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Updated: Sep 24, 2025
Legionella pneumophila Outer Membrane Vesicles: Isolation and Analysis of Their Pro-inflammatory Potential on Macrophages
Published on: February 22, 2017
Overabundance of Veillonella parvula promotes intestinal inflammation by activating macrophages via LPS-TLR4 pathway
Zhiyan Zhan1, Wenxue Liu2, Liya Pan1
1Department of Clinical Nutrition, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, China.
Abstract:
Hirschsprung's disease-associated enterocolitis (HAEC) is the most common complication of Hirschsprung's disease (HSCR). The microbiome pattern of intestinal flora in HAEC patients was significantly abnormal compared to that in HSCR patients. The overabundance of V. parvula was detected in the gut of HAEC patients. To elucidate the pathological mechanisms of the overabundance of V. parvula, we established and analyzed inflammatory models induced by LPS or single-bacterial strain transplantation in vivo. The transplantation of V. parvula induced inflammatory response in the colon of mice. Besides, we found that LPS from V. parvula can significantly impair the barrier function of colonic epithelial cells and then activate macrophages which impaired pacemaker function of interstitial cells of Cajal (ICCs). It was thus a vicious cycle, where the macrophage-related inflammation caused by V. parvula via LPS-TLR4 pathway damaged the intestinal motility, which further aggravated the intestinal flora dysbiosis and promoted the development of HAEC. Itaconic acid could break the vicious cycle by inhibiting the activation of macrophages. It could be a potential therapeutic strategy for HAEC patients with intestinal flora dysbiosis.
Insights
Hirschsprung
Area of Science:
- Gastroenterology
- Microbiology
- Immunology
Background:
- Hirschsprung's disease-associated enterocolitis (HAEC) is a severe complication of Hirschsprung's disease (HSCR).
- Intestinal dysbiosis and V. parvula overabundance are observed in HAEC patients.
Purpose of the Study:
- To investigate the pathological mechanisms of V. parvula overabundance in HAEC.
- To explore potential therapeutic strategies targeting V. parvula-induced inflammation.
Main Methods:
- In vivo inflammatory models induced by LPS or V. parvula transplantation in mice.
- Analysis of colonic epithelial barrier function, macrophage activation, and interstitial cells of Cajal (ICCs) function.
- Assessment of itaconic acid's therapeutic potential.
Main Results:
- V. parvula transplantation induced colon inflammation in mice.
- V. parvula LPS impaired colonic epithelial barrier function and activated macrophages.
- Macrophage activation by V. parvula LPS via the LPS-TLR4 pathway disrupted ICC pacemaker function, leading to a vicious cycle.
- Itaconic acid inhibited macrophage activation, breaking this cycle.
Conclusions:
- V. parvula overabundance contributes to HAEC pathogenesis through LPS-induced inflammation and disruption of intestinal motility.
- Itaconic acid shows potential as a therapeutic agent for HAEC by mitigating inflammation and restoring intestinal function.
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