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

Journal Article · · Physiological Reports
DOI:https://doi.org/10.14814/phy2.13182· OSTI ID:1416011
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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)
+ Show Author Affiliations

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-C 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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
National Institutes of Health (NIH); National Institute of Diabetes and Kidney Diseases (NIDDK); USDOE
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1416011
Journal Information:
Physiological Reports, Vol. 5, Issue 6; ISSN 2051-817X
Publisher:
American Physiological Society and The Physiological SocietyCopyright Statement
Country of Publication:
United States
Language:
English

References (28)

Interactions Between Commensal Bacteria and Gut Sensorimotor Function in Health and Disease journal November 2005
QIIME allows analysis of high-throughput community sequencing data journal April 2010
Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome journal February 2012
Short-Chain Fatty Acids Regulate the Enteric Neurons and Control Gastrointestinal Motility in Rats journal May 2010
Irritable Bowel Syndrome: A Clinical Review journal March 2015
Inflammation Drives Dysbiosis and Bacterial Invasion in Murine Models of Ileal Crohn’s Disease journal July 2012
Epidemiology of Constipation in North America: A Systematic Review journal April 2004
The Microbiome in Infectious Disease and Inflammation journal April 2012
The short chain fatty acids, butyrate and propionate, have differential effects on the motility of the guinea pig colon journal September 2014
An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota journal December 2011
Complex Interactions Among Diet, Gastrointestinal Transit, and Gut Microbiota in Humanized Mice journal May 2013
Diarrhoea-predominant irritable bowel syndromedistinguishable by 16S rRNA gene phylotype quantifcation journal January 2009
A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis journal September 2013
Analysis of the Fecal Microbiota of Irritable Bowel Syndrome Patients and Healthy Controls with Real-Time PCR journal February 2005
Prevalence and temporal stability of selected clostridial groups in irritable bowel syndrome in relation to predominant faecal bacteria journal May 2006
Crosstalk between Muscularis Macrophages and Enteric Neurons Regulates Gastrointestinal Motility journal July 2014
Compounds possessing 5-HT3 receptor antagonistic activity inhibit intestinal propulsion in mice journal September 1996
Distinct microbial populations exist in the mucosa-associated microbiota of sub-groups of irritable bowel syndrome: Distinct mucosal microbiota in IBS journal November 2011
Lower Frequency of MMC Is Found in IBS Subjects with Abnormal Lactulose Breath Test, Suggesting Bacterial Overgrowth journal January 2002
The enteric microbiota in the pathogenesis and management of constipation journal February 2011
Simple Gas Chromatography Analysis of Faecal Butyrate: Application to Patients at Risk of Pouchitis journal January 2001
Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice journal September 2013
Butyrate enemas enhance both cholinergic and nitrergic phenotype of myenteric neurons and neuromuscular transmission in newborn rat colon journal June 2012
Breath methane in functional constipation: response to treatment with Ispaghula husk journal May 2015
Crosstalk between Muscularis Macrophages and Enteric Neurons Regulates Gastrointestinal Motility journal August 2014
Roseburia hominis: a novel guilty player in ulcerative colitis pathogenesis? journal October 2013
Short-chain fatty acids stimulate motility of the canine ileum journal October 1987
Influence of microbial species on small intestinal myoelectric activity and transit in germ-free rats journal March 2001

Cited By (5)

Targeting the gut microbiota for the treatment of irritable bowel syndrome journal November 2019
Gastrointestinal motility, dysbiosis and opioid-induced tolerance: is there a link? journal April 2019
The effect of probiotics and polysaccharides on the gut microbiota composition and function of weaned rats journal January 2018
Deletion of choline acetyltransferase in enteric neurons results in postnatal intestinal dysmotility and dysbiosis journal March 2018
Fecal imaging demonstrates that low-methoxyl pectin supplementation normalizes gastro-intestinal transit in mice given a liquid diet journal April 2018

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Related Subjects

60 APPLIED LIFE SCIENCES
gastrointestinal motility
gut microbiome
host-microbe interactions
irritable bowel syndrome