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Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases

Parada Venegas, D., De la Fuente, M. K., Landskron, G., Julieta Gonzalez, M., Quera, R., Dijkstra, G., Harmsen, H. J. M., Faber, K. N. & Hermoso, M. A., 11-Mar-2019, In : Frontiers in Immunology. 10, 16 p., 277.

Research output: Contribution to journalReview articleAcademicpeer-review

Ulcerative colitis (UC) and Crohn's disease (CD), collectively known as Inflammatory Bowel Diseases (IBD), are caused by a complex interplay between genetic, immunologic, microbial and environmental factors. Dysbiosis of the gut microbiome is increasingly considered to be causatively related to IBD and is strongly affected by components of a Western life style. Bacteria that ferment fibers and produce short chain fatty acids (SCFAs) are typically reduced in mucosa and feces of patients with IBD, as compared to healthy individuals. SCFAs, such as acetate, propionate and butyrate, are important metabolites in maintaining intestinal homeostasis. Several studies have indeed shown that fecal SCFAs levels are reduced in active IBD. SCFAs are an important fuel for intestinal epithelial cells and are known to strengthen the gut barrier function. Recent findings, however, show that SCFAs, and in particular butyrate, also have important immunomodulatory functions. Absorption of SCFAs is facilitated by substrate transporters like MCT1 and SMCT1 to promote cellular metabolism. Moreover, SCFAs may signal through cell surface G-protein coupled receptors (GPCRs), like GPR41, GPR43, and GPR109A, to activate signaling cascades that control immune functions. Transgenic mouse models support the key role of these GPCRs in controlling intestinal inflammation. Here, we present an overview of microbial SCFAs production and their effects on the intestinal mucosa with specific emphasis on their relevance for IBD. Moreover, we discuss the therapeutic potential of SCFAs for IBD, either applied directly or by stimulating SCFAs-producing bacteria through pre- or probiotic approaches.

Original languageEnglish
Article number277
Number of pages16
JournalFrontiers in Immunology
Volume10
Publication statusPublished - 11-Mar-2019

    Keywords

  • SCFAs, IBD, immune cells, IECs, intestinal mucosa, dysbiosis, BUTYRATE-PRODUCING BACTERIA, PROTEIN-COUPLED RECEPTOR, NF-KAPPA-B, INTERNATIONAL SCIENTIFIC ASSOCIATION, MONOCARBOXYLATE TRANSPORTER MCT1, MICROBIAL METABOLITE BUTYRATE, SUBSTRATE-INDUCED REGULATION, ULCERATIVE-COLITIS PATIENTS, COLONIC-MUCOSA, HISTONE DEACETYLATION

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