Interaction between intestinal mycobiota and microbiota shapes lung inflammation

Abstract

Gut microbiota is an intricate microbial community containing bacteria, fungi, viruses, archaea, and protozoa, and each of them contributes to diverse aspects of host health. Nevertheless, the influence of interaction among gut microbiota on host health remains uncovered. Here, we showed that the interaction between intestinal fungi and bacteria shaped lung inflammation during infection. Specifically, antifungal drug-induced dysbiosis of gut mycobiota enhanced lung inflammation during infection. Dysbiosis of gut mycobiota led to gut Escherichia coli (E. coli) overgrowth and translocation to the lung during infection, which induced lung accumulation of the CD45⁺F4/80⁺Ly6G⁻Ly6C⁻CD11b⁺CD11c⁺ macrophages. Clearance of macrophages or deletion of TLR4 (Toll-like receptor 4, recognition of LPS) rather than Dectin-1 (recognition of beta-1,3/1,6 glucans on fungi) blocked the antifungal drug-induced aggravation of lung inflammation during infection. These findings suggest that the interaction between intestinal mycobiota and commensal bacteria affects host health through the gut–lung axis, offering a potential therapeutic target for ameliorating lung inflammation during infection.