Project leader: Professor ERIKA ISOLAURI,
Department of Paediatrics, Turku University Central Hospital, Finland, erika.isolauri@utu.fi. Homepage http://www.utu.fi/research/nami/.

Co-investigators:
Professor Seppo Salminen, sepsal@utu.fi, University of Turku Departments of Biochemistry and Food Chemistry, Programme on Health Biosciences and Functional Foods Forum
Professor Heikki Arvilommi, National Public Health Institute

PhD students: (University Of Turku)
MSc Ulla Hoppu, ulla.hoppu@utu.fi
MSc Pasi Kankaanpää, pasi.kankaanpaa@perkinelmer.com
MSc Pirkka Kirjavainen, piviki@utu.fi
MD Samuli Rautava, samrau@utu.fi
MD Minna Rinne, minrin@utu.fi
Medical Student Anu Huurre, anjohu@utu.fi
Medical Student Jonna Aaltonen, jmaalt@utu.fi
MSc Tarja Piirainen, MSc Soili Alanne and MSc student Jenni Sallinen.

Postdoctoral investigators:
PhD Arthur Ouwehand, arthur.ouwehand@utu.fi
MD Marko Kalliomäki, markal@utu.fi
MD Taina Arvola, taina.arvola@uta.fi
PhD Fang He
MD Minna-Maija Grönlund, minna-maija.gronlund@tyks.fi
PhD Kirsi Laiho, klaiho@utu.fi
MD Tiina Ojala, tiiran@utu.fi
PhD Miguel Gueimondo, miguel.gueimondo@utu.fi

Results
The combined programme aims at the development of nutrition intervention strategies and foods with beneficial effects on a specific target population for reducing the risk of disease.

Probiotics administered pre- and postnatally for 6 months to 159 children at high risk of atopic disease reduced the prevalence of atopic eczema later in infancy and childhood to half (23 %) as compared with that in infants receiving placebo (46 %), and the effect was shown to extend beyond infancy. When probiotic supplementation was given to the lactating mother, the amount of TGF-beta in breast milk could be promoted, suggesting the anti-inflammatory cytokine network as one mechanism and breast milk as one route of action. 

Subsequently, we have aimed to broaden the current view of exclusion of dietary components on one hand, and sole supplementation on the other in identifying the contribution of early dietary factors in a probiotic intervention study on the appearance of atopic eczema in childhood. The previously observed protective effect of probiotics was shown to evolve in joint action with the dietary intake of particular nutrients, thus reducing the later risk of atopic eczema in a child.

Next, a subgroup of the study population was evaluated to assess the impact of probiotics and breastfeeding on the gut microecology and humoral immune responses. The total numbers of IgM-, IgA- and IgG-secreting cells at 12 months were higher in infants breastfed exclusively for at least for 3 months and supplemented with probiotics as compared with breastfed infants receiving placebo. Again, faecal Bifidobacterium and Lactobacillus/Enterococcus counts were higher in breastfed than formula-fed infants, and sCD14 in colostrum correlated with the numbers of IgM and IgA cells.

To judge from these results, probiotic effects evidently act cooperatively with other nutritional compounds, such as polyunsaturated fatty acids which are assimilated by probiotics, and the immunological milieu in the gut, underlining the importance of evaluating age- and diet-specific factors to promote the health benefits of specific strains.

A number of probiotics have a long history of safe use and a demonstrated safety record in human consumption, and no health concerns have been observed. The numerous immunological properties of probiotics have, however, raised concern over possible effects on the growth of infants. In the long-term follow-up of the study population, the perinatal administration of probiotics appears to be safe, as it did not influence the height or the weight-for-height of the children at 4 years of age with and without perinatal administration of probiotics. However, a trend was observed for weights to be lower in the group receiving probiotics perinatally necessitating further examination of the long-term safety effect of probiotics administration.

Long-term colonization by probiotics or impairment of the natural diversity of the gut microbiota has also been addressed with early or prenatal administration of probiotics. In the long-term follow-up of the gut microbiota of the study cohort, the probiotic impact on gut microbiota succession was shown to be temporary, not interfering the diversity of the microbiota later. Maternal consumption of resulted in lower occurrence of B adolescentis and higher occurrence of B breve in child; such microbiota profile has been associated with reduced risk of disease later in life.

Selected publications:

Isolauri E, Salminen S. Probiotics, Gut Inflammation and Barrier Function. Gastroenetrol Clin North Am 2005; 34: 437-50.

Laitinen K, Kalliomäki M, Poussa T, Lagström H, Isolauri E. Evaluation of diet and growth in children with and without atopic eczema: follow-up study from birth to four years. Brit J Nutr 2005; 94: 565-74.

Rinne MM, Gueimonde M, Kalliomäki M, Hoppu U, Salminen SJ, Isolauri E. Similar bifidogenic effects of prebiotic-supplemented partially hydrolyzed infant formula and breastfeeding on infant gut microbiota. FEMS Immunol Med Microbiol 2005; 43: 59-65.

 Gueimonde M, Sakata S, Kalliomäki M, Isolauri E, Benno Y, Salminen S. Effect of Maternal consumption of Lactobacillus GG on transfer and establishment of faecal bifidobacterail microbiota in neonates. J Pediatr Gastroenterol Nutr 2006; 42: 166-70.

Arvola T, Ruuska T, Keränen J, Hyöty H, Salminen S, Isolauri E. Rectal bleeding in infancy; clinical, allergologic and microbiologic examination. J Pediatr, in press.

 Laitinen K, Hoppu U, Hämäläinen M, Linderborg K, Moilanen E, Isolauri E. Breast milk fatty acids may link innate and adaptive immune regulation: analysis of soluble CD14, prostaglandin E2 and fatty acids. Pediatr Res, in press.

An abstract of the research plan (January 2003)

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