Alterations in the gut microbiota composition and diversity seem to play a role in the development of chronic diseases, including inflammatory bowel disease (IBD), leading to gut barrier disruption and induction of proinflammatory immune responses. This opens the door for the use of novel health-promoting bacteria. We selected five Parabacteroides distasonis strains isolated from human adult and neonates gut microbiota. We evaluated in vitro their immunomodulation capacities and their ability to reinforce the gut barrier and characterized in vivo their protective effects in an acute murine model of colitis. The in vitro beneficial activities were highly strain dependent: two strains exhibited a potent anti-inflammatory potential and restored the gut barrier while a third strain reinstated the epithelial barrier. While their survival to in vitro gastric conditions was variable, the levels of P. distasonis DNA were higher in the stools of bacteria-treated animals. The strains that were positively scored in vitro displayed a strong ability to rescue mice from colitis. We further showed that two strains primed dendritic cells to induce regulatory T lymphocytes from naïve CD4+ T cells. This study provides better insights on the functionality of commensal bacteria and crucial clues to design live biotherapeutics able to target inflammatory chronic diseases such as IBD.

• Klíčová slova
• IBD, colitis, functional screening, holobiont, immune response, live biotherapeutic products (LBP), microbiota, probiotics,
• MeSH
• Bacteroidetes genetika   imunologie   izolace a purifikace   MeSH
• Caco-2 buňky MeSH
• DNA bakterií genetika   metabolismus   MeSH
• dospělí MeSH
• feces mikrobiologie   MeSH
• idiopatické střevní záněty imunologie   mikrobiologie   MeSH
• kolitida chemicky indukované   imunologie   mikrobiologie   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• kyselina trinitrobenzensulfonová škodlivé účinky   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• novorozenec MeSH
• regulační T-lymfocyty imunologie   MeSH
• střevní mikroflóra imunologie   MeSH
• střevní sliznice imunologie   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• myši MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• DNA bakterií MeSH
• kyselina trinitrobenzensulfonová 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

Our study examined whether repeated preventive oral administration of live probiotic bacterial strains Escherichia coli O83:K24:H31 (Ec O83), Escherichia coli Nissle 1917 O6:K5:H1 (Ec Nis) and Lactobacillus casei DN 114001 (Lc) can protect mice against dextran sodium sulfate (DSS)-induced colitis. A significant decrease in average symptom score was observed in Ec O83-, Ec Nis- and Lc-pretreated group (p < 0.05). Significant differences in body mass loss between Lc pretreated mice with DSS-induced colitis were found when compared with nontreated mice (p < 0.05). PBS pretreated mice had a significantly shorter colon than Ec O83-, Ec Nis- and Lc-pretreated mice (p < 0.05). Administration of Lc significantly decreased the severity of DSS induced histological marks of inflammation (p < 0.05). A significant difference (p < 0.05) was also found in specific IgA level against given probiotic in enteral fluid between colitic mice and healthy mice pretreated with Ec 083 and Ec Nis.

• MeSH
• aplikace orální MeSH
• Escherichia coli MeSH
• histocytochemie MeSH
• imunoglobulin A analýza   MeSH
• kolon mikrobiologie   MeSH
• Lactobacillus casei MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• probiotika farmakologie   MeSH
• síran dextranu škodlivé účinky   MeSH
• střevní sliznice imunologie   patologie   MeSH
• ulcerózní kolitida chemicky indukované   imunologie   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• imunoglobulin A MeSH
• síran dextranu MeSH

One-week dextran sulfate treatment of conventional (CV) immunodeficient (SCID) mice gave rise to acute colitis in the colon mucosa; germ-free (GF) SCID mice did not exhibit any changes in colon morphology. Dextran sulfate application to CV immunocompetent (BALB/c) mice did induce substantial changes in the colon mucosa (grade 4); GF BALB/c mice showed mild changes in the colon morphology (grade 1) only. GF SCID mice and CV SCID mice died during the second round of dextran sulfate treatment suffering from chronic colitis; GF BALB/c mice exhibited mild crypt distortion while CV BALB/c mice showed a complete loss of the surface epithelium (grade 4), accompanied by T and B lymphocyte infiltration.

• MeSH
• imunokompetence * MeSH
• kolitida chemicky indukované   mikrobiologie   patologie   MeSH
• kolon mikrobiologie   patologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši SCID MeSH
• myši MeSH
• organismy bez specifických patogenů MeSH
• síran dextranu MeSH
• střevní sliznice patologie   MeSH
• zánět patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• srovnávací studie MeSH
• Názvy látek
• síran dextranu MeSH