Homeostasis of Gut Microbiota Protects against Susceptibility to Fungal Pneumonia
Jian Ji1,2,3, Yongli Ye1,2,3, Jiadi Sun1,2,3
1School of Food Science and Technology, International Joint Laboratory on Food Safety, Synergetic Innovation Center of Food Safety and Quality Control, Jiangnan University, Wuxi, Jiangsu, 214122, P. R. China.
Abstract:
Fungal pneumonia is a serious disease with great harm and high prevalence, presenting significant challenges in diagnosis and treatment. The gut and respiratory microbiota play a critical role in protecting lung health against fungal pneumonia. Here, it is established fungal pneumonia by infection via the sinopulmonary route with Fusarium graminearum (F. graminearum) to investigate the influence of gut microbiota state on susceptibility to fungal pneumonia in BALB/c mice. This findings revealed that F. graminearum spore exposure not only impaired pulmonary clearance mechanisms but also significantly upregulated the expression of proinflammatory cytokines, including interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α). Moreover, spore invasion led to an increase in Staphylococcus abundance and activation of both triglyceride and galactose metabolic pathways. Antibiotic treatment disrupted the gut and respiratory microbiota, facilitating F. graminearum lung colonization, which is evidenced by elevated inflammatory markers in alveolar fluid and dysregulated lung metabolism. It is demonstrated that the gut microbiota influences susceptibility to fungal pneumonia by acting as an intermediary in the gut-lung axis through the bloodstream, thereby modulating lung metabolism and inflammatory responses. These findings open avenues for novel therapeutic strategies, such as gut microbiota modulation, for the prevention and treatment of fungal pneumonia.
Insights
The gut microbiota influences fungal pneumonia susceptibility. Disrupting the gut and lung microbes with antibiotics increased Fusarium graminearum lung colonization and inflammation.
Area of Science:
- Microbiology
- Immunology
- Pulmonology
Background:
- Fungal pneumonia poses significant health challenges due to its prevalence and difficulty in diagnosis/treatment.
- The gut and respiratory microbiota are crucial for maintaining lung health and preventing fungal infections.
- Fusarium graminearum is a significant fungal pathogen causing pneumonia.
Purpose of the Study:
- To investigate how the gut microbiota state affects susceptibility to fungal pneumonia.
- To elucidate the mechanisms by which the gut microbiota influences lung inflammation and metabolism during fungal pneumonia.
Main Methods:
- Induction of fungal pneumonia in BALB/c mice via sinopulmonary infection with Fusarium graminearum.
- Analysis of pulmonary clearance, cytokine expression (IL-6, IL-1β, TNF-α), microbial abundance (Staphylococcus), and metabolic pathways (triglyceride, galactose).
- Assessment of the impact of antibiotic-induced microbiota disruption on fungal lung colonization and inflammatory markers.
Main Results:
- Fusarium graminearum infection impaired pulmonary clearance and increased pro-inflammatory cytokine expression.
- Spore invasion altered gut microbiota composition, increasing Staphylococcus abundance and activating specific metabolic pathways.
- Antibiotic treatment disrupted microbiota, exacerbating F. graminearum lung colonization, inflammation, and metabolic dysregulation.
- The gut microbiota acts as an intermediary in the gut-lung axis, influencing lung metabolism and inflammation via the bloodstream.
Conclusions:
- Gut microbiota composition significantly impacts susceptibility to fungal pneumonia.
- The gut-lung axis plays a critical role in modulating fungal pneumonia pathogenesis.
- Targeting gut microbiota modulation offers a potential therapeutic strategy for fungal pneumonia prevention and treatment.
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