Peptidoglycan-Chi3l1 interaction shapes gut microbiota in intestinal mucus layer

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• The gut microbiota in the intestinal mucus layer is crucial for host health.
• Mechanisms of host regulation of gut mucus microbial communities are largely unknown.

Purpose of the Study:

• To investigate the role of host-produced proteins in regulating gut microbiota composition within the intestinal mucus layer.
• To elucidate the function of Chitinase 3-like protein 1 (Chi3l1) in host-microbe interactions and its impact on gut homeostasis and disease.

Main Methods:

• Stimulation of intestinal epithelial cells by gut microbiota to induce Chi3l1 expression.
• Analysis of Chi3l1 secretion into the mucus layer and its interaction with bacterial peptidoglycan.
• Assessment of Chi3l1 deficiency effects on gut microbiota and dextran sodium sulfate-induced colitis.
• Fecal microbiota transplantation and targeted bacterial replenishment (Lactobacillus) to restore gut homeostasis.

Main Results:

• Host-regulated bacterial colonization in the gut mucus layer is mediated by Chi3l1.
• Chi3l1 interacts with bacterial peptidoglycan, promoting colonization, especially for Gram-positive bacteria like Lactobacillus.
• Chi3l1 deficiency leads to gut dysbiosis and exacerbates colitis.
• Restoration of Lactobacillus or fecal microbiota transplantation ameliorates colitis in Chi3l1-deficient mice.

Conclusions:

• A 'scaffold model' of microbiota homeostasis is proposed, involving Chi3l1-bacteria cell wall interactions.
• An imbalanced gut microbiota in the intestinal mucus contributes to colitis development.
• Chi3l1 is a key host factor in maintaining gut barrier function and microbial balance.