Butyrate and the Fine-Tuning of Colonic Homeostasis: Implication for Inflammatory Bowel Diseases

• Published in: International journal of molecular sciences Vol. 22; no. 6; p. 3061
• Main Authors: Gasaly, Naschla, Hermoso, Marcela A., Gotteland, Martín
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 17.03.2021; MDPI
• Subjects: Animals; Bacteria; Butyrates - pharmacology; Colon; Colon - drug effects; Colon - pathology; Dietary fiber; E coli; Epigenesis, Genetic - drug effects; Fatty acids; Fermentation; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - genetics; Homeostasis; Homeostasis - drug effects; Homeostasis - genetics; Humans; Immune system; Inflammation; Inflammatory bowel disease; Inflammatory Bowel Diseases - pathology; Metabolism; Metabolites; Microbiota; Microorganisms; Patients; Physiology; Polyphenols; Proteins; Review; oxygen gradient; paradoxical effect; stem cells; mitochondrial function; butyrate-producing bacteria; GPR109A; GPR41; aryl hydrocarbon receptor 1; gut microbiota; HDAC
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22063061

This review describes current evidence supporting butyrate impact in the homeostatic regulation of the digestive ecosystem in health and inflammatory bowel diseases (IBDs). Butyrate is mainly produced by bacteria from the Firmicutes phylum. It stimulates mature colonocytes and inhibits undifferentiated malignant and stem cells. Butyrate oxidation in mature colonocytes (1) produces 70–80% of their energetic requirements, (2) prevents stem cell inhibition by limiting butyrate access to crypts, and (3) consumes oxygen, generating hypoxia and maintaining luminal anaerobiosis favorable to the microbiota. Butyrate stimulates the aryl hydrocarbon receptor (AhR), the GPR41 and GPR109A receptors, and inhibits HDAC in different cell types, thus stabilizing the gut barrier function and decreasing inflammatory processes. However, some studies indicate contrary effects according to butyrate concentrations. IBD patients exhibit a lower abundance of butyrate-producing bacteria and butyrate content. Additionally, colonocyte butyrate oxidation is depressed in these subjects, lowering luminal anaerobiosis and facilitating the expansion of Enterobacteriaceae that contribute to inflammation. Accordingly, gut dysbiosis and decreased barrier function in IBD seems to be secondary to the impaired mitochondrial disturbance in colonic epithelial cells.