Researchers investigated the effect of indole exposure on  Salmonella  virulence and infection. A competitive index test was used to compare the fitness of indole-treated and non-treated  Salmonella  in infecting mice. In addition, the effect of indole on other Salmonella functions important for infection such as motility, invasion, intracellular survival, and SPI-1 gene expression was also investigated.

Scientists also investigated the mechanism by which indole mediated down-regulation of  Salmonella  virulence and the combinatorial effect of indole on SPI-1 gene expression in the presence of short chain fatty acids ( SCFAs ).

The intestinal microbiota (the dynamic community of ~ 10 14  microorganisms present in the human gastrointestinal (GI) tract) is an important mediator of several aspects of health, including promoting defense against pathogen colonization. The protective effect of the microbiota against pathogenic infections is termed as colonization resistance 

Researchers previously demonstrated that indole, a microbial metabolite of tryptophan, reduce enterohemorrhagic Escherichia coli O157: H7 attachment to intestinal epithelial cells and biofilm formation, suggesting that indole may be an effector / attenuator of colonization for a number of enteric pathogens.

Here, researchers report that indole attenuates Salmonella Typhimurium ( Salmonella ) virulence and invasion as well as increasing resistance to colonization in host cells. Indole-exposed Salmonella colonized mice less effectively compared to solvent-treated controls, as evident by competitive index values ??less than 1 in multiple organs.

Indole-exposed Salmonella demonstrated 160-fold less invasion of HeLa epithelial cells and 2-fold less invasion of J774A.1 macrophages compared to solvent-treated controls. However, indole did not affect Salmonella intracellular survival in J774A.1 macrophages suggesting that indole primarily affects Salmonella invasion.

The decrease in invasion was corroborated by a decrease in expression of multiple Salmonella Pathogenicity Island-1 (SPI-1) genes. They also identified that the effect of indole was mediated by both PhoPQ-dependent and independent mechanisms. Indole also synergistically enhanced the inhibitory effect of a short chain fatty acid cocktail on SPI-1 gene expression.

Lastly, indole-treated HeLa cells were 70% more resistant to Salmonella invasion suggesting that indole also increased resistance of epithelial cells to colonization. The study results demonstrate that indole is an important microbiota metabolite that has direct anti-infective effects on Salmonella and host cells, revealing novel mechanisms of pathogen colonization resistance .