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Published on: December 8, 2014
Colonic phosphocholine is correlated with Candida tropicalis and promotes diarrhea and pathogen clearance
Xihong Zhou1,2,3, Yiwen He1,4, Jingqing Chen5
1Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, the Chinese Academy of Sciences, Changsha, China.
Abstract:
Diarrhea is characterized by alterations in the gut microbiota, metabolites, and host response to these changes. Studies have focused on the role of commensal bacteria in diarrhea; however, the effect of fungi on its pathogenesis remains unexplored. Here, using post-weaned piglets with or without diarrhea, we found an unexpected decrease in the abundance of Candida tropicalis in diarrheal piglets. We also observed increased accumulation of reactive oxygen species (ROS) and the formation of neutrophil extracellular traps (NETs) in the colonic tissues of diarrheal piglets. Using dectin-1-knockout mice, we found that the over-accumulation of ROS killed C. tropicalis by promoting NET formation, which was dependent on dectin-1. The decreased abundance of C. tropicalis resulted in reduced phosphocholine consumption. Then, colonic phosphocholine accumulation drives water efflux by increasing cAMP levels by activating adenylyl cyclase, which promotes the clearance of pathogenic bacteria. Collectively, we demonstrated that phosphocholine is correlated with colonic C. tropicalis and promotes diarrhea and pathogen clearance. Our results suggest that mycobiota colonizing the colon might be involved in maintaining intestinal metabolic homeostasis through the consumption of certain metabolites.
Insights
Diarrhea involves gut fungi like Candida tropicalis. Reduced fungal presence leads to phosphocholine buildup, causing diarrhea and pathogen clearance by altering gut homeostasis.
Area of Science:
- Microbiology
- Gastroenterology
- Immunology
Background:
- Diarrhea is linked to gut microbiota changes, but fungal roles are understudied.
- Commensal bacteria are known to influence gut health, yet the mycobiota's impact on diarrhea remains unclear.
Purpose of the Study:
- Investigate the role of fungi, specifically Candida tropicalis, in diarrhea pathogenesis.
- Explore the relationship between fungal abundance, host immune response, and metabolic alterations during diarrhea.
Main Methods:
- Comparative analysis of gut mycobiota in diarrheal and healthy piglets.
- Assessment of reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) in colonic tissues.
- Utilized dectin-1-knockout mice to study fungal-host interactions and ROS-mediated fungal clearance.
Main Results:
- A decrease in Candida tropicalis abundance was observed in diarrheal piglets.
- Increased ROS and NET formation were found in the colons of diarrheal piglets, leading to C. tropicalis clearance via dectin-1.
- Reduced C. tropicalis led to decreased phosphocholine consumption, resulting in its accumulation and subsequent promotion of diarrhea and pathogen clearance.
Conclusions:
- Candida tropicalis plays a role in maintaining intestinal metabolic homeostasis by consuming phosphocholine.
- Phosphocholine accumulation, driven by reduced C. tropicalis, contributes to diarrhea and aids in clearing pathogenic bacteria.
- Gut mycobiota may be crucial in regulating intestinal metabolic balance and host defense mechanisms.
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