Antibiotics can make some vaccines less effective. Scientists suspect gut bacteria may play a role

While vaccines and antibiotics are important medicines, in some cases, one might make the other less effective.

That's according to a study in Nature that found babies exposed to antibiotics in the first few weeks of life were less likely to be adequately protected by early-childhood vaccinations than those who hadn't.

The study is part of a growing body of research in people of all ages examining how — and why — antibiotics can shape vaccine responses.

David Lynn, a immunologist at Flinders University and the South Australian Health and Medical Research Institute (SAHMRI), urged parents not to be alarmed, and stressed people should not stop or delay either antibiotics or vaccinations.

"It's just … at a population scale, there's an increased proportion of infants who have a lower-than-desirable protection."

Understanding exactly why this is the case, and working out how to fix it, is something he and his team are keen to discover.

Increasingly, evidence suggests that the community of microbes in our gut, called the gut microbiome, plays an important part in our immune system's response to vaccines, and that antibiotics might temporarily weaken it.

Antibiotics affect vaccine response

Vaccines stimulate production of immune compounds called antibodies, which can help protect against invading pathogens.

If an individual has enough antibodies in their blood to be clinically protected against a disease, they've reached what's known as the "seroprotective threshold".

But loads of factors can affect how many antibodies your body makes.

To see if antibiotics affected seroprotection in babies, Professor Lynn and his team compared antibody levels in 111 fully vaccinated infants exposed to antibiotics — who were given them directly or via breastmilk — to levels in 80 babies who'd had no contact with antibiotics.

"What we found was [babies that were given antibiotics and] particularly those infants that got antibiotics directly, had impaired or significantly lower antibody responses," Professor Lynn said.

That was particularly apparent at 15 months of age: "Somewhere around 20 per cent were less likely to reach the seroprotective threshold."

But he stressed that those numbers were "back of the envelope" figures, and more research was needed to confirm them.

"Thankfully it's not a huge number, but it is an appreciable number of infants each year," he said.

Bali Pulendran, a immunologist at Stanford University in the US, has conducted similar studies, but focused on adults instead of infants.

A 2019 study by his team published in Cell looked at how antibiotics might change the gut bacteria — and therefore the immune response — to the seasonal flu vaccine.

The researchers analysed two groups: One that had pre-existing immunity to the flu, and a second, smaller group that didn't.

Everyone was given a flu shot, and half of each group also got antibiotics alongside it.

Afterwards, the gut microbiome of those who received antibiotics became less diverse, as expected. Despite this, antibiotics did not seem to lower the vaccine's effectiveness in the group with pre-existing flu immunity.

But antibiotics did seem to have an effect in the smaller group without flu immunity, which produced fewer antibodies in response to the vaccine, and were less protected against one strain of flu.

According to Professor Pulendran, the more recent Nature study is "compelling".

"It links real-world patterns of antibiotic exposure to vaccine outcomes in a vulnerable population," he said.

"It adds weight to the idea that maintaining a healthy microbiome is important for optimising vaccine effectiveness."

Gut bacteria providing vaccine 'boost'

It's unknown exactly why antibiotics lower the effectiveness of certain vaccines.

According to Natalie Stevens, an immunologist who works at SAHMRI and Flinders University, this effect is likely partly due to our immune system needing a "boost" from the gut microbiome to function correctly.

These signals may be in the form of substances called metabolites, which gut microbes produce when they digest our food.

"These are compounds that your body doesn't make on its own," Dr Stevens, who was not part of the Nature study but works with Professor Lynn, said.

"If you don't have a gut microbiome, or if you don't have the right kinds of gut microbes, you might have an imbalance in these molecules, and we think these molecules are having direct effects on immune cells."

So when our gut bacteria are wiped out when we take antibiotics, we end up with fewer of those molecules too — at least until the microbes repopulate our body.

But not all vaccines are affected by our gut bacteria, which may also help explain another part of the puzzle, according to Dr Stevens.

"Vaccines often contain compounds in them called adjuvants, which help to make the immune system more responsive," she said.

Dr Stevens suggests the microbiome might be working as a type of adjuvant, boosting the immune system in the same way.

How probiotics could help

As it's not advisable or recommended to stop taking antibiotics when they're needed, Professor Lynn's team went looking for ways to quickly restore gut bacteria after antibiotics. 

One solution could be adding good bacteria back to the gut in the form of probiotics.

Unlike an adult's gut microbiome, the gut bacteria of babies tend to be dominated by just a few bacterial groups, including one called Bifidobacterium, which is already available as a probiotic.

"Our preclinical data suggests that administering a widely used probiotic [Bifidobacterium] can lead to restored antibody responses to vaccinations," Professor Lynn said.

While the team has only shown this in mice so far, they are now testing Bifidobacterium probiotics in a human infant trial.

'World's largest' study to look into link in adults

Meanwhile, Dr Stevens and the team are currently investigating the role of gut bacteria and vaccines in adults. 

She said the trial, known as the Antibiotics and Vaccine Immune Response Study, would be "the largest study of its kind in the world."

"We think we will be able to use the data to answer a lot of questions about how the microbiota influences immunity in adults."

Their research involves injecting trial participants with antibiotics and measuring their response to a vaccine that hasn't been used in Australia for decades: tuberculosis.

"One of the reasons we picked it is because we don't give it in Australia much at all," Dr Stevens said.

The vaccine doesn't have an adjuvant, but she said that it has been known to "boost" the immune response more generally.

"This non-specific protection seems stronger in some regions of the world … so that leads us to suspect the gut microbiota might be involved in these responses too."

While research in this area is ongoing, all three researchers recommend getting vaccinated on time, and using antibiotics as recommended by your doctor.

"It is certainly true that antibiotics don't inactivate vaccines or prevent them from working altogether. The more nuanced picture emerging is that antibiotics can modulate the magnitude and quality of the response," Professor Pulendran said.