Epithelial hypoxia maintains colonization resistance against Candida albicans 2024 Savage et al

Highlights

• C. albicans depletes sorbitol in gnotobiotic mice and needs oxygen to catabolize it
  
  
• E. coli requires oxygen respiration to limit a post-antibiotic C. albicans bloom
  
  
• Depletion of Clostridia by antibiotics disrupts anaerobiosis to boost Candida growth
  
  
• 5-ASA restores epithelial hypoxia to curb post-antibiotic C. albicans growth
  

Summary

Antibiotic treatment promotes the outgrowth of intestinal Candida albicans, but the mechanisms driving this fungal bloom remain incompletely understood. We identify oxygen as a resource required for post-antibiotic C. albicans expansion. C. albicans depleted simple sugars in the ceca of gnotobiotic mice but required oxygen to grow on these resources in vitro, pointing to anaerobiosis as a potential factor limiting growth in the gut. Clostridia species limit oxygen availability in the large intestine by producing butyrate, which activates peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling to maintain epithelial hypoxia. Streptomycin treatment depleted Clostridia-derived butyrate to increase epithelial oxygenation, but the PPAR-γ agonist 5-aminosalicylic acid (5-ASA) functionally replaced Clostridia species to restore epithelial hypoxia and colonization resistance against C. albicans. Additionally, probiotic Escherichia coli required oxygen respiration to prevent a post-antibiotic bloom of C. albicans, further supporting the role of oxygen in colonization resistance. We conclude that limited access to oxygen maintains colonization resistance against C. albicans.

Open access, https://www.sciencedirect.com/science/article/pii/S193131282400180X