Dietary L-arabinose-induced gut dysbiosis exacerbates bacterial infection

Abstract

Background Gut 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.Results We demonstrate the effect of L-arabinose on bacterial infection by using Salmonella enterica serovar Typhimurium (S. Tm). L-arabinose triggers severe inflammation in the gut and aggravates systemic infection of S. Tm in conventional mice. In addition, L-arabinose represses the expression of Salmonella Pathogenicity 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 activates yfiA to maintain the stability of HilD. In a streptomycin-pretreated mouse model, L-arabinose supplementation promotes S. Tm initial bloom and is unable to alter the disease progression of Salmonella infection. However, in the presence of microbiota, L-arabinose induces a dramatic expansion of Enterobacteriaceae, thereby decreasing the microbiota diversity and causing more severe systemic infections.Conclusions Our 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.