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
- 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
Background: Mucosal mast cells (MC) are key players in IgE-mediated food allergy (FA). The evidence on the interaction between gut microbiota, MC and susceptibility to FA is contradictory. Objective: We tested the hypothesis that commensal bacteria are essential for MC migration to the gut and their maturation impacting the susceptibility to FA. Methods: The development and severity of FA symptoms was studied in sensitized germ-free (GF), conventional (CV), and mice mono-colonized with L. plantarum WCFS1 or co-housed with CV mice. MC were phenotypically and functionally characterized. Results: Systemic sensitization and oral challenge of GF mice with ovalbumin led to increased levels of specific IgE in serum compared to CV mice. Remarkably, despite the high levels of sensitization, GF mice did not develop diarrhea or anaphylactic hypothermia, common symptoms of FA. In the gut, GF mice expressed low levels of the MC tissue-homing markers CXCL1 and CXCL2, and harbored fewer MC which exhibited lower levels of MC protease-1 after challenge. Additionally, MC in GF mice were less mature as confirmed by flow-cytometry and their functionality was impaired as shown by reduced edema formation after injection of degranulation-provoking compound 48/80. Co-housing of GF mice with CV mice fully restored their susceptibility to develop FA. However, this did not occur when mice were mono-colonized with L. plantarum. Conclusion: Our results demonstrate that microbiota-induced maturation and gut-homing of MC is a critical step for the development of symptoms of experimental FA. This new mechanistic insight into microbiota-MC-FA axis can be exploited in the prevention and treatment of FA in humans.
- MeSH
- biologické markery MeSH
- buněčná diferenciace genetika imunologie MeSH
- cytokiny metabolismus MeSH
- degranulace buněk genetika imunologie MeSH
- gnotobiologické modely MeSH
- mastocyty imunologie metabolismus MeSH
- metagenom MeSH
- metagenomika metody MeSH
- mikrobiota * imunologie MeSH
- modely nemocí na zvířatech MeSH
- myši MeSH
- náchylnost k nemoci MeSH
- potravinová alergie etiologie metabolismus patologie MeSH
- RNA ribozomální 16S MeSH
- střevní mikroflóra MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Good genes, good food, good friends. That is what parents hope will sustain and nurture the harmonious growth of their children. The impact of the genetic background and nutrition on postnatal growth has been in the spot light for long, but the good friends have come to the scene only recently. Among the good friends perhaps the most crucial ones are those that we are carrying within ourselves. They comprise the trillions of microbes that collectively constitute each individual's intestinal microbiota. Indeed, recent epidemiological and field studies in humans, supported by extensive experimental data on animal models, demonstrate a clear role of the intestinal microbiota on their host's juvenile growth, especially under suboptimal nutrient conditions. Genuinely integrative approaches applicable to invertebrate and vertebrate systems combine tools from genetics, developmental biology, microbiology, nutrition, and physiology to reveal how gut microbiota affects growth both positively and negatively, in healthy and pathological conditions. It appears that certain natural or engineered gut microbiota communities can positively impact insulin/IGF-1 and steroid hormone signaling, thus contributing to the host juvenile development and maturation.
- MeSH
- lidé MeSH
- nutriční stav fyziologie MeSH
- potraviny * MeSH
- stárnutí MeSH
- střeva mikrobiologie MeSH
- střevní mikroflóra fyziologie MeSH
- vývojová biologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
PURPOSE OF REVIEW: This review focuses on the recent discoveries about the impact of intestinal microbiota on mammalian host juvenile growth. RECENT FINDINGS: Intestinal microbiota is a powerful modulator of many facets of multicellular host's physiology. Recent results from human field studies and animal research have clearly shown that not only the nutrition, but also the intestinal microbiota impacts host postnatal growth kinetics. Absence of microbiome leads to stunted growth in mammalian gnotobiotic models and changes in the composition of the intestinal microbiota can impact the postnatal growth kinetics both positively and negatively under normal nutritional conditions as well as in undernutrition. Strikingly, specific bacterial strains are able to interact with GH/IGF-1 somatotropic axis activity, thus directly impacting host juvenile development. SUMMARY: Intestinal microbiota dictates the pace of host postnatal growth. This newly described role envisages that therapy with specific bacterial strains, together with re-nutritional strategies, might successfully alleviate the long-term sequelae of undernutrition during childhood in humans.
- MeSH
- Bacteria MeSH
- insulinu podobný růstový faktor I metabolismus MeSH
- lidé MeSH
- podvýživa komplikace mikrobiologie prevence a kontrola MeSH
- poruchy růstu etiologie metabolismus mikrobiologie prevence a kontrola MeSH
- probiotika terapeutické užití MeSH
- růst MeSH
- růstový hormon metabolismus MeSH
- savci mikrobiologie MeSH
- střeva mikrobiologie MeSH
- střevní mikroflóra * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Germ-free animals have been used to define the vital role of commensal bacteria on the maturation of the host immune system. However, the role of bacterial residues in diet in this setting is poorly understood. Here we investigated the effect of bacterial contamination in sterile diet on the level of allergic sensitization in germ-free mice. Sterile grain-based diets ST1 and R03 were tested for the level of bacterial contamination. ST1 contained higher amount of bacterial DNA, approximately ten times more endotoxin, and induced higher, TLR4-dependent, cytokine production in dendritic cells compared to R03. In a germ-free mouse model of sensitization to the major birch pollen allergen Bet v 1, feeding on ST1 for at least two generations was associated with decreased production of allergen-specific IgE and IgG1 antibodies in sera in comparison to R03. Furthermore, reduced levels of allergen-specific and ConA-induced cytokines IL-4, IL-5 and IL-13 accompanied by increased levels of IFN-γ were detected in splenocytes cultures of these mice. Our results show that contamination of experimental diet with bacterial residues, such as endotoxin, significantly affects the development of allergic sensitization in germ-free mice. Therefore, careful selection of sterile food is critical for the outcomes of germ-free or gnotobiotic experimental models of immune-deviated diseases.
- MeSH
- alergie imunologie patologie MeSH
- antigeny rostlinné imunologie MeSH
- buněčná diferenciace účinky léků MeSH
- chov MeSH
- cytokiny biosyntéza MeSH
- dendritické buňky účinky léků MeSH
- dieta * MeSH
- DNA bakterií analýza MeSH
- endotoxiny toxicita MeSH
- epitopy imunologie MeSH
- gnotobiologické modely MeSH
- HEK293 buňky MeSH
- imunizace * MeSH
- imunoglobulin A imunologie MeSH
- imunoglobulin G imunologie MeSH
- kontaminace DNA MeSH
- kultivované buňky MeSH
- lidé MeSH
- ligandy MeSH
- mitogeny farmakologie MeSH
- myši inbrední BALB C MeSH
- slezina patologie MeSH
- toll-like receptor 4 metabolismus MeSH
- trávicí systém imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
The main goal in reversing the allergy epidemic is the development of effective prophylactic strategies. We investigated the prophylactic effect of neonatal mother-to-offspring mono-colonization with Bifidobacterium longum ssp. longum CCM 7952 on subsequent allergic sensitization. Adult male and female germ-free (GF) mice were mono-colonized with B. longum, mated and their offspring, as well as age-matched GF controls, were sensitized with the major birch pollen allergen Bet v 1. Furthermore, signaling pathways involved in the recognition of B. longum were investigated in vitro. Neonatal mono-colonization of GF mice with B. longum suppressed Bet v 1-specific IgE-dependent β-hexosaminidase release as well as levels of total IgE and allergen-specific IgG2a in serum compared to sensitized GF controls. Accordingly, Bet v 1-induced production of both Th1- and Th2-associated cytokines in spleen cell cultures was significantly reduced in these mice. The general suppression of Bet v 1-specific immune responses in B. longum-colonized mice was associated with increased levels of regulatory cytokines IL-10 and TGF-β in serum. In vitro, B. longum induced low maturation status of bone marrow-derived dendritic cells and production of IL-10 in TLR2-, MyD88-, and MAPK-dependent manner. Our data demonstrate that neonatal mono-colonization with B. longum reduces allergic sensitization, likely by activation of regulatory responses via TLR2, MyD88, and MAPK signaling pathways. Thus, B. longum might be a promising candidate for perinatal intervention strategies against the onset of allergic diseases in humans.
- MeSH
- alergie prevence a kontrola MeSH
- antigeny rostlinné imunologie MeSH
- Bifidobacterium růst a vývoj MeSH
- cytokiny sekrece MeSH
- gastrointestinální trakt mikrobiologie MeSH
- gnotobiologické modely MeSH
- hexosaminidasy metabolismus MeSH
- imunizace MeSH
- imunoglobulin E krev MeSH
- imunologická tolerance MeSH
- modely nemocí na zvířatech MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: The use of recombinant lactic acid bacteria (LAB) as vehicles for mucosal delivery of recombinant allergens is an attractive concept for antigen-defined allergy prevention/treatment. Interventions with LAB are of increasing interest early in life when immune programming is initiated. Here, we investigated the effect of neonatal colonization with a recombinant LAB producing the major birch pollen allergen Bet v 1 in a murine model of type I allergy. METHODS: We constructed a recombinant Lactobacillus (L.) plantarum NCIMB8826 strain constitutively producing Bet v 1 to be used for natural mother-to-offspring mono-colonization of germ-free BALB/c mice. Allergen-specific immunomodulatory effects of the colonization on humoral and cellular immune responses were investigated prior and after sensitization to Bet v 1. RESULTS: Mono-colonization with the Bet v 1 producing L. plantarum induced a Th1-biased immune response at the cellular level, evident in IFN-γ production of splenocytes upon stimulation with Bet v 1. After sensitization with Bet v 1 these mice displayed suppressed IL-4 and IL-5 production in spleen and mesenteric lymph node cell cultures as well as decreased allergen-specific antibody responses (IgG1, IgG2a, and IgE) in sera. This suppression was associated with a significant up-regulation of the regulatory marker Foxp3 at the mRNA level in the spleen cells. CONCLUSION: Intervention at birth with a live recombinant L. plantarum producing a clinically relevant allergen reduces experimental allergy and might therefore become an effective strategy for early intervention against the onset of allergic diseases.
- MeSH
- alergeny aplikace a dávkování genetika imunologie MeSH
- antigeny rostlinné genetika imunologie MeSH
- bříza genetika imunologie MeSH
- časná přecitlivělost MeSH
- cytokiny biosyntéza imunologie MeSH
- forkhead transkripční faktory genetika metabolismus MeSH
- imunizace MeSH
- imunoglobulinové izotypy krev imunologie MeSH
- Lactobacillus plantarum genetika imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- novorozená zvířata MeSH
- pyl genetika imunologie MeSH
- regulační T-lymfocyty imunologie MeSH
- slezina cytologie imunologie MeSH
- Th1 buňky imunologie MeSH
- Th2 buňky imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
