**3. Probiotic mechanisms of antagonism against bacterial growth and gene expression**

In 1969, Greenberg [65] described the phenomena that *Salmonella typhimurium* was completely excluded from maggots of blowflies. The term "competitive exclusion" was used to define the scenario in which one species of bacteria more vigorously competes for the receptor sites in the intestinal tract than another species. There are a variety of mechanisms used by one bacterial species to exclude or reduce the growth of another species such as creation of a hostile environment, blocking available receptor sites, production and secretion of antimicrobial products and specific metabolites, and competitive depletion of essential nutrients [66].

Lactobacilli and bifidobacteria have been shown to inhibit a broad range of pathogens including *E. coli*, *Salmonella*, *Helicobacter pylori*, *Listeria monocytogenes* and *rotavirus* [6, 67–73]. Competition for host cell surface receptors by some probiotics has been successful against some enteropathogens [74–76]. *L. rhamnosus* can prevent enterohemorrhagic *E. coli* (EHEC) internalization [77]. Probiotic inhibition of pathogen binding to host cells relies heavily on steric hindrance [78].

Lactobacilli have been shown to produce bacteriocins that are active against some foodborne pathogens [79]. Additionally production of various metabolites and low molecular weight products by probiotics have been shown to have antimicrobial and antifungal properties such as low molecular weight species, deconjugated bile acids, and cyclic dipeptides among others [80–85]. *Enterococcus faecium* BGPAS1–3 has been shown to produce a cell wall product that has an anti-listerial effect, prevents tight junction disruption, as well as modulating the TLR2/TLR4 immune response to *Listeria monocytogenes* ATCC19111 [86]. *L. plantarum* ATCC 8014 has recently been shown to have *in vitro* antimicrobial activity against *C. butryicum* ATCC 860, *C. difficile* ATCC 9689, and *C. perfringens* ATCC 12924 suggesting that this probiotic strain may have therapeutic potential [87].

The production of antimicrobial substances such as lactic and acetic acid is one example of probiotics making the host environment hostile for pathogens. *Lactobacillus* co-cultivation with *E. coli* O157:H7 in broth culture produced organic acids which lead to a decrease in both pH and *stx2A* expression [88]. Low pH also prevented the induction of Stx prophage [89]. Mice given *Lactobacillus reuteri* with *E. coli* O157:H7 had decreased intestinal pathogen count, weight gain, and less kidney damage than controls [90]. The presence of probiotics in cattle feed reduced the amount *E. coli* O157:H7 seen in cattle [91]. *Bifidobacterium* strains decrease STEC and *in vivo* expression of Shiga toxin due to low pH and production of acetate [92, 93]. Pre-treatment with live Lactobacilli before *Salmonella enterica Javiana* infection in a tissue culture model showed decrease expression of virulence genes, less cytotoxicity, and reduced host production of inflammatory cytokines [94].
