The intestinal microbiota is known to influence postnatal growth. We previously found that a strain of Lactiplantibacillus plantarum (strain LpWJL) buffers the adverse effects of chronic undernutrition on the growth of juvenile germ-free mice. Here, we report that LpWJL sustains the postnatal growth of malnourished conventional animals and supports both insulin-like growth factor-1 (IGF-1) and insulin production and activity. We have identified cell walls isolated from LpWJL, as well as muramyl dipeptide and mifamurtide, as sufficient cues to stimulate animal growth despite undernutrition. Further, we found that NOD2 is necessary in intestinal epithelial cells for LpWJL-mediated IGF-1 production and for postnatal growth promotion in malnourished conventional animals. These findings indicate that, coupled with renutrition, bacteria cell walls or purified NOD2 ligands have the potential to alleviate stunting.

• MeSH
• acetylmuramyl-alanyl-isoglutamin farmakologie   terapeutické užití   MeSH
• buněčná stěna chemie   MeSH
• epitelové buňky mikrobiologie   fyziologie   MeSH
• gnotobiologické modely MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• inzulin metabolismus   MeSH
• Lactobacillaceae * fyziologie   MeSH
• myši MeSH
• podvýživa * patofyziologie   terapie   MeSH
• poruchy růstu patofyziologie   terapie   MeSH
• růst * účinky léků   fyziologie   MeSH
• signální adaptorový protein Nod2 * metabolismus   MeSH
• střeva * mikrobiologie   fyziologie   MeSH
• střevní mikroflóra * fyziologie   MeSH
• střevní sliznice mikrobiologie   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• gnotobiologické modely * MeSH
• myši MeSH
• střevní mikroflóra MeSH
• Check Tag
• myši MeSH

Significant effort has been made to understand mechanisms leading to the initiation of autoimmune diseases. One hypothesis determines infection as the triggering cause in genetically predisposed individuals. The main aim of this project is to gain new knowledge of the mechanisms and possibilities of regulation of sight-threatening autoimmune uveitis. Special emphasis will be put on clarifying the influence of microorganisms (including commensal bacteria) and participation of innate immunity in the process of uveitis, and their directed regulation. To achieve these goals, the analysis of intraocular fluids, serum and microbiome of patients with autoimmune uveitis, and model of the experimental autoimmune uveitis (EAU) in mice, including the unique gnotobiotic model, will be used. The experimental results will be compared to those from clinical research of patients with autoimmune uveitis. The acquired data will contribute to the definition of new therapeutic strategies in human uveitis and thus help to attain a higher quality of prevention of blindness in affected patients.

Mechanismus vzniku autoimunitního procesu je stále předmětem intenzívního výzkumu. Jedna z hypotéz určuje za spouštěcí prvek u geneticky predisponovaných jedinců infekční proces. Hlavním cílem navrhovaného projektu je získat nové poznatky o mechanismu vzniku a možnostech ovlivnění zrak-ohrožující autoimunitní uveitidy. Zvláštní důraz bude kladen na objasnění vlivu mikroorganismů (včetně komensálních) a podíl vrozené imunity v procesu uveitidy a na jejich cílenou regulaci. K dosažení těchto cílů bude využita analýza nitroočních tekutin, séra a mikrobiomu pacientů s autoimunitní uveitidou a model experimentální autoimunitní uveitidy (EAU) u myši, včetně unikátního modelu gnotobiotického. Výsledky získané z pokusů na experimentálním modelu budou porovnány s klinickým výzkumem u pacientů s autoimunitní uveitidou. Získané poznatky přispějí k navržení nového léčebného protokolu uveitid v humánní medicíně, a tím k dosažení vyšší kvality prevence slepoty následkem uveitidy.

• MeSH
• autoimunitní nemoci mikrobiologie   MeSH
• Escherichia coli MeSH
• gnotobiologické modely MeSH
• lidé MeSH
• mikrobiota MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• přirozená imunita MeSH
• probiotika terapeutické užití   MeSH
• uveitida mikrobiologie   MeSH
• zánět prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• myši MeSH

• Konspekt
• Ortopedie. Chirurgie. Oftalmologie
• NLK Obory
• oftalmologie
• alergologie a imunologie
• mikrobiologie, lékařská mikrobiologie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

Mucosal surfaces are colonized by highly diverse commensal microbiota. Coating with secretory IgA (SIgA) promotes the survival of commensal bacteria while it inhibits the invasion by pathogens. Bacterial coating could be mediated by antigen-specific SIgA recognition, polyreactivity, and/or by the SIgA-associated glycans. In contrast to many in vitro studies, only a few reported the effect of SIgA glycans in vivo. Here, we used a germ-free antibody-free newborn piglets model to compare the protective effect of SIgA, SIgA with enzymatically removed N-glycans, Fab, and Fc containing the secretory component (Fc-SC) during oral necrotoxigenic E. coli O55 challenge. SIgA, Fab, and Fc-SC were protective, whereas removal of N-glycans from SIgA reduced SIgA-mediated protection as demonstrated by piglets' intestinal histology, clinical status, and survival. In vitro analyses indicated that deglycosylation of SIgA did not reduce agglutination of E. coli O55. These findings highlight the role of SIgA-associated N-glycans in protection. Further structural studies of SIgA-associated glycans would lead to the identification of those involved in the species-specific inhibition of attachment to corresponding epithelial cells.

• MeSH
• aglutinace MeSH
• Escherichia coli fyziologie   MeSH
• glykosylace MeSH
• gnotobiologické modely MeSH
• imunoglobulin A sekreční metabolismus   MeSH
• imunoglobuliny - Fab fragmenty metabolismus   MeSH
• infekce vyvolané Escherichia coli imunologie   MeSH
• jednořetězcové protilátky metabolismus   MeSH
• novorozená zvířata MeSH
• odolnost vůči nemocem MeSH
• polysacharidy metabolismus   MeSH
• prasata MeSH
• těhotenství MeSH
• zvířata MeSH
• Check Tag
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• Bacteria růst a vývoj   imunologie   metabolismus   MeSH
• bakteriální nálož MeSH
• bydlení zvířat MeSH
• chov zvířat MeSH
• druhová specificita MeSH
• gnotobiologické modely * MeSH
• interakce hostitele a patogenu MeSH
• lidé MeSH
• mikrobiota * MeSH
• modely nemocí na zvířatech MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• práce podpořená grantem MeSH
• úvodní články MeSH
• úvodníky MeSH

Germ-free animals (GF) are those without a microbiome since birth. This particular biological model has become one of special interest with the growing evidence of importance of the microbiome in the life, development, adaptation, and immunity of humans and animals in the environments in which they live. Anatomical differences observed in GF compared with conventionally-reared animals (CV) has given rise to the question of the influence of commensal microflora on the development of structure and function (even immunological) of the bowel. Only recently, thanks to achievements in microscopy and associated methods, structural differences can be better evaluated and put in perspective with the immunological characteristics of GF vs. CV animals. This study, using a GF rat model, describes for the first time the possible influence that the presence of commensal microflora, continuously stimulating mucosal immunity, has on the collagen scaffold organization of the colon mucosa. Significant differences were found between CV and GF mucosa structure with higher complexity in the CV rats associated to a more activated immune environment. The immunological data suggest that, in response to the presence of a microbiome, an effective homeostatic regulation in developed by the CV rats in healthy conditions to avoid inflammation and maintain cytokine levels near the spontaneous production found in the GF animals. The results indicated that collagen scaffold adapted to the immune microenvironment; therefore, it is apparent that the microbiome was able to condition the structure of the colon mucosa.

• MeSH
• gnotobiologické modely * MeSH
• kolon MeSH
• krysa rodu rattus MeSH
• mikrobiota * MeSH
• slizniční imunita MeSH
• střevní sliznice MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Cancer, bacteria, and immunity relationships are much-debated topics in the last decade. Microbiome's importance for metabolic and immunologic modulation of the organism adaptation and responses has become progressively evident, and models to study these relationships, especially about carcinogenesis, have acquired primary importance. The availability of germ-free (GF) animals, i.e., animals born and maintained under completely sterile conditions avoiding the microbiome development offers a unique tool to investigate the role that bacteria can have in carcinogenesis and tumor development. The comparison between GF animals with the conventional (CV) counterpart with microbiome can help to evidence conditions and mechanisms directly involving bacterial activities in the modulation of carcinogenesis processes. Here, we review the literature about spontaneous cancer and cancer modeling in GF animals since the early studies, trying to offer a practical overview on the argument.

• MeSH
• Bacteria MeSH
• gnotobiologické modely * MeSH
• karcinogeneze MeSH
• mikrobiota * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

An effective prevention from T1D is presently unknown. The primary objective of this study is to test whether gluten-free diet (GFD) instituted in children shortly after T1D onset can decelerate the decline in beta cell function as compared to age and gender-matched controls. Our hypothesis is that GFD since diabetes onset will help preserve the beta cell mass and function, which will be observable by a reduction in C-peptide AUC decline in mixed-meal tolerance test relative to the normal diet group. Secondary objectives are: 1) to investigate whether GFD modifies the immune parameters; 2) to assess the differences in fecal microbiome between children on normal diet and children on GFD, 3) to investigate the effect of gut microbiome transfer from children on GFD with the extremes of beta-cell loss to germ-free NOD mice in an attempt to replicate the difference in response to GFD observed in humans. The identification of a nutritional factor in T1D would - upon proper replication in other studies - open avenues towards implementing a simple and well established T1D intervention.

Úsilí o nalezení účinného preventivního nástroje diabetu 1. typu (T1D) dosud selhává. Kazuistická sdělení ukazují, že bezlepková dieta (GFD) může vést ke kompletní remisi diabetu 1. typu v období bezprostředně po jeho manifestaci, účinnost GFD na zmírnění průběhu autoimunitní inzulitídy byla prokázána též na myším modelu. Primárním cílem projektu je prokázat, zda GFD zahájená bezprostředně po manifestaci T1D ovlivní reziduální kapacitu beta buněk v porovnání s kontrolní skupinou. Testovanou hypotézou je možnost prezervace beta buněk (vyjádřená pomocí poklesu AUC C-peptidu při testu smíšenou stravou) zavedením GFD. Sekundárními cíli je posouzení efektu GFD na imunitní systém a na střevní mikrobiom. Vliv specifické kombinace mikrobiálního osídlení střeva bude následně testován na modelu germ-free NOD myší. Průkaz účinnosti GFD na kapacitu reziduálních beta buněk by otevřel nové možnosti prevence T1D.

• MeSH
• beta-buňky MeSH
• bezlepková dieta MeSH
• diabetes mellitus 1. typu dietoterapie   prevence a kontrola   MeSH
• dítě MeSH
• experimentální diabetes mellitus MeSH
• gnotobiologické modely MeSH
• imunita MeSH
• lidé MeSH
• myši inbrední NOD MeSH
• střevní mikroflóra MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• hodnotící studie MeSH

• Konspekt
• Pediatrie
• NLK Obory
• pediatrie
• diabetologie
• nutriční terapie, dietoterapie a výživa
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

Salmonella Typhimurium is a Gram-negative bacterium that causes enterocolitis in humans and pigs. Lipopolysaccharide (LPS) is a component of the outer leaflet of Gram-negative bacteria that provokes endotoxin shock. LPS can be synthesized completely or incompletely and creates S (smooth) or R (rough) chemotypes. Toll-like receptors (TLR) 2, 4, and 9 initiate an inflammatory reaction to combat bacterial infections. We associated/challenged one-week-old gnotobiotic piglets with wild-type S. Typhimurium with S chemotype or its isogenic ∆rfa mutants with R chemotype LPS. The wild-type S. Typhimurium induced TLR2 and TLR4 mRNA expression but not TLR9 mRNA expression in the ileum and colon of one-week-old gnotobiotic piglets 24 h after challenge. The TLR2 and TLR4 stimulatory effects of the S. Typhimurium ∆rfa mutants were related to the completeness of their LPS chain. The transcription of IL-12/23 p40, IFN-γ, and IL-6 in the intestine and the intestinal and plasmatic levels of IL-12/23 p40 and IL-6 but not IFN-γ were related to the activation of TLR2 and TLR4 signaling pathways. The avirulent S. Typhimurium ∆rfa mutants are potentially useful for modulation of the TLR2 and TLR4 signaling pathways to protect the immunocompromised gnotobiotic piglets against subsequent infection with the virulent S. Typhimurium.

• MeSH
• gnotobiologické modely fyziologie   MeSH
• ileum metabolismus   mikrobiologie   MeSH
• kolon metabolismus   mikrobiologie   MeSH
• miniaturní prasata MeSH
• mutace fyziologie   MeSH
• prasata MeSH
• Salmonella typhimurium genetika   izolace a purifikace   MeSH
• salmonelóza genetika   metabolismus   patologie   MeSH
• toll-like receptor 4 metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Crohn's disease is linked to a decreased diversity in gut microbiota composition as a potential consequence of an impaired anti-microbial response and an altered polarization of T helper cells. Here, we evaluated the immunomodulatory properties of two potential probiotic strains, namely a Bifidobacterium animalis spp. lactis Bl 5764 and a Lactobacillus reuteri Lr 5454 strains. Both strains improved colitis triggered by either 2,4,6-trinitrobenzenesulfonic acid (TNBS) or Citrobacter rodentium infection in mice. Training of dendritic cells (DC) with Lr 5454 efficiently triggered IL-22 secretion and regulatory T cells induction in vitro, while IL-17A production by CD4+ T lymphocytes was stronger when cultured with DCs that were primed with Bl 5764. This strain was sufficient for significantly inducing expression of antimicrobial peptides in vivo through the Crohn's disease predisposing gene encoding for the nucleotide-binding oligomerization domain, containing protein 2 (NOD2). In contrast, NOD2 was dispensable for the impact on antimicrobial peptide expression in mice that were monocolonized with Lr 5454. In conclusion, our work highlights a differential mode of action of two potential probiotic strains that protect mice against colitis, providing the rational for a personalized supportive preventive therapy by probiotics for individuals that are genetically predisposed to Crohn's disease.

• MeSH
• antiflogistika nesteroidní farmakologie   MeSH
• Bifidobacterium animalis * MeSH
• Citrobacter rodentium patogenita   MeSH
• dendritické buňky fyziologie   MeSH
• enterobakteriální infekce mikrobiologie   MeSH
• gnotobiologické modely MeSH
• kolitida chemicky indukované   mikrobiologie   patologie   terapie   MeSH
• kyselina trinitrobenzensulfonová toxicita   MeSH
• Limosilactobacillus reuteri * MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• probiotika farmakologie   MeSH
• proteiny asociované s pankreatitidou genetika   MeSH
• regulační T-lymfocyty fyziologie   MeSH
• střevní mikroflóra MeSH
• T-lymfocyty pomocné-indukující fyziologie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH