**9. Probiotics and respiratory tract infections (RTI)**

Two studies have examined the effect in adults of a combined multi-strain probiotic and multivitamin/mineral supplement containing L. gasseri, B. longum and B. bifidum on the incidence, duration and severity of common cold infections and aspects of immune function (de Vrese et al, 2006; Winkler et al, 2005). Both studies found a reduction in severity and duration, as well as enhanced expression of immune cells, while only Winkler et al. (2005) found a reduction in incidence. The major difference between studies is dose—the same probiotic strains were used for both, as well as the same assessment methods for the illness—suggesting that although the dose used by de Vrese et al. (2006) (5 9 107 CFU) was enough to attenuate symptoms and duration, a higher dose such as that used by Winkler et al. (2005) (5 9 108 CFU per day) was needed for prevention of infections. The lower dose may promote a systemic immune response sufficient to reduce severity and duration but not incidence, while the higher dose may stimulate systemic immunity via the mechanism of

Intestinal Microbial Flora – Effect of Probiotics in Newborns 15

distribution of T and B lymphocytes, primed in the gut, which proliferate to the mucosalassociated lymphoid tissue (MALT), where the B cells differentiate into immunoglobulinproducing cells after specific antigenic exposure, leading to an inhibition of colonisation by

Olivares et al. (2006) also found an immunostimulatory effect in subjects given a multistrain probiotic containing L. gasseri and L. corniformis, compared with a standard yoghurt containing S. thermophilus and L. bulgaricus, although this study provides no evidence for the efficacy of a greater number of strains, since two non-comparable treatments were used. Gluck and Gebbers (2003) investigated colonisation by nasal pathogens and showed a 19% reduction in the group given probiotics (L. rhamnosus GG, Bifidobacterium lactis, L. acidophilus, S. thermophilus) compared to no reduction with placebo. Despite this reduction in colonisation, no data are given as to whether subjects became unwell during the study period, making conclusions as to actual health benefits difficult to draw. In a similar study, Hatakka et al. (2007) found no effect of a probiotic mixture on incidence and duration of otitis and upper respiratory infections on children aged 6 months to 10 years; a lower dose than that used by Gluck and Gebbers (2003) may explain the disparity between results. It may also be that ingested probiotics have less effect on the aural mucosa

In a 7-month study with over 1,000 subjects, Lin et al. (2009) examined the protective effect of two single probiotics (L. casei and L. rhamnosus, given individually) and one multi-strain mixture containing the 2 lactobacilli and 10 other organisms. Reduced physician visits, as well as decreased incidence of bacterial, and viral respiratory disease were seen in all groups compared with placebo, but there was no significant difference in effectiveness between the preparations even though the multi-strain probiotic was given at a tenfold higher dose than the individual strains. However, in the case of prevention of gastro-intestinal tract

compared to that on the nasal mucosa, or that the effects are strain-specific.

Fig. 2.

pathogenic strains.

Fig. 1. The direct introduction of probiotics, that positively influences the intestinal microbial population, determining a reduction of more pathogenic species in the bowel reservoir, can improve enteral nutrition reducing time of dependence on intravenous nutrition and might contribute to a better outcome in high risk newborns.

Fig. 2.

14 New Advances in the Basic and Clinical Gastroenterology

Fig. 1. The direct introduction of probiotics, that positively influences the intestinal microbial population, determining a reduction of more pathogenic species in the bowel reservoir, can improve enteral nutrition reducing time of dependence on intravenous

nutrition and might contribute to a better outcome in high risk newborns.

distribution of T and B lymphocytes, primed in the gut, which proliferate to the mucosalassociated lymphoid tissue (MALT), where the B cells differentiate into immunoglobulinproducing cells after specific antigenic exposure, leading to an inhibition of colonisation by pathogenic strains.

Olivares et al. (2006) also found an immunostimulatory effect in subjects given a multistrain probiotic containing L. gasseri and L. corniformis, compared with a standard yoghurt containing S. thermophilus and L. bulgaricus, although this study provides no evidence for the efficacy of a greater number of strains, since two non-comparable treatments were used.

Gluck and Gebbers (2003) investigated colonisation by nasal pathogens and showed a 19% reduction in the group given probiotics (L. rhamnosus GG, Bifidobacterium lactis, L. acidophilus, S. thermophilus) compared to no reduction with placebo. Despite this reduction in colonisation, no data are given as to whether subjects became unwell during the study period, making conclusions as to actual health benefits difficult to draw. In a similar study, Hatakka et al. (2007) found no effect of a probiotic mixture on incidence and duration of otitis and upper respiratory infections on children aged 6 months to 10 years; a lower dose than that used by Gluck and Gebbers (2003) may explain the disparity between results. It may also be that ingested probiotics have less effect on the aural mucosa compared to that on the nasal mucosa, or that the effects are strain-specific.

In a 7-month study with over 1,000 subjects, Lin et al. (2009) examined the protective effect of two single probiotics (L. casei and L. rhamnosus, given individually) and one multi-strain mixture containing the 2 lactobacilli and 10 other organisms. Reduced physician visits, as well as decreased incidence of bacterial, and viral respiratory disease were seen in all groups compared with placebo, but there was no significant difference in effectiveness between the preparations even though the multi-strain probiotic was given at a tenfold higher dose than the individual strains. However, in the case of prevention of gastro-intestinal tract

Intestinal Microbial Flora – Effect of Probiotics in Newborns 17

and the intestinal mucosa of the host may have been somewhat disturbed by modern perinatal care. It is fundamental to try to decrease these possible negative influences and to discover in the near future the possible means to help manipulate positively the gut

Betta, P.; Sciacca, P.; Trovato, L. et al. (2007) Probiotics in the prevention of Bacterial and

Bin-Nun, A.; Bromiker, R.; Wilschanski, M. et al. (2005) Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr, 147(2):192-6. Björkstén, B.; Naaber, P.; Sepp, E. & Mikelsaar, M. (1999) The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin Exp Allergy, 29(3):342–346 Boyle, R.J.; Bath-Hextall, F.J.; Leonardi-Bee, J. et al (2008). Probiotics for treating eczema.

Brandtzaeg, P. (2001) Nature and function of gastrointestinal antigen-presenting cells.

Cummings, J.H. & Macfarlane, G.T. (1991) The control and consequences of bacterial

Cummings, J.H. & Macfarlane, G.T. (1997) Colonic microflora: nutrition and health.

Dai, D. & Walker, W.A. (1999). Protective nutrients and bacterial colonization in the

Deshpande, G.; Rao, S. & Patole, S. (2007) Probiotics for prevention of necrotising

de Vrese, M.; Winkler, P.; Rautenberg, P. et al, (2006) Probiotic bacteria reduced duration

Fanaro, S.; Chierici, R.; Guerrini P. & Vigi, V. (2003) Intestinal microflora in early infancy

Fukushima, Y.; Kawata, Y.; Hara, H.; Terada, A. & Mitsuoka, T. (1998) . Effect of a probiotic formula on intestinal immunoglobulin A production in healthy children, 42:39-44. Caramia, C. (2004) Probiotics: from Metchnikoff to the current preventive and therapeutic

Gleeson, M.; Pyne, D.B. & Callister R. (2004) The missing links in exercise effects on mucosal

Gluck, U. & Gebbers, J.O. (2003) Ingested probiotics reduce nasal colonization with

Gothefors, L. (1989) Effects of diet on intestinal flora. Acta Paediatr Scand Suppl, 351:118-21. Grönlund, M.M.; Lehtonen, O.P.; Eerola, E. & Kero, P. (1999) Fecal microflora in healthy

pathogenic bacteria (Staphylococcus aureus, Streptococcus pneumoniae, and beta-

infants born by different methods of delivery: permanent changes in intestinal flora

entercolitis in preterm neonates with very low birthweight: a systematic reiew of

and severity but not the incidence of common cold episodes in a double blind,

fermentation in the human colon. J Appl Bacteriol, 70:443-59.

Candida infections in newborns submitted to greater surgical interventions and admitted in NICU. Retrospective Group Controlled Study. ESPGHAN, Barcelona,

microbiotia of infants (Rautava, 2007).

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**11. References** 

infections, the probiotic mixture was significantly more effective than the single strains. This may be due to the exceptionally high dose given in the multi-strain treatment, resulting in larger numbers of probiotic bacteria competing with pathogens for binding sites and or nutrients in the gut.

Another point of interest in this study is that despite large differences in dose, the two single strains did not have statistically different effects, suggesting strain-specificity in dose and effect for individual species. These data support the theory that supplementation with certain multi-strain probiotics can reduce severity, duration, and possibly incidence of RTIs, and in the case of Lin et al. (2009) that a multi-strain probiotic may be more effective than a single-strain. There is some evidence for immunostimulation, even in cases where illness still occurs. Further consistency could be added to this evidence with the establishment, by testing varied concentrations of probiotic bacteria, of an optimum dose that prevents pathogenic colonisation of the mucosa as well as the incidence and severity of illness. Testing this dose with and without vitamin and mineral supplementation may reveal a synergy between both types of supplement.

Further work should be done to determine the relative efficacy of single- and multi-strain probiotics in this area.
