Animals are constantly exposed to a diversity of health challenges and the gastrointestinal tract (GIT) is a major, if not the principal, site of exposure. Animal models and a limited number of human clinical studies have shown that the assemblages and metabolic activities of the resident bacteria are important determinants of the effectiveness of the various host defense mechanisms and thereby influence the ability of animals to respond to health challenges. The assemblages of bacteria resident in the GIT provide a first line of defense that can exclude invading pathogens, reduce the proliferation of opportunistic pathogens already resident in the GIT, and reduce the availability, carcinogenicity, or toxicity of noxious chemicals. The mucosa of the GIT is a second, multilayered line of defense that includes the mucous and other secretions, the epithelial cells, and immune-associated cells scattered within and under the epithelium. The final line of defense contends with pathogens or noxious chemicals that transcend the mucosal barrier and enter the host and consists of the innate and acquired components of the systemic immune system and the xenobiotic metabolizing enzymes. The lactic acid producing bacteria (LAB) are considered to be immunomodulatory and directly or indirectly influence the GIT and systemic defense functions. Corresponding with this, supplementing the diet with inulin, oligofructose, or other nondigestible oligosaccharides that increase the densities and metabolic capacities of the LAB enhances defense mechanisms of the host, increases resistance to various health challenges, and accelerates recovery of the GIT after disturbances.