How Gut Microbiota Can Help Protect Your Lungs from Flu Damage

Influenza News: Every year, influenza A virus (IAV) causes significant health problems, leading to more than 300,000 deaths worldwide. While most people know about the respiratory symptoms of the flu, many are unaware that gastrointestinal symptoms like diarrhea and stomach pain often accompany the infection. Recent research has shed light on the connection between our gut health and lung health, showing that our gut microbiota (GM) plays a crucial role in defending our lungs against flu-induced damage. This Influenza News report covers a study by researchers from the First Affiliated Hospital of Anhui Medical University, Hefei, China.


Gut microbiota-derived acetate attenuates lung injury induced by influenza infection via protecting airway tight junctions
Gut microbiota-derived acetate is a key mediator of the gut-lung axis in lung injury induced by IAV infection. Schematic diagram illustrating IAV infection induced dysbiosis of GM, leading to a decrease in circulating acetate levels through the gut–lung axis. Improvement of GM, protection of airway epithelial TJs via GPR43-AMPK-dependent pathway and consequently reduced inflammatory lung damage
 
The Gut-Lung Connection
Our gut is home to a diverse community of microbes that help maintain our overall health. This relationship is known as the gut-lung axis, which means that the health of our gut can significantly impact the health of our lungs. In the case of influenza, the virus disrupts the tight junctions (TJs) in our airway epithelium. TJs are crucial structures that maintain the integrity of the airway barrier, preventing harmful substances from entering our lungs.
 
Key Findings
The study found that mice infected with IAV had lower levels of beneficial gut bacteria, specifically those that produce acetate, a short-chain fatty acid (SCFA). Acetate is essential because it activates a receptor called GPR43, which helps protect the integrity of airway TJs and reduces inflammation.
 
How Acetate Works
When the gut microbiota is healthy, it produces acetate, which travels through the bloodstream to the lungs. There, it binds to GPR43 receptors on the epithelial cells lining the airways. This binding triggers a cascade of protective effects, including the activation of AMPK, an enzyme that plays a role in cellular energy balance and inflammation control.
 
Experiments and Results
The researchers conducted several experiments to understand the role of acetate in lung protection better:
-Mouse Model of IAV Infection: Mice infected with the flu virus showed a significant decrease in acetate-producing bacteria (Bacteroides, Bifidobacterium, and Akkermansia) in their guts. This led to lower acetate levels in both the gut and bloodstream, which in turn made the lungs more susceptible to damage.
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-Antibiotic Treatment: Mice treated with antibiotics to deplete their gut bacteria showed worse lung damage when infected with IAV. This damage was mitigated when these mice were given acetate, highlighting the protective role of this SCFA.
 
-Fecal Microbiota Transplantation (FMT): Transferring gut bacteria from healthy mice to IAV-infected mice restored their gut health and increased acetate levels, which protected the lungs from flu-induced damage.
 
Human Study
The researchers also studied 26 human subjects, half of whom had IAV. They found that those with the flu had significantly lower levels of acetate in their guts and blood. This reduction in acetate correlated with increased lung inflammation and damage, reinforcing the findings from the mouse models.
 
Protective Mechanisms of Acetate
Acetate works by activating the GPR43 receptor, which is present on the surface of cells in various tissues, including the lungs. When acetate binds to GPR43, it triggers a signaling pathway involving the enzyme AMPK. This pathway helps maintain the integrity of the TJs in the airway epithelium, preventing the flu virus from causing extensive damage. Additionally, this pathway reduces the production of inflammatory cytokines, which are responsible for the severe inflammation seen in flu infections.
 
Importance of Tight Junctions
TJs are crucial for maintaining the barrier function of epithelial cells, which line our respiratory and gastrointestinal tracts. When TJs are intact, they prevent pathogens and toxins from entering the bloodstream. However, during IAV infection, these junctions are often disrupted, leading to increased permeability and allowing harmful substances to penetrate the lungs. By protecting TJs, acetate helps preserve the barrier function of the airway epithelium, reducing the severity of lung damage caused by the flu.
 
Implications for Treatment
The findings from this study suggest that therapies aimed at restoring or enhancing gut health could be effective in mitigating the severity of flu infections. This approach could be particularly beneficial for people at high risk of severe flu complications, such as the elderly or those with chronic respiratory conditions. Supplementing with acetate or promoting the growth of acetate-producing bacteria in the gut through diet or probiotics could be potential strategies for protecting against flu-induced lung damage.
 
Practical Recommendations
Maintaining a healthy gut microbiota can be achieved through several lifestyle and dietary measures:
 
-Balanced Diet: Eating a diet rich in fiber, fruits, vegetables, and whole grains can promote the growth of beneficial gut bacteria.
 
-Probiotics and Prebiotics: Consuming foods or supplements that contain probiotics (live beneficial bacteria) and prebiotics (food for these bacteria) can help maintain a healthy gut microbiota.
 
-Avoid Unnecessary Antibiotics: Overuse of antibiotics can disrupt the balance of gut bacteria. Only use antibiotics when prescribed by a healthcare professional.
 
-Regular Exercise: Physical activity has been shown to positively influence gut health and overall well-being.
 
Conclusion
This study highlights the critical role of gut health in protecting our lungs from flu-induced damage. By maintaining a healthy gut microbiota and ensuring adequate levels of acetate, we can bolster our body's defenses against respiratory infections. Improving gut health through diet, probiotics, or even fecal transplants could be a potential strategy for preventing and treating flu-related lung injuries.
 
Final Thoughts
As we continue to understand the intricate connections between different parts of our body, it's becoming clear that our health is a complex, interconnected system. Taking care of our gut health is a vital part of this puzzle, offering a promising avenue for improving our resilience against various diseases, including respiratory infections like the flu. By paying attention to our diet, lifestyle, and the health of our gut microbiota, we can take proactive steps to protect our lungs and overall health.
 
The study findings were published in the peer reviewed Journal of Translational Medicine.
https://link.springer.com/article/10.1186/s12967-024-05376-4
 
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