Nutrients such as glucose, amino acids and some vitamins that are soluble in water are absorbed by the small intestine mainly across cell membranes (via special membrane transporters) or by a poorly understood "paracellular" pathway between intestinal cells. The principal investigators previously showed that flying animals (birds and perhaps bats) exhibit enhanced intestinal paracellular absorption as compared with nonflying mammals. Bats may provide a superior mammalian model system to advance understanding of the mechanism(s) of enhanced paracellular absorption. This project will test more extensively whether bats have relatively high paracellular absorption and will determine in bats the mechanistic reasons for enhanced paracellular absorption. Paracellular absorption will be measured in a number of bat species for comparison with nonflying mammals of similar size and diet. Detailed comparative physiological, histological and molecular measurements will be made in species of the two groups. Knowledge from this project could provide important insights for understanding and manipulating absorption of nutrients, toxins, and drugs for human and animal health.
A graduate student, a postdoctoral scholar, as well as undergraduate and high school students, some from underrepresented groups, will be trained in integrative biology, emphasizing concepts and methods spanning from the whole-animal to the molecular. International collaborations in Argentina and Australia are supported and enhanced.
Vertebrates can absorb water-soluble nutrients from the intestine into blood via two pathways: one where nutrients pass through intestinal cells to blood, which involves special proteins in the cells’ membranes called transporters, and a second pathway in which nutrients pass through the junctions between the intestinal cells, called the paracellular pathway (Image 1). The transporters are specific for some nutrients or groups of them, whereas the paracellular pathway is less selective and also allows absorption of other water soluble substances that are not nutrients, such as drugs and toxins. We found that flying vertebrates, the birds and bats, have a greater capacity for absorption by the paracellular pathway at the whole-animal level than nonflying mammals (Image 2). These differences in nutrient-sized probe absorption can be demonstrated at the tissue level (Image 3). This physiological difference in intestinal paracellular permeability probably evolved in flyers to compensate for less intestinal surface area (Image 4), which is selected for in fliers to save energy and maneuverability. High paracellular nutrient absorption might result from small intestines having more tight junctions through which substances can be absorbed, or tight junctions that are more permeable to nutrient-sized molecules. This is an area of active investigation, but there is some evidence that both may be occurring in bats and birds. These findings may benefit humans because bats may provide a superior model system to advance understanding of the mechanistic bases of enhanced paracellular absorption, which can be important for understanding and manipulating absorption of hydrosoluble nutrients, toxins, and drugs for human and animal health or possibly for understanding pathological conditions in which permeability is enhanced as in inflammatory bowel diseases. Also, for wildlife, the paracellular pathway permits greater absorption of water soluble toxins made by humans and naturally occurring in foods. For bats and birds with high intestinal permeability, vulnerability to hydrophilic toxins could be an important ecological driving force, constraining food exploratory behavior, limiting the breadth of the dietary niche, and selecting for compensatory behaviors such as searching for and ingesting specific substances that inhibit hydrophilic toxin absorption. In the United States, a graduate student, a postdoctoral scholar, four undergraduates and one high school student, some from underrepresented groups, were trained in integrative biology, emphasizing concepts and methods spanning from the whole-animal to the molecular. The postdoctoral scholar and graduate student were mentored in directing research, which includes designing, analyzing and writing up experiments, administrative duties such as managing animal care and use protocols, directing personnel (e.g., undergraduate assistants), and they are encouraged and mentored in writing complementary research proposals. Also, the postdoctoral scholar and the graduate student were involved in scientific teaching at the University of Wisconsin-Madison. International collaborations in Argentina and Australia were also supported, including training of a postdoctoral scholar, undergraduate and three graduate students.
