FIG 3.

Intestinal epithelial dysfunction contributes to dysbiosis associated expansion of Enterobacteriaceae. (A and B, left panels) During gut homeostasis, β-oxidation of microbiota-derived butyrate causes epithelial hypoxia, which supports an anaerobic environment in the lumen of the large intestine. As a consequence, the lack of luminal oxygen drives a dominance of beneficial obligate anaerobic bacteria (green) in the gut microbiota. (A and B, right panels) During gut dysbiosis, colonocytes decrease their oxidative capacity, either due to antibiotic mediated decrease in butyrate-dependent PPAR-γ signaling (A) or due to HFD-induced mitochondrial dysfunction. The resulting epithelial dysfunction disrupts anaerobiosis in the lumen and increases the availability of alternative electron acceptors, driving an expansion of facultative anaerobic Enterobacteriaceae by aerobic and anaerobic respiration. SCFAs, short-chain fatty acids.