Mechanisms of Adaptation in Human Short Bowel Syndrome
Condition: Short Bowel Syndrome
MeSH terms: Short Bowel Syndrome; Syndrome
Study type: Observational

Summary: 
      This is an observational, natural history trial of mechanisms of gut adaptation in adult
      short bowel syndrome (SBS). Patients with SBS (< 200 cm small bowel ± colon) will be studied
      initially 2-9 months after the last small bowel resection and again exactly 6 months after
      the initial study. GCRC-studies will examine intestinal nutrient absorption, gut barrier
      functions and gut mucosal biopsy specimens for markers of nutrient transport and cell
      proliferation and apoptosis.
    

Detailed description: 
      Short bowel syndrome (SBS) is a condition that occurs after massive surgical removal of
      sections of the small bowel required to treat conditions such as Crohn's disease, lack of
      adequate blood flow to the intestine, trauma, twisting of the bowel and other disorders.
      Patients with SBS develop severe diarrhea, weight loss, loss of nutrients in the stool,
      malnutrition, dehydration and deficiency of specific nutrients. SBS is thus a major cause of
      intestinal failure in adults and children. SBS has a high rate of death and medical
      complications and patients experience enormous health care-related costs and decreased
      quality of life. Patients with SBS often require intravenous feeding [known as parenteral
      nutrition (PN)] due to chronic malabsorption and malnutrition and also commonly develop
      infections from intestinal bacteria, suggesting abnormalities in the intestinal "barrier" to
      bacteria present in the intestine. In animal models of SBS, increased growth of the
      intestinal lining (mucosa) and improved nutrient absorption occur over time (intestinal
      adaptation). Although SBS patients commonly exhibit decreased diet-induced diarrhea within
      the first 2 years after intestinal surgery, very little is known about how the intestinal
      mucosa adapts in patients with SBS. The proposed pilot study will be the first comprehensive
      study of serial changes in gut mucosal structure and function in the early period (2-30
      months) of SBS in humans. Our Specific Aims are designed to determine: 1) whether the
      residual small bowel and colonic mucosa in SBS patients exhibits adaptive growth, with
      concomitantly improved nutrient absorption and gut barrier function; 2) The underlying
      mechanisms of early gut adaptation in human SBS, by evaluating changes in mucosal cell growth
      and production of key molecules that are responsible for nutrient transport/absorption and
      gut barrier function; and 3) The utility of plasma citrulline concentrations and serum
      flagellin antibody titers as markers for human intestinal absorptive capacity and gut barrier
      function, respectively. Our research will provide important and new information on the
      natural history and underlying causes of early intestinal adaptation in man. This information
      will be valuable in the design of future therapeutic studies in patients with SBS that hold
      promise for improving the rehabilitation of these individuals.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        1) Adults aged 18-75 with less than 200cm small bowel remaining after latest(SBR); 2)
        Subject able to enter the study within 2-24 months of latest SBR; 3)(BMI) ≥ 17 kg/m2; 4)
        Subject is living at home, clinically stable and expected to survive at least one year; 5)
        Subject able to take some oral solid diet and oral medications; 6) Intact stomach and
        duodenum and at least 30 cm of in-continuity jejunum and/or ileum (presence of residual
        colon is not a specific eligibility criterion); 7) Accurate records available on residual
        small bowel/colonic length (accurate tape measurement in operation room or small bowel
        follow-through performed within 3 months of entry); 8) Subject has the ability to
        understand the requirements of the study, provide written informed consent and agrees to
        participate in all assessments.
      
Biospecimen description: 
      Intestinal biopsy samples