Usefulness of an experimental model of the infant gut.

For several decades, the human-related microflora has been of great interest. Indeed, the microbial community inhabiting the gastrointestinal tract has been recognized as a major factor in human health and disease. Colonization of all external and internal sites in humans and animals begins at birth and results, after several weeks or months, in the establishment of a stable autochthonous microflora. The human ecosystem is composed mainly of bacteria that must cooperate closely with one another, as well as with their host, and any distortion in this “winwin” arrangement can lead to disease. Although numerous reports have stated the important role of intestinal microflora in the health and well-being of the host, details of these roles are still scarce. The autochthonous intestinal microflora is believed to play a major role in colonization resistance by preventing overgrowth of potential pathogens. However, it is still not clear which bacteria or groups of bacteria, or which host factors are involved. Only some of the biochemical factors and mechanisms that contribute to colonisation resistance are known, including competition for nutrients, bacteriocins, short chain fatty acids and extra cellular enzymes. Moreover, adaptive mechanisms, such as those of the gutassociated lymphoid tissue (GALT) that produces secretory immunoglobulin A, can be stimulated by the microflora. In fact, the resident microflora is the main antigenic stimulus most likely responsible for the activation and development of the GALT at birth, and for its modulation through regulatory mechanisms (1,2). At birth, the bacteria settle in the neonatal intestine through a gradual process and include aerobic, facultative anaerobic, and anaerobic bacterial species acquired from the maternal flora or the external environment (3). Although the newborn is commonly exposed to a wide range of different bacteria, not all are able to establish themselves in their gastrointestinal tract. Various factors are known to influence the colonization pattern; among them, mode of delivery, gestational age, environment, and mode of feeding. A caesarean delivery limits transfer of bacteria from the mother to the infant. Consequently, cesarean born infants are colonized with anaerobic bacteria, especially bacteroides and bifidobacteria, later than vaginally delivered infants. Environmental factors, such as obstetrical practices and hygiene level, which decrease bacterial exposure during the neonatal period, influence the intestinal colonization pattern. Likewise, antibiotics given either to the newborn or to the mother during the perinatal period may profoundly modify this pattern. The most studied factor is the nature of the diet, which is known to play a crucial role. Indeed, breast-feeding is associated with protection from infections such as gastroenteritis, respiratory tract infections, acute otitis media, urinary tract infection, neonatal bacteremia, and necrotizing enterocolitis (4). Part of this protective effect may be due to the differences between the intestinal flora of breast-fed babies and that of bottle-fed babies. Indeed, since the early work of Tissier (5), bifidobacteria have been regarded as predominant members of the intestinal flora in breast-fed infants (6) and the most important genus in the health promoting effect. They are thought to play a role in the colonisation resistance by inhibiting the growth of potential pathogenic bacteria such as Enterobacteria, clostridia, and bacteroides. If some studies reported similar high levels of bifidobacteria in breast and bottle-fed infants, the numbers of most other bacteria, i.e. enterobacteria, enterococci, bacteroides, clostridia, lactobacilli, were always significantly higher in the latter group (6). Furthermore, beneficial effects on the mucosal immune system were shown through immunomodulation by bifidobacteria in vitro and in experimental models (2). In addition, Sudo et al, using germ-free mice associated with intestinal flora, showed that only early colonization by bifidobacteria may down-regulate the development of IgE antibody responses and the resulting susceptibility to food allergy diseases (7). Evidence has shown that the first colonizing bacteria at birth may establish a permanent niche by inducing specific and lasting glycocalix as well as by modulating enterocyte gene expression (8), giving them a major role, thus putting a competitive disadvantage to late-comers. Moreover, a modification in colonization was noticed by several authors, with a delayed colonization by enteric Laboratoire de Microbiologie, Faculté des Sciences Pharmaceutiques et Biologiques, Université René Descartes, 4 avenue de l’Observatoire, 75270 Paris cedex 06; (e-mail: mjbutel@pharmacie. univ-paris5.fr). Journal of Pediatric Gastroenterology and Nutrition 37:109–111 © August 2003 Lippincott Williams & Wilkins, Inc., Philadelphia