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

Abstract

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.

Gastrointestinal (GI) Tract Microbiome-Derived Neurotoxins—Potent Neuro-Inflammatory Signals From the GI Tract via the Systemic Circulation Into the Brain

“…Interestingly, there is recent evidence that SCFAs can signal through G-protein coupled receptors (GPCRs) at the cell surface, including GPCR41, GPCR43, and GPCR109a and these activate signaling cascades that control multiple immune functions. Recent transgenic mouse studies support a key role of these GPCRs in the regulation of intestinal inflammation (Sears, 2009;Fathi and Wu, 2016;Lukiw, 2016a,b;Castillo-Álvarez and Marzo-Sola, 2019;Fox et al, 2019;Parada Venegas et al, 2019).…”

Short chain fatty acids enhance expression and activity of the umami taste receptor in enteroendocrine cells via a Gαi/o pathway

“…To determine whether SCFAs can influence the expression of taste GPCRs, STC-1 cells were incubated for 2 hrs with SCFAs in a 3:1:1 molar ratio of acetate:propionate:butyrate at 5 or 10mM (final concentration) chosen to reflect the physiological SCFA concentrations in the proximal and distal colon(3,4). qPCR was used to analyze the relative changes in expression of the transcripts of TAS1R1, TAS1R2, TAS1R2, TAS2 (108) and TAS2 (138).…”

“…Of particular note are colonic short-chain fatty acids (SCFAs), the anaerobic fermentation of non-digestible carbohydrates, components of high-fiber diets. These are carboxylic acids with fewer than six carbons (Cs), which can reach high luminal concentrations of 10 −1 M (2),(3). 95% of the SCFAs produced in the GI tract are acetate (2Cs), propionate (3Cs) and butyrate (4Cs) (3,4).…”

“…These are carboxylic acids with fewer than six carbons (Cs), which can reach high luminal concentrations of 10 −1 M (2),(3). 95% of the SCFAs produced in the GI tract are acetate (2Cs), propionate (3Cs) and butyrate (4Cs) (3,4). These SCFAs, in particular propionate, are currently of interest, not only due to their ability to regulate anorectic gut hormone release, but also to promote weight loss, reduce abdominal adiposity and improve insulin sensitivity (5–8).…”

Assessment of Ecosystem Services and Capabilities of Communities from different Scales and Niches - Implications on Sustainability Goals

“…ESs seldom occur in isolation and are usually inter-dependent either based on direct/indirect mechanistic evidence or observed associations. For instance, the ability of the gut microbiota to produce short chain fatty acids is linked to maintenance of the gut barrier integrity via mechanistic effects (Mörkl et al, 2018;Morrison & Preston, 2016;Parada Venegas et al, 2019). Facilitation of symbiotic relationship by the soil microbiota is closely linked to plant health and immunity as well as the control of pathogens (Harman & Uphoff, 2019;Vannier et al, 2019).…”