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.

抗生素治疗可促进肠道白色念珠菌的生长，但驱动这种真菌大量繁殖的机制仍不完全清楚。我们确定氧气是抗生素后白色念珠菌扩张所需的资源。白色念珠菌消耗了无菌小鼠盲肠中的单糖，但在体外需要氧气才能在这些资源上生长，这表明厌氧是限制肠道生长的潜在因素。梭状芽胞杆菌通过产生丁酸盐来限制大肠中的氧气可用性，丁酸盐激活过氧化物酶体增殖物激活受体γ（PPAR-γ）信号以维持上皮缺氧。链霉素治疗耗尽梭状芽孢杆菌衍生的丁酸盐以增加上皮氧合，但 PPAR-γ 激动剂 5-氨基水杨酸 (5-ASA) 功能性地取代梭状芽胞杆菌物种以恢复上皮缺氧和对白色念珠菌的定植抵抗力。此外，益生菌大肠杆菌需要氧气呼吸来防止抗生素后白色念珠菌的繁殖，进一步支持了氧气在定植抵抗中的作用。我们得出的结论是，有限的氧气获取可以维持对白色念珠菌的定植抵抗力。