“Early life is a critical time for our gut microbiota and immune system. Both take shape during the first two years of life. It’s also the time when most of us get our vaccines.

So, it’s important we understand how the gut microbiome affects vaccine responses during this time. This knowledge could help us improve how much immunity vaccines provide to babies.

There is a lot of variety in how infants respond to vaccines across countries. Vaccination against the stomach bug rotavirus, gives protective immunity in 98% of Finnish children, but only 46% in Bangladesh. It’s an established vaccine, that does well in some countries, but not in other countries.

Many factors such as hygiene, diet, socioeconomic and environmental circumstances can contribute to differences like this. But research shows common patterns in the gut microbial communities of babies that respond better to vaccines, highlighting that our gut microbes are important too.

Bacteria that boost vaccines responses

Bifidobacterium and Bacteroides are naturally occurring beneficial bacteria that live in our gut, that help contribute to a healthy microbial ecosystem. Both bacteria appear to affect how well infants respond to vaccines.

If an infant has a lot of Bifidobacterium in their microbiota, they almost always seem to do better when it comes to vaccination compared to infants that don’t have much of the bacteria.

Several studies show this same pattern across different countries. Whether in Europe, Ghana or Bangladesh, children who respond well to vaccines share a similar microbiota rich in Bifidobacterium and Bacteroides.

Infant microbiomes

There are many aspects that can have an impact on infant microbiota, in any country.

Initial colonisation of the gut by microbes happens during and shortly after birth. Babies are exposed to a whole range of bacteria, fungi and viruses.

How you are born can shape your microbiome. Babies delivered by vaginal birth are exposed to different maternal microbiota than those delivered by caesarean section.

Breastfeeding promotes Bifidobacterium because the bacteria feed off compounds found in breast milk.

The immune system in infancy

Exactly how beneficial bacteria like Bifidobacterium and Bacteroides boost vaccine responses is yet to be uncovered. But the gut microbiome and immunity have a close relationship, particularly early in life.

Research shows that gut microbiota supports the immune system in a variety of ways. Gut microbes are essential for the development of immune cells called B cells, which are important for triggering the production of antibodies.

Human studies have investigated the effect of how antibiotics change the microbiome and affect the immune response to influenza, polio, rotavirus, tetanus, and BCG vaccination. There is either no improvement or the vaccines are less effective, with the altered microbiota. This links the connection between microbiota disturbances and a change in immune response.

Although it can be difficult to compare lots of studies, as each use slightly different methods, the role of the microbiome in vaccination immune response appears to be a common pattern. In the future, it would be great for there to be a standardised method to make it easier to compare research from human studies.

Equalising effectiveness of vaccines

In my PhD I am working to find products important for vaccination response that Bifidobacterium bacteria make. My PhD is a joint project between Professor Lindsay Hall’s group, who are experts in Bifidobacterium, and Professor Simon Carding’s group who work on Bacteroides and bacterial products.

We hope that if we find a particular strain or product of the beneficial bacteria involved in the immune response, we could give it to those babies that lack it and boost their response to vaccines.

It would work as a probiotic, encouraging a gut microbiome ecosystem that can help an infant respond better to a vaccine. This could potentially replace current adjuvants, substances which are included in vaccines to enhance the immune system response. Adjuvants can sometimes be responsible for side effects of vaccines like a sore arm.

Difference in delivery of vaccines

Another important aspect of the effectiveness of vaccines is how the vaccine is delivered to infants.

Oral vaccines are easier to deliver but tend to be less effective. This is probably because if you take something orally, it has to go through the oesphoagus and things can be degraded in the stomach.

In the Carding Group we are looking at using molecules produced by Bacteroides and Bifidobacterium, such as membrane vesicles. They are very sturdy so even if you swallow them, they will not be degraded by stomach acid. They can survive different temperatures and be stored at room temperature too.

You could either swallow or inhale via the nose, and then you have the vaccine directly where you need it, and without needing a needle, or –80 freezer.

I am looking at what effect these vesicle molecules have on immune cells and cells that line the gut.

I am fascinated by the gut microbiota because it has an impact on so many different levels, whether it’s cardiovascular health, neurological, or immunological health.

We still have a lot to learn when it comes to the interaction between our gut microbiota and the rest of our body.”

• Read more about the early-life gut microbiome and vaccine efficacy in Anne’s review article in the Lancet