Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases
By Daniela Parada Venegas, M. De la Fuente, G. Landskron, María-Julieta González, R. Quera, G. Dijkstra, H. Harmsen, K. Faber, M. Hermoso. Frontiers in Immunology, 2019
3,307 citations recorded by the source corpus.
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.
Subfields: Genetics, Molecular Biology, Surgery
View Paper: https://www.semanticscholar.org/paper/a23675b34054b95a542fb8cf5922b45533c38629
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Citations in the corpus
- Strengthening the Immune System and Reducing Inflammation and Oxidative Stress through Diet and Nutrition: Considerations during the COVID-19 Crisis (2020, background): “are regulated by the diet, and given their importance in their immunomodulatory functions, their intake has been very much discussed in relation to inflammatory diseases in Westernized countries [163,164].”
- Gut Microbiota and Immune System Interactions (2020, background): “Some bacteria, including Faecalibacterium prausnitzii, Roseburia intestinalis, and Anaerostipes butyraticus [3] digest complex carbohydrates via fermentation, creating short-chain fatty acids (SCFAs) [4–6] that modulate host immune cells and serve as a carbon source for colonocytes [7,8].”
- Short chain fatty acids and its producing organisms: An overlooked therapy for IBD? (2021, background): “Second, butyrate also acts as a hypoxia inducible factor 1 (HIF 1) stabilizer, a transcription factor that coordinates barrier protection [5,36].”