Interaction between intestinal mycobiota and microbiota shapes lung inflammation

Area of Science:

• Microbiology
• Immunology
• Host-microbe interactions

Background:

• The gut microbiota, comprising bacteria, fungi, viruses, archaea, and protozoa, plays a crucial role in host health.
• The intricate interactions within the gut microbiota and their impact on host physiology are not fully understood.
• The gut-lung axis highlights communication pathways between the gut microbiome and lung immunity.

Purpose of the Study:

• To investigate the role of interactions between gut fungi and bacteria in modulating lung inflammation during infection.
• To elucidate the mechanisms by which gut dysbiosis affects lung inflammatory responses.

Main Methods:

• Utilized antifungal drugs to induce gut mycobiota dysbiosis in a model of infection.
• Investigated the overgrowth and translocation of gut bacteria, specifically Escherichia coli (E. coli).
• Analyzed the accumulation of specific macrophage populations (CD45+F4/80+Ly6G-Ly6C-CD11b+CD11c+) in the lungs.
• Assessed the roles of macrophage depletion and Toll-like receptor 4 (TLR4) signaling versus Dectin-1 signaling in inflammation.

Main Results:

• Antifungal drug-induced gut mycobiota dysbiosis exacerbated lung inflammation during infection.
• This dysbiosis led to Escherichia coli (E. coli) overgrowth and translocation to the lungs.
• Lung inflammation was mediated by the accumulation of specific macrophages, and its aggravation was blocked by macrophage clearance or TLR4 deletion, but not Dectin-1 deletion.
• These findings implicate TLR4 signaling in response to bacterial components like LPS.

Conclusions:

• The interaction between intestinal mycobiota and commensal bacteria significantly influences host health via the gut-lung axis.
• Gut dysbiosis, particularly affecting fungi, can lead to bacterial translocation and subsequent lung inflammation.
• Targeting the gut-lung axis, specifically the interplay between fungi and bacteria, presents a potential therapeutic strategy for managing lung inflammation during infections.