Over 2,500 serotypes of Salmonella enterica subspecies enterica exist, however research has focused on epidemiologically relevant serotypes. Changes in a Simulator of the Human Intestinal Microbial Ecosystem (SHIME) model mimicking a healthy human adult were assessed following the introduction of one high virulence (S. Heidelberg (S428)) and one low virulence (S. Falkensee (S37)) S. enterica isolate. Differences in isolate survival, microbial community and metabolic composition, and prophage induction in the gastrointestinal model were analyzed. S. Heidelberg (S428) had enhanced survival and a greater impact on the gastrointestinal metabolome compared to S. Falkensee (S37). Both isolates caused a significant shift in the beta-diversity of proximal colon samples compared to the control. Potential prophage induction was found early (0 h and 6 h) in the treatment period. Community shifts in response to high and low virulence S. enterica strains in the gastrointestinal environment may therefore contribute to their epidemiological importance.