**2. Intestinal microbiota in newborn**

The normal human microflora is a complex ecosystem that somehow depends on enteric nutrients for establishing colonization. At birth ,the digestive tract is sterile. This balance of the intestinal microflora is similar to that of adult from about two years of age (Hammerman et al, 2004).

<sup>\*</sup> Corresponding Author

Intestinal Microbial Flora – Effect of Probiotics in Newborns 5

protective function, in particular the "barrier effect", referring to the physiological capacity of the endogenous bacterial microflora to inhibit colonization of the intestine by pathogenic microorganism. It is already known that the intestinal microbial flora influences food digestion ,absorption and fermentation, the immune system response, peristalsis, production of vitamins such as B-vitamins, influencing moreover the turnover of intestinal epithelial cells. In addition the metabolism of gut microflora influences hormonal secretion. Bacterial colonization of human gut by environmental microbes begins immediately after birth; the composition of intestinal microbiota, relatively simple in infants, becomes more complex with increasing in age, with a high degree of variability among human individuals. It is believed that microbial diversity is an important factor in determining the stability of the ecosystem and that fecal loss of diversity predisposes the preterm gastrointestinal colonization of antibiotic-resistant bacteria and fungi with the consequent potential risk of

The mucosal membrane of the intestines, with an area of approximately 200 m2, is constantly challenged by the enormous amount of antigens from food, from the intestinal microbial flora and from inhaled particles that also reach the intestines. It is not surprising therefore that approximately the eighty per cent of the immune system is found in the area of the intestinal tract and it is particularly prevalent in the small intestine. The intestinal immune system is referred as GALT (gut-associated-lymphoid tissue). It consists of Peyer's patches, which are units of lymphoid cells, single lymphocytes scattered in the lamina

The immune system of infants is not fully developed. The structures of the mucosal immune system are fully developed in utero by 28 weeks gestation, but in the absence of intrauterine infections, activation does not occur until after birth. Maturation of the mucosal immune system and establishment of protective immunity is usually fully developed in the first years of life. In addition the exposure to pathogenic and commensal bacteria, the major modifier of the development patterns in the neonatal period, depends on infant feeding

Bacterial colonisation of the intestine is important for the development of the immune system. The intestine has an important function in working as a barrier.This barrier is maintained by tight-junctions between the epithelial cells, by production of IgA antibodies and by influencing the normal microbial flora. It is extremely important that only harmless

Studies show that individuals allergic to cow´s milk have defective IgA production and an increased permeability of the intestinal mucosa. This results in an increased absorption of macromolecules by the intestinal mucosa. The increased permeability is most probably caused by local inflammations due to immunological reactions against the allergen. This

During the past century our lifestyle has dramatically changed regarding hygienic measures, diet, standards of living and usage of medical drugs. Today our diet largely

substances are absorbed while the harmful substances are secreted via the faeces.

infection (Cummings & Macfarlane, 1991; Montalto et al, 2009; Neish, 2002).

propria and intraepithelial lymphocytes spread in the intestinal epithelia.

**2.2 Gut microflora and immunity** 

practices. (Brandtzaeg, 2001; Gleeson et al, 2004)

**2.3 Modification of the intestinal flora micro-ecosystem** 

damages the intestinal mucosa


Table 1. Composition and topographical features of intestinal microbiota

Diet and environmental conditions can influence this ecosystem. At birth intestinal colonization derives from microorganism of the vaginal mucoses of the mother and faecal microflora . The microbial imprinting depends on the mode and location of delivery. Literature data shows that infants born in a hospital environment, by caesarean section, have a high component of anaerobic microbial flora (Clostridia) and high post of Gram-negative enterobacteria. Those born prematurely by vaginal delivery and breast-feed have a rather rich in Lactobacilli and Bifidobacteria microflora. (Grönlund et al, 1999; Hall et al, 1990)

Diet can influence the microbiota, while breast-feeding promotes an intestine microbiota in which Bifidobacteria predominate, while coliform, enterococci and bacteroides predominate in formula bottle-fed baby.

Escherichia coli and Streptococcus are included among the first bacteria to colonize the digestive tract. After them, strict anaerobes (Bacteroides, Bifidobacteri ,Clostridium) establish during the first week of life, when the diet plays a fundamental role. (Mackie et al, 1999). The pattern of bacterial colonization in the premature neonatal gut is different from the one of healthy, full term infant gut. Aberrant pre-term infants admitted to NICU, born by caesarean section, are more often separated from their mother and kept in an aseptic intensive care setting, treated with broad-spectrum antibiotics. This is the reason why they show a highly modified bacterial flora, consisting of less than 20 species of bacteria, with a predominance of Staphylococcus (aureus and coagulase negative) among aerobic microorganisms, and Enterobacteriaceae (Klebsiella), among enterococci and anaerobic Clostridia (Dai et al, 1999; Gothefor, 1989).

It is believed that microbial diversity is an important factor in determining the stability of the ecosystem and that the fecal loss of diversity predisposes the preterm gastrointestinal colonization of antibiotic-resistant bacteria and fungi colonization with a consequent potential risk of infection, thus contributing to the development of necrotizing enterocolitis (NEC) (Fanaro et al, 2003; Sakata et al, 1985)

#### **2.1 Structure and function of intestinal microbial flora**

The intestinal microbial flora has numerous functions, even if the most of them has not yet been identified. Among these functions, we can report its anatomical –functional role, its

bacteria 101\_103 unit /ml Lactobacillus,Streptococcus,

bacteroides ,bifidobacterium clostridium

/ml Enterobacteriacee (Citrobacter, Klebsiella,Proteus)o(Pseudomonas) Candida.

Diet and environmental conditions can influence this ecosystem. At birth intestinal colonization derives from microorganism of the vaginal mucoses of the mother and faecal microflora . The microbial imprinting depends on the mode and location of delivery. Literature data shows that infants born in a hospital environment, by caesarean section, have a high component of anaerobic microbial flora (Clostridia) and high post of Gram-negative enterobacteria. Those born prematurely by vaginal delivery and breast-feed have a rather rich

Diet can influence the microbiota, while breast-feeding promotes an intestine microbiota in which Bifidobacteria predominate, while coliform, enterococci and bacteroides predominate

Escherichia coli and Streptococcus are included among the first bacteria to colonize the digestive tract. After them, strict anaerobes (Bacteroides, Bifidobacteri ,Clostridium) establish during the first week of life, when the diet plays a fundamental role. (Mackie et al, 1999). The pattern of bacterial colonization in the premature neonatal gut is different from the one of healthy, full term infant gut. Aberrant pre-term infants admitted to NICU, born by caesarean section, are more often separated from their mother and kept in an aseptic intensive care setting, treated with broad-spectrum antibiotics. This is the reason why they show a highly modified bacterial flora, consisting of less than 20 species of bacteria, with a predominance of Staphylococcus (aureus and coagulase negative) among aerobic microorganisms, and Enterobacteriaceae (Klebsiella), among enterococci and anaerobic Clostridia

It is believed that microbial diversity is an important factor in determining the stability of the ecosystem and that the fecal loss of diversity predisposes the preterm gastrointestinal colonization of antibiotic-resistant bacteria and fungi colonization with a consequent potential risk of infection, thus contributing to the development of necrotizing enterocolitis

The intestinal microbial flora has numerous functions, even if the most of them has not yet been identified. Among these functions, we can report its anatomical –functional role, its

Aerobes

Anaerobes

Mouth 200 species Stomach,duodenum pH 2,5-3,5 destructive to most of

Jejunum,ileum 10 4\_ 10 6 unit /ml bifidobacteria and

Table 1. Composition and topographical features of intestinal microbiota

Colon 300-400 several species 1010\_ 1011 unit

in Lactobacilli and Bifidobacteria microflora. (Grönlund et al, 1999; Hall et al, 1990)

in formula bottle-fed baby.

(Dai et al, 1999; Gothefor, 1989).

(NEC) (Fanaro et al, 2003; Sakata et al, 1985)

**2.1 Structure and function of intestinal microbial flora** 

protective function, in particular the "barrier effect", referring to the physiological capacity of the endogenous bacterial microflora to inhibit colonization of the intestine by pathogenic microorganism. It is already known that the intestinal microbial flora influences food digestion ,absorption and fermentation, the immune system response, peristalsis, production of vitamins such as B-vitamins, influencing moreover the turnover of intestinal epithelial cells. In addition the metabolism of gut microflora influences hormonal secretion.

Bacterial colonization of human gut by environmental microbes begins immediately after birth; the composition of intestinal microbiota, relatively simple in infants, becomes more complex with increasing in age, with a high degree of variability among human individuals. It is believed that microbial diversity is an important factor in determining the stability of the ecosystem and that fecal loss of diversity predisposes the preterm gastrointestinal colonization of antibiotic-resistant bacteria and fungi with the consequent potential risk of infection (Cummings & Macfarlane, 1991; Montalto et al, 2009; Neish, 2002).

#### **2.2 Gut microflora and immunity**

The mucosal membrane of the intestines, with an area of approximately 200 m2, is constantly challenged by the enormous amount of antigens from food, from the intestinal microbial flora and from inhaled particles that also reach the intestines. It is not surprising therefore that approximately the eighty per cent of the immune system is found in the area of the intestinal tract and it is particularly prevalent in the small intestine. The intestinal immune system is referred as GALT (gut-associated-lymphoid tissue). It consists of Peyer's patches, which are units of lymphoid cells, single lymphocytes scattered in the lamina propria and intraepithelial lymphocytes spread in the intestinal epithelia.

The immune system of infants is not fully developed. The structures of the mucosal immune system are fully developed in utero by 28 weeks gestation, but in the absence of intrauterine infections, activation does not occur until after birth. Maturation of the mucosal immune system and establishment of protective immunity is usually fully developed in the first years of life. In addition the exposure to pathogenic and commensal bacteria, the major modifier of the development patterns in the neonatal period, depends on infant feeding practices. (Brandtzaeg, 2001; Gleeson et al, 2004)

Bacterial colonisation of the intestine is important for the development of the immune system. The intestine has an important function in working as a barrier.This barrier is maintained by tight-junctions between the epithelial cells, by production of IgA antibodies and by influencing the normal microbial flora. It is extremely important that only harmless substances are absorbed while the harmful substances are secreted via the faeces.

Studies show that individuals allergic to cow´s milk have defective IgA production and an increased permeability of the intestinal mucosa. This results in an increased absorption of macromolecules by the intestinal mucosa. The increased permeability is most probably caused by local inflammations due to immunological reactions against the allergen. This damages the intestinal mucosa

#### **2.3 Modification of the intestinal flora micro-ecosystem**

During the past century our lifestyle has dramatically changed regarding hygienic measures, diet, standards of living and usage of medical drugs. Today our diet largely

Intestinal Microbial Flora – Effect of Probiotics in Newborns 7

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

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

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 &

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

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

The presence of Bifidobacteria in artificial milk can contribute to the induction of a significant increase of Bifidobacteria in the intestinal tract, promotes the development of a protective microflora, similar to that one of the breast- fed newborn, contributes to the modulation of immune-defenses, giving them a major efficiency (Langhendries et al, 1995;

response, topographically located in the intestinal tract.

contact (immune cells, enterocytes, etc.).

Young, 1998).

**3.4 Safety** 

ill children

safety (Hammerman et al, 2006)

Fukushima et al, 1998).

**4. Probiotics and gastrointestinal disorders** 

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 producing bacteria .

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 & Young, 1998).
