**1. Introduction**

Probiotic microorganisms have been extensively studied for their beneficial effects in not only maintaining the normal gut mucosa but also protection from allergens, pathogens, and toxins [1, 2]. The gastrointestinal tract (GI) and its associated microbiota is a complex system that allows for the digestion and absorption of critical nutrients. Additionally, the presence of the commensal bacteria leads to the development and regulation of the mucosal immune system [3]. It is believed that 60% of all fecal matter mass in humans consists of bacteria and that there are between 1010 and 1012 colony-forming units per gram of intestinal content in the colon [4]. The intestinal epithelium is a physical and biochemical barrier that seeks to protect mammalian cells from infection and injury from contaminants such as toxins, pathogenic bacteria, commensal bacteria, and even other luminal contents. Specialized intestinal epithelial cells (IECs) are able to sense and respond to these stimuli with appropriate responses such as increasing their barrier function to activation of anti-pathogenic immune mechanisms [3].

The International Scientific Association for Probiotics and Prebiotics (ISAPP) in 2014 agreed on a consensus definition of probiotics based on the previous Food and Agriculture Organization of the United Nations and World Health Organization (WHO) definition. ISAPP defines probiotics as 'live microorganisms that, when administered in adequate amounts, confer a health benefit on the host" [5]. Probiotics have been used for the treatment of *Helicobacter pylori* infection, irritable bowl syndrome, and inflammatory bowel disease (ulcerative colitis and Crohn's disease) in addition to enhancing the immune system of healthy individuals [6–12].

Though *in vivo* and *in vitro* studies suggest that probiotics can be beneficial [1, 2, 13], the exact mechanism(s) remains to be fully explained. Four mechanism are believed to be involved: (a) maintenance of the gut epithelial barrier, (b) competitive exclusion of pathogenic organisms, (c) secretion of antimicrobial products, and (d) regulation of the mucosal immune system in favor of the hosts.

The major defensive mechanism of the gut is the intestinal barrier which maintains epithelial integrity and to protect the host from the environment. In defense of this barrier, there exists the mucous layer, antimicrobial peptides, secretory IgA and the epithelial junction adhesion complex [14]. Disruption of these defense mechanisms allows for the bacteria and food antigens to reach the submucosa, which can induce an inflammatory response potentially leading to the intestinal disorders such as inflammatory bowel disease [15, 16].

### **1.1 Probiotics**

The most common probiotic strains used are *Lactobacillus*, *Bifidobacteria*, and the yeast strain *Saccharomyces cerevisiae* var. *boulardii*. Lactic acid bacteria and bifidobacteria have been shown to remove heavy metals [17], cyanotoxins [18], and mycotoxin from *in vitro* aqueous solutions [19, 20].

In regards to maintenance of the gut epithelial barrier, one can upregulate the genes important for this process [21]. Lactobacilli treatment has been shown to affect several genes including E-cadherin and β-catenin that affect adherence cell junctions in a cell culture model. The phosphorylation and abundance of adherence junction proteins including PKCδ [22] has been seen with Lactobacilli treatment. The probiotic *Escherichia coli* Nissle 1917 strain (EcN1917) can initiate repair of the intestinal barrier after damage by enteropathogenic *E. coli* by enhancing the expression and redistribution of tight junction proteins of the zonula occludens (ZO-2) and PKC [23, 24]. Treatment with *Lactobacillus casei* DN-114001 [25] and VSL#3 (an eight combination probiotic strain mixture) [26] also affect the gut barrier.

Another method to promote epithelial barrier function may be to increase mucin production thereby leading to increased barrier function as well as exclusion of pathogens and toxins. There have been contradictory data for both *in vitro* and *in vivo* experiments as to whether mucin production occurs in response to probiotic treatment. Some studies have suggested *Lactobacillus* adhesion is required to increase mucin production, which may not occur *in vivo* [27, 28]. However, a *Lactobacillus acidophilus* A4 cell extract has been shown to increase *MUC2* expression in HT29 cells independent of attachment [29]. VSL#3 has also been shown to increase expression of *MUC2*, *MUC3*, and *MUC5AC* in HT-29 cells [26]. *In vivo* studies of mucin production have also been inconsistent. VSL#3 given to mice for 14 days did not show any increase in mucin production or thickness [30] whereas rats given VSL#3 for 7 days have a 60-fold increase in *MUC2* expression and secretion [31].

#### **1.2 Prebiotics**

Prebiotics and their beneficial effects on human health have been of interest in recent years because of their perceived safety since they are derived from dietary products. The definition of prebiotics has changed somewhat from their initial description in 1995 by Glenn Gibson and Marcel Roberfroid [32]. Today, the general consensus is that "dietary prebiotics" are "selectively fermented ingredients that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health" [33]. There are many types of prebiotics but they can be segregated into the following groups [33]: (1) fructans,

**101**

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

i.e. cocoa-derived flavanols [33, 43].

energy for several other species [44].

the innate system.

(2) galacto-oligosaccharides (GOS), (3) starch and glucose-derived oligosaccharides, (4) other oligosaccharides, and (5) non-carbohydrate oligosaccharides. Fructans, such as inulin and fructose-oligosaccharides (FOS)/oligofructose, generally have a linear chain of fructose with a β(2 + 1) linkage usually with terminal glucose units with a β(2 + 1) linkage with variable degrees of polymerization (DP) [33–36]. GOS is the product of lactose extension that can be classified into two subgroups: (i) excess galactose at C3, C4 or C6 and (ii) derived from enzymatic trans-glycosylation [33]. The product of the enzymatic trans-glycosylation is a mixture of tri-to pentasaccharides with galactose known as trans-galacto-oligosaccharides (TOS) [37, 38]. In addition, there are GOSs derived from lactulose, an isomer of lactose, as well as raffinose family of oligosaccharides (RFO) [33, 37]. Starch that is resistant to the upper gut digestion is known as resistant starch (RS) and is considered a prebiotic along with polydextrose (glucose-derived oligosaccharide) [39, 40]. Pectin derived oligosaccharides (POS) are derived from an extension of galacturonic acid or rhamnose [33]. The carboxyl groups of POS can be modified with methyl esterification as well as acetylated at C2 or C3. Additionally, many different types of sugars (i.e. arabinose, galactose, and xylose) or ferulic acid can be linked to the side chains of POS [41, 42]. Though most of the accepted compounds defined as prebiotics are carbohydrates, there are some non-carbohydrate compounds that are recommended to be classified as prebiotics,

How do prebiotics affect human health? What mechanism(s) are involved? Since prebiotics are derived from dietary products, they provide the metabolic energy for the gut microbiota. This means that they can affect the composition and function of these microorganisms. For example, GOSs can stimulate the growth of *Bifidobacteria* and *Lactobacilli* to a high degree while *Enterobacteria*, *Bacteroidetes*, and *Firmicutes* growth levels occurred at a lower level [35]. Cross-feeding, the production of a by-product that can sustain another microorganism, can occur and an example is the degradation of resistant starch by *Ruminococcus bromii* to provide

In addition to feeding the gut microbiota, the fermentation of prebiotics can generate metabolites such as short chain fatty acids (SCFA) (i.e. lactic acid, butyric acid, and propionic acid) that have dramatic effects not only on the intestinal environment but can affect distant organ sites as well as the immune system. SCFAs decrease the pH of the gut that can alter the composition of the microbiota [45, 46]. A pH unit decrease affects acid sensitive species such as *Bacteroides* and increases butyrate production by *Firmicutes* [45]. Butyrate itself has been shown to be important for intestinal cell development [47]. As reviewed in [33], propionate affects the TH2 helper cells, macrophages, and dendritic cells while peptidoglycan stimulates

Bacterial pathogens are microorganisms that have the ability to cause disease due to their specialized virulence factors or that can arise from a dysbiosis such as from antibiotic treatment that can eliminate the normal healthy flora of the gut leading to opportunistic infections from commensals or normally non-pathogenic organisms.

**2.1 Bacterial pathogens, virulence factors, and mechanisms of pathogenesis**

*monocytogenes*, *Vibrio cholera*, *Shigella flexneri*, Shiga toxin producing *E. coli*

Some of the best-known bacterial pathogens are *Salmonella enterica*, *Listeria* 

**2. Bacterial infections and the disruption of gut homeostasis**

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

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

as inflammatory bowel disease [15, 16].

and mycotoxin from *in vitro* aqueous solutions [19, 20].

**1.1 Probiotics**

(d) regulation of the mucosal immune system in favor of the hosts.

Though *in vivo* and *in vitro* studies suggest that probiotics can be beneficial [1, 2, 13], the exact mechanism(s) remains to be fully explained. Four mechanism are believed to be involved: (a) maintenance of the gut epithelial barrier, (b) competitive exclusion of pathogenic organisms, (c) secretion of antimicrobial products, and

The major defensive mechanism of the gut is the intestinal barrier which maintains epithelial integrity and to protect the host from the environment. In defense of this barrier, there exists the mucous layer, antimicrobial peptides, secretory IgA and the epithelial junction adhesion complex [14]. Disruption of these defense mechanisms allows for the bacteria and food antigens to reach the submucosa, which can induce an inflammatory response potentially leading to the intestinal disorders such

The most common probiotic strains used are *Lactobacillus*, *Bifidobacteria*, and the yeast strain *Saccharomyces cerevisiae* var. *boulardii*. Lactic acid bacteria and bifidobacteria have been shown to remove heavy metals [17], cyanotoxins [18],

In regards to maintenance of the gut epithelial barrier, one can upregulate the genes important for this process [21]. Lactobacilli treatment has been shown to affect several genes including E-cadherin and β-catenin that affect adherence cell junctions in a cell culture model. The phosphorylation and abundance of adherence junction proteins including PKCδ [22] has been seen with Lactobacilli treatment. The probiotic *Escherichia coli* Nissle 1917 strain (EcN1917) can initiate repair of the intestinal barrier after damage by enteropathogenic *E. coli* by enhancing the expression and redistribution of tight junction proteins of the zonula occludens (ZO-2) and PKC [23, 24]. Treatment with *Lactobacillus casei* DN-114001 [25] and VSL#3 (an eight combination probiotic strain mixture) [26] also affect the gut barrier. Another method to promote epithelial barrier function may be to increase mucin production thereby leading to increased barrier function as well as exclusion of pathogens and toxins. There have been contradictory data for both *in vitro* and *in vivo* experiments as to whether mucin production occurs in response to probiotic treatment. Some studies have suggested *Lactobacillus* adhesion is required to increase mucin production, which may not occur *in vivo* [27, 28]. However, a *Lactobacillus acidophilus* A4 cell extract has been shown to increase *MUC2* expression in HT29 cells independent of attachment [29]. VSL#3 has also been shown to increase expression of *MUC2*, *MUC3*, and *MUC5AC* in HT-29 cells [26]. *In vivo* studies of mucin production have also been inconsistent. VSL#3 given to mice for 14 days did not show any increase in mucin production or thickness [30] whereas rats given VSL#3 for 7 days have a 60-fold increase in *MUC2* expression

Prebiotics and their beneficial effects on human health have been of interest in recent years because of their perceived safety since they are derived from dietary products. The definition of prebiotics has changed somewhat from their initial description in 1995 by Glenn Gibson and Marcel Roberfroid [32]. Today, the general consensus is that "dietary prebiotics" are "selectively fermented ingredients that results in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health" [33]. There are many types of prebiotics but they can be segregated into the following groups [33]: (1) fructans,

**100**

and secretion [31].

**1.2 Prebiotics**

(2) galacto-oligosaccharides (GOS), (3) starch and glucose-derived oligosaccharides, (4) other oligosaccharides, and (5) non-carbohydrate oligosaccharides.

Fructans, such as inulin and fructose-oligosaccharides (FOS)/oligofructose, generally have a linear chain of fructose with a β(2 + 1) linkage usually with terminal glucose units with a β(2 + 1) linkage with variable degrees of polymerization (DP) [33–36]. GOS is the product of lactose extension that can be classified into two subgroups: (i) excess galactose at C3, C4 or C6 and (ii) derived from enzymatic trans-glycosylation [33]. The product of the enzymatic trans-glycosylation is a mixture of tri-to pentasaccharides with galactose known as trans-galacto-oligosaccharides (TOS) [37, 38]. In addition, there are GOSs derived from lactulose, an isomer of lactose, as well as raffinose family of oligosaccharides (RFO) [33, 37]. Starch that is resistant to the upper gut digestion is known as resistant starch (RS) and is considered a prebiotic along with polydextrose (glucose-derived oligosaccharide) [39, 40]. Pectin derived oligosaccharides (POS) are derived from an extension of galacturonic acid or rhamnose [33]. The carboxyl groups of POS can be modified with methyl esterification as well as acetylated at C2 or C3. Additionally, many different types of sugars (i.e. arabinose, galactose, and xylose) or ferulic acid can be linked to the side chains of POS [41, 42]. Though most of the accepted compounds defined as prebiotics are carbohydrates, there are some non-carbohydrate compounds that are recommended to be classified as prebiotics, i.e. cocoa-derived flavanols [33, 43].

How do prebiotics affect human health? What mechanism(s) are involved? Since prebiotics are derived from dietary products, they provide the metabolic energy for the gut microbiota. This means that they can affect the composition and function of these microorganisms. For example, GOSs can stimulate the growth of *Bifidobacteria* and *Lactobacilli* to a high degree while *Enterobacteria*, *Bacteroidetes*, and *Firmicutes* growth levels occurred at a lower level [35]. Cross-feeding, the production of a by-product that can sustain another microorganism, can occur and an example is the degradation of resistant starch by *Ruminococcus bromii* to provide energy for several other species [44].

In addition to feeding the gut microbiota, the fermentation of prebiotics can generate metabolites such as short chain fatty acids (SCFA) (i.e. lactic acid, butyric acid, and propionic acid) that have dramatic effects not only on the intestinal environment but can affect distant organ sites as well as the immune system. SCFAs decrease the pH of the gut that can alter the composition of the microbiota [45, 46]. A pH unit decrease affects acid sensitive species such as *Bacteroides* and increases butyrate production by *Firmicutes* [45]. Butyrate itself has been shown to be important for intestinal cell development [47]. As reviewed in [33], propionate affects the TH2 helper cells, macrophages, and dendritic cells while peptidoglycan stimulates the innate system.
