Colorectal carcinoma: Importance of colonic environment for anti-cancer response and systemic immunity

Vannucci, Luca; Štěpánková, Renata; Grobárová, Valéria; Kozáková, Hana; Rossmann, P; Klimešová, Klára; Benson, Veronika; Šíma, Petr; Fišerová, Anna; Tlaskalová‐Hogenová, Helena

doi:10.3109/15476910903334343

Cited by 19 publications

(14 citation statements)

References 94 publications

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“…This effect, together with potent immune suppression, then leads to massive tumor progression (41). Here, we showed that IRAK-M deficient mice have lower levels of IFN-γ and decreased expression of IL-18 in their colons, which suggests inhibition of anti-tumor immunity.…”

Section: Discussionmentioning

confidence: 99%

Altered Gut Microbiota Promotes Colitis-Associated Cancer in IL-1 Receptor–Associated Kinase M–Deficient Mice

Klimešová

Kverka

Zákostelská

et al. 2013

Inflammatory Bowel Diseases

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Background Microbial sensing by Toll-like receptors (TLR) and its negative regulation have important role in the pathogenesis of inflammation-related cancer. In this study, we investigated the role of negative regulation of TLR signaling and gut microbiota in the development of colitis-associated cancer in mouse model. Methods Colitis-associated cancer was induced by azoxymethane and dextran sodium sulfate in wild-type and in Interleukin-1 receptor associated kinase-M (IRAK-M) deficient mice with or without antibiotic (ATB) treatment. Local cytokine production was analyzed by multiplex cytokine assay or ELISA, and regulatory T cells were analyzed by flow cytometry. Changes in microbiota composition during tumorigenesis were analyzed by pyrosequencing, and β-glucuronidase activity was measured in intestinal content by fluorescence assay. Results ATB treatment of wild-type mice reduced the incidence and severity of tumors. As compared with non-treated mice, ATB-treated mice had significantly lower numbers of regulatory T cells in colon, altered gut microbiota composition, and decreased β-glucuronidase activity. However, the β-glucuronidase activity was not as low as in germ-free mice. IRAK-M deficient mice not only developed invasive tumors, but ATB-induced decrease in β-glucuronidase activity did not rescue them from severe carcinogenesis phenotype. Furthermore, IRAK-M deficient mice had significantly increased levels of pro-inflammatory cytokines in the tumor tissue. Conclusions We conclude that gut microbiota promotes tumorigenesis by increasing the exposure of gut epithelium to carcinogens and that IRAK-M negative regulation is essential for colon cancer resistance even in conditions of altered microbiota. Therefore, gut microbiota and its metabolic activity could be potential targets for colitis-associated cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Altered Gut Microbiota Promotes Colitis-Associated Cancer in IL-1 Receptor–Associated Kinase M–Deficient Mice

Klimešová

Kverka

Zákostelská

et al. 2013

Inflammatory Bowel Diseases

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“…The cause of gastrointestinal tumours is implicating chronic inflammation in response to an adverse bacterial flora as a promotion of neoplastic progression, and the intestinal environment is considered important in both colorectal cancer development and modulation of mucosal immunity [7]. During inflammation in UC-patients, different members of the Enterobacteriaceae family and different Clostridium species have been found to increase in accordance with a decrease in bifidobacteria and lactobacilli [8], [9].…”

Section: Introductionmentioning

confidence: 99%

Blueberry Husks and Probiotics Attenuate Colorectal Inflammation and Oncogenesis, and Liver Injuries in Rats Exposed to Cycling DSS-Treatment

et al. 2012

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Long-term colonic inflammation promotes carcinogenesis and histological abnormalities of the liver, and colorectal tumours frequently arise in a background of dysplasia, a precursor of adenomas. Altered colonic microbiota with an increased proportion of bacteria with pro-inflammatory characteristics, have been implicated in neoplastic progression. The composition of the microbiota can be modified by dietary components such as probiotics, polyphenols and dietary fibres. In the present study, the influence of probiotics in combination with blueberry husks on colorectal carcinogenesis and subsequent liver damage was evaluated. Colorectal tumours were induced in rats by cyclic treatment with dextran sulphate sodium (DSS). Blueberry husks and a mixture of three probiotic strains ( Bifidobacterium infantis DSM 15159, Lactobacillus gasseri , DSM 16737 and Lactobacillus plantarum DSM 15313) supplemented a basic diet fortified with oats. The condition of the rats was monitored using a disease activity index (DAI). A qualitative and quantitative histological judgement was performed on segments of distal colon and rectum and the caudate lobe of the liver. The formation of short-chain fatty acids, bacterial translocation, the inflammatory reaction and viable count of lactobacilli and Enterobaceriaceae were addressed. Blueberry husks with or without probiotics significantly decreased DAI, and significantly reduced the number of colonic ulcers and dysplastic lesions. With a decreased proportion of blueberry husk in the diet, the probiotic supplement was needed to achieve a significant decrease in numbers of dysplastic lesions. Probiotics decreased faecal viable count of Enterobacteriaceae and increased that of lactobacilli. Blueberry husks with or without probiotics lowered the proportion of butyric acid in distal colon, and decreased the haptoglobin levels. Probiotics mitigated hepatic injuries by decreasing parenchymal infiltration and the incidence of stasis and translocation. The results demonstrate a dietary option for use of blueberry husks and probiotics to delay colonic carcinogenesis and hepatic injuries in the rat model.

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“…This was linked to increased activities of fecal bacterial enzymes, as well as modification of sulfidogenesis and biliary acid metabolism with an impact on development of procarcinogenic conditions. 146,147 Interestingly, microbiota products can influence not only the local intestinal environment but also distant organs. Gut microbiota can metabolize certain plant-derived foods into biologically active compounds, e.g., enterolignans, that may play a role in carcinogenesis.…”

Section: Cancermentioning

confidence: 99%

The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases

et al. 2011

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Colorectal carcinoma: Importance of colonic environment for anti-cancer response and systemic immunity

Cited by 19 publications

References 94 publications

Altered Gut Microbiota Promotes Colitis-Associated Cancer in IL-1 Receptor–Associated Kinase M–Deficient Mice

Altered Gut Microbiota Promotes Colitis-Associated Cancer in IL-1 Receptor–Associated Kinase M–Deficient Mice

Blueberry Husks and Probiotics Attenuate Colorectal Inflammation and Oncogenesis, and Liver Injuries in Rats Exposed to Cycling DSS-Treatment

The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases

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