Intestinal Microecology in Chronic Constipation
Condition: Other Constipation; Irritable Bowel Syndrome
MeSH terms: Irritable Bowel Syndrome; Constipation
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine whether the bacteria normally present in the bowels
      are different in people with constipation and to see what effect the treatment with the Food
      and Drug Administration (FDA) - approved drug, lubiprostone, has on these bacteria.
    

Detailed description: 
      Chronic constipation is a common condition with a heterogeneous pathophysiology and resulting
      clinical manifestations. Recent evidence in the literature and collected in our laboratory
      confirm that there are differences in the gut microbiota between healthy individuals and
      those with a variety of disorders (e.g., inflammatory bowel disease, irritable bowel syndrome
      and obesity) suggesting that the development of certain disorders may be determined by the
      composition of the gut microbiota. Existing evidence warrants further investigation of the
      role of the microbial ecology of the human gut in constipation and an exploration of
      modification of the gut microbiota as a means to treat constipation by its actions on the
      colonic metabolism of nutrient substrates to alter colonic transit and fluid fluxes.

      The proposed research will exploit our proven capability to use high-throughput molecular
      genomic techniques to define the intestinal microbiome in order to help define the role of
      the gut microbiota in chronic constipation and will explore the potential value of altering
      the microbiota as a management strategy in constipation. The linkage of high-throughput
      genomic analyses with cause-and-effect understanding of how the gut microbiota affects bowel
      function may lead to a reliable means to manage the gut microbiota with the intent to prevent
      and/or treat constipation. The immediate goals of this project are to expand on existing
      information about the microbial ecology in the human intestines focusing on its relationship
      with constipation using molecular microbiological techniques and to assess the effects on the
      gut microorganisms resulting from the use of the FDA-approved medication, lubiprostone.
      Lubiprostone is a member of a novel therapeutic class called prostones and is an orally
      active, bicyclic fatty acid that selectively acts on type 2 chloride channels to stimulate
      chloride secretion which induces a net increase in luminal fluid secretion. Unlike
      antibiotic, probiotic and prebiotic agents, it has no known direct effects on the gut
      microbiota. It is FDA-approved for the treatment of chronic constipation in men and women and
      for women with constipation-predominant IBS (C-IBS). The rationale for using lubiprostone to
      modify the gut microbiota stems from the use of similar strategies for controlling
      recalcitrant small intestinal bacterial overgrowth (i.e., altering fluid fluxes in the gut
      lumen).

      We believe that this research will greatly improve our understanding of the role that the gut
      microbiota play in the development of constipation and potentially lead to new strategies
      with which to combat this common problem.
    

Intervention name(s): Lubiprostone
Intervention type(s): Drug
Intervention description(s): Following the initial stool and breath collections and because of differences in the FDA-approved dosing for the 2 subtypes of chronic constipation, (that is, chronic constipation (CC) versus constipation due to irritable bowel syndrome (C-IBS), the CC subjects received open-label lubiprostone 24 mcg orally twice daily for 4 weeks; while the C-IBS subjects received open-label lubiprostone 8 mcg orally twice daily for 4 weeks.
Other intervention name(s): Amitiza
Intervention MeSH terms: Lubiprostone
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Chronic Constipation; Constipation Predominant Irritable Bowel Syndrome; Intestinal Microecology