31001762 OR The role of intestinal microbiota in the pathogenesis of colorectal carcinoma
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The symbiotic relationship between intestinal microbiota and the host is a major mechanism of prevention against the development of chronic and metabolic diseases. The intestinal microbiota provides several physiological functions of the organism from the creation of a natural functional barrier with a subsequent immunostimulatory activity up to affecting the energy metabolism of the host. Disruption of physiological intestinal microbiota is reported as one of the major etiological factors of initiation and progression of colorectal carcinoma (CRC). Chronic low-grade inflammation is associated with the development of CRC, through the production of inflammatory cytokines and reactive oxygen species. CRC occurs in association with high-protein and high-fat diets in combination with low-fiber intake. The problem of intestinal dysbiosis and oncological diseases is a multidisciplinary problem and it is necessary to focus on several fields of medicine such as public health, clinical pharmacology, and internal medicine. The aim of this review is describing the role of gut dysbiosis in pathogenesis of colorectal carcinoma.
- MeSH
- cytokiny imunologie MeSH
- dieta MeSH
- dysbióza * MeSH
- gastrointestinální trakt mikrobiologie patofyziologie MeSH
- kolorektální nádory mikrobiologie patologie MeSH
- lidé MeSH
- reaktivní formy kyslíku metabolismus MeSH
- střevní mikroflóra * MeSH
- symbióza MeSH
- zánět MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Metagenomic approaches are currently being used to decipher the genome of the microbiota (microbiome), and, in parallel, functional studies are being performed to analyze the effects of the microbiota on the host. Gnotobiological methods are an indispensable tool for studying the consequences of bacterial colonization. Animals used as models of human diseases can be maintained in sterile conditions (isolators used for germ-free rearing) and specifically colonized with defined microbes (including non-cultivable commensal bacteria). The effects of the germ-free state or the effects of colonization on disease initiation and maintenance can be observed in these models. Using this approach we demonstrated direct involvement of components of the microbiota in chronic intestinal inflammation and development of colonic neoplasia (i.e., using models of human inflammatory bowel disease and colorectal carcinoma). In contrast, a protective effect of microbiota colonization was demonstrated for the development of autoimmune diabetes in non-obese diabetic (NOD) mice. Interestingly, the development of atherosclerosis in germ-free apolipoprotein E (ApoE)-deficient mice fed by a standard low-cholesterol diet is accelerated compared with conventionally reared animals. Mucosal induction of tolerance to allergen Bet v1 was not influenced by the presence or absence of microbiota. Identification of components of the microbiota and elucidation of the molecular mechanisms of their action in inducing pathological changes or exerting beneficial, disease-protective activities could aid in our ability to influence the composition of the microbiota and to find bacterial strains and components (e.g., probiotics and prebiotics) whose administration may aid in disease prevention and treatment.
- MeSH
- autoimunitní nemoci etiologie mikrobiologie MeSH
- gastrointestinální trakt mikrobiologie MeSH
- gnotobiologické modely MeSH
- imunita MeSH
- lidé MeSH
- metagenom imunologie MeSH
- modely nemocí na zvířatech MeSH
- nádory etiologie mikrobiologie MeSH
- sliznice imunologie MeSH
- zánět etiologie mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Sporadic colorectal cancer (CRC) represents an enormous problem worldwide. Large intestinal microbiota play an important role in the colorectal carcinogenesis. The aim of the study was to investigate anti-Outer membrane protein C (anti-OmpC) antibodies, aimed at porin C, which is embedded in the outer membrane of gram-negative bacteria, in patients with colorectal adenoma (CRA), CRC and controls. The study included 22 patients with CRA (11 men, 11 women, aged 26-79, mean 65 ± 12), 11 patients with CRC (9 men, 2 women, aged 50-83, mean 66 ± 11) and 45 controls, blood donors (24 men, 21 women, aged 20-58, mean 38 ± 10). Serum anti-OmpC antibodies were investigated by means of ELISA. Values of 0-20 U/mL were considered to be negative; values >25 U/mL were assessed as positive. A total of 9/11 (82 %) patients with CRC had positive anti-OmpC antibodies. Anti-OmpC antibodies were negative or grey-zone in 37/45 (82 %) controls. Serum anti-OmpC were found to be significantly higher in patients with CRC (median 42.4, interquartile range (IQR) 22.2) compared to controls (median 18.3, IQR 12.4), p < 0.001. No statistically significant difference in anti-OmpC was found between controls (median 18.3, IQR 12.4) and CRA patients (median 17.7, IQR 16.5), p = 0.326. Anti-OmpC were significantly higher in patients with CRC (median 42.4, IQR 22.2) compared to patients with CRA (median 17.7, IQR 16.5), p = 0.011. Positivity of anti-OmpC antibodies was found in patients with CRC, which supports the contribution of gram-negative large intestinal microbiota to the pathogenesis of CRC.
- MeSH
- dospělí MeSH
- ELISA MeSH
- kolorektální nádory patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- poriny imunologie MeSH
- protilátky bakteriální krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH