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.

• Keywords
• IBD, colitis, functional screening, holobiont, immune response, live biotherapeutic products (LBP), microbiota, probiotics,
• MeSH
• Bacteroidetes genetics   immunology   isolation & purification   MeSH
• Caco-2 Cells MeSH
• DNA, Bacterial genetics   metabolism   MeSH
• Adult MeSH
• Feces microbiology   MeSH
• Inflammatory Bowel Diseases immunology   microbiology   MeSH
• Colitis chemically induced   immunology   microbiology   MeSH
• Real-Time Polymerase Chain Reaction MeSH
• Trinitrobenzenesulfonic Acid adverse effects   MeSH
• Humans MeSH
• Disease Models, Animal MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Infant, Newborn MeSH
• T-Lymphocytes, Regulatory immunology   MeSH
• Gastrointestinal Microbiome immunology   MeSH
• Intestinal Mucosa immunology   MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Mice MeSH
• Infant, Newborn MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• DNA, Bacterial MeSH
• Trinitrobenzenesulfonic Acid 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
• Autoimmune Diseases etiology   microbiology   MeSH
• Gastrointestinal Tract microbiology   MeSH
• Germ-Free Life * MeSH
• Immunity MeSH
• Humans MeSH
• Metagenome immunology   MeSH
• Disease Models, Animal MeSH
• Neoplasms etiology   microbiology   MeSH
• Mucous Membrane immunology   MeSH
• Inflammation etiology   microbiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review 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
• Acute Disease MeSH
• Antigens, Bacterial administration & dosage   immunology   MeSH
• Administration, Oral MeSH
• Bacteroides immunology   MeSH
• Chronic Disease MeSH
• Cytokines blood   immunology   MeSH
• Colitis therapy   MeSH
• Metagenome immunology   MeSH
• Mice, Inbred BALB C MeSH
• Mice, SCID MeSH
• Mice MeSH
• Antibodies, Bacterial blood   immunology   MeSH
• Intestinal Mucosa immunology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Antigens, Bacterial MeSH
• Cytokines MeSH
• Antibodies, Bacterial 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
• Administration, Oral MeSH
• Escherichia coli MeSH
• Histocytochemistry MeSH
• Immunoglobulin A analysis   MeSH
• Colon microbiology   MeSH
• Lacticaseibacillus casei MeSH
• Disease Models, Animal MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Probiotics pharmacology   MeSH
• Dextran Sulfate adverse effects   MeSH
• Intestinal Mucosa immunology   pathology   MeSH
• Colitis, Ulcerative chemically induced   immunology   prevention & control   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Immunoglobulin A MeSH
• Dextran Sulfate 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
• Immunocompetence * MeSH
• Colitis chemically induced   microbiology   pathology   MeSH
• Colon microbiology   pathology   MeSH
• Disease Models, Animal MeSH
• Mice, Inbred BALB C MeSH
• Mice, SCID MeSH
• Mice MeSH
• Specific Pathogen-Free Organisms MeSH
• Dextran Sulfate MeSH
• Intestinal Mucosa pathology   MeSH
• Inflammation pathology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Comparative Study MeSH
• Names of Substances
• Dextran Sulfate MeSH