Supplementary Figure 3 from Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery (original) (raw)
Related papers
British Journal of Surgery, 2018
Background The pathogenesis of colorectal cancer recurrence after a curative resection remains poorly understood. A yet-to-be accounted for variable is the composition and function of the microbiome adjacent to the tumour and its influence on the margins of resection following surgery. Methods PubMed was searched for historical as well as current manuscripts dated between 1970 and 2017 using the following keywords: ‘colorectal cancer recurrence’, ‘microbiome’, ‘anastomotic leak’, ‘anastomotic failure’ and ‘mechanical bowel preparation’. Results There is a substantial and growing body of literature to demonstrate the various mechanisms by which environmental factors act on the microbiome to alter its composition and function with the net result of adversely affecting oncological outcomes following surgery. Some of these environmental factors include diet, antibiotic use, the methods used to prepare the colon for surgery and the physiological stress of the operation itself. Conclusion...
Pharmaceutical Biology, 2016
Context Inulin, a non-digestible carbohydrate isolated from Helianthus tuberosus L. (Asteraceae), has been shown to alter the gut beneficial bacteria including Lactobacillus spp. and Bifidobacteria. Inulin also influences the activities of intestinal microbiota that could prevent the colon cancer development. Objective This study determines the effect of hydrolysed inulin with different degrees of polymerisation on alteration of intestinal microbiota and their activities on azoxymethane (AOM)induced preneoplastic aberrant crypt foci (ACF) in rats. Materials and methods Seventy-two male Sprague-Dawley rats were randomly divided into six groups (three control and three AOM-treated groups) and the animal were fed with either a normal diet or diet containing 10% of long-chain inulin (InuL) or short-chain inulin (InuS), respectively, for 17 weeks. Colon cancer was induced in rats by injecting AOM subcutaneously at the 8th and 9th week of the study period. At the end of the experiment, cecal contents of rats were examined for selected microbiota, organic acids, putrefactive compounds and microbial enzymes. ACF formation was microscopically examined. Results The inulin diets significantly increased the weight and decreased the pH of the caecal content. The rats fed with InuL-supplemented diet showed approximately 2.9-and 6.8-fold increases in the biomass of Lactobacillus spp. and Bifidobacteria, respectively. Naive and AOMtreated rats fed with inulin-supplemented diet showed 1.3and1.3and 1.3and2.2-fold decreases in the biomass of Escherichia coli and Salmonella enterica serovar Typhi, respectively. Inulins significantly decreased the colonic concentration of phenol, p-cresol and indole. Reduction in the activity of microbial enzymes such as b-glucuronidase, azoreductase and nitroreductase were observed in inulin-treated animals. Reduction in the ACF formation has been observed in inulin-treated groups. Discussion and conclusion The present study demonstrates that dietary administration of inulin reduces the formation of preneoplastic lesions in the colon, possibly by altering the microecology and microbial activities on carcinogenesis.
World Journal of Gastroenterology
Human body is colonized by a huge amount of microorganisms mostly located in the gastrointestinal tract. These dynamic communities, the environment and their metabolites constitute the microbiota. Growing data suggests a causal role of a dysbiotic microbiota in several pathologies, such as metabolic and neurological disorders, immunity dysregulations and cancer, especially the well-studied colorectal cancer development. However, many were preclinical studies and a complete knowledge of the pathogenetic mechanisms in humans is still absent. The gut microbiota can exert direct or indirect effects in different phases of colorectal cancer genesis. For example, Fusobacterium nucleatum promotes cancer through cellular proliferation and some strains of Escherichia coli and Bacteroides fragilis produce genotoxins. However, dysbiosis may also cause a proinflammatory state and the stimulation of a Th17 response with IL-17 and IL-22 secretion that have a pro-oncogenic activity, as demonstrated for Fusobacterium nucleatum. Microbiota has a crucial role in several stages of postoperative course; dysbiosis in fact seems related with surgical site infections and Enterococcus faecalis (and other collagenase-producers microbes) are suggested as a cause of anastomotic leak. Consequently, unbalanced presence of some species, together with altered immune response may also have a prognostic role. Microbiota has also a substantial role in effectiveness of chemotherapy, chemoresistance and in the related side effects. In other words, a complete knowledge of the fine pathological mechanisms of gut microbiota may provide a wide range of new diagnostic tools other than therapeutic targets in the light of tailored medicine.
Changes chemopreventive markers in colorectal cancer development after inulin supplementation
Bratislava Medical Journal, 2014
Background: Natural dietary compounds such as prebiotics modulate microbial composition and could prevent the colon cancer development as potential chemopreventive agent. Objectives: Effect of prebiotic-inulin on biochemical, microbial and chemopreventive markers were examined in Sprague-Dawley rats during experimental chemically dimethylhydrazine induced colon cancer development. Methods: Rats were divided to 3 groups: control group (CG), group with dimethylhydrazine (DMH) and group with DMH and prebiotic (DMH+PRE). The effi cacy of the prebiotic inulin (PRE) on the activities of β-glucuronidase, short chain fatty acids (SCFAs), counts of coliforms and lactobacilli, immunoreactivity of cyclooxygenase-2 (COX-2), transcription nuclear factor kappa beta (NFκB) and inducible nitric oxide synthase (iNOS) in colon tissue were examined. Results: Inulin signifi cantly decreased coliforms counts (p<0.01), increased lactobacilli counts (p<0.001), and decreased activity of β-glucuronidase (p<0.01) in fresh caecal digesta. Butyric and propionic acids concentrations were increased after inulin supplementation in comparison to DMH group. Application of inulin decreased immunoreactivity and numbers of COX-2, NFκB and iNOS positive cells in colon tissue in comparison to DMH group. Conclusion: Inulin suppressed expression observed markers, which play an important role in carcinogenesis and in the infl ammatory process, which predisposes to the use of inulin in the prevention or treatment of infl ammatory bowel disease (Tab. 1, Fig. 2, Ref. 17). Text in PDF www.elis.sk.
Influence of the intestinal microbiome on anastomotic healing in the colon and rectum
Seminars in Colon and Rectal Surgery, 2017
Colonic and rectal anastomotic leak has long plagued the surgeons, without much improvement despite decades of advances in suture technique and technology. At the intersection of microbiotal changes in flux via a combination of environmental factors and the virulent pathology of the organisms colonizing the gastrointestinal tract, lies an underappreciated mechanism and thus possible solution for anastomotic failure. Through pre-operative preparation, intra-operative manipulation, and post-operative management, the flora is constantly changing. This article explores the shifts in composition and expression of the digestive flora in response to external factors and the effects thus far observed on anastomotic healing, as well as proposed therapeutic strategies given the leading theories on microbiotal pathogenesis of anastomotic leak.
Journal of Nutrition, 2014
Background: Few studies have focused on the ability of prebiotics to prevent pathogen-induced cellular changes or alter the composition of the intestinal microbiota in complimentary relevant cell and animal models of inflammatory bowel disease. Objective: The objective of this study was to determine if pretreatment with inulin and a short-chain fructo-oligosaccharide (sc-FOS) prevents enterohemorrhagic Escherichia coli (EHEC) O157:H7 infection in Caco2-bbe epithelial cells and what effect 10% wt:v sc-FOS or inulin has on C57BL/6 mice under sham conditions or pretreatment with prebiotics before Citrobacter rodentium infection (10 8 colony-forming units). Methods: Actin rearrangement and tight junction protein (zona occludin-1) were examined with immunofluorescence. Barrier function was assessed by a fluorescent probe and by measuring transepithelial electrical resistance (TER). Alterations in cytokine gene expression and microbiome were assessed with quantitative reverse transcriptase-polymerase chain reaction and fluorescence in situ hybridization. Short-chain fatty acids (SCFAs) were measured by GC. Results: sc-FOS added to monolayers altered actin polymerization without affecting TER or permeability to a fluorescein isothiocyanate (FITC) probe, whereas inulin increased TER (P < 0.005) and altered actin arrangement without affecting FITC permeability. Neither prebiotic attenuated EHEC-induced decreases in barrier function. Prebiotics increased interleukin 10 (Il10) and transforming growth factor-b (Tgfb) cytokine responses alone (P < 0.05) or with EHEC O157:H7 infection (P < 0.05) in vitro. Increases in tumor necrosis factor-a (Tnfa) (P < 0.05) and decreases in chemokine CXC motif ligand 8 (Cxcl8) (P < 0.05) expression were observed with prebiotic treatment prior to EHEC infection. No differences were noted in barrier function or cytokine responses in the absence or presence of C. rodentium in vivo. Alterations in microbiome were evident at 6 d and 10 d postinfection in treatment groups, but a change in C. rodentium load was not observed. Inulin and sc-FOS (P < 0.05) increased fecal SCFAs in the absence of infection. Conclusion: This study provides new insights as to how prebiotics act in complementary in vitro and in vivo models of intestinal injury.
Pages: 96-105Caco-2) and non-tumoral (IEC-6) intestinal epithelial cells
2017
Objective: Colorectal cancer (CRC) is the second leading cause of cancer death in occidental countries. Chronic inflammatory bowel disease (crohn's disease and ulcerative colitis) is associated with an increased risk for CRC development. The aim of this work was to investigate the relationship between inflammatory status and absorption of nutrients with a role in CRC pathogenesis. Materials and Methods: In this experimental study, we evaluated the in vitro effect of tumour necrosis factor-alpha (TNF-α), interferon-γ (IF-γ), and acetylsalicylic acid on 14 C-butyrate (14 C-BT), 3 H-folic acid (3 H-FA) uptake, and on proliferation, viability and differentiation of Caco-2 and IEC-6 cells in culture. Results: The proinflammatory cytokines TNF-α and INF-γ were found to decrease uptake of a low concentration of 14 C-BT (10 µM) by Caco-2 (tumoral) and IEC-6 (normal) intestinal epithelial cell lines. However, the effect of TNF-α and INF-γ in IEC-6 cells is most probably related to a cyto...
Role of the intestinal microbiome in colorectal cancer surgery outcomes
World Journal of Surgical Oncology, 2019
Objectives Growing evidence supports the role of the intestinal microbiome in the carcinogenesis of colorectal cancers, but its impact on colorectal cancer surgery outcomes is not clearly defined. This systematic review aimed to analyze the association between intestinal microbiome composition and postoperative complication and survival following colorectal cancer surgery. Methods A systematic review was conducted according to the 2009 PRISMA guidelines. Two independent reviewers searched the literature in a systematic manner through online databases, including Medline, Scopus, Embase, Cochrane Oral Health Group Specialized Register, ProQuest Dissertations and Theses Database, and Google Scholar. Human studies investigating the association between the intestinal microbiome and the short-term (anastomotic leakage, surgical site infection, postoperative ileus) and long-term outcomes (cancer-specific mortality, overall and disease-free survival) of colorectal cancer surgery were select...
Assessment of Intestinal Permeability in Rats by Permeation of Inulin-Fluorescein
Journal of Basic and Clinical Physiology and Pharmacology, 2000
The measurement of intestinal permeability is widely used to assess different aspects of mucosal barrier disorders and related disease states, and has been proposed for evaluation of disease activity. To provide a simple method for assessment of intestinal permeability, we examined the permeation of inulin-fluorescein (InFl) in rat models of small intestinal injury and colitis. Small intestinal or colonic inflammation was induced by either i.p. administration of indomethacin or rectal administration of trinitrobenzene sulfonic acid (TNBS), respectively. For monitoring of intestinal permeability, InFl was administered orally or rectally to rats with small intestinal or colonic inflammation, respectively, and its level in blood was determined by the fluorescence intensity in the plasma. In small intestinal injury, InFl reached its peak in plasma 3 h after oral administration, while in colitis the InFl peak was reached 1 h after rectal administration. The highest permeability was observed at 72 h or 12 h after induction of small intestinal or colonic inflammation, respectively. In small intestinal injury the InFl permeation, as measured by its plasma level prior to sacrifice, was in agreement with intestinal damage evaluated after sacrifice. In colitis, the permeability at 12 h after induction of the disease correlated well with mortality. These findings