Skip to main content
. 2022 Jan 20;23(3):1105. doi: 10.3390/ijms23031105

Figure 3.

Figure 3

Interplay between the microbiota-accessible carbohydrates (MACs), the gut microbiota, the production short chain fatty acids (SCFAs), and the enterocytes (mainly colonocytes). The main pathways involved are summarized in the two enterocytes. (1) Following initial digestion and intestinal transit, the dietary MACs meet the gut microbiota, which is characterized by high and physiological diversity and no bacterial overgrowth. (2) SCFA-producing bacteria, mainly in the colon, will digest MACs and increase the luminal content of SCFAs. (3) In this environment, the abundance of A. muciniphila increases and is associated with protective effects on mucin and tight junction integrity. (4) In addition, a diet enriched in MACs will positively stimulate the immune system, leading to plasma cell-mediated production of immunoglobulins A (IgA) with further control on microbiota function, diversity, and prevention of overgrowth. (5) In the colonocyte, SCFAs are absorbed by colonocytes via passive diffusion or via active transport mediated by H+-dependent monocarboxylate transporters (MCTs). (6) The SCFAs acetate, butyrate, and propionate are converted to acetyl-CoA or propynyl-CoA by pathways involving the acetyl-CoA carboxylases (ACSSs) and beta oxidation. (7) This step produces ATP, which contributes to the maintenance of cell homeostasis, including the function of tight junctions. (8) Via stimulation of receptors at the apical membrane, SCFAs promote the secretion of gut hormones, such as glucagon-like peptide 1 (GLP1) and peptide YY (PYY), γ-aminobutyric acid (GABA), and serotonin (5-HT). At this level, butyrate inhibits (-) histone deacetylases (HDACs) with consequent anti-inflammatory effect by reducing NF-κB-induced pro-inflammatory mediators, such as TNF-α, IL-6, IL-12, and iNOS [43]. (9) Intracellular SCFAs contribute to inhibition (-) of HDAC. Acetate activates the inflammasome nucleotide-binding oligomerization domain 3 (NLRP3) with secretion of the protective IL-18 from epithelial cells, which maintains the tight junction’s function. (10) Colon-derived SCFAs reach the systemic circulation promoting anti-inflammatory and immunomodulatory effects as well as increasing insulin secretion, maintaining energy homeostasis, and improving liver and brain function.