The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases

Tlaskalová‐Hogenová, Helena; Štěpánková, Renata; Kozáková, Hana; Hudcovic, Tomáš; Vannucci, Luca; Tučková, Ludmila; Rossmann, P; Hrnčíř, Tomáš; Kverka, Miloslav; Zákostelská, Zuzana Jirásková; Klimešová, Klára; Přibylová, Jaroslava; Bártová, Jiřina; Sánchez, Daniel; Fundová, Petra; Borovská, Dana; Šrůtková, Dagmar; Zı́dek, Zdeňek; Schwarzer, Martin; Drastich, Pavel; Funda, David P.

doi:10.1038/cmi.2010.67

Cited by 616 publications

(443 citation statements)

References 160 publications

(165 reference statements)

Supporting

Mentioning

423

Contrasting

Unclassified

Order By: Relevance

“…28 Germ-free animals represent a unique tool to study the interactions of hosts with specific probiotic strains or with defined probiotic mixtures and to investigate their impacts on the development of the immune system. 6,29 Using a mouse model of allergic sensitization to the major birch pollen allergen Bet v 1, we have previously shown that neonatal colonization of GF mice with Bifidobacterium longum is able to prevent allergic sensitization, 20 but the underlying mechanism of the host-bacteria interaction in gnotobiotic models is still far from being elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…This dysbiosis has been linked to the increased permeability of the epithelium 3,4 and the development of chronic inflammatory diseases, such as allergies and inflammatory bowel disease. [5][6][7] Allergies have become a serious health burden in developed countries. In accordance with the general hypothesis of Strachan 8 that the rapid increase in allergic diseases in humans is dependent on microbial deprivation early in life, reduced bacterial diversity and lower counts of lactobacilli and bifidobacteria have been detected in the gut of allergic children.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization

et al. 2015

Self Cite

View full text Add to dashboard Cite

Increasing numbers of clinical trials and animal experiments have shown that probiotic bacteria are promising tools for allergy prevention. Here, we analyzed the immunomodulatory properties of three selected lactobacillus strains and the impact of their mixture on allergic sensitization to Bet v 1 using a gnotobiotic mouse model. We showed that Lactobacillus (L.) rhamnosus LOCK0900, L. rhamnosus LOCK0908 and L. casei LOCK0919 are recognized via Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptors and stimulate bone marrow-derived dendritic cells to produce cytokines in species-and strain-dependent manners. Colonization of germ-free (GF) mice with a mixture of all three strains (Lmix) improved the intestinal barrier by strengthening the apical junctional complexes of enterocytes and restoring the structures of microfilaments extending into the terminal web. Mice colonized with Lmix and sensitized to the Bet v 1 allergen showed significantly lower levels of allergen-specific IgE, IgG1 and IgG2a and an elevated total IgA level in the sera and intestinal lavages as well as an increased transforming growth factor (TGF)-b level compared with the sensitized GF mice. Splenocytes and mesenteric lymph node cells from the Lmix-colonized mice showed the significant upregulation of TGF-b after in vitro stimulation with Bet v 1. Our results show that Lmix colonization improved the gut epithelial barrier and reduced allergic sensitization to Bet v 1. Furthermore, these findings were accompanied by the increased production of circulating and secretory IgA and the regulatory cytokine TGF-b. Thus, this mixture of three lactobacillus strains shows potential for use in the prevention of increased gut permeability and the onset of allergies in humans. Cellular & Molecular Immunology

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…Findings so far strongly suggest that events that occur in the early life stages of life have a profound impact on the organism's later development (1), structure (2), and function (3). Traditionally, the study of animal development has focused on understanding how interactions among animal cells trigger developmental pathways.…”

mentioning

confidence: 99%

Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development

Galindo-Villegas

García‐Moreno

Oliveira

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

204

161

View full text Add to dashboard Cite

How fish larvae are protected from infection before the maturation of adaptive immunity, a process which may take up to several weeks in most species, has long been a matter of speculation. Using a germfree model, we show that colonization by commensals in newly hatched zebrafish primes neutrophils and induces several genes encoding proinflammatory and antiviral mediators, increasing the resistance of larvae to viral infection. Commensal microbe recognition was found to be mediated mainly through a TLR/MyD88 signaling pathway, and professional phagocytes were identified as the source of these immune mediators. However, the induction of proinflammatory and antiviral genes, but not of antimicrobial effector genes, also required the covalent modification of histone H3 at gene promoters. Interestingly, chromatin modifications were not altered by commensal microbes or hatching. Taken together, our results demonstrate that gene-specific chromatin modifications are associated with the protection of zebrafish larvae against infectious agents before adaptive immunity has developed and prevent pathologies associated with excessive inflammation during development.epigenetic | cytokines | evolution | gene regulation | live imaging

show abstract

“…The early exposure to high glucose levels was strongly associated with CRC, and the HRs proportionally increased with the length of the exposure to IFG [9]. There are many mechanistic hypotheses to account for this association between hyperglycemia and CRC, including hyperinsulinemia occurring through insulin-like growth factor signaling [10][11][12], chronic inflammation [12,13], delayed bowel transit time [14], changes in bile acid [15], and imbalanced microbiota in the bowel [16].…”

Section: Hyperglycemiamentioning

confidence: 99%

Impaired fasting glucose, single-nucleotide polymorphisms, and risk for colorectal cancer in Koreans

2016

View full text Add to dashboard Cite

OBJECTIVES:Numerous studies have demonstrated that fasting serum glucose (FSG) levels and certain single-nucleotide polymorphisms (SNPs) are related to an increased risk of colorectal cancer (CRC); however, their combined effects are still unclear. METHODS:Of a total of 144,527 men and women free of cancer at baseline, 317 developed CRC during 5.3 years of follow-up. A case-cohort study (n = 1,691) was used, consisting of participants with a DNA sample available. Three well-known SNPs (rs3802842, rs6983267, rs10795668) were genotyped. Hazard ratios (HR) and 95% confidence intervals (CI) of CRC, colon and rectal cancer were calculated, with the Cox proportional hazard models. RESULTS:The crude incidence rates per 100,000 person-years were 41.1 overall, 48.4 for men, and 29.3 for women. Among participants with dysglycemia, SNPs rs3802842 and rs6983267 were both associated with an increased risk of CRC (HR, 3.2; 95% CI, 1.9 to 5.5 and HR, 1.8; 95% CI, 1.1 to 3.1, respectively) and rectal cancer (HR, 3.4; 95% CI, 1.8 to 6.6 and HR, 3.3; 95% CI, 1.6 to 7.1, respectively). The interaction effect of dysglycemia and SNPs was positive, that is, resulted in an elevated risk of CRC, but was not statistically significant. CONCLUSIONS:This study demonstrates that both high FSG and certain SNPs are major risk factors for CRC and rectal cancer but that they did not interact synergistically. The difference in effect size of the SNPs according to CRC subtype (i.e., colon or rectal cancer) and presence of dysglycemia merits further research.

show abstract

The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases

Cited by 616 publications

References 160 publications

Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization

Colonization of germ-free mice with a mixture of three lactobacillus strains enhances the integrity of gut mucosa and ameliorates allergic sensitization

Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development

Impaired fasting glucose, single-nucleotide polymorphisms, and risk for colorectal cancer in Koreans

Contact Info

Product

Resources

About