Diet is a strong modifier of microbiome and mucosal microenvironment in the gut. Recently, components of western-type diets have been associated with metabolic and immune diseases. Here, we studied how high-sugar diet (HSD) consumption influences gut mucosal barrier and immune response under steady state conditions and in a mouse model of acute colitis. We found that HSD significantly increased gut permeability, spleen weight, and neutrophil levels in spleens of healthy mice. Subsequent dextran sodium sulfate administration led to severe colitis. In colon, HSD significantly promoted neutrophil infiltration and increased the levels of IL-6, IL-1β, and TNF-α. Moreover, HSD-fed mice had significantly higher abundance of pathobionts, such as Escherichia coli and Candida, in fecal samples. Although germ-free mice colonized with microbiota of conventionally reared mice that consumed different diets had equally severe colitis, mice colonized with HSD microbiota showed markedly increased infiltration of neutrophils to the gut. The induction of colitis in Toll-like receptor 4 (TLR4)-deficient HSD-fed mice led to significantly milder colitis than in wild-type mice. In conclusion, our results suggested a significant role of HSD in disruption of barrier integrity and balanced mucosal and systemic immune response. In addition, these processes seemed to be highly influenced by resident potentially pathogenic microbiota or metabolites via the TLR4 signaling pathway.
- MeSH
- chronická nemoc MeSH
- dieta * MeSH
- DNA vazebné proteiny nedostatek metabolismus MeSH
- feces MeSH
- kolitida genetika imunologie patologie MeSH
- monosacharidy škodlivé účinky MeSH
- myši inbrední BALB C MeSH
- permeabilita MeSH
- regulace genové exprese MeSH
- signální transdukce * MeSH
- síran dextranu MeSH
- slizniční imunita MeSH
- střeva patologie MeSH
- střevní mikroflóra * MeSH
- stupeň závažnosti nemoci MeSH
- T-lymfocyty imunologie MeSH
- toll-like receptor 4 metabolismus MeSH
- zánět mikrobiologie patologie MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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
- 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
- MeSH
- diabetes mellitus 2. typu komplikace MeSH
- hodnocení rizik MeSH
- ischemická choroba srdeční diagnóza MeSH
- kalcinóza MeSH
- lidé MeSH
- nemoci koronárních tepen MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- novinové články MeSH
- Publikační typ
- abstrakt z konference MeSH
