In direct antagonism, probiotics kill or inhibit the pathogen to limit infection, or they down-regulate the expression of virulence factors, such as adhesins or toxins, required for pathogenesis. Probiotics can also interact with the immune system (immunomodulation) to enhance the functionality of innate and/or adaptive immunity, or to limit the ability of the pathogen to initiate or facilitate an immune response. Through “exclusion,” probiotics can alter the microenvironment to prevent pathogens from gaining access to appropriate receptors, to limit pathogen attachment, entry, or translocation, or to improve barrier function. A beneficial microbe may use a combination of these mechanisms, and may employ different mechanisms against different pathogens. B, B cell; DC, dendritic cell; IEC, intestinal epithelial cell; M, M cell; MAC, macrophage; T, T cell; TJ, tight junction.

(A) The devastating synergy between enteric infections and undernutrition is influenced by the environment, the human genome, host nutrition, and the human microbiome. Various interventions (red boxes) may inhibit progression to the next step in the cycle, minimizing both acute and chronic morbidities. (B) Employing a spectrum of disease outcome measures would lend greater insight into the pathology underlying enteric and diarrheal diseases, while providing a more complete understanding of interventions targeting basic steps of enteric and diarrheal disease pathogenesis. Adapted with permission from Wiley: Nutrition Reviews,⁴ copyright 2008. http://www.http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1753-4887.