**7.1 Tight junction protein expression**

The intestinal bacteria or probiotics change the expression and distribution of TJ proteins (Mennigen & Bruewe, 2009). Several studies investigated the effects of different probiotics on TJ protein expression and distribution under pathological conditions. Occludin is an integral plasma-membrane protein located at the TJs. Zonula occludens-1 (ZO-1) is a peripheral membrane protein and it is found to be associated with the cytoplasmic surfaces of TJs (Gottardi et al., 1996). Probiotic bacteria *Streptococcus thermophilus* and *Lactobacillus acidophilus* prevent the reduction in phosphorylation of occludin and zonula occludens-1 (ZO-1) caused by enteroinvasive *Escherichia coli* (EIEC) infection (Resta-Lenert & Barrett, 2003). Re-distribution of ZO-1 protein has been observed after epithelial cells were treated by a pathologic bacterium *Salmonella dublin*. However, treatment of epithelial cells with multi-microbe probiotic product VSL#3 prevented the redistribution of ZO-1 (Ng et al., 2009).

#### **7.2 Epithelial adherence and pathogen exclusion**

Many intestinal bacteria can adhere to the outer mucus layer to form a biofilm on their surface (Guarner & Malageda, 2003). This is an important mechanism for intestinal barrier. Three different situations in favor of the host and against pathogens should be considered. One of them is exclusion of pathogens by probiotics competitively. The second is the prevention of pathogen adhesion. And the third is displacement of adhered pathogen. Sherman et al. (2005) have reported that *Lactobacillus rhamnosus* and *acidophilus* could adhere to intestinal epithelial cells *in vitro* and pre-treatment of these probiotic strains reduced the binding of EPEC and EHEC. Additionally, *Lactobacillus* strains can directly compete with other pathogens, such as *Salmonella* species, for binding sites on human mucins or Caco-2 cell surfaces. It has been observed that the mentioned probiotics can also displace bound pathogens, although more slowly and to a lesser extent (Lee et al., 2003). There is a competition between pathogens and probiotics for sources of nutrients as well as a competition for adherence to mucosa or displacement from mucosa. This competition is useful for exclusion of pathogens and for strengthening intestinal barrier.

#### **7.3 Mucus secretion**

It has been reported by *in vivo* and *in vitro* studies that certain bacteria contribute to strengthen mucosal barrier by increasing mucus secretion. Mattar et al. (2002) reported that *Lactobacillus casei* GG increased mucin expression in the human intestinal cell lines Caco-2 (MUC2) and HT29 (MUC2 and MUC3), thus blocking pathogenic *Escherichia coli* invasion and adherence. Additionally, Otte & Podolsky (2004) observed that VSL#3 increased expression of MUC2, MUC3 in HT29 cells. Probiotics induce this mucus expression increasing effect by modifying gene expressions. For example, it has been observed that MUC2 and MUC3 mRNA expressions were increased after incubation of epithelial cells with *Lactobacillus plantarum* 299v (Mack et al., 1999). Similarly Caballero-Franco et al. (2007) have reported that basal luminal mucin content increased by 60% in Wistar rats that were orally administered the probiotic mixture VSL#3 on a daily basis for seven days. In addition, they exposed isolated rat colonic loops to the VSL#3 probiotic formula, which significantly stimulated colonic mucin (MUC) secretion and MUC2 gene.

Probiotics also contributes to strengthening of intestinal barrier with some mechanisms other than above mentioned ones. For example, Polyphosphate (poly-P) is produced by probiotics and it is a bioactive molecule that induced cytoprotective heat shock protein through activation of the integrin–p38 mitogen-activated protein kinase pathway, and it prevents oxidant-induced intestinal barrier weakening. Furthermore, poly-P ameliorated epithelial injury (Segawa et al., 2011). It has been reported that multi-microbe probiotic product VSL#3 normalized monolayer permeability and conductance in stimulated tissues, thus strengthened barrier integrity (Madsen et al., 2001). It has been determined that *Lactobacillus rhamnousus* GG prevented cytokine induced apoptosis in young adult mouse colon cell model (YAMC) and human colonic epithelial carcinoma cell line (HT29) (Yan & Polk, 2002).

#### **8. References**

64 New Advances in the Basic and Clinical Gastroenterology

treated with probiotics, bacteria used as probiotic easily pass lamina propria and trigger

It has been determined by *in vivo* and *in vitro* studies that probiotics strengthen intestinal barrier. This effect occurs through species specific various mechanisms. These mechanisms are the inhibition of apoptosis of epithelial cells, the regulation of TJ proteins expression and the distribution, prevention of attachments of pathogens to mucosa, and the regulation of

The intestinal bacteria or probiotics change the expression and distribution of TJ proteins (Mennigen & Bruewe, 2009). Several studies investigated the effects of different probiotics on TJ protein expression and distribution under pathological conditions. Occludin is an integral plasma-membrane protein located at the TJs. Zonula occludens-1 (ZO-1) is a peripheral membrane protein and it is found to be associated with the cytoplasmic surfaces of TJs (Gottardi et al., 1996). Probiotic bacteria *Streptococcus thermophilus* and *Lactobacillus acidophilus* prevent the reduction in phosphorylation of occludin and zonula occludens-1 (ZO-1) caused by enteroinvasive *Escherichia coli* (EIEC) infection (Resta-Lenert & Barrett, 2003). Re-distribution of ZO-1 protein has been observed after epithelial cells were treated by a pathologic bacterium *Salmonella dublin*. However, treatment of epithelial cells with multi-microbe probiotic product VSL#3 prevented the redistribution of ZO-1 (Ng et al.,

Many intestinal bacteria can adhere to the outer mucus layer to form a biofilm on their surface (Guarner & Malageda, 2003). This is an important mechanism for intestinal barrier. Three different situations in favor of the host and against pathogens should be considered. One of them is exclusion of pathogens by probiotics competitively. The second is the prevention of pathogen adhesion. And the third is displacement of adhered pathogen. Sherman et al. (2005) have reported that *Lactobacillus rhamnosus* and *acidophilus* could adhere to intestinal epithelial cells *in vitro* and pre-treatment of these probiotic strains reduced the binding of EPEC and EHEC. Additionally, *Lactobacillus* strains can directly compete with other pathogens, such as *Salmonella* species, for binding sites on human mucins or Caco-2 cell surfaces. It has been observed that the mentioned probiotics can also displace bound pathogens, although more slowly and to a lesser extent (Lee et al., 2003). There is a competition between pathogens and probiotics for sources of nutrients as well as a competition for adherence to mucosa or displacement from mucosa. This competition is

It has been reported by *in vivo* and *in vitro* studies that certain bacteria contribute to strengthen mucosal barrier by increasing mucus secretion. Mattar et al. (2002) reported that *Lactobacillus casei* GG increased mucin expression in the human intestinal cell lines Caco-2 (MUC2) and HT29 (MUC2 and MUC3), thus blocking pathogenic *Escherichia coli* invasion and adherence. Additionally, Otte & Podolsky (2004) observed that VSL#3 increased

useful for exclusion of pathogens and for strengthening intestinal barrier.

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**7.1 Tight junction protein expression** 

**7.2 Epithelial adherence and pathogen exclusion** 

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**4** 

*Brazil* 

**The Benefits of Probiotics in Human and Animal Nutrition** 

Jacques Nicoli and Luis Gustavo Braga

*Universidade Estadual de Santa Cruz* 

Camila Boaventura, Rafael Azevedo, Ana Uetanabaro,

At birth, the gastrointestinal tract of any animals is sterile, and it is rapidly colonized by bacteria from the mother and the environment. This colonization by the gut microbiota plays an important role in intestinal tract maturation of newborn (in terms of anatomy, digestive physiology, and immunology) (Hooper 2004). After this colonization, considering healthy human individuals, the gastrointestinal tract harbors 10 or more times as many microbes than there are eukaryotic cells (1014 viable cells for indigenous microbiota/1013 body cells).These microorganisms, altogether weighing approximately 1.5 kg, can be considered as a complementary major organ, responsible for three main functions: colonization resistance, immunomodulation, and nutritional contribution (Hayashi et al., 2002; Zoetendal et al., 2011). Colonization resistance inhibits the installation of exogenous microorganisms as well as the uncontrolled multiplication of microorganisms belonging to the indigenous microbiota. Immunomodulation maintains the immune system under a watchful state, which permits a faster but adequate response in the case of infectious aggression. Nutritional contribution furnishes complementary sources of vitamins,

Unfortunately, several factors can disturb both the initial colonization and posterior maintenance of the gut microbiota, leading to a microbial ecosystem with beneficial functions transitorily or irreversibly less efficient. As examples, the type of delivery (cesarean or natural) or the reduction of mother-child contacts (premature baby in an incubator or in an intensive care unit) interfere with the supply of microorganisms necessary for post-natal colonization. Additionally, the alimentation (breast- or formula-fed) and the ingestion of antibacterial drugs may be other factors that modify the normal sequence of colonization (Harmsen et al., 2000; Bonnemaison et al., 2003; Westerbeek et al., 2006; Chen et al., 2007). Once installed, the beneficial functions of the microbiota are very powerful but also fragile and can be disturbed by ingestion of drugs (especially antibiotics), drastic changes in diet or stress. In view of what was presented above, the importance of a correct initial colonization and a subsequent preservation of the gut microbiota is evident to obtain optimal functions from this microbial ecosystem. When disturbances of the indigenous microbiota functions are forecasted or installed, you should think about the possibility of compensating failures of these functions. In this sense, probiotics can be considered as

**1. Introduction** 

enzymes, and energy substrates (volatile fatty acids).

in the neonatal gnotobiotic pig. *Journal Of Anmal Scence*, Vol. 85, No. 12, pp (3256- 66).

