Tu105 - Early-life Dysbiosis and Its Impact on Neuroimmune Interactions in Allergic Asthma

Abstract Text: Early-life dysbiosis is linked to increased susceptibility to allergic asthma. In murine models, perinatal exposure to vancomycin (an antibiotic depleting short-chain fatty acid-producing bacteria) exacerbates allergic responses in adulthood. Dysbiosis induced in adulthood does not affect immunological skewing, highlighting a critical developmental window for the influence of microbiota on immune and tissue maturation. Many immune cells that reside near nerves express receptors for neuromediators. While dysbiosis impacts the enteric nervous system, its effects on autonomic function in distant tissues remains unclear. This study examines neuroimmune interactions in the context of early-life dysbiosis, focusing on neuroimmune mediators driving Th2 responses.

Methodology:
1. Dysbiosis Model: C57BL/6J breeding pairs receive vancomycin (200 mg/L) in drinking water; pups are reared on treatment water until weaning.
2. We optimized a spectral flow cytometry panel to comprehensively profile immune cells in lung tissue from male and female mice.
3. Bulk proteomics is used to identify neuroimmune mediators in dysbiotic lungs; key mediators (serotonin, Substance P, CGRP) are validated via qPCR.
4. Immunohistochemistry will illustrate spatial relationships between IgE-bearing immune cells and autonomic nerve fibers in dysbiotic versus normobiotic lungs.

Preliminary flow cytometry results demonstrate increased FcεRIα-bound IgE expression on immune cells in female dysbiotic lungs, with lesser effects seen in males. As FcεRIα also appears on lung-innervating vagal afferents (Crosson T, et al. JACI. 2021), this suggests a neuroimmune axis mediating enhanced Th2 responses. This research will reveal the impact of dysbiosis on neuroimmune interactions, potentially guiding the use of neuromodulatory drugs for allergic disease management.