**7. The effect of probiotics on the intestinal barrier functions**

Intestinal barrier is a morphologic and physiologic structure placed between tissues and intestinal lumen which is known as external environment and it ensures continuing of events such as absorption and secretion between them. Intestinal lumen consists of microclimate on epithelial cells and lamina propria under epithelium. It regulates nutrients absorption, water and ion fluxes, and represents the first defensive barrier against toxins and enteric pathogens. Intestinal barrier consists of internal and external layers; the internal layer includes intestinal epithelial cells and tight junctions (TJ), the external layer includes bacteria and a mucus layer (Catalioto et al., 2011).

The intestinal epithelium is formed by a monolayer epithelial cells, the spaces between epithelial cells is sealed by tight junctions. Tight junctions are specific structures comprised of transmembrane proteins. Microclimate consists of unstirred water layer, glycocalyx, and mucus layer. Lamina propria is a layer existed under epithelial cells. In this layer there are cells of innate and acquired immunity secreting immunoglobulins and cytokines which are substantial for intestinal barrier.

Proper intestinal barrier function is essential for maintaining optimal health and balance throughout the body. The epithelium of the intestinal mucosa prevents the passage of commensal and pathogenic microorganisms. Therefore, it is the first line of defense against luminal antigens and toxins. An impairment of this intestinal barrier is critical for pathogenesis of several diseases such as inflammatory bowel disease, celiac disease (Chichlowski et al., 2008) and atopic dermatitis (Rosenfeldt et al., 2004).

Development of physical and functional intestinal barrier begins during embryonic period. In human, enterocytes appear in intestinal mucosa at 8th weeks, and TJ appear at 10th weeks of pregnancy. Functional immune barrier becomes functional after the formation of panet cells at 12th weeks. In this period, panet cells produce antimicrobial defensins and lysozymes. Mucins, which start to be expressed at 6.5th weeks of pregnancy and increase in time, constitute functional barrier. Although the development of intestinal barrier begins at prenatal period, it continues through postnatal period (Patel & Lin, 2010). Because, intestinal barrier is not yet fully developed in preterm infants, aberrant inflammatory and apoptotic responses to bacteria may occur. When premature infants

The Impact of Probiotics on the Gastrointestinal Physiology 65

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

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 &

Abrams, G.D. & Bishop, I.E. (1967). Effect of the normal microbial flora on gastrointestinal

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Awad, W.A., Ghareeb, K. & Böhm, J. (2010). Effect of addition of a probiotic micro-organism

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Barbara, G., Stanghellini, V., Brandi, G., Cremon, C., Di Nardo, G., De Giorgio, R. &

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to broiler diet on intestinal mucosal architecture and electrophysiological

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Corinaldesi, R. (2005). Interactions between commensal bacteria and gut sensorimotor function in health and disease. *Am J Gastroenterol,* Vol. 100, No. 11,

& Shirazi-Beechey, S.P. (2011). Sodium/glucose cotransporter-1, sweet receptor, and disaccharidase expression in the intestine of the domestic dog and cat: two

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stimulated colonic mucin (MUC) secretion and MUC2 gene.

Polk, 2002).

**8. References** 

treated with probiotics, bacteria used as probiotic easily pass lamina propria and trigger immune reaction there.

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 mucus secretion.
