Does the gut microbiome impact viral diseases like influenza?

Author: Dr Alena Pribyl

26 March 2020

 

 

With the current world-wide impacts of the COVID-19 outbreak, there are questions arising about the role that the immune system plays in fighting other viral infections such as influenza. There is still a lot to learn about the ways the gut microbiome interacts with our immune system and influences respiratory infection. We do know that there is increasing evidence that a health gut microbiome may help improve immunity.

There is also increasing interest in how the gut microbiome is involved and how it may influence the immune system’s ability to fight viral infections. Although we still have much to learn about these interactions, below is a brief summary of some of the latest research in this area. It’s important to note that most studies thus far have been in animal models and it is difficult to say how these findings will translate to humans.

 

How the gut microbiome may influence the immune response
to influenza

Studies have shown us that the substances our gut microbiome produce can interact and influence our bodily systems, including the immune system. The immune system reacts when it perceives a threat such as a pathogen or disease-producing microbe in the body and launches defense mechanisms to neutralize the invader and protect healthy cells from infection. It also helps the body to recover through adaptive or acquired immunity (leaving a permanent memory of the pathogen1). You can read more about how your gut bacteria support general immunity in Microba Nutritionist Christine Stewart’s blog here.

When it comes to influenza specifically, studies in animal models have indicated the gut microbiome is involved in the immune response during infection. In particular, mice infected with influenza A that had an intact gut microbiome showed increased expression of the Toll-like receptor 7 (TLR7) signaling pathway compared to mice with no gut microbiome (germ free)2. TLR7 is a pattern recognition receptor that helps the host recognize the influenza virus as an invader and mount an immune attack3. TLR7 is also important for producing virus-specific antibodies and in developing an immunological “memory” when the host is vaccinated4. Indeed, a recent study in humans observed that gut microbiome loss (from taking antibiotics) in people with low pre-existing immunity impaired their ability to develop flu-specific antibodies when vaccinated5. This strongly suggests that the gut microbiome is playing a key role in modulating immunity.

 

What happens to the gut microbiome after influenza

As your patient is recovering from a respiratory virus, they may be at increased risk for developing a secondary bacterial infection as a result of a disrupted gut microbiome. Mice models have indicated that as a result of the immune response mounted against respiratory influenza, it can lead to the following impacts on the gut microbiome6,7:

  • Depletion of commensal gut bacteria and decreased microbial diversity
  • A disrupted mucus barrier
  • Enrichment of pro-inflammatory Proteobacteria in the gut.
  • Increased susceptibility to secondary infection by pathogens, such as Salmonella.

Thus, it is important that while your patient is sick and afterwards, that they are supporting their gut microbiome by doing their best to maintain a healthy diet with lots of plant-based foods rich in fibre and phytochemicals.

 

How are patients with existing issues affected?

With many healthy people generally bouncing back quite quickly from influenza or being able to easily influence their gut microbiome with diet post-infection, it’s important to understand how more vulnerable patients are impacted. This can also include those who have recently been on (or are still taking) antibiotics or other immune-suppressing medication.

Animal models indicate that a gut microbiome depleted by antibiotics will impair the immune response to viral infection and delay clearance of the virus8,9. This means that it’s important to help your patients to re-build their gut microbiome after a course of antibiotics. In general, making sure your patients have a diverse and well-balanced microbiome will support their immune system in times of infection and long term.

 

How do SCFAs influence respiratory influenza?

It’s well known that short chain fatty acids (SCFAs) are important for maintaining good gut health and overall health. For example, when it comes to the immune system the SCFAs butyrate, propionate and acetate can suppress inflammation through various mechanisms, help maintain the intestinal cell barrier and even boost production of antimicrobial peptides10.

Research suggests that SCFAs may also have a role to play when it comes to respiratory infections. When mice were fed an inulin-rich, high-fibre diet they had increased levels of circulating SCFAs, which protected them against a severe influenza infection by reducing tissue damage and boosting their adaptive immunity compared to mice fed a fibre-poor diet11. Additionally, a recent human study of stem cell transplant recipients observed that patients with a higher abundance of butyrate-producing bacteria were five-fold less likely to develop a viral lower respiratory tract infection12.

 

Think about the gut this flu season

Although there is still much to learn about all the ways the gut microbiome interacts with our immune system and influences respiratory infection, there is increasing evidence that a healthy gut microbiome may help improve immunity and the body’s response to infection. This flu season, as you are helping your patients boost their immunity, make sure to think about helping them improve their gut microbiome as well. The easiest way to do this is through a healthy diet consisting of a diverse range of wholegrains, vegetables, legumes, fruits, nuts and seeds!</span/

 

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About the Author

Dr Pribyl is a senior scientist at Microba with a passion for science outreach and communication. Dr Pribyl’s work at the University of Queensland developing the science content to present metagenomic gut microbiome profiles later became the basis for Microba’s Insight™ Report.

References

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2. Wu, S. et al. Microbiota Regulates the TLR7 Signaling Pathway Against Respiratory Tract Influenza A Virus Infection. Current Microbiology 67, 414–422 (2013).

3. Stegemann-Koniszewski, S. et al. Respiratory Influenza A Virus Infection Triggers Local and Systemic Natural Killer Cell Activation via Toll-Like Receptor 7. Frontiers in Immunology 9, 245 (2018).

4. Jeisy-Scott, V. et al. TLR7 Recognition Is Dispensable for Influenza Virus A Infection but Important for the Induction of Hemagglutinin-Specific Antibodies in Response to the 2009 Pandemic Split Vaccine in Mice. Virol. 86, 10988 (2012).

5. Hagan, T. et al. Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans. Cell 178, 1313-1328.e13 (2019).

6. Yildiz, S., Mazel-Sanchez, B., Kandasamy, M., Manicassamy, B. & Schmolke, M. Influenza A virus infection impacts systemic microbiota dynamics and causes quantitative enteric dysbiosis. Microbiome 6, 9 (2018).

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