**2.** *E. coli* **as a probiotic**

International Scientific Association for Probiotics and Prebiotics (ISAPP) defines probiotics as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host" [10]. Although fermented foods with 105 –108 microorganisms per gram can be constituted probiotics, recent oral supplementations contain 1010–12 live cells per single dose [11, 12]. *Lactobacillus* sp., *Bifidobacterium* sp., *Streptococcus* sp., *Enterococcus* sp., and *Saccharomyces boulardii* are common probiotics [13]. Some *Bacillus*, *E. coli,* and *Clostridium* sp. were found to be probiotics.

Commensal and probiotic *E. coli* modulates innate adaptive immune responses in the intestinal epithelium by activating the secretion of defensins, cytokines, IgA, and CD4 T cells. Additionally, siderophore production and iron scavenging by probiotic *E. coli* strains prevent the survival of the pathogens [14]. Interestingly, Alfred Nissle discovered an *E. coli* strain that prevented the growth of pathogenic *Salmonella* when it was cultured with stool samples [15]. The strain was isolated from a soldier who had no diarrhea when other soldiers had suffered *Shigella* infection. Upon oral supplementation, this strain was protected from diarrhea and this strain was named as *E. coli* Nissle 1917(EcN) from the year after its use [16]. Commercially, this strain is known as Mutaflor. EcN is the most commonly used gram-negative probiotic [17]. Interestingly, EcN could get established in swine herds with variation in the colonization of individual animals [18]. Some other *E. coli* strains have also been shown to possess probiotic properties (**Table 1**).

## **3. Probiotic** *E. coli* **Nissle 1917**

EcN is effective against infection by *Salmonella enterica* serovar, *Typhimurium* strain C17, *Yersinia enterocolitica*, *Shigella flexneri*, *Legionella pneumophila*, and *Listeria monocytogenes* [19]. EcN is serum sensitive, forms semi-rough colony, and *Potential of* Escherichia coli *Probiotics for Improved Health and Disease Management DOI: http://dx.doi.org/10.5772/intechopen.100380*

has low levels of smooth lipopolysaccharide (sLPS) [23]. *EcN* prevents the colonization of pathogens by efficient adhesion with the help of fimbriae and capsule to the epitheliumt but not activating inflammation as its lipopolysaccharide (LPS) has a short O chain and weak binding to toll-like receptor 4. EcN decreases pro-inflammatory cytokine and increases anti-inflammatory cytokine formation [24]. EcN repairs leaky gut by increasing the expression and phosphorylation of tight junction protein zonula occludens-1 (ZO-1), ZO-2, and claudin 14 [25–27]. Additionally, EcN prevents disruption of epithelial tight junctions by inhibiting NF-κB-mediated activation of the MLCK-P-MLC signaling pathway [28]. EcN mediates pathogen elimination by secretion of low molecular weight microcin H47 and microcin S. Probiotic EcN, but not commensal *E. coli* MG1655, increases serotonin (5-hydroxytryptamine) secretion by enterochromaffin cells [29].

Interestingly, bacteria are known to secrete vesicles known as membrane vesicles (MVs) [30]. Gram-negative bacterial outer membrane vesicles contain LPS and the size and complexity of O-antigen, the number, and nature of fatty acid components of lipid A determining the beneficial or toxic effects on the host cells. EcN outer membrane vesicles (OMVs) prevent the inflammation and progression of dextran sodium sulfate (DSS)-induced colitis in mice [26, 31, 32]. EcN OMVs get internalized by macrophages and activate the phagocytosis, which increases pro-inflammatory cytokine secretion and killing of pathogens [33].
