Arabinose, lactulose and polyols raised Salmonella Typhimurium loads over 100-fold in mice
In mice given two high doses of low-digestible sugars, Salmonella colonized the gut, spread to organs and caused colitis without antibiotic pretreatment.
A study in Nature Communications reports that acute overconsumption of low-digestible sugars (LDSs) weakened colonization resistance against Salmonella enterica serovar Typhimurium (S.Tm) in mice 
doi.orgNature Communicationsdoi.orgOpen source ↗. The tested sugars were arabinose, lactulose and polyols, which are used as sugar substitutes. On day 1 after infection, mice given LDSs excreted more than 100 times more S.Tm in feces than PBS controls doi.orgNature Communicationsdoi.orgOpen source ↗. The experiments were done in mice, not in humans.
Experimental design and infection course
C57BL/6 mice with a specified-pathogen-free microbiota received two oral gavages of 132 mg of a carbohydrate, one hour before and four hours after infection with 5 × 10^7 S.Tm doi.orgNature Communicationsdoi.orgOpen source ↗. The doses exceeded the typical daily intake of fermentable short-chain carbohydrates in mice on standard chow, 16–184 mg per day, assuming 3 g of food doi.orgNature Communicationsdoi.orgOpen source ↗. The LDSs were L- and D-arabinose, lactulose, erythritol, sorbitol and maltitol. Mice pretreated with 25 mg of streptomycin served as a comparison group.
Fecal S.Tm loads fell by day 2, then a second bloom followed. By days 3–4 the loads reached 107–1011 CFU/g of feces, comparable to streptomycin-pretreated mice doi.orgNature Communicationsdoi.orgOpen source ↗. S.Tm was also found in the liver, spleen and mesenteric lymph nodes. Fecal lipocalin, a marker of inflammation, was 102–105 ng/g on days 2–4, and histopathology on day 4 showed colitis doi.orgNature Communicationsdoi.orgOpen source ↗. Inflammation was higher than in PBS controls but milder than in streptomycin-pretreated mice doi.orgNature Communicationsdoi.orgOpen source ↗.
Mechanism and virulence
The authors studied arabinose in more detail. Its rapid fermentation by the microbiota acidified the intestine, perturbed the microbial community, changed short-chain fatty acid levels and increased amino acid availability, which can support pathogen growth doi.orgNature Communicationsdoi.orgOpen source ↗.
Arabinose intake was also associated with higher SPI-1 expression and a broader tissue tropism, including more translocation into Peyer's patches and ileal tissue and spread to the small intestine doi.orgNature Communicationsdoi.orgOpen source ↗. The authors report positive selection for invasive Salmonella doi.orgNature Communicationsdoi.orgOpen source ↗. Unlike after antibiotic perturbation, colonization in this model required both the SPI-1 and SPI-2 type III secretion systems, which links virulence to pathogen fitness doi.orgNature Communicationsdoi.orgOpen source ↗. According to the authors, dietary perturbations can both compromise colonization resistance and enhance pathogen virulence doi.orgNature Communicationsdoi.orgOpen source ↗.
