Indole-3-Propionic Acid Shows Long-Term Protection Against Asthma

Recent research published in the journal Immunity shows that a certain molecule called indole-3-propionic acid (IPA) is crucial in long-term protection against asthma. The investigators believe that in the future, the molecule, which is produced by gut bacteria, can potentially be trialed as a treatment—likely in the form of a dietary supplement—for children who are at risk of asthma to prevent the disease’s development.^1,2

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According to the investigators, allergic asthma is emphasized by a dysregulated interaction between the airway epithelium and dendritic cells, which then results in the release of T helper 2-associated cytokines (eg, interleukin [IL]-4, IL-5, and IL-13), an increase of eosinophils, mucus, and immunoglobulin E levels. Prior research also shows strong links between the environment, gut microbiota, and the risk of childhood atopy and asthma. The gut microbiota develops a stable ecosystem during the first years of life, and, according to the investigators, infants who are at a high risk of childhood atopy and asthma are more likely to have a disrupted and delayed maturation of the gut microbiome.²

Knowing that antibiotic use early in life can disrupt microbial colonization and increases the risk of developing both allergies and asthma, investigators evaluate mice who were given early-life antibiotics, but not during adulthood. The findings demonstrate that these mice were more susceptible to allergic airway inflammation from house dust mites. The antibiotics had also decreased the systemic levels of IPA, therefore, inducing long-term, changes to the mice’s cellular stress, metabolism, and mitochondrial respiration in the lung epithelium. Further, early-life IPA supplementation protected mice who were given early-life antibiotics against exacerbated house dust mite-induced allergic airway inflammation during adulthood. These findings indicate that IPA can be a candidate for the prevention of allergic airway inflammation early in life.²

“We know that recurrent use of antibiotics early in life disrupts a person’s healthy gut microbiota and increases the risk of allergies and asthma. We have discovered that a consequence of antibiotic treatment is the depletion of bacteria that produce IPA, thus reducing a key molecule that has the potential to prevent asthma,” said senior author Ben J. Marsland, PhD, professor department of Immunology, Mucosal Immunology Research Group, School of Translational Medicine, Monash University, Melbourne, VIC, Australia, in a news release.¹

Recurrent courses of antibiotics or delayed maturation of the gut microbiota within the first year of life is correlated with an increased risk of developing asthma and atopy. The investigators emphasize that the gut microbiota is significant in maintaining immune homeostasis—notably earlier in life—and represents a key, opportune window of time.²

Marsland emphasizes that the first years of life are crucial in developing stable gut microbiota in an individual. “It is shaped first by food intake —both milk and solid foods—as well as genetics and environmental exposures. Infants at high risk of allergies and asthma have been shown to have a disrupted and delayed maturation of the gut microbiome,” he said in the news release.¹

Despite this finding, the authors also note that specific mechanisms and microbial factors continue to remain poorly understood. Future research will need to be conducted to better understand these mechanisms while also further investigating the role of IPA in young patients at a risk of asthma.^1,2

“The use of antibiotics in the first year of life can have the unintentional effect of reducing bacteria which promote health, and we now know from this research that antibiotics lead to reduced IPA, which we have found is critical early in life as our lung cells mature, making it a candidate for early life prevention of allergic airway inflammation,” concluded Marsland in the news release.¹

References

1. Monash University. Early life antibiotic increases risk of asthma: providing clues to a potential prevention adult asthma. News release. July 15, 2024. Accessed July 23, 2024. https://www.eurekalert.org/news-releases/1051179

2. Perdijk O, Butler A, Macowan M, et al. Antibiotic-driven dysbiosis in early life disrupts indole-3-propionic acid production and exacerbates allergic airway inflammation in adulthood. Immunity. 2024. doi:10.1016/j.immuni.2024.06.010