**2.2 The mammalian host response to bacterial infections**

Probiotic strains have been shown to induce the release of defensins, small peptides/proteins active against bacteria, fungi, and viruses but also are able to stabilize the gut barrier from epithelial cells. Host cells are able to mount as a first line of defense against pathogens increased production of antimicrobial proteins (AMPs) such as α- and β-defensins, cathelicidins, C-type lectins and ribonucleases. Many of these proteins disrupt the cell wall structures of the bacterial membrane either through enzymatic (i.e. lysozyme, phospholipase A2) or non-enzymatic mechanisms (i.e. pore formation by defensins and cathelicidins) [56–58].

The effect of commensal and probiotic bacteria on the host immune system is complex and not fully understood. It is believed that the effect of probiotic bacteria in modulating the immune system lies with its potential interactions with the host innate immune system by activating pattern recognition receptors (PRRs) that recognize common structures called pathogen-associated molecular patterns (PAMPs) shared by the vast majority of pathogens. Of note are the potential interactions with toll-like receptors (TLRs), extracellular C-type lectin receptors (CLRs), and intracellular nucleotide-binding oligomerization domain-containing protein (NOD)-like receptors (NLRs) that recognize PAMPs such as lipopolysaccharide (LPS), peptidoglycan, lipoprotein, flagellin, and CpGDNA. Activation of these receptor complexes will activate multiple downstream signaling pathways that may induce a pro- or anti-inflammatory response. Dysregulation of the pro-inflammatory response has been implicated in Crohn's disease with human intestinal inflammation as well as human autoinflammatory disease [59]. However, expression levels of some of these PRRs are low in immune cells therefore the ability to rapidly induce the expression of the PRRs such as NLRP3 in response to PAMP stimuli are absolutely critical in the defense against potential pathogens [60–64].

**103**

cytokines [94].

*Prebiotics, Probiotics, and Bacterial Infections DOI: http://dx.doi.org/10.5772/intechopen.89052*

**and gene expression**

**3. Probiotic mechanisms of antagonism against bacterial growth** 

of pathogen binding to host cells relies heavily on steric hindrance [78].

gesting that this probiotic strain may have therapeutic potential [87].

**4. Probiotics and inhibition of bacterial toxins**

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 sug-

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

*Clostridium botulinum* is an ubiquitous, gram-positive, anaerobic spore-forming organism that is the causative agent of botulinum. The botulinum neurotoxins are one of the most lethal toxins known to mankind with a parenteral lethal dosage of 0.1–1 ng/kg and an oral dose of 1 μg/kg. Due to this high toxicity and potential for bioterrorism, botulinum neurotoxins (BoNTs) are considered Tier 1 category Select Agents by the Centers for Disease Control and Prevention (CDC). BoNTs are a public health and safety threat in the form of foodborne, wound, and infant botulism.

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 *Prebiotics and Probiotics - Potential Benefits in Nutrition and Health*

tions (i.e. cytotoxicity).

intestinal microbiota [53–55].

(STEC) (i.e. *E. coli* 0157:H7), *Clostridium difficile*, *Clostridium perfringens*, and *Clostridium botulinum*. Both Gram-positive and Gram-negative pathogens must develop mechanisms to outcompete the normal gut microbiota, bind/invade cells, avoid detection and killing from the host immune system. Some important pathogen virulence mechanisms consist of specialized secretion systems that encode factors important for all the above steps in pathogenesis. The type III secretion systems (TTSS/T3SS) encoded by some Gram-negative pathogens such as *Salmonella*, *Vibrio*, *Shigella*, *Escherichia coli*, and *Yersinia* are well-known examples. Other specialized secretion systems are the T4SS and T6SS. T6SSs are prevalent in both pathogens and commensals suggesting their importance in the intestinal environment [48]. For non-intracellular pathogens, bacterial toxins [i.e., Listeriolysin O (LLO), botulinum neurotoxins (BoNTs), alpha toxin-*C. perfringens*, TcdA/TcdB-*C. difficile*] are important virulence factors that can bind to and enter the intestinal epithelium and/or their target cells to effect their func-

One important growth restriction system on the part of hosts/intestinal flora is the sequestration of iron, which is absolutely required for growth. For example, *Salmonella enterica* can evade lipocalin-2-mediated growth restriction by producing modified siderophores that cannot be bound by lipocalin-2 [49]. The T4SS and T6SS systems can be utilized for intra-and-inter bacterial species warfare. *Bacteroides* strains encoding the T6SS have been shown to target sensitive *Bacteroides* spp. suggesting they limit their competition [50–52]. *Salmonella*, *Vibrio*, and *E. coli* have also been shown to use T6SS against their competition, the

Probiotic strains have been shown to induce the release of defensins, small peptides/proteins active against bacteria, fungi, and viruses but also are able to stabilize the gut barrier from epithelial cells. Host cells are able to mount as a first line of defense against pathogens increased production of antimicrobial proteins (AMPs) such as α- and β-defensins, cathelicidins, C-type lectins and ribonucleases. Many of these proteins disrupt the cell wall structures of the bacterial membrane either through enzymatic (i.e. lysozyme, phospholipase A2) or non-enzymatic mechanisms (i.e. pore formation by defensins and cathelicidins) [56–58].

The effect of commensal and probiotic bacteria on the host immune system is complex and not fully understood. It is believed that the effect of probiotic bacteria in modulating the immune system lies with its potential interactions with the host innate immune system by activating pattern recognition receptors (PRRs) that recognize common structures called pathogen-associated molecular patterns (PAMPs) shared by the vast majority of pathogens. Of note are the potential interactions with toll-like receptors (TLRs), extracellular C-type lectin receptors (CLRs), and intracellular nucleotide-binding oligomerization domain-containing protein (NOD)-like receptors (NLRs) that recognize PAMPs such as lipopolysaccharide (LPS), peptidoglycan, lipoprotein, flagellin, and CpGDNA. Activation of these receptor complexes will activate multiple downstream signaling pathways that may induce a pro- or anti-inflammatory response. Dysregulation of the pro-inflammatory response has been implicated in Crohn's disease with human intestinal inflammation as well as human autoinflammatory disease [59]. However, expression levels of some of these PRRs are low in immune cells therefore the ability to rapidly induce the expression of the PRRs such as NLRP3 in response to PAMP stimuli are absolutely critical in the

**2.2 The mammalian host response to bacterial infections**

defense against potential pathogens [60–64].

**102**
