Psoriasis is a chronic, immune-mediated, inflammatory disease primarily affecting the skin. It is currently coming to light that patients with psoriasis have disrupted intestinal barrier and often suffer from comorbidities associated with the gastrointestinal tract. Moreover, there is growing evidence of both cutaneous and intestinal paradoxical reactions during biologic treatment in patients with psoriasis. This review focuses on barrier defects and changes in immune responses in patients with psoriasis, which play an important role in the development of the disease but are also influenced by modern biological treatments targeting IL-17 and TNFα cytokines. Here, we highlight the relationship between the gut-skin axis, microbiota, psoriasis treatment, and the incidence of paradoxical reactions, such as inflammatory bowel disease in patients with psoriasis. A better understanding of the interconnection of these mechanisms could lead to a more personalized therapy and lower the incidence of treatment side effects, thereby improving the quality of life of the affected patients.

• Klíčová slova
• Biologics, Gut microbiota, Gut–skin axis, IBD, IL-17, Psoriasis, Skin adverse events, Skin microbiota, TNFα,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Psoriatic patients have altered microbiota, both in the intestine and on the skin. It is not clear, however, whether this is a cause or consequence of the disease. In this study, using an experimental mouse model of psoriasis induced by imiquimod (IMQ), we show that oral treatment with a broad spectrum of antibiotics (MIX) or metronidazole (MET) alone mitigates the severity of skin inflammation through downregulation of Th17 immune response in conventional mice. Since some antibiotics, including MET, can influence immune system reactivity, we also evaluated the effect of MIX in the same model under germ-free (GF) conditions. GF mice treated with MET did not show milder signs of imiquimod-induced skin inflammation (IISI) which supports the conclusion that the therapeutic effect is mediated by changes in microbiota composition. Moreover, compared to controls, mice treated with MIX had a significantly higher abundance of the genus Lactobacillus in the intestine and on the skin. Mice treated with MET had a significantly higher abundance of the genera Bifidobacterium and Enterococcus both on the skin and in the intestine and of Parabacteroides distasonis in the intestine. Additionally, GF mice and mice monocolonized with either Lactobacillus plantarum or segmented filamentous bacteria (SFB) were more resistant to IISI than conventional mice. Interestingly, compared to GF mice, IMQ induced a higher degree of systemic Th17 activation in mice monocolonized with SFB but not with L. plantarum. The present findings provide evidence that intestinal and skin microbiota directly regulates IISI and emphasizes the importance of microbiota in the pathogenesis of psoriasis.

• Klíčová slova
• animal model, antibiotics, germ-free, imiquimod, intestine, microbiota, psoriasis, skin,
• Publikační typ
• časopisecké články 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

BACKGROUND: Microbial sensing by Toll-like receptors (TLR) and its negative regulation have an important role in the pathogenesis of inflammation-related cancer. In this study, we investigated the role of negative regulation of Toll-like receptors 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 enzyme-linked immunosorbent assay, 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. Compared with nontreated 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 proinflammatory 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.

• MeSH
• azoxymethan toxicita   MeSH
• cytokiny genetika   metabolismus   MeSH
• gastrointestinální trakt mikrobiologie   MeSH
• karcinogeny toxicita   MeSH
• kinázy asociované s receptory interleukinu-1 fyziologie   MeSH
• kolitida chemicky indukované   komplikace   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• messenger RNA genetika   MeSH
• metagenom * MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• nádory tračníku etiologie   metabolismus   patologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• průtoková cytometrie MeSH
• receptory interleukinu-1 metabolismus   MeSH
• regulační T-lymfocyty imunologie   metabolismus   patologie   MeSH
• signální transdukce MeSH
• síran dextranu toxicita   MeSH
• toll-like receptory genetika   metabolismus   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• azoxymethan MeSH
• cytokiny MeSH
• Irak3 protein, mouse MeSH Prohlížeč
• karcinogeny MeSH
• kinázy asociované s receptory interleukinu-1 MeSH
• messenger RNA MeSH
• receptory interleukinu-1 MeSH
• síran dextranu MeSH
• toll-like receptory MeSH

One of the promising approaches in the therapy of ulcerative colitis is administration of butyrate, an energy source for colonocytes, into the lumen of the colon. This study investigates the effect of butyrate producing bacterium Clostridium tyrobutyricum on dextran sodium sulphate (DSS)-induced colitis in mice. Immunocompetent BALB/c and immunodeficient severe combined immunodeficiency (SCID) mice reared in specific-pathogen-free (SPF) conditions were treated intrarectally with C. tyrobutyricum 1 week prior to the induction of DSS colitis and during oral DSS treatment. Administration of DSS without C. tyrobutyricum treatment led to an appearance of clinical symptoms - bleeding, rectal prolapses and colitis-induced increase in the antigen CD11b, a marker of infiltrating inflammatory cells in the lamina propria. The severity of colitis was similar in BALB/c and SCID mice as judged by the histological damage score and colon shortening after 7 days of DSS treatment. Both strains of mice also showed a similar reduction in tight junction (TJ) protein zonula occludens (ZO)-1 expression and of MUC-2 mucin depression. Highly elevated levels of cytokine tumour necrosis factor (TNF)-α in the colon of SCID mice and of interleukin (IL)-18 in BALB/c mice were observed. Intrarectal administration of C. tyrobutyricum prevented appearance of clinical symptoms of DSS-colitis, restored normal MUC-2 production, unaltered expression of TJ protein ZO-1 and decreased levels of TNF-α and IL-18 in the descending colon of SCID and BALB/c mice, respectively. Some of these features can be ascribed to the increased production of butyrate in the lumen of the colon and its role in protection of barrier functions and regulation of IL-18 expression.

• MeSH
• akutní nemoc MeSH
• antigeny CD11b biosyntéza   genetika   MeSH
• aplikace rektální MeSH
• bakteriální translokace MeSH
• butyráty metabolismus   MeSH
• Clostridium tyrobutyricum fyziologie   MeSH
• fosfoproteiny biosyntéza   genetika   MeSH
• imunokompetence MeSH
• interleukin-18 biosyntéza   genetika   MeSH
• kolon metabolismus   mikrobiologie   patologie   MeSH
• mastné kyseliny metabolismus   MeSH
• membránové proteiny biosyntéza   genetika   MeSH
• mucin 2 biosyntéza   genetika   MeSH
• muciny biosyntéza   MeSH
• myši inbrední BALB C MeSH
• myši SCID MeSH
• myši MeSH
• organismy bez specifických patogenů MeSH
• probiotika terapeutické užití   MeSH
• protein zonula occludens 1 MeSH
• síran dextranu toxicita   MeSH
• těžká kombinovaná imunodeficience genetika   imunologie   MeSH
• TNF-alfa biosyntéza   genetika   MeSH
• ulcerózní kolitida chemicky indukované   genetika   imunologie   mikrobiologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny CD11b MeSH
• butyráty MeSH
• fosfoproteiny MeSH
• interleukin-18 MeSH
• mastné kyseliny MeSH
• membránové proteiny MeSH
• Muc2 protein, mouse MeSH Prohlížeč
• mucin 2 MeSH
• muciny MeSH
• protein zonula occludens 1 MeSH
• síran dextranu MeSH
• Tjp1 protein, mouse MeSH Prohlížeč
• TNF-alfa 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

Commensal bacteria have been shown to modulate the host mucosal immune system. Here, we report that oral treatment of BALB/c mice with components from the commensal, Parabacteroides distasonis, significantly reduces the severity of intestinal inflammation in murine models of acute and chronic colitis induced by dextran sulphate sodium (DSS). The membranous fraction of P. distasonis (mPd) prevented DSS-induced increases in several proinflammatory cytokines, increased mPd-specific serum antibodies and stabilized the intestinal microbial ecology. The anti-colitic effect of oral mPd was not observed in severe combined immunodeficient mice and probably involved induction of specific antibody responses and stabilization of the intestinal microbiota. Our results suggest that specific bacterial components derived from the commensal bacterium, P. distasonis, may be useful in the development of new therapeutic strategies for chronic inflammatory disorders such as inflammatory bowel disease.

• MeSH
• akutní nemoc MeSH
• antigeny bakteriální aplikace a dávkování   imunologie   MeSH
• aplikace orální MeSH
• Bacteroides imunologie   MeSH
• chronická nemoc MeSH
• cytokiny krev   imunologie   MeSH
• kolitida terapie   MeSH
• metagenom imunologie   MeSH
• myši inbrední BALB C MeSH
• myši SCID MeSH
• myši MeSH
• protilátky bakteriální krev   imunologie   MeSH
• střevní sliznice imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antigeny bakteriální MeSH
• cytokiny MeSH
• protilátky bakteriální MeSH

OBJECTIVE: It is an open question whether multifunctional galectin-3 can be a serum marker in inflammatory bowel disease. METHODS: Western blots and commercial ELISA detected and quantitated the lectin immunocytochemistry using double labeling localized it in tissue sections. RESULTS: Serum concentrations were significantly increased in specimen of patients with active and remission-stage ulcerative colitis and Crohn's disease, associated with emerging positivity of CD14(+) cells. CONCLUSION: Enhanced concentration of galectin-3 in serum reflects presence of disease and points to its involvement in the pathogenesis.

• MeSH
• biologické markery MeSH
• Crohnova nemoc krev   MeSH
• elektroforéza v polyakrylamidovém gelu MeSH
• Escherichia coli metabolismus   MeSH
• fluorescein-5-isothiokyanát MeSH
• fluorescenční barviva MeSH
• galektin 3 krev   MeSH
• idiopatické střevní záněty krev   chemicky indukované   diagnóza   MeSH
• imunohistochemie MeSH
• kolitida chemicky indukované   MeSH
• kolon metabolismus   MeSH
• lektiny metabolismus   MeSH
• lidé MeSH
• lipopolysacharidové receptory analýza   metabolismus   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• síran dextranu MeSH
• ulcerózní kolitida krev   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• fluorescein-5-isothiokyanát MeSH
• fluorescenční barviva MeSH
• galektin 3 MeSH
• lektiny MeSH
• lipopolysacharidové receptory MeSH
• síran dextranu MeSH