Antibiotics in early life increase risk of asthma and allergies in adulthood

Taking antibiotics at a young age can make the body more prone to asthma and allergies later in life. This might be preventable by adding a simple supplement, concludes immunologist Olaf Perdijk from Utrecht University. His comprehensive study is published today in the journal Immunity.

Antibiotics are essential for eliminating harmful bacteria and have significantly advanced our healthcare. However, scientists have suspected for years that use of antibiotics in early life might be linked to developing asthma and allergies.

Various studies suggest that antibiotics disrupt the balance of beneficial bacteria in the gut, which can lead to a dysfunctional immune system and a higher risk of allergies. There seems to be a connection between these gut perturbations and lung inflammation, but how this works has been unclear until now.

Examining cells in detail

Research by immunologist Olaf Perdijk and colleagues now confirms these suspicions. His research also clarifies which mechanisms play a crucial role in this. "In earlier studies, these mechanisms weren't noticed because the entire immune system seemed to function normally. It's only when you examine all lung cells, including the non-immune cells, in detail that you can solve the puzzle", says Perdijk.

Solving the puzzle

Perdijk solved this puzzle by studying mice. He provided antibiotics to young mice and observed that the composition of their gut bacteria changed. This disruption caused the gut bacteria to produce less of a protective substance called IPA, or indole-3-propionic acid.

Normally, this substance is transported from the gut into the bloodstream and protects the lungs. Too little IPA leads to permanent lung damage, making the lungs more sensitive to foreign substances. This sensitivity can lead to allergic reactions and inflammation when the lungs are exposed to allergens like house dust mites.

Permanent impact

Perdijk's research points out that the lung damage may be permanent, even if the gut bacteria fully recover after the antibiotic treatment. According to Perdijk, this shows how significant and lasting the impact of antibiotics can be.

Preventing adverse effects

However, Perdijk suspects there are ways to counteract or even completely prevent the adverse effects. Again, the key could be IPA: administering IPA may compensate for the microbial dysbiosis induced by antibiotic use. Some mice in Perdijk's study received both antibiotics and IPA. Their lungs and airways appeared unaffected and functioned normally, and did not develop exacerbated inflammation.

Natural substance

Although Perdijk's research is based on studies in mice, he expects that these findings are translatable to humans. The question now is whether IPA supplementation during antibiotics treatment can also prevent allergies in humans. Follow-up research will need to determine if this is possible, as well as how IPA should be administered and in what doses.

If IPA is found to be protective in humans, it shouldn't be too complicated to apply, according to Perdijk. "IPA is a natural product. It naturally occurs in our bloodstream and is non-toxic. Moreover, it can be produced on an industrial scale quite easily."

Future research

Perdijk's research was performed at Monash University in Melbourne. Currently, Perdijk works at Utrecht University. Here he aims to build more fundamental knowledge on microbial-derived substances, and their depletion by antibiotics use. "While antibiotics are essential and will remain so to combat infections, many questions remain about how we can improve treatments, for example by supplementing microbial products," says Perdijk.

"One question is what long-term effects microbial products have on metabolism and the functioning of immune cells, as well as for which diseases they are particularly relevant. By deciphering the underlying mechanisms, we might develop new treatments to prevent allergies and metabolic diseases in the future."

More information:
Antibiotic-driven dysbiosis in early life disrupts indole-3-propionic acid production and exacerbates allergic airway inflammation in adulthood, Olaf Perdijk, Alana Butler, Matthew Macowan, Roxanne Chatzis, Edyta Bulanda, Rhiannon D. Grant, Nicola L. Harris, Tomasz P. Wypych, Benjamin J. Marsland, Immunity. DOI: 10.1016/j.immuni.2024.06.010

Provided by Utrecht University