NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY VOLUME 9 | OCTOBER 2012 | 565 Department of Pediatrics, Turku University Hospital, Kiinamyllynkatu 4–8, 20520 Turku, Finland (S. Rautava). Department of Pediatrics, University of Turku, Kiinamyllynkatu 4–8, 20520 Turku, Finland (R. Luoto, E. Isolauri). Functional Foods Forum, University of Turku, Itäinen Pitkäkatu 4A, 20520 Turku, Finland (S. Salminen). Correspondence to: E. Isolauri erika.isolauri@utu.fi Microbial contact during pregnancy, intestinal colonization and human disease Samuli Rautava, Raakel Luoto, Seppo Salminen and Erika Isolauri Abstract | Interaction with colonizing intestinal bacteria is essential for healthy intestinal and immunological development in infancy. Advances in understanding early host–microbe interactions indicate that this early microbial programming begins in utero and is substantially modulated by mode of birth, perinatal antibiotics and breastfeeding. Furthermore, it has become evident that this stepwise microbial colonization process, as well as immune and metabolic programming by the microbiota, might have a long-lasting influence on the risk of not only gastrointestinal disease, but also allergic, autoimmune and metabolic disease, in later life. Modulating early host–microbe interaction by maternal probiotic intervention during pregnancy and breastfeeding offers a promising novel tool to reduce the risk of disease. In this Review, we describe the current body of knowledge regarding perinatal microbial contact, initial intestinal colonization and its association with human disease, as well as means of modulating early host–microbe interaction to reduce the risk of disease in the child. Rautava, S. et al. Nat. Rev. Gastroenterol. Hepatol. 9, 565–576 (2012); published online 14 August 2012; doi:10.1038/nrgastro.2012.144 Introduction Our understanding with regard to the influence of microbes on human health has gradually expanded from pathogens causing infectious disease to a mutu- ally beneficial interaction with indigenous micro- organisms that contribute to normal human physiology and immune homeostasis. That gastrointestinal dis- orders, such as IBD or infectious gastroenteritis, are associated with perturbations of gut microbiota com- position (discussed elsehwere 1 ) is now well established. The vital role of contact with environmental and colo- nizing bacteria in early infancy for healthy immune and metabolic maturation beyond the gastrointestinal tract has been brought to our attention during the past two decades. Advances in elucidating early host–microbe interac- tions identify two hitherto largely unknown areas of interest. First, groundbreaking experimental and clini- cal studies suggest that microbial contact in utero and during the neonatal period, modified by mode of deliv- ery and breastfeeding, exert marked effects on immune and metabolic programming in the fetus and infant. 2,3 Second, reports from clinical studies indicate that early microbial contact has a long-term influence on intes- tinal colonization patterns—that is, microbiological programming (Box 1)—and so, consequently, on the immune responder phenotype, metabolic status and risk of disease later in life. 4–8 In our opinion, the concept of early origins of human disease should, therefore, be revised to include the multiple interactions between maternal environmental and indigenous microbes during pregnancy and birth, and their association with mode of delivery, perinatal antibiotic exposure, breast-milk composition and immune physiology in the mother, fetus and infant. In this Review, we describe the current body of knowl- edge regarding the importance of perinatal microbial contact to health and disease in the gut, and the body as a whole. We also suggest that modulating the complex network of prenatal and postnatal metabolic, immuno- logical and microbiological interactions with specific probiotics could provide a powerful tool to reduce risk of disease in the child. Development of intestinal microbiota Microbes are present in all natural environments. The fact that the most predominant species (such as Bifidobacterium spp.) present in the indigenous intes- tinal microbiota of human infants 9–11 are not found in substantial quantities in the environment suggests that infants acquire their commensal bacteria from other humans, presumably, and most importantly, from the mother. Conventionally, the human fetus has been considered sterile and microbial colonization has been thought to begin during birth and then develop under the influence of breastfeeding and skin-to-skin contact with the mother. Contact with the enormous bacterial load of the extrauterine world during and after birth marks the beginning of massive bacterial colonization of mucosal surfaces, particularly the gastrointestinal tract. Consistent with this notion, lactobacilli residing in the birth canal need to be characterized as they might be one important source of intestinal microbes during the first days of life. 12–14 Competing interests The authors declare no competing interests. FOCUS ON GUT MICROBIOTA © 2012 Macmillan Publishers Limited. All rights reserved