Grant: Discovery Grants Program - Individual

The gastrointestinal tract is a critical organ facilitating feed digestion, feed passage, and nutrient absorption. As contents of the gastrointestinal tract are external to animals, the lining of the gastrointestinal tract (epithelium) must also prevent potentially harmful molecules and organisms from crossing its barrier. Compounds that cross gain access to lymphatic or systemic circulation and can induce local and systemic inflammation and translocation of these molecules or organisms are thought to be central to the progression for some metabolic disorders and diseases such as liver abscesses and laminitis in cattle. The ability for the gastrointestinal tract to promote absorption of nutrients while preventing translocation or passage of harmful molecules and organisms is referred to as selective permeability and is a crucial component of the immune system. The latter is emphasized when considering that the gastrointestinal tract is the organ with the greatest exposed surface area and is extensively colonized by microorganisms. While characteristics of gastrointestinal tract permeability have been well investigated in monogastric species, only recently have researchers evaluated the barrier function of the gastrointestinal tract in ruminants such as cattle and sheep.   There are numerous situations that may cause disruption to barrier function. For example, exposure to a transient and marked reduction in feed intake causes a decrease in total gastrointestinal tract barrier function potentially allowing non-desired molecules or organisms to cross the gastrointestinal barrier. The relevance of a transient reduction in feed intake should not be understated as such circumstances occur when cattle are exposed to heat stress, when affected by infectious disease, in response to digestive disorders, in relation to transportation events, and around parturition. Given the lack of data for ruminants, there is ongoing debate about the regions of the gastrointestinal tract that are most affected, sex-based effects, the severity of the insult required to compromise barrier function, the recovery response, and the underlying mechanisms regulating these responses.  The hypothesis of the proposed program is that the distal regions of the small intestine and proximal regions of the large intestine are at greatest risk for a reduction in selective permeability, with females affected to a greater extent, and that those distal regions recover more rapidly than the foregut regions of the gastrointestinal tract. To test the hypothesis, we will: 1) determine regional differences in barrier function of the gastrointestinal tract in cattle when exposed to a transient and marked reduction in feed intake; 2) determine how the severity of the exposure to low feed intake (duration of exposure and magnitude of reduction) affect regional permeability; 3) determine whether there are sex-based effects  for the reduction in gastrointestinal barrier function.