Dietary L-arabinose-induced gut dysbiosis exacerbates bacterial infection

Abstract

AbstractBackgroundGut microbiota is essential for providing colonization resistance against pathogens. Dietary sugars markedly shift the composition of the intestinal microbiota and alter host susceptibility to enteric infections. However, the role of dietary sugars in intestinal pathophysiology and colitis pathogenesis remains controversial.ResultsWe demonstrate the effect of L-arabinose on bacterial infection by usingSalmonella entericaserovar Typhimurium (S. Tm). L-arabinose triggers severe inflammation in the gut and aggravates systemic infection ofS. Tm in conventional mice. In addition, L-arabinose represses the expression ofSalmonellaPathogenicity Island 1 (SPI-1) genes by negatively regulating the activity of the cyclic 3’ 5’-AMP (cAMP)-cAMP receptor protein (CRP) complex. The cAMP-CRP complex activatesyfiAto maintain the stability of HilD. In a streptomycin-pretreated mouse model, L-arabinose supplementation promotesS. Tm initial bloom and is unable to alter the disease progression ofSalmonellainfection. However, in the presence of microbiota, L-arabinose induces a dramatic expansion ofEnterobacteriaceae, thereby decreasing the microbiota diversity and causing more severe systemic infections.ConclusionsOur work reveals that a high intake of dietary L-arabinose disrupts gut homeostasis in response to enteric infections, which offers new perspectives for dietary strategies and supplementation for diabetics.