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 constipation 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 ofBacteroides ovatusandParabacteroides distasonisin 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-C fecal microbiota significantly increased GI transit time when compared to control microbiota recipients. IBS-C-associated gut microbiota also impacted colonic contractile properties. Our findings support the concept that constipation is characterized by disease-associated steady states caused by reinforcement of pathophysiological factors in host-microbe interactions.
Department of Medicine, University of Chicago, Chicago, Illinois.
Ketrija
K
Touw
Department of Medicine, University of Chicago, Chicago, Illinois.
Daina L
DL
Ringus
Department of Medicine, University of Chicago, Chicago, Illinois.
Nathaniel
N
Hubert
Department of Medicine, University of Chicago, Chicago, Illinois.
Yunwei
Y
Wang
Department of Medicine, University of Chicago, Chicago, Illinois.
Vanessa A
VA
Leone
Department of Medicine, University of Chicago, Chicago, Illinois.
Anuradha
A
Nadimpalli
Department of Surgery, University of Chicago, Chicago, Illinois.
Betty R
BR
Theriault
Department of Medicine, University of Chicago, Chicago, Illinois.
Yong E
YE
Huang
Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, Minnesota.
Johnathan D
JD
Tune
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana.
Paul B
PB
Herring
Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, Minnesota.
Gianrico
G
Farrugia
Enteric NeuroScience Program, Division of Gastroenterology and Hepatology, Mayo Clinic Rochester, Rochester, Minnesota.
Purna C
PC
Kashyap
Institute for Genomics and Systems Biology, Argonne National Laboratory, Argonne, Illinois.
Dionysios A
DA
Antonopoulos
Department of Medicine, University of Chicago, Chicago, Illinois echang@medicine.bsd.uchicago.edu.
Eugene B
EB
Chang
D000818:Animals; D003248:Constipation / Q000139:chemically induced / Q000382:microbiology*; D000069467:Fecal Microbiota Transplantation; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000382:microbiology*; D008139:Loperamide; D008297:Male; D051379:Mice
D008139:Loperamide
Gastrointestinal motility; gut microbiome; host‐microbe interactions; irritable bowel syndrome