PROBIOTICS,PREBIOTICS, AND NEW FOODS Microflora in Inflammatory Bowel Diseases A Pediatric Perspective Eugenia Bruzzese, MD, PhD, Roberto Berni Canani, MD, PhD, Giulio De Marco, MD, and Alfredo Guarino, MD Abstract: Several lines of evidence link inflammatory bowel dis- eases to modifications of intestinal microflora. Epidemiologic and clinical data suggest a triggering role for select agents in ulcerative colitis and in Crohn disease. Experimental evidence indicates that in- testinal microorganisms are needed for developing intestinal inflam- mation in IL-10 knockout mice, and this is associated with an in- creased number of adherent clostridia and a decrease of lactobacilli and bifidobacteria. It may be hypothesized that a host–agent-specific relationship leads to an abnormal immune response, which may be genetically driven in select inflammatory bowel diseases. However, different from adults, the pattern of intestinal microflora undergoes profound changes during the early stage of life, contributing to the development of the immune system. A close relationship exists be- tween microbiologic and immunologic imprinting. The microbio- logic imprinting in neonates may be modified using bacterial probi- otics that colonize the intestine, modify the immune response, and decrease the risk for atopy. Probiotics may decrease the recurrences of inflammatory bowel diseases. Preliminary evidence of intestinal antiinflammatory effects has been detected in children with cystic fi- brosis. Overall these data provide the rationale to investigate the in- teraction between intestinal microflora and the local and general im- mune response in children with, or at risk for, inflammatory bowel diseases. This approach may be a key for understanding the patho- physiology of intestinal inflammation and may disclose novel strate- gies to educate better the immune system, particularly during its de- velopmental stage. Key Words: Inflammatory bowel disease, microflora, probiotics, children (J Clin Gastroenterol 2004;38:S91–S93) INTESTINAL MICROFLORA AND MICROBIOLOGIC IMPRINTING The pattern of intestinal microflora, although quite stable in the adult host, undergoes major ecologic modifica- tions during the early stages of life. Intestinal colonization be- gins during the newborn period, when a true “microbiologic imprinting” occurs. This lasts approximately 2 weeks in ani- mals but takes longer in humans, proceeding along diet modi- fications until weaning, after which the microbial pattern slowly shifts toward the adult pattern. This is eventually reached around 3 years of age. Fecal flora of breast-fed infants is dominated by bifidobacteria, whereas formula-fed infants have a more complex microbiota with no bacterial genus pre- dominance. Maternal vaginal and fecal flora is the primary source of microorganisms to the newborn host. Intestinal mi- croflora modifiers include age, type of delivery, diet, use of antibiotics, gastric pH, intestinal peristalsis, and immune sys- tem. Administration of probiotics or prebiotics early after birth is effective in influencing the composition of intestinal micro- flora. Thus, the manipulation of intestinal microflora, particu- larly during the first weeks of life, leads to a specific micro- biologic imprinting that may reduce or increase the risk of de- veloping diseases. INTERACTION BETWEEN ENTERIC MICROFLORA AND THE IMMUNE SYSTEM A close interaction exists between microbes and the im- mune system, particularly during the early stages of life. Germ-free animals lack the normal inflammatory infiltrate in the submucosal layer, their lymphoid structures are not well developed, and serum immunoglobulins are low. In germ-free animals, suppressor cell activity is absent and animals are not tolerant to antigens given through parenteral route, but become so after oral administration of lipopolysaccharide. A relation- ship exists between microbiologic imprinting and the risk for immune-related diseases such as atopic eczema. Infants who will eventually develop atopy harbor more clostridia and less bifidobacteria and lactobacilli. 1 Neonates exposed to Lactoba- cillus GG had a decreased risk of eczema during the first 4 years of age. 2 In contrast, when probiotics were administered to allergic adults, little effect was observed, indicating an age- related pattern of the interaction between intestinal microecol- ogy and immune response. 3 Thus microbiologic imprinting af- fects immunologic imprinting, and the immune system may be “educated” by enteric bacteria. This process, however, occurs Received for publication January 13, 2004; accepted February 12, 2004. From the Department of Pediatrics, University “Federico II,” Naples, Italy. Reprints: Alfredo Guarino, MD, Department of Pediatrics, University “Federico II,” Via S. Pansini 5, 80131 Naples, Italy (e-mail: alfguari@ unina.it). Copyright © 2004 by Lippincott Williams & Wilkins J Clin Gastroenterol • Volume 38, Supp. 2, July 2004 S91