ARTICLE Intestinal Infections and Prebiotics: The Role of Oligosaccharides in Promoting Health Arland T. Hotchkiss Jr, PhD, Randal K. Buddington, PhD Prebiotic oligosaccharides exert activity against pathogens partly by stimulating the growth and/or activity of commensal bacteria that provide health benefits (lower pH, bacteriocin production, immune system modulation, competitive exclusion). This review describes alternative mechanisms of action whereby prebiotics enhance host defenses against acute infections and chronic diseases by directly inhibiting bacterial adhesion, invasion, and toxin binding to epitheial receptors and by potentially modulating gene expression by host cells. Emphasis is placed on human milk and pectic oligosaccharides as animal and plant examples of prebiotics with alternative functions in enhancing resistance to intestinal infections. Many of these oligosaccharides have immunomodulating activity that, in combination with prebiotic influences, contributes to improving host health. Pectic oligosaccharides, which mimic acidic human milk oligosaccharides, modulate T-helper (Th)1/Th2 immune responses in an influenza vaccine model and decrease allergic asthma parameters in mice. Key words: bacteria, gut, pathogens, commensal bacteria, probiotics, human milk, pectin, bacterial adhesion, immunomodulation, chronic disease P athogens and probiotics meet in the gut and face a number of shared challenges. These include survival in a hostile and acidic environment (gastric juice and bile salts), competition for nutrients and colonization space (adhesion/attachment/retention in the intestinal mucosal epithelium) with existing commensal microbiota that produce bacteriocins, and interactions with the host immune system. 1 The responses to the challenges have the potential to impact host health (positive for probiotics and commensals and negative for infectious pathogens). Beneficial and pathogenic bacteria use similar strategies for survival and competition in the gut (fimbriae, bile salt tolerance mechanisms, IgA proteases, IgA-binding pro- teins, quorum sensing, and oxidative stress genes). 2 Although expression of these strategies by pathogens is often referred to as virulence factors because inactivation usually results in avirulent pathogens, many innocuous and health-promoting commensal bacteria share these factors. A distinction must be drawn between the shared survival and colonization strategies employed by all gut- associated bacteria and the pathogen-specific factors, such as toxins, which damage the host, or internalins, which facilitate entry into host cells. Another important con- sideration is the temporal scale between resistance to acute intestinal infections and prevention of chronic diseases because both are influenced by the gut microbiota. If the mechanism of infection resistance is mediated by beneficial bacteria, then it may take 2 or more weeks for the gut microbiota composition to change adequately in response to prebiotic supplementation of food or feed to elicit the desired responses. Therefore, immediate responses to prebiotics involving direct interactions with pathogens and host cells (eg, immunomodulation) may play important roles in the prevention of infections and chronic disease in combination with the recognized resistance to acute gastrointestinal (GI) infections con- ferred by changes in bacterial composition. The majority of selectively fermented dietary ingredi- ents that result in specific changes in the composition and/ or activity of the intestinal host health-promoting micro- biota (ie, prebiotics 3,4 ) are oligosaccharides. Oligosaccha- rides are the key structures involved in intestinal interac- tions between bacteria and the host. Some of these oligosaccharides are prebiotics, but the prebiotic status is Arland T. Hotchkiss Jr: U.S. Department of Agriculture, Agricultural Research Service, Eastern Regional Research Center, Wyndmoor, PA; Randal K. Buddington: Department of Health and Sport Sciences, University of Memphis, Memphis, TN. Reprint requests: Arland T. Hotchkiss Jr, PhD, U.S. Department of Agriculture, Agricultural Research Service, Eastern Regional Research Center, 600 E. Mermaid Lane, Wyndmoor, PA 19038; e-mail: arland.hotchkiss@ars.usda.gov. DOI 10.2310/6180.2011.00009 # 2011 Decker Publishing Functional Food Reviews, Vol 3, No 3 (Fall), 2011: pp 119–134 119