Conversations with Betsy Foxman: The respiratory microbiome and reducing influenza risk

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For most science-minded non-scientists, the idea of the human microbiome mostly brings to mind bacteria associated with our digestive system. However, there are more areas on and in the body with significant bacterial populations. Betsy Foxman set aside her time to discuss the role respiratory microbiota plays during influenza infection.

SCIENTIFIC INQUIRER: Most people are familiar with the microbiota in our guts. Besides the obvious, how does the respiratory microbiota differ?

BETSY FOXMAN: Besides obvious differences in taxonomic composition, it’s important to consider differences in how they modulate the host immune response. There is growing evidence suggesting the gut microbiome plays an important role in the body’s immune homeostasis. In the context of influenza virus infections, we were interested in the respiratory microbiome since it’s located at the primary site of infection and may play a role in local immune response.

SCINQ: What prompted this study to be undertaken?

BF: We wanted to explore whether the microbiome was a potential target for reducing influenza risk. The relationship between the microbiome and influenza had been observed in several animal models but no studies had yet been conducted in a human population.

SCINQ: Can you explain the key differences between the five nasal/oropharyngeal community states (CST)? When do they tend to shift from one CST to another Are certain bacteria more important?

BF: The 15 oligotypes displayed on Figure 2 of our article explains most of the taxonomic differences between the five CSTs. In terms of population characteristics, CST 4 was notably different from other CSTs as it was rare among young children and was more prevalent and stable among older individuals.

In our study, we found that community shifts were common even within a 2-week period. We would need to characterize the microbiota at multiple time points for each study participant in order to describe the specific timing of these shifts.

There are two general approaches to analyzing microbiota data: 1) clustering methods to identify distinct bacterial communities or 2) taxa-specific analysis that account for multiple testing. We used both approaches in our study. Using the latter approach, we found three oligotypes associated with influenza infection (Alloprevotella, Prevotella, and Bacteroides). However, further work is needed to determine whether these taxa play a biological role in mediating infection or are a proxy of other unknown factors.

SCINQ: Can you describe how you designed your study?

BF: Our study design allowed us to determine the association between nose/throat microbiome and risk of influenza for the following reasons. First, we knew that each household was exposed to influenza, because households were enrolled following identification of a household member with influenza. Second, we could confirm that other household members did not have influenza at time of enrollment. Thus, the microbiome at enrollment was pre-influenza microbiome. Third, because participants were followed every 2-3 days to identify whether or not they had influenza, we detected all secondary cases. And finally, we had information on household and individual characteristics so we could take them in account in our analysis.

SCINQ: What did you discover regarding respiratory microbiota and influenza infections?

BF: We found the respiratory microbiota is associated with influenza susceptibility in a human population.

SCINQ: Can you speculate why CST 4 was less susceptible to infections than the other CSTs?

BF: At this point, it’s difficult to speculate why individuals with CST 4 were less susceptible in our study population. Further work is needed to better understand the drivers of this association. For example, we could use metagenomics to identify functional differences and we could measure the immune response to examine the role of the host.

SCINQ: Since people with CST 4 were less likely to develop influenza, post-influenza bacterial pneumonia infections were also less likely. Do you know whether it decreased the likelihood of bacterial infections in general?

BF: You bring up an important concern. The majority of influenza deaths are due to secondary bacterial infections. We wanted to investigate this by looking at how the microbiome changes when someone is infected. To our surprise, we found community shifts were quite common in both influenza cases and among individuals who were never infected. We did not collect information related to post-influenza bacterial pneumonia, but we hope to explore this in the future.

SCINQ: What was the significance of measuring microbiota stability and taking it into account in the study?

BF: There is some evidence suggesting that microbiome stability may play an important role in disease. In other words, community stability may be just as important as bacterial composition. We were interested in seeing whether influenza virus disrupted the microbiota, but our study was inadequately powered as community shifts were common in both influenza cases and uninfected participants.

SCINQ: What is the next step that needs to be taken in establishing the role of microbiota in protecting against influenza infection?

BF: The next steps would be to conduct more comprehensive studies that consider the pathogen, the microbiome, and the host. Although we identified an association between the microbiota (i.e. who’s there) and influenza susceptibility, we need to take a closer look at what’s happening through virus sequencing, metagenomics, and immune response measurements.

For more information about Betsy Foxman visit her lab page.

IMAGE SOURCE: Creative Commons

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