Consumption of low-digestible sugars increase susceptibility to Salmonella Typhimurium infection

Low-digestible carbohydrates (LDCs), including dietary fibers and sugars that resist absorption, are generally considered beneficial for the gut microbiota. However, we show that ingestion of certain LDCs, particularly low digestible sugars (LDSs) such as arabinose, lactulose, and polyols commonly used as sugar substitutes (e.g., erythritol, maltitol, and sorbitol), can compromise colonization resistance against the common foodborne pathogen Salmonella enterica serovar Typhimurium. Acute overconsumption of these sugars results in elevated fecal pathogen loads, systemic dissemination, and colitis in infected mice. Focusing on arabinose, we found that rapid fermentation of this sugar acidifies the intestinal environment and shifts the microbiota composition. Metabolomic profiling revealed altered short-chain fatty acid levels and elevated availability of amino acids, which serve as carbon and nitrogen sources for pathogen growth. Arabinose consumption also impacts virulence by broadening tissue tropism, enhancing systemic infection, and selecting for fully virulent, invasive Salmonella through modulation of microbiota–pathogen interactions. These findings reveal how diet can impact the gut microbiota in ways that enhance pathogen colonization and virulence, posing potential risks for enteric infections.