Bifidobacterium Infantis 35624 Protects Against Salmonella-Induced Reductions in Digestive Enzyme Activity in Mice by Attenuation of the Host Inflammatory Response

OBJECTIVES: Salmonella-induced damage to the small intestine may decrease the villi-associated enzyme activity, causing malabsorption of nutrients and diarrhea, and thus contribute to the symptoms of infection. The objective of this study was to determine the mechanism by which different doses and durations of Salmonella infection and lipopolysaccharide (LPS) affect brush border enzyme activity in the mouse, and to determine if the probiotic Bifidobacterium longum subspecies infantis 35624 could attenuate the intestinal damage. METHODS: BALB/c mice were challenged with Salmonella enterica serovar Typhimurium UK1 at various doses (10(2)-10(8) colony-forming unit (CFU)) and durations (10(6) CFU for 1-6 days). Mice were also treated with B. longum subsp. infantis 35624 for 2 weeks before and during a 6-day S. Typhimurium challenge (10(6) CFU), or before injection of LPS. The small intestine was assessed for morphological changes, mRNA expression of cytokines, and activity of the brush border enzymes sucrase-isomaltase, maltase, and alkaline phosphatase. RESULTS: S. Typhimurium infection significantly reduced the activity of all brush border enzymes in a dose- and time-dependent manner (P<0.05). This also occurred following injection of LPS. Pre-treatment with B. longum subsp. infantis 35624 prevented weight loss, protected brush border enzyme activity, reduced the small intestinal damage, and inhibited the increase in interleukin (IL)-10 and IL-8 expression due to Salmonella challenge. CONCLUSIONS: Salmonella infection reduces the small intestinal brush border enzyme activity in mice, with the level of reduction and associated weight loss increasing with dose and duration of infection. B. longum subsp. infantis 35624 treatment attenuated the effect of Salmonella infection on brush border enzyme activity and weight loss, which may be due to modulation of the host immune response

E. coli Nissle 1917 Affects Salmonella Adhesion to Porcine Intestinal Epithelial Cells

BACKGROUND: The probiotic Escherichia coli strain Nissle 1917 (EcN) has been shown to interfere in a human in vitro model with the invasion of several bacterial pathogens into epithelial cells, but the underlying molecular mechanisms are not known. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we investigated the inhibitory effects of EcN on Salmonella Typhimurium invasion of porcine intestinal epithelial cells, focusing on EcN effects on the various stages of Salmonella infection including intracellular and extracellular Salmonella growth rates, virulence gene regulation, and adhesion. We show that EcN affects the initial Salmonella invasion steps by modulating Salmonella virulence gene regulation and Salmonella SiiE-mediated adhesion, but not extra- and intracellular Salmonella growth. However, the inhibitory activity of EcN against Salmonella invasion always correlated with EcN adhesion capacities. EcN mutants defective in the expression of F1C fimbriae and flagellae were less adherent and less inhibitory toward Salmonella invasion. Another E. coli strain expressing F1C fimbriae was also adherent to IPEC-J2 cells, and was similarly inhibitory against Salmonella invasion like EcN. CONCLUSIONS: We propose that EcN affects Salmonella adhesion through secretory components. This mechanism appears to be common to many E. coli strains, with strong adherence being a prerequisite for an effective reduction of SiiE-mediated Salmonella adhesion

Escherichia coli strains colonising the gastrointestinal tract protect germfree mice against Salmonella typhimurium infection

BACKGROUND—Escherichia coli is part of the normal gastrointestinal microflora which exerts a barrier effect against enteropathogens. Several E coli strains develop a protective effect against other Enterobacteriaceae.
AIMS—Two E coli strains, EM0, a human faecal strain, and JM105 K-12 were tested for their ability to prevent in vivo and in vitro infection by Salmonella typhimurium C5.
METHODS—Inhibition of C5 cell invasion by E coli was investigated in vitro using Caco-2/TC7 cells. The protective effect of E coli was examined in vivo in germfree or conventional C3H/He/Oujco mice orally infected by the lethal strain C5.
RESULTS—EMO expresses haemolysin and cytotoxic necrotising factor in vitro. In vitro, the two strains did not prevent the growth of C5 by secreted microcins or modified cell invasion of C5. In vivo, establishment of EM0 or JM105 in the gut of germfree mice resulted in a significant increase in the number of surviving mice: 11/12 and 9/12, respectively, at 58 days after infection (2×10(6)/mouse) versus 0/12 in control germfree group at 13 days after infection. Colonisation level and translocation rate of C5 were significantly reduced during the three days after infection. In contrast, no reduction in faecal C5 excretion was observed in C5 infected conventional mice (1×10(8)/mouse) receiving the EM0 or JM105 cultures daily.
CONCLUSIONS—Establishment of E coli strains, which do not display antimicrobial activity, protects germfree mice against infection and delays the establishment of C5 in the gut. Possible mechanisms of defence are discussed.


Keywords: Escherichia coli; gastrointestinal infection; Salmonella; germfree mice; bacterial antagonis