**3.2 Effect of probiotics**

Among their effects, the most important are: competition to the more valid nutrients and enteric epithelial anchorage sites; reduction of intestinal pH values for high production of lactic acid from lactose and acetic acid from carbohydrates, which selects the growth of lactobacilli; production of bacteriocins, peptides with bactericidal activity towards related bacteria species; metabolism of certain nutrients in the volatile fatty acids; activation of mucosal immunity, with increased synthesis of secretory IgA, and phagocytosis; stimulation of production of various cytokines

#### **3.3 Mechanism of action of probiotics**

The functional interactions between bacteria, gut epithelium, gut mucosal immune system and systemic immune system are the basis of the mechanisms of direct and indirect effects of probiotics. The direct effect of probiotics in the lumen are: competition with pathogens for nutrients, production of antimicrobial substances and in particular organic acids competitive inhibition on the receptor sites, change in the composition of mucins hydrolysis of toxins, receptorial hydrolisis, and nitric oxide (NO), while the indirect effect largely depends on the site of interaction between the probiotic and the effectors of the immune response, topographically located in the intestinal tract.

There is evidence, in vitro and in vivo, on effects of different probiotics on specific mechanisms of the immune response. The starting point is the interaction between probiotic and the host intestinal mucosa, but it seems clear that not all probiotics have the same initial contact (immune cells, enterocytes, etc.).

There are several literature data that have demonstrated the interaction between probiotics and the immune system, in particular it has been demonstrated their capacity to stimulate the production of intestinal mucines, their trophic effect on intestinal epithelium, the reestablishment of the intestinal mucosa integrity, the stimulation of the IgA-mediated immune response against viral pathogens. All these effects have been demonstrated in experimental studies and in some clinical studies, even if it is not still clear the main mechanism of action and it is conceivable that different mechanisms of action contribute to the efficacy of probiotics, with a different role in different clinical situations (Vanderhoof & Young, 1998).

### **3.4 Safety**

6 New Advances in the Basic and Clinical Gastroenterology

includes industrially produced sterilized food and the use of different kinds of preservatives. This has led to a decreased intake of bacteria, particularly lactic acid

The widespread use of antibiotics in healthcare and agriculture, antibacterial substance is also something new for human kind. We have in so many ways sterilized our environment, which is detrimental to the microbial (Cummings & Macfarlane G.T., 1997; Vanderhoof &

The term 'probiotic' was proposed in 1965 to denote an organism or substance that contributes to the intestinal microbial balance. The definition of probiotics has subsequently evolved to emphasise a beneficial effect to health over effects on microbiota composition, underscoring the requirement of rigorously proven clinical efficacy. Most probiotic bacterial strains were originally isolated from the intestinal microbiota of healthy humans and the probiotics most thoroughly investigated thus far belong to the genera lactobacilli and

Probiotics have several effects, including modulating the gut microbiota, promoting mucosal barrier functions, inhibiting mucosal pathogen adherence and interacting with the innate and adaptive immune systems of the host, which may promote resistance against pathogens. The intestinal microbiota constitutes an important aspect of the mucosal barrier the function of which is to restrict mucosal colonisation by pathogens, to prevent pathogens

Prerequisites for probiotics' efficacy are human origin, resistance transit gastric capacity to colonize survival in and adhesion, competitive exclusion of pathogens or harmful antigens to specific areas of the gastrointestinal tract, vitality, verifiable and stability conservation, production substances with antimicrobial action, exclusion of resistance transferable antibiotic. No pathogenicity and / or toxicity has ever been demonstrated on the host.

Among their effects, the most important are: competition to the more valid nutrients and enteric epithelial anchorage sites; reduction of intestinal pH values for high production of lactic acid from lactose and acetic acid from carbohydrates, which selects the growth of lactobacilli; production of bacteriocins, peptides with bactericidal activity towards related bacteria species; metabolism of certain nutrients in the volatile fatty acids; activation of mucosal immunity, with increased synthesis of secretory IgA, and phagocytosis; stimulation

The functional interactions between bacteria, gut epithelium, gut mucosal immune system and systemic immune system are the basis of the mechanisms of direct and indirect effects of probiotics. The direct effect of probiotics in the lumen are: competition with pathogens for

from penetrating the mucosa and to initiate and regulate immune responses

producing bacteria .

**3. What are probiotics?** 

bifidobacteria (Caramia G., 2004).

**3.1 Proved beneficial effects on the host** 

**3.2 Effect of probiotics** 

of production of various cytokines

**3.3 Mechanism of action of probiotics** 

Young, 1998).

The oral consumption of viable bacteria in infancy naturally raises safety concerns. Products containing probiotics are widely available in many countries and, despite the growing use of such products in recent years, no increase in Lactobacillus bacteraemia has been detected. Nevertheless, the average yearly incidence of Lactobacillus bacteraemia in Finland between the years 1995 and 2000 was 0.3 cases/100,000 inhabitants. Importantly, 11 out of the 48 isolated strains were identical to Lactobacillus GG, the most commonly used probiotic strain. Lactobacillus bacteraemia is considered to be of clinical significance; immunesuppression, prior prolonged hospitalisation and surgical interventions have been identified as predisposing factors. Nonetheless, clinical trials with products containing both lactobacilli and bifidobacteria have demonstrated the safety of these probiotics in infants and children, and in a recent study, the use of L. casei was found to be safe also in critically ill children

In a trial assessing the safety of long-term consumption of infant formula containing B. lactis and S. thermophilus, the supplemented formulas were demonstrated to be safe and well tolerated. No serious adverse effects have been reported in the trials involving premature neonates, but it should be noted that the studies were not primarily designed to assess their safety (Hammerman et al, 2006)
