Economic losses in the nursery phase of pork production can largely be attributed to the underdeveloped gastrointestinal tract (GIT) and immune system of weaned pigs, which greatly increases their susceptibility to potential pathogens. Enterotoxigenic Escherichia coli (ETEC) is a common enteric pathogen that results in secretory diarrhea and leads to reductions in growth performance and increases in mortality, morbidity, and treatment costs. Vaccinations and antibiotics have traditionally been used as means of prevent or mitigating ETEC infections; however, with the increase in antibiotic resistant pathogens and pressure from the consumer population, pork producers are in need of alternative strategies. Dietary inclusion of direct-fed microbials have been proposed as a potential dietary strategy to prevent or mitigate the negative effects associated with weaning and ETEC infections due to their suggested ability to exert beneficial effects on the host’s GIT, immune system, and microbial population. Nonetheless, having an understanding of how disease physiologically impacts the pig is essential to developing effective alternative dietary technologies to prevent or mitigate disease. Therefore, the objectives of this thesis were to characterize the impact of an ETEC challenge in weaned pigs on growth, intestinal function, immune response, and mucosal microbiota, and to evaluate the potential beneficial effects of Bacillus-based DFMs under normal physiological and ETEC challenge conditions.

To achieve our objective, two experiments were conducted. The results of Experiment 1 (Chapter 2) revealed that Bacillus-based DFMs did not affect body weight or growth performance of healthy nursery pigs housed in a commercial-like environment compared to the control diet, which may be a result of contrasting effects of the DFM products and dietary ingredients, such as zinc oxide. Experiment 2 (Chapters 3 and 4) investigated the impact of an F18 ETEC challenge on growth performance, intestinal function, immune response, and mucosal microbiota of weaned pigs, as well as evaluated the potential protective effects of two Bacillus-based DFMs (DFM1 And DFM2). The ETEC challenge increased fecal scores, reduced rectal temperature, impaired intestinal barrier integrity, altered immune response, resulting in reduced growth performance during 10-d post-challenge period. The ETEC challenge also induced dysbiosis in the mucosa-associated microbiota by increasing the abundance of potentially pathogenic bacteria and reducing the abundance of beneficial microbes. Our results suggest that the supplementation of DFM2 may potentially alleviate negative impacts of an ETEC challenge by improving intestinal barrier integrity and reducing bacterial pathogen load in the GIT microbial population.