Live biotherapeutic products constitute an emerging therapeutic approach to prevent or treat inflammatory bowel diseases. Lactobacillus acidophilus is a constituent of the human microbiota with probiotic potential, that is illustrated by improvement of intestinal inflammation and antimicrobial activity against several pathogens. In this study, we evaluated the immunomodulatory properties of the L. acidophilus strain BIO5768 at steady state and upon acute inflammation. Supplementation of naïve mice with BIO5768 heightened the transcript level of some IL-17 target genes encoding for protein with microbicidal activity independently of NOD2 signaling. Of these, the BIO5768-induced expression of Angiogenin-4 was blunted in monocolonized mice that are deficient for the receptor of IL-17 (but not for NOD2). Interestingly, priming of bone marrow derived dendritic cells by BIO5768 enhanced their ability to support the secretion of IL-17 by CD4+ T cells. Equally of importance, the production of IL-22 by type 3 innate lymphoid cells is concomitantly heightened in response to BIO5768. When administered alone or in combination with Bifidobacterium animalis spp. lactis BIO5764 and Limosilactobacillus reuteri, BIO5768 was able to alleviate at least partially intestinal inflammation induced by Citrobacter rodentium infection. Furthermore, BIO5768 was also able to improve colitis induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). In conclusion, we identify a new potential probiotic strain for the management of inflammatory bowel diseases, and provide some insights into its IL-17-dependent and independent mode of action.
- MeSH
- Bifidobacterium animalis MeSH
- Enterobacteriaceae Infections therapy MeSH
- Inflammatory Bowel Diseases * therapy MeSH
- Interleukin-17 MeSH
- Colitis * chemically induced therapy microbiology MeSH
- Trinitrobenzenesulfonic Acid adverse effects MeSH
- Lactobacillus acidophilus * MeSH
- Lymphocytes MeSH
- Mice MeSH
- Immunity, Innate * MeSH
- Probiotics * pharmacology therapeutic use MeSH
- Inflammation MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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.
- 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
- Keywords
- makrocirkulace,
- MeSH
- Anti-Bacterial Agents therapeutic use MeSH
- Adult MeSH
- Escherichia coli pathogenicity MeSH
- Hypoxia MeSH
- Colitis surgery diagnosis microbiology MeSH
- Comorbidity MeSH
- Laparotomy MeSH
- Humans MeSH
- Inflammation Mediators MeSH
- Multiple Organ Failure diagnosis drug therapy physiopathology MeSH
- Peritonitis surgery diagnosis microbiology MeSH
- Disease Progression MeSH
- Resuscitation MeSH
- Sepsis * surgery diagnosis etiology drug therapy complications nursing physiopathology therapy MeSH
- Shock, Septic * surgery etiology drug therapy complications physiopathology MeSH
- Systemic Inflammatory Response Syndrome etiology MeSH
- Vasoconstrictor Agents administration & dosage classification MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- Review 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
- Anti-Inflammatory Agents, Non-Steroidal pharmacology MeSH
- Bifidobacterium animalis * MeSH
- Citrobacter rodentium pathogenicity MeSH
- Dendritic Cells physiology MeSH
- Enterobacteriaceae Infections microbiology MeSH
- Germ-Free Life MeSH
- Colitis chemically induced microbiology pathology therapy MeSH
- Trinitrobenzenesulfonic Acid toxicity MeSH
- Limosilactobacillus reuteri * MeSH
- Disease Models, Animal MeSH
- Mice, Inbred BALB C MeSH
- Mice, Inbred C57BL MeSH
- Mice, Knockout MeSH
- Probiotics pharmacology MeSH
- Pancreatitis-Associated Proteins genetics MeSH
- T-Lymphocytes, Regulatory physiology MeSH
- Gastrointestinal Microbiome MeSH
- T-Lymphocytes, Helper-Inducer physiology MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Keywords
- poradiační kolitida, poléková kolitida,
- MeSH
- Bacterial Infections diagnosis microbiology therapy MeSH
- Diagnosis, Differential * MeSH
- Inflammatory Bowel Diseases * diagnosis etiology MeSH
- Colitis, Ischemic diagnosis classification therapy MeSH
- Colitis etiology microbiology therapy MeSH
- Humans MeSH
- Mycoses microbiology therapy MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Radiotherapy adverse effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- MeSH
- Acute Disease * MeSH
- Anaphylaxis * classification pathology MeSH
- Medical History Taking MeSH
- Bacteria classification pathogenicity drug effects MeSH
- Diagnosis, Differential MeSH
- Fever of Unknown Origin etiology MeSH
- Fever diagnosis etiology therapy MeSH
- Communicable Diseases * diagnosis classification therapy MeSH
- Clostridium Infections diagnosis drug therapy pathology therapy MeSH
- Colitis diagnosis etiology microbiology therapy MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
- MeSH
- Anti-Bacterial Agents pharmacology therapeutic use MeSH
- Cefuroxime pharmacology therapeutic use MeSH
- Klebsiella Infections drug therapy MeSH
- Respiratory Tract Infections drug therapy MeSH
- Soft Tissue Infections * drug therapy MeSH
- Wound Infection * drug therapy MeSH
- Klebsiella pneumoniae drug effects MeSH
- Colitis * drug therapy microbiology MeSH
- Comorbidity MeSH
- Coronary Artery Bypass MeSH
- Humans MeSH
- Postoperative Complications * drug therapy MeSH
- Surgical Clearance MeSH
- Premedication methods MeSH
- Aged MeSH
- Tigecycline MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Case Reports MeSH
A decrease in the abundance and biodiversity of intestinal bacteria within the Firmicutes phylum has been associated with inflammatory bowel disease (IBD). In particular, the anti-inflammatory bacterium Faecalibacterium prausnitzii, member of the Firmicutes phylum and one of the most abundant species in healthy human colon, is underrepresented in the microbiota of IBD patients. The aim of this study was to investigate the immunomodulatory properties of F. prausnitzii strain A2-165, the biofilm forming strain HTF-F and the extracellular polymeric matrix (EPM) isolated from strain HTF-F. For this purpose, the immunomodulatory properties of the F. prausnitzii strains and the EPM were studied in vitro using human monocyte-derived dendritic cells. Then, the capacity of the F. prausnitzii strains and the EPM of HTF-F to suppress inflammation was assessed in vivo in the mouse dextran sodium sulphate (DSS) colitis model. The F. prausnitzii strains and the EPM had anti-inflammatory effects on the clinical parameters measured in the DSS model but with different efficacy. The immunomodulatory effects of the EPM were mediated through the TLR2-dependent modulation of IL-12 and IL-10 cytokine production in antigen presenting cells, suggesting that it contributes to the anti-inflammatory potency of F. prausnitzii HTF-F. The results show that F. prausnitzii HTF-F and its EPM may have a therapeutic use in IBD.
- MeSH
- Antigens, Surface metabolism MeSH
- Cytokines genetics metabolism MeSH
- Dendritic Cells immunology metabolism MeSH
- Extracellular Matrix metabolism MeSH
- Phenotype MeSH
- Forkhead Transcription Factors genetics metabolism MeSH
- Transcription, Genetic MeSH
- Inflammatory Bowel Diseases etiology metabolism pathology MeSH
- Colitis chemically induced genetics immunology metabolism microbiology MeSH
- Lymph Nodes immunology metabolism MeSH
- Inflammation Mediators metabolism MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Ruminococcus metabolism ultrastructure MeSH
- Dextran Sulfate adverse effects MeSH
- Spleen immunology metabolism MeSH
- Intestinal Mucosa metabolism microbiology pathology MeSH
- Toll-Like Receptor 2 genetics metabolism MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Cíl práce: posoudit úspěšnost léčby kolitidy způsobené Clostridium difficile metodou fekální bakterioterapie. Materiál a metodiky: Prospektivní analýza průběhu léčby klostridiové kolitidy pomocí fekální bakterioterapie u 80 dospělých pacientů hospitalizovaných na Klinice infekčních chorob Fakultní nemocnice Brno od 1.1.2010-31.12.2014. Výsledky: Ve studovaném období podstoupilo fekální bakterioterapii 80 pacientů. V 78 případech proběhla aplikace ultrafiltrátu nasojejunální sondou, ve dvou případech rektálním nálevem. U 6 pacientů bylo aplikováno 20 g stolice s úspěšností 50 %. U 9 pacientů nebyl výsledek hodnotitelný. U zbylých 65 jedinců byla při aplikaci 40 g stolice celková úspěšnost 83,1 %. V souboru nebyly pozorovány žádné závažné nežádoucí účinky ani letalita. Závěry: Fekální bakterioterapie je účinná a bezpečná metoda v léčbě klostridiové kolitidy.
Introduction: The aim of the study is to assess the efficacy of fecal bacteriotherapy in the treatment of Clostridium difficile colitis. Materials and methods: A prospective study of fecal bacteriotherapy in 80 adult patients hospitalized in the Clinic of Infectious Diseases, University Hospital Brno between 1 January 2010 and 31 December 2014. Results: During the study period, 80 patients were treated with fecal bacteriotherapy. The majority of the study group received fecal bacteriotherapy via a nasojejunal tube (n=78) and two patients via a rectal enema. Six patients were instilled with 20 g of feces, with a success rate of 50 %. The outcomes of nine patients were unevaluable. In the rest of 65 patients, the success rate with 40 g of feces was 83.1 %. There were no severe adverse events or mortality associated with fecal bacteriotherapy. Conclusions: Fecal bacteriotherapy is a safe and effective treatment modality in Clostridium difficile colitis.
- Keywords
- dárcovství stolice,
- MeSH
- Adult MeSH
- Feces * microbiology MeSH
- Clostridium Infections * therapy MeSH
- Colitis microbiology therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Prospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Intestines microbiology MeSH
- Vancomycin therapeutic use MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- MeSH
- Clostridioides difficile * pathogenicity drug effects MeSH
- Cross Infection * epidemiology microbiology mortality MeSH
- Colitis drug therapy microbiology mortality MeSH
- Humans MeSH
- Meningitis, Bacterial drug therapy microbiology MeSH
- Pseudomonas aeruginosa * pathogenicity drug effects MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Case Reports MeSH