result of the interaction of genetic, environmental, barrier and microbial factors leading to chronic inflammation in the intestine. Patients with IBD had a higher risk of developing colorectal carcinoma (CRC), of which the subset was classified as colitis-associated cancers. Genetic polymorphism of innate immune receptors had long been considered a major risk factor for IBD, and the mutations were also recently observed in CRC. Altered microbial composition (termed microbiota dybiosis) and dysfunctional gut barrier manifested by epithelial hyperpermeability and high amount of mucosa-associated bacteria were observed in IBD and CRC patients. The findings suggested that aberrant immune responses to penetrating commensal microbes may play key roles in fueling disease progression. Accumulative evidence demonstrated that mucosa-associated bacteria harbored colitogenic and protumoral properties in experimental models, supporting an active role of bacteria as pathobionts (commensal-derived opportunistic pathogens). Nevertheless, the host factors involved in bacterial dysbiosis and conversion mechanisms from lumen-dwelling commensals to mucosal pathobionts remain unclear. Based on the observation of gut leakiness in patients and the evidence of epithelial hyperpermeability prior to the onset of mucosal histopathology in colitic animals, it was postulated that the epithelial barrier dysfunction associated with mucosal enrichment of specific bacterial strains may predispose the shift to disease-associated microbiota. The speculation of leaky gut as an initiating factor for microbiota dysbiosis that eventually led to pathological consequences was proposed as the “common ground hypothesis”, which will be highlighted in this review. Overall, the understanding of the core interplay between gut microbiota and epithelial barriers at early subclinical phases will shed light to novel therapeutic strategies to manage chronic inflammatory disorders and colitis-associated cancers.     

Tumor-derived exosomes: Potential biomarkers and therapeutic target in the treatment of colorectal cancer

Colorectal cancer (CRC) is the third most common cause of cancer-related death in men and women in many countries. Early detection of CRC helps to prevent the advanced stages of the disease, and may thereby improve the survival of these patients. A noninvasive test with high specificity and sensitivity is required for this. Exosomes are lipid bilayer membrane nanovesicles that are released into most body fluids and especially in the microenvironment of cancer. They carry various proteins, lipids, and nucleic materials such as DNA, RNA, messenger RNA (mRNA), and microRNA (miRNA), and may also alter the function of target cells. In this review, we aimed to describe the biogenesis, composition, function, and the role of tumor-derived exosomes in cancer progression. Moreover, their applications in tumor diagnosis and treatment are described, with a particular focus on CRC.     

Therapeutic potential of melatonin in colorectal cancer: Focus on lipid metabolism and gut microbiota

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies. The occurrence and development of CRC are complicated processes. Obesity and dysbacteriosis have been increasingly regarded as the main risk factors for CRC. Understanding the etiology of CRC from multiple perspectives is conducive to screening for some potential drugs or new treatment strategies to limit the serious side effects of conventional treatment and prolong the survival of CRC patients. Melatonin, a natural indoleamine, is mainly produced by the pineal gland, but it is also abundant in other tissues, including the gastrointestinal tract, retina, testes, lymphocytes, and Harder's glands. Melatonin could participate in lipid metabolism by regulating adipogenesis and lipolysis. Additionally, many studies have focused on the potential beneficial effects of melatonin in CRC, such as promotion of apoptosis; inhibition of cell proliferation, migration, and invasion; antioxidant activity; and immune regulation. Meaningfully, gut microbiota is the main determinant of all aspects of health and disease (including obesity and tumorigenesis). The gut microbiota is of great significance for understanding the relationship between obesity and increased risk of CRC. Although the current understanding of how the melatonin-mediated gut microbiota coordinates a variety of physiological and pathological activities is fairly comprehensive, there are still many unknown topics to be explored in the face of a complex nutritional status and a changeable microbiota. This review summarizes the potential links among melatonin, lipid metabolism, gut microbiota, and CRC to promote the development of melatonin as a preventive and therapeutic agent for CRC.     

Application of open-access databases to determine functional connectivity between resveratrol-binding protein QR2 and colorectal carcinoma

Colorectal cancer (CRC) is a major cause of cancer-associated deaths worldwide. Recently, oral administration of resveratrol (trans-3,5,4′-trihydroxystilbene) has been reported to significantly reduce tumor proliferation in colorectal cancer patients, however, with little specific information on functional connections. The pathogenesis and development of colorectal cancer is a multistep process that can be categorized using three phenotypic pathways, respectively, chromosome instability (CIN), microsatellite instability (MSI), and CpG island methylator (CIMP). Targets of resveratrol, including a high-affinity binding protein, quinone reductase 2 (QR2), have been identified with little information on disease association. We hypothesize that the relationship between resveratrol and different CRC etiologies might be gleaned using publicly available databases. A web-based microarray gene expression data-mining platform, Oncomine, was selected and used to determine whether QR2 may serve as a mechanistic and functional biotarget within the various CRC etiologies. We found that QR2 messenger RNA (mRNA) is overexpressed in CRC characterized by CIN, particularly in cells showing a positive KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation, as well as by the MSI but not the CIMP phenotype. Mining of Oncomine revealed an excellent correlation between QR2 mRNA expression and certain CRC etiologies. Two resveratrol-associated genes, adenomatous polyposis coli (APC) and TP53, found in CRC were further mined, using cBio portal and Colorectal Cancer Atlas which predicted a mechanistic link to exist between resveratrol→QR2/TP53→CIN. Multiple web-based data mining can provide valuable insights which may lead to hypotheses serving to guide clinical trials and design of therapies for enhanced disease prognosis and patient survival. This approach resembles a BioGPS, a capability for mining web-based databases that can elucidate the potential links between compounds to provide correlations of these interactions with specific diseases.     

Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer

Recent reports have suggested the involvement of gut microbiota in the progression of colorectal cancer (CRC). We utilized pyrosequencing based analysis of 16S rRNA genes to determine the overall structure of microbiota in patients with colorectal cancer and healthy controls; we investigated microbiota of the intestinal lumen, the cancerous tissue and matched noncancerous normal tissue. Moreover, we investigated the mucosa-adherent microbial composition using rectal swab samples because the structure of the tissue-adherent bacterial community is potentially altered following bowel cleansing. Our findings indicated that the microbial structure of the intestinal lumen and cancerous tissue differed significantly. Phylotypes that enhance energy harvest from diets or perform metabolic exchange with the host were more abundant in the lumen. There were more abundant Firmicutes and less abundant Bacteroidetes and Proteobacteria in lumen. The overall microbial structures of cancerous tissue and noncancerous tissue were similar; however the tumor microbiota exhibited lower diversity. The structures of the intestinal lumen microbiota and mucosa-adherent microbiota were different in CRC patients compared to matched microbiota in healthy individuals. Lactobacillales was enriched in cancerous tissue, whereas Faecalibacterium was reduced. In the mucosa-adherent microbiota, Bifidobacterium, Faecalibacterium, and Blautia were reduced in CRC patients, whereas Fusobacterium, Porphyromonas, Peptostreptococcus, and Mogibacterium were enriched. In the lumen, predominant phylotypes related to metabolic disorders or metabolic exchange with the host, Erysipelotrichaceae, Prevotellaceae, and Coriobacteriaceae were increased in cancer patients. Coupled with previous reports, these results suggest that the intestinal microbiota is associated with CRC risk and that intestinal lumen microflora potentially influence CRC risk via cometabolism or metabolic exchange with the host. However, mucosa-associated microbiota potentially affects CRC risk primarily through direct interaction with the host.     

The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer?

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States, and, even though 5-15% of the total CRC cases can be attributed to individual genetic predisposition, environmental factors could be considered major factors in susceptibility to CRC. Lifestyle factors increasing the risks of CRC include elevated body mass index, obesity, and reduced physical activity. Additionally, a number of dietary elements have been associated with higher or lower incidence of CRC. In this context, it has been suggested that diets high in fruit and low in meat might have a protective effect, reducing the incidence of colorectal adenomas by modulating the composition of the normal nonpathogenic commensal microbiota. In addition, it has been demonstrated that changes in abundance of taxonomic groups have a profound impact on the gastrointestinal physiology, and an increasing number of studies are proposing that the microbiota mediates the generation of dietary factors triggering colon cancer. High-throughput sequencing and molecular taxonomic technologies are rapidly filling the knowledge gaps left by conventional microbiology techniques to obtain a comprehensive catalog of the human intestinal microbiota and their associated metabolic repertoire. The information provided by these studies will be essential to identify agents capable of modulating the massive amount of gut bacteria in safe noninvasive manners to prevent CRC. Probiotics, defined as "live microorganisms which, when administered in adequate amounts, confer a health benefit on the host" (219), are capable of transient modulation of the microbiota, and their beneficial effects include reinforcement of the natural defense mechanisms and protection against gastrointestinal disorders. Probiotics have been successfully used to manage infant diarrhea, food allergies, and inflammatory bowel disease; hence, the purpose of this review was to examine probiotic metabolic activities that may have an effect on the prevention of CRC by scavenging toxic compounds or preventing their generation in situ. Additionally, a brief consideration is given to safety evaluation and production methods in the context of probiotics efficacy.     

Current understanding of microbiota- and dietary-therapies for treating inflammatory bowel disease

Inflammatory bowel disease (IBD) is a result of chronic inflammation caused, in some part, by dysbiosis of intestinal microbiota, mainly commensal bacteria. Gut dysbiosis can be caused by multiple factors, including abnormal immune responses which might be related to genetic susceptibility, infection, western dietary habits, and administration of antibiotics. Consequently, the disease itself is characterized as having multiple causes, etiologies, and severities. Recent studies have identified >200 IBD risk loci in the host. It has been postulated that gut microbiota interact with these risk loci resulting in dysbiosis, and this subsequently leads to the development of IBD. Typical gut microbiota in IBD patients are characterized with decrease in species richness and many of the commensal, and beneficial, fecal bacteria such as Firmicutes and Bacteroidetes and an increase or bloom of Proteobacteria. However, at this time, cause and effect relationships have not been rigorously established. While treatments of IBD usually includes medications such as corticosteroids, 5-aminosalicylates, antibiotics, immunomodulators, and anti-TNF agents, restoration of gut dysbiosis seems to be a safer and more sustainable approach. Bacteriotherapies (now called microbiota therapies) and dietary interventions are effective way to modulate gut microbiota. In this review, we summarize factors involved in IBD and studies attempted to treat IBD with probiotics. We also discuss the potential use of microbiota therapies as one promising approach in treating IBD. As therapies based on the modulation of gut microbiota becomes more common, future studies should include individual gut microbiota differences to develop personalized therapy for IBD.     

Targeting the gut microbiota with resveratrol: a demonstration of novel evidence for the management of hepatic steatosis

Resveratrol is a natural polyphenol that has been reported to reduce the risk of obesity and nonalcoholic fatty liver disease (NAFLD). Recent evidence has demonstrated that the gut microbiota plays an important role in the protection against NAFLD and other metabolic diseases. The present study aimed to investigate the relationship between the gut microbiota and the beneficial effects of resveratrol on the amelioration of NAFLD in mice. We observed marked decreases in body weight and liver steatosis and improved insulin resistance in high-fat diet (HFD)-fed mice treated with resveratrol. Furthermore, we found that resveratrol treatment alleviated NAFLD in HFD-fed mice by improving the intestinal microenvironment, including gut barrier function and gut microbiota composition. On the one hand, resveratrol improved gut intestinal barrier integrity through the repair of intestinal mucosal morphology and increased the expression of physical barrier- and physiochemical barrier-related factors in HFD-fed mice. On the other hand, in HFD-fed mice, resveratrol supplementation modulated the gut bacterial composition. The resveratrol-induced gut microbiota was characterized by a decreased abundance of harmful bacteria, including Desulfovibrio, Lachnospiraceae_NK4A316_group and Alistipes, as well as an increased abundance of short-chain fatty acid (SCFA)-producing bacteria, such as Allobaculum, Bacteroides and Blautia. Moreover, transplantation of the HFDR-microbiota into HFD-fed mice sufficiently decreased body weight, liver steatosis and low-grade inflammation and improved hepatic lipid metabolism. Collectively, resveratrol would provide a potentially dietary intervention strategy against NAFLD through modulating the intestinal microenvironment.     

Increased rectal microbial richness is associated with the presence of colorectal adenomas in humans

Differences in the composition of the gut microbial community have been associated with diseases such as obesity, Crohn''s disease, ulcerative colitis and colorectal cancer (CRC). We used 454 titanium pyrosequencing of the V1–V2 region of the 16S rRNA gene to characterize adherent bacterial communities in mucosal biopsy samples from 33 subjects with adenomas and 38 subjects without adenomas (controls). Biopsy samples from subjects with adenomas had greater numbers of bacteria from 87 taxa than controls; only 5 taxa were more abundant in control samples. The magnitude of the differences in the distal gut microbiota between patients with adenomas and controls was more pronounced than that of any other clinical parameters including obesity, diet or family history of CRC. This suggests that sequence analysis of the microbiota could be used to identify patients at risk for developing adenomas.     

Recent advancements in the exploitation of the gut microbiome in the diagnosis and treatment of colorectal cancer

Over the last few decades it has been established that the complex interaction between the host and the multitude of organisms that compose the intestinal microbiota plays an important role in human metabolic health and disease. Whilst there is no defined consensus on the composition of a healthy microbiome due to confounding factors such as ethnicity, geographical locations, age and sex, there are undoubtably populations of microbes that are consistently dysregulated in gut diseases including colorectal cancer (CRC). In this review, we discuss the most recent advances in the application of the gut microbiota, not just bacteria, and derived microbial compounds in the diagnosis of CRC and the potential to exploit microbes as novel agents in the management and treatment of CRC. We highlight examples of the microbiota, and their derivatives, that have the potential to become standalone diagnostic tools or be used in combination with current screening techniques to improve sensitivity and specificity for earlier CRC diagnoses and provide a perspective on their potential as biotherapeutics with translatability to clinical trials.     

Inflammation-associated enterotypes,host genotype,cage and inter-individual effects drive gut microbiota variation in common laboratory mice

Background

Murine models are a crucial component of gut microbiome research. Unfortunately, a multitude of genetic backgrounds and experimental setups, together with inter-individual variation, complicates cross-study comparisons and a global understanding of the mouse microbiota landscape. Here, we investigate the variability of the healthy mouse microbiota of five common lab mouse strains using 16S rDNA pyrosequencing.

Results

We find initial evidence for richness-driven, strain-independent murine enterotypes that show a striking resemblance to those in human, and which associate with calprotectin levels, a marker for intestinal inflammation. After enterotype stratification, we find that genetic, caging and inter-individual variation contribute on average 19%, 31.7% and 45.5%, respectively, to the variance in the murine gut microbiota composition. Genetic distance correlates positively to microbiota distance, so that genetically similar strains have more similar microbiota than genetically distant ones. Specific mouse strains are enriched for specific operational taxonomic units and taxonomic groups, while the ''cage effect'' can occur across mouse strain boundaries and is mainly driven by Helicobacter infections.

Conclusions

The detection of enterotypes suggests a common ecological cause, possibly low-grade inflammation that might drive differences among gut microbiota composition in mammals. Furthermore, the observed environmental and genetic effects have important consequences for experimental design in mouse microbiome research.     

Gut microbiome in tumorigenesis and therapy of colorectal cancer

Colorectal cancer (CRC) is the malignant tumor with the highest incidence in the digestive system, and the gut microbiome plays a crucial role in CRC tumorigenesis and therapy. The gastrointestinal tract is the organ harboring most of the microbiota in humans. Changes in the gut microbiome in CRC patients suggest possible host–microbe interactions, thereby hinting the potential tumorigenesis, which provides new perspective for preventing, diagnosing, or treating CRC. In this review, we discuss the effects of gut microbiome dysbiosis on CRC, and reveal the mechanisms by which gut microbiome dysbiosis leads to CRC. Gut microbiome modulation with the aim to reverse the established gut microbial dysbiosis is a novel strategy for the prevention and treatment of CRC. In addition, this review summarizes that probiotic antagonize CRC tumorigenesis by protecting intestinal barrier function, inhibiting cancer cell proliferation, resisting oxidative stress, and enhancing host immunity. Finally, we highlight clinical applications of the gut microbiome, such as gut microbiome analysis-based biomarker screening and prediction, and microbe modulation-based CRC prevention, treatment enhancement, and treatment side effect reduction. This review provides the reference for the clinical application of gut microbiome in the prevention and treatment of CRC.     

Role of SCFAs in gut microbiome and glycolysis for colorectal cancer therapy

Increased risk of colorectal cancer (CRC) is associated with altered intestinal microbiota as well as short-chain fatty acids (SCFAs) reduction of output The energy source of colon cells relies mainly on three SCFAs, namely butyrate (BT), propionate, and acetate, while CRC transformed cells rely mainly on aerobic glycolysis to provide energy. This review summarizes recent research results for dysregulated glucose metabolism of SCFAs, which could be initiated by gut microbiome of CRC. Moreover, the relationship between SCFA transporters and glycolysis, which may correlate with the initiation and progression of CRC, are also discussed. Additionally, this review explores the linkage of BT to transport of SCFAs expressions between normal and cancerous colonocyte cell growth for tumorigenesis inhibition in CRC. Furthermore, the link between gut microbiota and SCFAs in the metabolism of CRC, in addition, the proteins and genes related to SCFAs-mediated signaling pathways, coupled with their correlation with the initiation and progression of CRC are also discussed. Therefore, targeting the SCFA transporters to regulate lactate generation and export of BT, as well as applying SCFAs or gut microbiota and natural compounds for chemoprevention may be clinically useful for CRCs treatment. Future research should focus on the combination these therapeutic agents with metabolic inhibitors to effectively target the tumor SCFAs and regulate the bacterial ecology for activation of potent anticancer effect, which may provide more effective application prospect for CRC therapy.     

Alterations in intestinal microbiota of colorectal cancer patients receiving radical surgery combined with adjuvant CapeOx therapy

An intricate relationship exists and interactions occur between gut microbiota and colorectal cancer(CRC). Radical surgery combined with adjuvant chemotherapy(AC) serves as the mainstream therapeutic scheme for most CRC patients. The current research was conducted to assess the effect of surgery or chemotherapy on gut microbiota. Forty-three CRC patients who received radical surgery and AC were enrolled. Fecal samples were collected preoperatively, postoperatively, and after the first to fifth cycles of postoperative chemotherapy. The microbial community of each sample was analyzed using high throughput 16S rRNA amplicon sequencing. Compared with preoperative samples, fecal samples collected postoperatively exhibited a significant decrease of obligate anaerobes, tumor-related bacteria, and butyric acid-producing bacteria. However, a significant increase of some conditional pathogens was observed. In addition, the AC regimen(CapeOx) was found to alter intestinal microbiota dramatically. In particular, several changes were observed after chemotherapy including an increase of pathogenic bacteria, the "rebound effect" of chemotherapy-adapted bacteria, the shift of lactate-utilizing microbiota from Veillonella to Butyricimonas and Butyricicoccus, as well as the decrease of probiotics. Both radical surgery and CapeOx chemotherapy exert a non-negligible effect on the gut microbiota of CRC patients. Microbiota-based intervention may be beneficial for patients during postoperative clinical management.     

Dysbiosis Signature of Fecal Microbiota in Colorectal Cancer Patients

The human gut microbiota is a complex system that is essential to the health of the host. Increasing evidence suggests that the gut microbiota may play an important role in the pathogenesis of colorectal cancer (CRC). In this study, we used pyrosequencing of the 16S rRNA gene V3 region to characterize the fecal microbiota of 19 patients with CRC and 20 healthy control subjects. The results revealed striking differences in fecal microbial population patterns between these two groups. Partial least-squares discriminant analysis showed that 17 phylotypes closely related to Bacteroides were enriched in the gut microbiota of CRC patients, whereas nine operational taxonomic units, represented by the butyrate-producing genera Faecalibacterium and Roseburia, were significantly less abundant. A positive correlation was observed between the abundance of Bacteroides species and CRC disease status (R?=?0.462, P?=?0.046?<?0.5). In addition, 16 genera were significantly more abundant in CRC samples than in controls, including potentially pathogenic Fusobacterium and Campylobacter species at genus level. The dysbiosis of fecal microbiota, characterized by the enrichment of potential pathogens and the decrease in butyrate-producing members, may therefore represent a specific microbial signature of CRC. A greater understanding of the dynamics of the fecal microbiota may assist in the development of novel fecal microbiome-related diagnostic tools for CRC.     

Analyzing the Secretome of Gut Microbiota as the Next Strategy For Early Detection of Colorectal Cancer

Dysbiosis of gut microbiome can contribute to inflammation, and subsequently initiation and progression of colorectal cancer (CRC). Throughout these stages, various proteins and metabolites are secreted to the external environment by microorganisms or the hosts themselves. Studying these proteins may help enhance our understanding of the host–microorganism relationship or they may even serve as useful biomarkers for CRC. However, secretomic studies of gut microbiome of CRC patients, until now, are scarcely performed. In this review article, the focus is on the roles of gut microbiome in CRC, the current findings on CRC secretome are highlighted, and the emerging challenges and strategies to drive forward this area of research are addressed.