The human microbiota is a complex ecosystem that colonizes body surfaces and interacts with host organ systems, especially the immune system. Since the composition of this ecosystem depends on a variety of internal and external factors, each individual harbors a unique set of microbes. These differences in microbiota composition make individuals either more or less susceptible to various diseases, including cancer. Specific microbes are associated with cancer etiology and pathogenesis and several mechanisms of how they drive the typical hallmarks of cancer were recently identified. Although most microbes reside in the distal gut, they can influence cancer initiation and progression in distant tissues, as well as modulate the outcomes of established cancer therapies. Here, we describe the mechanisms by which microbes influence carcinogenesis and discuss their current and potential future applications in cancer diagnostics and management.

• Klíčová slova
• Fecal microbiota transplantation, Gut microbiota, Hallmarks of cancer, Tumor microenvironment,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Continuous activation of the immune system inside a tissue can lead to remodelling of the tissue structure and creation of a specific microenvironment, such as during the tumour development. Chronic inflammation is a central player in stimulating changes that alter the tissue stroma and can lead to fibrotic evolution. In the colon mucosa, regulatory mechanisms, including TGF-β1, avoid damaging inflammation in front of the continuous challenge by the intestinal microbiome. Inducing either DSS colitis or AOM colorectal carcinogenesis in AVN-Wistar rats, we evaluated at one month after the end of each treatment whether immunological changes and remodelling of the collagen scaffold were already in development. At this time point, we found in both models a general downregulation of pro-inflammatory cytokines and even of TGF-β1, but not of IL-6. Moreover, we demonstrated by multi-photon microscopy the simultaneously presence of pro-fibrotic remodelling of the collagen scaffold, with measurable changes in comparison to the control mucosa. The scaffold was significantly modified depending on the type of induced stimulation. These results suggest that at one month after the end of the DSS or AOM inductions, a smouldering inflammation is present in both induced conditions, since the pro-inflammatory cytokines still exceed, in proportion, the local homeostatic regulation of which TGF-β1 is a part (inflammatory threshold). Such an inflammation appears sufficient to sustain remodelling of the collagen scaffold that may be taken as a possible pathological marker for revealing pre-neoplastic inflammation.

• Klíčová slova
• AOM, DSS-induced colitis, IL-6, chronic inflammation, collagen, colorectal cancer, tissue scaffold, tumour niche,
• Publikační typ
• časopisecké články MeSH

Host's physiology is significantly influenced by microbiota colonizing the epithelial surfaces. Complex microbial communities contribute to proper mucosal barrier function, immune response, and prevention of pathogen invasion and have many other crucial functions. The oral cavity and large intestine are distant parts of the digestive tract, both heavily colonized by commensal microbiota. Nevertheless, they feature different proportions of major bacterial and fungal phyla, mostly due to distinct epithelial layers organization and different oxygen levels. A few obligate anaerobic strains inhabiting the oral cavity are involved in the pathogenesis of oral diseases. Interestingly, these microbiota components are also enriched in gut inflammatory and tumor tissue. An altered microbiota composition - dysbiosis - and formation of polymicrobial biofilms seem to play important roles in the development of oral diseases and colorectal cancer. In this review, we describe the differences in composition of commensal microbiota in the oral cavity and large intestine and the mechanisms by which microbiota affect the inflammatory and carcinogenic response of the host.

• Klíčová slova
• Fusobacterium, biofilm, dysbiosis, microbiome, mycobiome, oral diseases, pathobiont,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Psoriasis is a chronic inflammatory skin disease in which Th17 cells play a crucial role. Since indigenous gut microbiota influences the development and reactivity of immune cells, we analyzed the link among microbiota, T cells and the formation of psoriatic lesions in the imiquimod-induced murine model of psoriasis. To explore the role of microbiota, we induced skin inflammation in germ-free (GF), broad-spectrum antibiotic (ATB)-treated or conventional (CV) BALB/c and C57BL/6 mice. We found that both mice reared in GF conditions for several generations and CV mice treated with ATB were more resistant to imiquimod-induced skin inflammation than CV mice. The ATB treatment dramatically changed the diversity of gut bacteria, which remained stable after subsequent imiquimod application; ATB treatment resulted in a substantial increase in the order Lactobacillales and a significant decrease in Coriobacteriales and Clostridiales. Moreover, as compared to CV mice, imiquimod induced a lower degree of local and systemic Th17 activation in both GF and ATB-treated mice. These findings suggest that gut microbiota control imiquimod-induced skin inflammation by altering the T cell response.

• MeSH
• Actinobacteria účinky léků   fyziologie   MeSH
• aktivace lymfocytů účinky léků   MeSH
• aminochinoliny farmakologie   MeSH
• antibakteriální látky farmakologie   MeSH
• buňky Th17 účinky léků   imunologie   mikrobiologie   MeSH
• Clostridiales účinky léků   fyziologie   MeSH
• druhová specificita MeSH
• exprese genu MeSH
• gnotobiologické modely MeSH
• imichimod MeSH
• interleukin-17 genetika   imunologie   MeSH
• jaderné receptory - podrodina 1, skupina F, člen 3 genetika   imunologie   MeSH
• kůže účinky léků   imunologie   mikrobiologie   patologie   MeSH
• Lactobacillales účinky léků   fyziologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• psoriáza chemicky indukované   imunologie   mikrobiologie   patologie   MeSH
• receptory antigenů T-buněk gama-delta genetika   imunologie   MeSH
• střevní mikroflóra účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminochinoliny MeSH
• antibakteriální látky MeSH
• imichimod MeSH
• interleukin-17 MeSH
• jaderné receptory - podrodina 1, skupina F, člen 3 MeSH
• receptory antigenů T-buněk gama-delta MeSH
• Rorc protein, mouse MeSH Prohlížeč

The microbiota is a crucial modulator of the immune system. Here, we evaluated how its absence or reduction modifies the inflammatory response in the murine model of experimental autoimmune uveoretinitis (EAU). We induced EAU in germ-free (GF) or conventionally housed (CV) mice and in CV mice treated with a combination of broad-spectrum antibiotics either from the day of EAU induction or from one week prior to induction of disease. The severity of the inflammation was assessed by fundus biomicroscopy or by histology, including immunohistology. The immunophenotyping of T cells in local and distant lymph nodes was performed by flow cytometry. We found that GF mice and mice where the microbiota was reduced one week before EAU induction were protected from severe autoimmune inflammation. GF mice had lower numbers of infiltrating macrophages and significantly less T cell infiltration in the retina than CV mice with EAU. GF mice also had reduced numbers of IFN-γ and IL-17-producing T cells and increased numbers of regulatory T cells in the eye-draining lymph nodes. These data suggest that the presence of microbiota during autoantigen recognition regulates the inflammatory response by influencing the adaptive immune response.

• MeSH
• adaptivní imunita MeSH
• aktivace lymfocytů MeSH
• antibakteriální látky farmakologie   MeSH
• autoantigeny imunologie   MeSH
• autoimunitní nemoci chemicky indukované   imunologie   mikrobiologie   MeSH
• bakteriální nálož účinky léků   MeSH
• gnotobiologické modely MeSH
• interferon gama biosyntéza   MeSH
• interleukin-17 biosyntéza   MeSH
• makrofágy imunologie   MeSH
• mikrobiota * imunologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• oči imunologie   patologie   MeSH
• oční proteiny imunologie   MeSH
• proteiny vázající retinol imunologie   MeSH
• průtoková cytometrie MeSH
• regulační T-lymfocyty imunologie   MeSH
• retina imunologie   MeSH
• retinitida chemicky indukované   etiologie   imunologie   mikrobiologie   MeSH
• uveitida chemicky indukované   imunologie   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• Názvy látek
• antibakteriální látky MeSH
• autoantigeny MeSH
• interferon gama MeSH
• interleukin-17 MeSH
• interstitial retinol-binding protein MeSH Prohlížeč
• oční proteiny MeSH
• proteiny vázající retinol MeSH