Figure 5

Proposed mechanism of dietary FOS induced intestinal permeability. 1 High levels of FOS fermentation products increase intestinal permeability in vivo [5, 40, 41]. 2 Excess SCFAs cause intracellular acidification of epithelial cells. When protonated-SCFA diffuse from the gut lumen into epithelial cells [47, 84]. The SCFA cause intracellular acidification and induce proton pump activity (NHE and NBC transporters) which may lead to ATP depletion [43, 45]. 3 Reduced ATP levels, by increased energy demand, chronic mitochondrial uncoupling or any other cause of disturbed energy metabolism, are compensated by increased mitochondrial gene expression and mitochondrial biogenesis [27, 85]. 4 Disturbed energy metabolism leads to increased permeability. In agreement: ATP-depletion in epithelial cell lines causes paracellular hyperpermeability [28-30] and uncoupling of intestinal mitochondria leads to increased bacterial translocation, immune cell infiltration and ulceration in rats [31, 32]. Calcium supplementation of a FOS diet counteracts FOS induced intestinal permeability. Calcium prevents acidification of intestinal contents during fermentation and thus formation of protonated-SCFA.