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Title: Mutual reinforcement of pathophysiological host-microbe interactions in intestinal stasis models

Chronic diseases arise when there is mutual reinforcement of pathophysiological processes that cause an aberrant steady state. Such a sequence of events may underlie chronic constipation, which has been associated with dysbiosis of the gut. In this study we hypothesized that assemblage of microbial communities, directed by slow gastrointestinal transit, affects host function in a way that reinforces constipation and further maintains selection on microbial communities. In our study, we used two models – an opioid-induced consti- pation model in mice, and a humanized mouse model where germ-free mice were colonized with stool from a patient with constipation-predominant irritable bowel syndrome (IBS-C) in humans. We examined the impact of pharmacologically (loperamide)-induced constipation (PIC) and IBS-C on the structural and functional profile of the gut microbiota. Germ-free (GF) mice were colonized with microbiota from PIC donor mice and IBS-C patients to determine how the microbiota affects the host. PIC and IBS-C promoted changes in the gut microbiota, characterized by increased relative abundance of Bacteroides ovatus and Parabacteroides distasonis in both models. PIC mice exhibited decreased luminal concentrations of butyrate in the cecum and altered metabolic profiles of the gut microbiota. Colonization of GF mice with PIC-associated mice cecal or human IBS-Cmore » fecal microbiota significantly increased GI transit time when compared to control microbiota recipients. IBS-C-associated gut microbiota also impacted colonic contractile properties. Lastly, our findings support the concept that constipation is characterized by dis- ease-associated steady states caused by reinforcement of pathophysiological factors in host-microbe interactions.« less
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  1. Univ. of Chicago, Chicago, IL (United States)
  2. Mayo Clinic Rochester, Rochester, MN (United States)
  3. Indiana Univ. School of Medicine, Indianapolis, IN (United States)
  4. Argonne National Lab. (ANL), Argonne, IL (United States)
Publication Date:
Grant/Contract Number:
Accepted Manuscript
Journal Name:
Physiological Reports
Additional Journal Information:
Journal Volume: 5; Journal Issue: 6; Journal ID: ISSN 2051-817X
American Physiological Society and The Physiological Society
Research Org:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org:
National Institutes of Health (NIH); National Institute of Diabetes and Kidney Diseases (NIDDK); USDOE
Country of Publication:
United States
60 APPLIED LIFE SCIENCES; gastrointestinal motility; gut microbiome; host-microbe interactions; irritable bowel syndrome
OSTI Identifier: