Large roundworm induced malabsorption: modulation of intestinal porcine nutrient transport

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The roundworm Ascaris suum is the most important parasite in pig farming in Europe. Infections are acquired by ingestion of embryonated eggs containing the infective third-stage larva. These larvae hatch after ingestion by the host, reach the liver via the mesenteric veins and remain within the liver tissue during a histotropic phase until they continue migration via blood stream into the lungs. Following migration through alveoli, larvae reach the oral cavity via the trachea and are subsequently swallowed. Thus, they reach the gastrointestinal tract about 4 weeks post infection, where they develop into the preadult stage and finally into sexually mature adults and complete the life cycle by producing large amounts of eggs. Infected pigs most commonly show unspecific clinical signs like decreased performance and retardation of growth. Within the host, the development of Ascaris suum has well been described; however, mechanisms of action of this parasite are mostly unknown. Few data obtained from pigs as well as studies comprising laying hens indicate an influence of Ascaris suum on intestinal nutrient transport mechanisms. Therefore, the aim of the project is the investigation of the effect of an Ascaris suum-infection in pigs on intestinal transport of glucose, amino acids and dipeptides. Additionally, the effect of excretory-secretory antigens as well as cuticle antigens of the parasite on these transport mechanisms will be evaluated as these antigens are in direct contact with the intestinal wall. Analyses will be conducted utilizing in vitro-measurements of the intact epithelium after mucosal addition of nutrients via electrophysiological response. Furthermore, measurements on nutrient flux rates employing radioactively labeled substrates as well as uptake studies into membrane vesicles of luminal and basolateral membranes of enterocytes will be conducted. Molecular approaches comprising quantitative real-time PCR, immunoblotting and immunohistochemistry to evaluate transcription and expression of transporter systems will complete the functional analyses. The expected insights will not only contribute to a better understanding of the host-parasite interactions, but will also provide the basis for new, innovative therapeutic approaches. Beside therapeutic intervention concerning malabsorption in porcine or human ascariosis, this may also include the potential identification of target molecules contributing to the development of therapeutics for the treatment of etiologically different absorption disorders or obesity. This precludes the complete functional characterization of intestinal nutrient transport systems in response to A. suum infections, which will be achieved by the planned project.