Recent findings show that the host of micro-organisms living inside all of us – collectively known as the “microbiome” –play a wide range of roles in human health, from the development of allergies to risk of cardiovascular disease. Dr. Vanessa Harris of the Amsterdam Institute for Global Health and Development added to this list at this year’s 12th International Rotavirus Symposium, where she presented her group’s research on how the intestinal microbiome may affect immune responses to rotavirus vaccination. We reached out to Dr. Harris to discuss her lab’s newest findings in this exciting avenue of rotavirus research.

What is the microbiome?

I think about the microbiome as being all the micro-organisms that inhabit our body.  These micro-organisms can be bacteria, but also – for example – viruses, fungi and parasites.  We know that the microbiome can have many different effects on health, but so much is unknown about exactly how it can influence human biology – which makes this field a very exciting one to work in. 

In our research, we concentrate on the bacteria that live in our intestines, known as the bacterial intestinal microbiome.  We believe that differences in the types and amount of bacteria living in the intestine can influence babies’ responses to vaccines. 

Could you please explain how the microbiome may affect the development of an immune response to a vaccine?

This is a great question! This is possible for several reasons: first, we know that the bacteria in the intestine are important for the maturation of a baby’s immune system. For example, in animals, when babies don’t have any bacteria in their intestines, they have weaker immune systems. This is probably because the intestinal microbiome helps to train babies’ immune systems to mature and fight infections effectively.  We also know that some bacteria train the immune system better than others and a baby is dependent on a well-trained immune system to develop good protection against a disease in response to vaccination.

Second, some bacteria in the intestine can help the immune system make a stronger immune response.  For example, when mice had certain bacteria in their intestines (flagellated Escherichia coli), an influenza vaccine provided better protection against the flu compared to when they did not have this type of bacteria. 

Finally, certain infections have evolved to use the bacteria in the intestine to infect humans more efficiently.  When mice do not have any bacteria in their intestines, for example, they are less susceptible to a number of viruses that infect the intestines.  Because some vaccines act like real infections in the intestine, they may also be dependent on the types of bacteria in the intestine to work properly. 

Why did you decide to begin to investigate the gut microbiome as a potential reason why rotavirus vaccines seems to work better in some places than in others?

I think one of the most puzzling questions about the current rotavirus vaccines are why they work better in wealthy countries than poor ones where the vaccine is really necessary. 

We are not alone in believing that the microbiome could be one of the explanations for these differences in rotavirus vaccine immunogenicity and several groups are exploring this possibility in Africa and Asia. I think the primary reason that the microbiome is a plausible explanation for these differences is because infants in developing countries have significantly different types of bacteria in their intestines when you compare them to infants from wealthy, developed countries. These differences arise when they are born and persist into adulthood.  All of these findings prompted us to explore whether the intestinal microbiome could help explain the differences in rotavirus vaccine performance.

In your opinion, how do these findings further knowledge surrounding rotavirus vaccine research?

In our work, we compared the intestinal microbiomes of infants who did and did not have an immune response to the rotavirus vaccine in Ghana.  Our most important finding is that infants who develop immune protection from receiving the rotavirus vaccine have a significantly different microbiome than infants who do not get protection.  When we uncovered this difference, we compared the Ghanaian infants’ microbiomes to a large group of similarly healthy Dutch infants who developed strong immune responses to the rotavirus vaccine.  We saw that Ghanaian infants responding to the rotavirus vaccine had microbiomes that were significantly more similar to these healthy Dutch infants than Ghanaian infants not responding to the microbiome.  This supports our idea that differences in the microbiome are driving differences in response to the rotavirus vaccine between infants across countries.

What, in your opinion, was the most surprising finding of your study?

I think that the most surprising finding of our study was that the kinds of bacteria that comprised the microbiomes of rotavirus vaccine immune responders and non-responders were distinctly different.  We could not have predicted these bacteria ahead of time, but upon discovering them, they raise a whole set of new questions about how and why they could be influencing immune responses to the microbiome. 

Which of your findings do you think holds the most promise for future avenues of research?

This research has generated so many new questions for us! We have found that there is a relationship between certain bacteria in the intestinal microbiome and rotavirus vaccine responses, and now we want to understand why and how these bacteria might be influencing the vaccine.  We also want to know if there are other components of the microbiome besides the bacteria that could be influencing rotavirus responses.  I think that answers to these questions could help us to design better rotavirus vaccines – either by changing the way that rotavirus vaccines are administered or by using the research to identify and design evidence-based, targeted probiotics for vulnerable infants. We hope that this could better protect infants across the globe from severe rotavirus gastroenteritis. 

The 12th International Rotavirus Symposium was held on September 7-9, 2016 in Melbourne, Australia. The event was organized by the Sabin Vaccine Institute in collaboration with the Bill and Melinda Gates Foundation, the U.S. Centers for Disease Control and Prevention, the U.S. National Institutes of Health Fogarty International Center, Murdoch Childrens Research Institute, the University of Melbourne, PATH and the ROTA Council.