Funding outcome

Intestinal failure in babies is a condition in which the intestine lacks the length or ability to absorb the nutrients required for the babies to live and grow. This condition is most common in preterm babies, especially those with shortened intestine after surgery for diseases due to their immaturity. Many of these babies die from complications of this short bowel syndrome (SBS). This is primarily because they must have intravenous nutrition or parenteral nutrition (PN) to survive. While lifesaving, PN is complicated by frequent life threatening infections and/or severe liver disease. In order to not need PN the babies must have growth in their intestines, a process we call adaptation. Adaptation can be negatively impacted by the amount and types of bacteria that normally live in the intestine. This so called microbiome is intimately related to the development of our intestine during infancy and appears to be very disturbed in SBS, called dysbiosis. The only way to currently manage this dysbiosis is to use very strong and broadly effective antibiotics in a random manner. This is being done randomly because we simply cannot measure the microbes over time in these young children in a cheap and effective manner. We do not think this is the right approach for the babies as it targets all bacteria in the intestine. While we want to target the 'bad' bacteria we also end up decreasing bacteria that are working in the intestine to help adaptation and nutrient absorption. This is a positive benefit of how we evolved with our microbiome, so we don't actually want to wipe out these 'good' bacteria. This broad approach can also encourage the bacteria to develop resistance to the antibiotic treatments and this can be a huge problem to manage if the babies get sick with infections from gut bacteria, which is a major cause of death for these babies. This research study will test a novel idea to use the feces of healthy piglets infused into SBS piglets to provide them with a healthy microbiome. We will be testing if this approach is possible and safe in our novel piglet model of SBS that mimics SBS and intestinal failure as is seen in human babies. We are the only laboratory to have this model in North America. This means we do research this is meaningful for babies with SBS. We will work with a global expert in the microbiome, Karen Madsen, to prove that fecal microbial transplantation (FMT) is possible in SBS piglets and to examine the relationship between adaptation and FMT. These studies must first be done in animal models, it is simply not ethical to test such new approaches in vulnerable and sick preterm babies. This study is a critical first step to developing and testing the safety of a novel treatment that may be helpful for babies with SBS to reduce dysbiosis and its consequences like life threatening infections.