intestinal failure & clinical nutrition

summary

Intestinal failure is the inability of the intestine to absorb sufficient fluid and nutrients to sustain life. This may result from diseases that require a large part of the intestine to be surgically removed. Despite advances in nutrition therapy, intestinal failure remains a major clinical problem. Infants are especially challenging, as needs for growth must be balanced against complications of therapy including liver disease and infection. The aim of our research is to improve knowledge of how the bowel adapts to the loss in bowel length and to develop treatment strategies aimed at improving clinical outcome of patients with intestinal failure.

group leader(s)

Professor Julie Bines
Intestinal Failure & Clinical Nutrition
Murdoch Childrens Research Institute
Royal Children's Hospital
Flemington Road
Parkville, Victoria 3052

T +61 3 9345 4107
E julie.bines@rch.org.au

group leader biography

current research projects

Project 1: Mechanisms associated with intestinal adaptation following massive small bowel resection

An important key to improved clinical outcome after a large part of the bowel is removed, is the ability of the remaining bowel to adapt. Through the process of adaptation, the small bowel increases in surface area and functional capacity to compensate for the loss of bowel length. Over the past decade we have studied the mechanisms associated with the adaptive response that occurs following bowel removal. We have shown that there is a time-related sequence of events following bowel removal. Changes first occur in the levels of hormone that stimulate bowel growth followed by changes in the structure of the bowel lining and muscles of the bowel (as shown in figure 1). Understanding these important events may provide an important clue into the timing of specific treatments aimed at increasing the repair and adaptation of the remaining intestine.

Project 2: Changes in intestinal motility following massive small bowel resection: The key to improved clinical outcome in short bowel syndrome (SBS)

The main symptoms experienced by patients with SBS relate to disturbances in intestinal motility, including diarrhoea, recurrent vomiting, malabsorption, dehydration and electrolyte imbalance, malnutrition and bacterial overgrowth. Despite this, most previous studies of SBS have focused on adaptation- associated changes in the intestinal lining and very little is known about the characteristics of gastrointestinal motility following resection. Even less is known about the mechanisms that may influence changes in motility and may provide an opportunity to improve nutrient and fluid absorption and minimise complications associated with dysmotile segments. Using new innovative technologies such as spatio-temporal mapping together with older, established methods we will examine how clinically relevant growth factor and pharmacological interventions influence gut movement and clinical outcome following the surgical removal of small bowel.

Project 3: Novel therapies aimed at enhancing intestinal adaptation following massive small bowel resection

Long-term parenteral nutrition (PN) remains as the cornerstone treatment for short bowel syndrome (SBS). Although PN provides the nutrients to sustain life and growth in patients with SBS, it is associated with significant morbidity and mortality. Surgical approaches including intestinal transplantation may provide benefit in some patients but carry risks of long-term immunosuppression. Therapeutic strategies aimed at increasing adaptation of the remaining bowel may provide a better alternative by eliminating the need for either PN or transplantation.

Over the past decade we have established a preclinical model to study the process of adaptation after resection, as it relates to children, using the juvenile pig. Due to similarities in the gastrointestinal tract and nutrition of the human and the pig, the pig is accepted as the most suitable model for the study of the intestine and diet in humans. We are currently examining the influence of colostrum, GLP-2, antibiotics and probiotics on intestinal adaptation following small bowel resection.

Project 4: Improving oral vaccine efficacy in developing countries: the role of nutrition, infection and inflammation

Oral vaccines offer several advantages over parenteral immunisation however significant decreases in the immunogenicity of oral vaccines (including the Sabin type one and three poliovirus vaccine, attenuated bovine rotavirus vaccine, and live oral cholera vaccine), have been reported in developing countries. Although it is likely that this poor outcome is due to defects in the mucosal immune system which result form the conditions prevalent in these countries, this correlation has not be explored. We propose that prevalent conditions in these countries; such as poor nutritional status, persistent diarrhoea and chronic inflammation lead to a compromised intestinal mucosa, which is then unable to process orally administered vaccines at the mucosal surface, resulting in a failure to elicit an immune response. This unique study explores the effect of nutrition depletion/supplementation, infection and inflammation on mucosal immunogenicity following oral vaccination in a juvenile mouse model.

team members

• Nicole Dellios - Research Assistant
• Wolfram Haller - HONORARY RESEARCH FELLOW
• Fran Justice - Research Assistant
• Susan Lapthorne - Research Officer
• Zoe Mccallum - RESEARCH ASSOCIATE
• Paula O'Malley - RESEARCH AFFILIATE
• Prue Pereira - Research Officer
• Megan Peterkin - RESEARCH ASSOCIATE

• Liz Rogers - RESEARCH ASSOCIATE
• Vared Schildkraut - HONORARY RESEARCH FELLOW
• Michelle Scurr - Research Assistant
• Helen Shalley - RESEARCH ASSOCIATE
• Sarah Thomas - Research Assistant
• Wonie Uahwatanasakul - RESEARCH AFFLIATE
• Guin Wilson - RESEARCH ASSOCIATE

publications

• Buttery JP., Danchin MH., Lee KJ., Carlin JB., McIntyre PB., Elliott EJ., Booy R., Bines JE. Intussusception following rotavirus vaccine administration: Post-marketing surveillance in the National Immunization Program in Australia. VACCINE 29 (16) : 3061 - 3066(2011) PubMed
• Crawford NW., Bines JE., Royle J., Buttery JP. Optimizing immunization in pediatric special risk groups. EXPERT REVIEW OF VACCINES 10 (2) : 175 - 186(2011) PubMed
• Gilbertson HR., Rogers EJ., Ukoumunne OC. Determination of a Practical pH Cutoff Level for Reliable Confirmation of Nasogastric Tube Placement. JOURNAL OF PARENTERAL AND ENTERAL NUTRITION 35 (4) : 540 - 544(2011) PubMed
• Haller W., Buttery J., Laurie K., Beyerle K., Hardikar W., Alex G. Immune Response to Pandemic H1N1 2009 Influenza A Vaccination in Pediatric Liver Transplant Recipients. LIVER TRANSPLANTATION 17 (8) : 914 - 920(2011) PubMed
• Justice FA., Nguyen LT., Tran SN., Kirkwood CD., Thi NT., Carlin JB., Bines JE. Recurrent intussusception in infants. JOURNAL OF PAEDIATRICS AND CHILD HEALTH 47 (11) : 802 - 805(2011) PubMed
• Pereira-Fantini PM., Thomas SL., Wilson G., Taylor RG., Sourial M., Bines JE. Short- and long-term effects of small bowel resection: a unique histological study in a piglet model of short bowel syndrome. HISTOCHEMISTRY AND CELL BIOLOGY 135 (2) : 195 - 202(2011) PubMed
• Wong T., Clifford V., McCallum Z., Shalley H., Peterkin M., Paxton G., Bines JE. Central Venous Catheter Thrombosis Associated With 70% Ethanol Locks in Pediatric Intestinal Failure Patients on Home Parenteral Nutrition: A Case Series. JOURNAL OF PARENTERAL AND ENTERAL NUTRITION (2011)