Lactobacillus delbrueckii surface protein P4430 attenuates intestinal inflammation by modulating macrophage polarization via Mincle.

Study Design

Population: low-birth-weight piglets, dextran sulfate sodium (DSS)-induced colitis mice, and UC patients
Methods: Lactobacillus delbrueckii and its surface proteins were studied; P4430, a DUF4430-domain-containing protein, was identified and tested for effects on macrophage polarization and inflammatory responses, including binding to and inhibiting Mincle

Ulcerative colitis (UC) is characterized by intestinal inflammation, barrier dysfunction, and dysbiosis, with limited treatment options. Here, we demonstrate that Lactobacillus delbrueckii is commonly reduced in low-birth-weight piglets, dextran sulfate sodium (DSS)-induced colitis mice, and UC patients. L. delbrueckii and its surface proteins mitigate intestinal inflammation in a macrophage-dependent manner. We further identify P4430, a DUF4430-domain-containing protein, as a key surface protein that protects against intestinal inflammation by suppressing M1 polarization and downregulating inflammatory responses of macrophages. Mechanistically, P4430 reduces inflammation by binding to and inhibiting Mincle, a C-type lectin receptor. These findings elucidate a key effector molecule of L. delbrueckii in modulating inflammatory responses and highlight the therapeutic potential of commensal bacteria and their cellular components in treating UC and possibly other intestinal inflammatory diseases.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Lactobacillus delbrueckii	—	Improved Colitis Symptoms	Beneficial	Moderate	View source "P4430 reduces inflammation by binding to and inhibiting Mincle... [and] protects against intestinal inflammation"
Lactobacillus delbrueckii	—	Reduced Intestinal Inflammation	Beneficial	Moderate	View source "L. delbrueckii and its surface proteins mitigate intestinal inflammation in a macrophage-dependent manner."