Shiga toxin increases intestinal transit to displace resident microbes and facilitate pathogen colonization.

Shiga toxin (Stx)-producing Escherichia coli (STEC) is a major cause of food-borne illnesses, and disease severity correlates with the production of Shiga toxins. While clinical symptoms such as bloody diarrhea and hemolytic uremic syndrome have been attributed to Stx, its contribution to bacterial fitness is not well understood. Here, we demonstrate that Stx2 enhances STEC colonization of the zebrafish gut by facilitating the partial displacement of gut resident microbes. Infection with Stx2-producing STEC strains or direct exposure of fish to purified Stx2 induces alterations in the zebrafish microbiome structure, impacting several bacterial phyla and genera, notably Pseudomonads. We show that Stx2 is sufficient to facilitate these changes by accelerating intestinal transit, leading to increased expulsion of select gut microbes, including resident Pseudomonas species. Additionally, prokinetic drug treatment causes similar changes in gut transit and expulsion of Pseudomonas. Collectively, these findings detail a novel mode of action of Stx2 on the host, and shed light on its contribution to bacterial fitness within the host intestine.