Optimizing gastrointestinal health in agricultural animals through basic science discovery, management, and nutrition
Disease in animals and people is a result of interactions between the host, environment, and pathogenic/immunologic factors. Interactions between the host with infectious pathogens and/or dysregulated metabolic and/or genetic factors are an essential part of the disease process. However, the presence of a pathogen or underlying risk factor alone is often insufficient to initiate disease due to the inherent epithelial and immunological defense barriers in the host. When animals (and people) are exposed to environmental stressors (e.g. psychological, nutrition, temperature, etc.), disease susceptibility is markedly increased. However, the biological mechanisms by which stress induces GI disease remain poorly understood and thus, targeted therapies remain limited.
We seek to (1) understand how environment and management-related stressors adversely impact GI health in animals and (2) develop and test new management strategies to prevent GI disease and improve animal well-being.
The impact of weaning stress on GI health in pigs
One major area of research in our laboratory is understanding how weaning stress impacts short- and long-term GI development and disease susceptibility and determine whether we can mitigate the adverse effects of weaning via management and dietary strategies. Weaning is the most stressful event a pig encounters during production. During weaning, the pig is faced with a multitude of concurrent stressors including maternal separation, diet changes, transport and commingling stress, and increased pathogen exposure (Madec et al., 1998). As a result, weaned pigs are more susceptible to intestinal dysfunction resulting in impaired growth and feed efficiency and increased susceptibility to infectious enteric pathogens. There are profound changes in the structure and function of the gut at weaning including a marked impairment in barrier function or increased permeability (Boudry et al., 2004; Moeser et al., 2007a), altered nutrient and electrolyte transport (Boudry et al., 2004; Moeser et al., 2007a), villus atrophy, and inflammation (Kelly et al., 1990; McCracken BA, 1999).
Although previous studies described above have focused on the short-term (1–2 weeks post-weaning) physiological and structural changes in the gut of the weaned pigs, we have accumulated extensive evidence that, depending on the degree of stress experienced at weaning, long-lasting alterations to intestinal function and pathogen defense are evident.
We demonstrated that weaning age has a significant impact on the severity of intestinal barrier injury induced by weaning. Specifically, we showed that weaning prior to 23 d of age induced a significant disruption in intestinal epithelial barrier function (increased intestinal permeability), increased electrogenic ion transport, and intestinal inflammation, compared with pigs weaned >23 d of age (Smith et al., 2010).
Further investigations revealed that the heightened intestinal injury in early-weaned pigs was independent of feed intake and systemic neuroendocrine responses (measured as serum CRF and cortisol (Moeser 2006). Instead, early weaning-induced intestinal barrier injury was shown to be mediated via activation of intestinal CRF receptors (Moeser et al. 2006).
In another study, McLamb et al. (2012) demonstrated that early-weaning stress in pigs resulted in increased clinical disease severity and intestinal injury in response to a later-life challenge with enterotoxigenic E. coli.
Taken together, our work has demonstrated that early-weaning stress induces lasting, deleterious changes to intestinal epithelial barrier and immune function resulting in increased stress sensitivity and disease severity. Our current investigations are aimed at defining the precise mechanisms by which stress lead to alterations in intestinal barrier and immune function and testing strategies (management and nutritional) to prevent and/or ameliorate stress-induced GI dysfunction.
