Gut Microbes Linked to Long-Term Allergies by Affecting Immune Cells and IgE Production In a recent publication in the Journal of Allergy and Clinical Immunology, researchers from the School of Biomedical Engineering (SBME) have uncovered a distinct sequence of events that contribute to the development of allergies and asthma. Their findings pave the way for new possibilities in preventing and treating these conditions. This study in mice aimed to uncover how the microbiome influences cellular and molecular mechanisms that increase susceptibility to type 2 allergic lung disease. Methods Researchers used low-dose vancomycin to reduce SCFA-fermenting bacteria in normal mice (called Vanc-dys mice after altering). They then assessed immune cell activity with and without SCFA supplementation. Finally, the investigators used genetically modified mice, specifically ILC2-deficient and STAT6-deficient strains, to understand the pathways leading to increased allergic disease susceptibility. Results The study found that in Vanc-dys mice, which had altered gut bacteria, there was a significant increase in a type of immune cell in the lungs called ILC2 (innate lymphoid cells type 2). These cells were more active and produced higher levels of specific signalling molecules, namely IL-2, IL-5, and IL-13, linked to allergic responses. When researchers used IL-33 treatment, the ILC2 cells also began producing more IL-4, a cytokine crucial in promoting allergic reactions. This activity triggered the growth of B1 cells, another immune cell type, leading to increased production of IgE, an antibody associated with allergies. As a result, the allergic inflammation in the lungs became worse. However, when the mice were given dietary short-chain fatty acids (SCFAs), particularly a type called butyrate, this heightened lung inflammation was reduced. This suggests that SCFAs can help counteract the negative effects of the altered gut microbiome on the immune system, potentially reducing the severity of allergic diseases. The study's senior author, Dr Kelly McNagny (he/him), professor in the SBME and the department of medical genetics, bme.ubc.ca: Our research finally shows how the gut bacteria and antibiotics shape a newborn’s immune system to make them more prone to allergies. When you see something like this, it really changes the way you think about chronic disease. This is a well-sculpted pathway that can have lasting consequences on susceptibility to chronic disease as an adult. Conclusion The study demonstrated that SCFAs help regulate a pathway involving ILC2 cells, B1 cells, and IgE linked to allergic responses. Administering vancomycin, an antibiotic that reduces SCFA-producing bacteria in the gut, during early life alters this pathway. This alteration increases the likelihood that the immune system will develop type 2 allergic lung diseases, like asthma, with this heightened risk persisting throughout life. Ahmed Kabil (he/him), the study’s first author and a PhD candidate in the SBME, bme.ubc.ca: We can now detect when a patient is on the verge of developing lifelong allergies simply by the increase in ILC2s. And we can potentially target those cell types instead of relying on supplementation with butyrate, which only works early in life. Also read: Maternal and Infant Antibiotic and Acid Suppressant Use and Risk of Eosinophilic Oesophagitis Read the full article Manage Cookie Preferences