Fig. 2

Intestinal dysbiosis leads to a breakdown of the normal gut barrier. Due most likely to the intermittent hypoxia induced by recurrent vaso-occlusive crises of the splanchnic vasculature, patients with SCD often experience intestinal dysbiosis. However, frequent diarrheal illnesses, malnutrition, and malaria further worsen the intestinal dysbiosis that may result in changes in the compositions of the intestinal microbes disrupt TJ formation and reductions in the production of SCFAs that enhance TJ formation and enterocyte health, while reduce enterocyte apoptosis. Deficiencies of the indole metabolites produced by microbial metabolism of tryptophan, enterocyte health is further compromised. A breach in the intestinal barrier results in an increased in gut permeability, enhancing translocation of enteric NTS and other microbes to cause systemic infections