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

Area of Science:

• Microbiome Research
• Gastroenterology
• Host-Microbe Interactions

Background:

• Chronic diseases, including constipation, involve self-reinforcing pathophysiological processes.
• Gut dysbiosis, an imbalance in microbial communities, is linked to chronic constipation.
• The interplay between gut microbiota and host function in constipation is not fully understood.

Purpose of the Study:

• To investigate how microbial community assembly, driven by slow gastrointestinal transit, reinforces constipation.
• To examine the impact of pharmacologically-induced constipation (PIC) and constipation-predominant irritable bowel syndrome (IBS-C) on gut microbiota structure and function.
• To determine the effect of constipation-associated microbiota on host gastrointestinal transit and colonic function.

Main Methods:

• Utilized an opioid-induced constipation (OIC) mouse model and a humanized mouse model colonized with IBS-C patient microbiota.
• Analyzed the structural and functional profiles of gut microbiota in both models.
• Colonized germ-free (GF) mice with microbiota from PIC or IBS-C donors to assess host effects.

Main Results:

• PIC and IBS-C induced significant changes in gut microbiota, notably increasing Bacteroides ovatus and Parabacteroides distasonis.
• PIC mice showed reduced cecal butyrate concentrations and altered microbial metabolic profiles.
• Colonization with constipation-associated microbiota accelerated GI transit time and altered colonic contractility in GF mice.

Conclusions:

• Constipation is characterized by disease-associated steady states driven by host-microbe interactions.
• Gut microbiota alterations play a crucial role in reinforcing slow transit and perpetuating constipation.
• Findings highlight the importance of targeting host-microbe interactions for constipation management.