Abstract
Salmonella enterica serovar Typhimurium (ST) is an enteropathogenic Gram-negative bacterium that causes infection following oral ingestion. ST spreads rapidly along the gastrointestinal tract (GIT) and invades the intestinal epithelium to ultimately reach internal body organs. The probiotic yeast Saccharomyces boulardii BIOCODEX (S.b-B) is prescribed for prophylaxis of diarrheal infectious diseases. We previously showed that S.b-B prevents weight loss in ST-infected mice and significantly decreases bacterial translocation to the spleen and liver. This study was designed to investigate the effect of S.b-B on ST migration along the GIT and the impact of the yeast on the host's early innate immune responses. Bioluminescent imaging (BLI) was used to evaluate the effect of S.b-B on the progression of luminescent Salmonella Typhimurium (ST-lux) in the GIT of mice pretreated with streptomycin. Photonic emission (PE) was measured in GIT extracts (stomach, small intestine, cecum and colon) at various time periods post-infection (PI). PE analysis revealed that, 45 min PI, ST-lux had migrated slightly faster in the mice treated with S.b-B than in the untreated infected animals. At 90 min PI, ST-lux had reached the cecum in both groups of mice. Adhesion of ST to S.b-B was visualized in the intestines of the mice and probably accounts for (1) the faster elimination of ST-lux in the feces, and (2) reduced translocation of ST to the spleen and liver. In the early phase of infection, S.b-B also modifies the host's immune responses by (1) increasing IFN-γ gene expression and decreasing IL-10 gene expression in the small intestine, and (2) elevating both IFN-γ, and IL-10 mRNA levels in the cecum. BLI revealed that S.b-B modifies ST migration and the host immune response along the GIT. Study findings shed new light on the protective mechanisms of S.b-B during the early phase of Salmonella pathogenesis.
Highlights
Gastrointestinal infections due to Salmonella enterica serovar Typhimurium are a major cause of diarrhea and mucosal inflammation and are responsible for severe systemic disease in both developing and industrial countries
Salmonella infections can be treated with antibiotics, these drugs are often not readily available in endemic areas, and antibiotic resistance is on the rise
As shown by our data, Bioluminescent imaging (BLI) is extremely useful for monitoring serovar Typhimurium (ST) infections of the gastrointestinal tract (GIT)
Summary
Gastrointestinal infections due to Salmonella enterica serovar Typhimurium are a major cause of diarrhea and mucosal inflammation and are responsible for severe systemic disease in both developing and industrial countries. Ingested Salmonella bacteria spread rapidly along the axis of the gastrointestinal tract (GIT) and penetrate the intestinal mucosa via three routes: (i) preferential invasion of specialized epithelial M cells situated in the dome region of Peyer’s patches or overlying, solitary intestinal lymphoid tissues, (ii) active invasion of enterocytes, and (iii) through dendritic cells that intercalate epithelial cells by extending protrusions into the gut lumen (reviewed in [1,2,3]). A lyophilized preparation of the probiotic yeast strain Saccharomyces boulardii (S.b-B) is used worldwide for the prevention and treatment of a variety of diarrheal diseases.
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