Propionate catabolism by CD-associated adherent-invasive E. coli counteracts its anti-inflammatory effect
| Autor: | Emilie Vazeille, Virginie Bonnin, Richard Bonnet, Nicolas Barnich, Tiphanie Faïs, Damien Richard, Allison Agus, Elisabeth Billard, Julien Delmas, Anthony Buisson, Mélissa Chervy, Guillaume Dalmasso, Jérémy Denizot |
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| Přispěvatelé: | Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de Pharmacologie Médicale [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Bactériologie [CHU Clermont-Ferrand], Infection Inflammation et Interaction Hôtes Pathogènes [CHU Clermont-Ferrand] (3IHP ), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Institut Universitaire de Technologie - Clermont-Ferrand (IUT Clermont-Ferrand), Université Clermont Auvergne (UCA), Ministère de la Recherche et de la Technologie, Inserm, INRAe, Région Auvergne Rhône Alpes, National Program 'Microbiote' (Inserm), Association François Aupetit (AFA), ANR-16-IDEX-0001,CAP 20-25,CAP 20-25(2016) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
gpr43 agonist treatment RC799-869 medicine.disease_cause Bacterial Adhesion Receptors G-Protein-Coupled Feces Mice 0302 clinical medicine Intestinal mucosa Crohn Disease adherent-invasive e. coli Intestinal Mucosa Receptor Escherichia coli Infections chemistry.chemical_classification Anti-Inflammatory Agents Non-Steroidal Gastroenterology Diseases of the digestive system. Gastroenterology 3. Good health Crohn's disease methyl-citrate pathway Infectious Diseases crohn’s disease Cytokines 030211 gastroenterology & hepatology Tumor necrosis factor alpha Research Article Research Paper Microbiology (medical) Agonist medicine.drug_class Biology Microbiology 03 medical and health sciences medicine Escherichia coli Animals Humans adherentinvasive E. coli propionate Colitis Macrophages [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology medicine.disease Fatty Acids Volatile [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Gastrointestinal Microbiome Gastrointestinal Tract 030104 developmental biology RAW 264.7 Cells chemistry Propionate Dysbiosis Colitis Ulcerative Propionates |
| Zdroj: | Gut Microbes, Vol 13, Iss 1 (2021) Gut microbes Gut microbes, Taylor & Francis, 2021, 13 (1), pp.1-19. ⟨10.1080/19490976.2020.1839318⟩ Gut microbes, 2021, 13 (1), pp.1-19. ⟨10.1080/19490976.2020.1839318⟩ Gut Microbes article-version (VoR) Version of Record |
| ISSN: | 1949-0984 1949-0976 |
| DOI: | 10.1080/19490976.2020.1839318⟩ |
| Popis: | International audience; Crohn's disease (CD) is a chronic and disabling inflammatory disorder of the gut that is profoundly influenced by intestinal microbiota composition, host genetics and environmental factors. Several groups worldwide have described an imbalance of the gut microbiome composition, called dysbiosis, in CD patients, with an increase in Proteobacteria and Bacteroidetes and a decrease in Firmicutes. A high prevalence of adherent-invasive Escherichia coli (AIEC) pathobionts has been identified in the intestinal mucosa of CD patients. A significant loss in the bacteria that produce short-chain fatty acids (SCFAs) with anti-inflammatory properties, such as propionate, is also a consequence of dysbiosis in CD patients. Here, the AIEC reference strain LF82 was able to degrade propionate in the gut, which was sufficient to counteract the anti-inflammatory effect of propionate both in in vitro models and in mice with DSS-induced colitis. The consumption of propionate by AIEC pathobionts leads to an increase in TNF-alpha production by macrophages upon infection through the bacterial methyl-citrate pathway. To induce the protective effects of SCFAs on the inflamed gut, we used a G-protein-coupled receptor 43 agonist (GPR43 agonist) that is not metabolizable by intestinal bacteria. Interestingly, this agonist showed anti-inflammatory properties and decreased the severity of colitis in AIEC-infected mice, as assessed by an improvement in the disease activity index (DAI) and a decrease in AIEC pathobiont encroachment. Taken together, these results highlight the effectiveness of GPR43 agonist treatment in the control of gut inflammation and improved our understanding of the ability of AIEC to modulate propionate availability to create an infectious niche to its advantage. |
| Databáze: | OpenAIRE |
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