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

Ketrija Touw, Daina L. Ringus, Nathaniel Hubert, Yunwei Wang, Vanessa A. Leone, Anuradha Nadimpalli, Betty R. Theriault, Yong E. Huang, Johnathan Tune, B. Herring, Gianrico Farrugia, Purna C. Kashyap, Dionysios A. Antonopoulos, Eugene B. Chang

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 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-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.

Original languageEnglish (US)
Article numbere13182
JournalPhysiological Reports
Volume5
Issue number6
DOIs
StatePublished - Mar 1 2017

Fingerprint

Constipation
Loperamide
Microbiota
Dysbiosis
Gastrointestinal Transit
Bacteroides
Metabolome
Cecum
Butyrates
Irritable Bowel Syndrome
Opioid Analgesics
Chronic Disease
Tissue Donors
Gastrointestinal Microbiome

Keywords

  • Gastrointestinal motility
  • gut microbiome
  • host-microbe interactions
  • irritable bowel syndrome

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology

Cite this

Touw, K., Ringus, D. L., Hubert, N., Wang, Y., Leone, V. A., Nadimpalli, A., ... Chang, E. B. (2017). Mutual reinforcement of pathophysiological host-microbe interactions in intestinal stasis models. Physiological Reports, 5(6), [e13182]. https://doi.org/10.14814/phy2.13182

Mutual reinforcement of pathophysiological host-microbe interactions in intestinal stasis models. / Touw, Ketrija; Ringus, Daina L.; Hubert, Nathaniel; Wang, Yunwei; Leone, Vanessa A.; Nadimpalli, Anuradha; Theriault, Betty R.; Huang, Yong E.; Tune, Johnathan; Herring, B.; Farrugia, Gianrico; Kashyap, Purna C.; Antonopoulos, Dionysios A.; Chang, Eugene B.

In: Physiological Reports, Vol. 5, No. 6, e13182, 01.03.2017.

Research output: Contribution to journalArticle

Touw, K, Ringus, DL, Hubert, N, Wang, Y, Leone, VA, Nadimpalli, A, Theriault, BR, Huang, YE, Tune, J, Herring, B, Farrugia, G, Kashyap, PC, Antonopoulos, DA & Chang, EB 2017, 'Mutual reinforcement of pathophysiological host-microbe interactions in intestinal stasis models', Physiological Reports, vol. 5, no. 6, e13182. https://doi.org/10.14814/phy2.13182
Touw, Ketrija ; Ringus, Daina L. ; Hubert, Nathaniel ; Wang, Yunwei ; Leone, Vanessa A. ; Nadimpalli, Anuradha ; Theriault, Betty R. ; Huang, Yong E. ; Tune, Johnathan ; Herring, B. ; Farrugia, Gianrico ; Kashyap, Purna C. ; Antonopoulos, Dionysios A. ; Chang, Eugene B. / Mutual reinforcement of pathophysiological host-microbe interactions in intestinal stasis models. In: Physiological Reports. 2017 ; Vol. 5, No. 6.
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abstract = "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 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-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.",
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