Transplanted Human Microbiota and Enteric Pathogen Challenge Enhanced Susceptibility to Allergen-Mediated Asthma in a Murine Model
Sunday, March 4, 2018: 2:15 PM
S220EF (Convention Center)
Susan L. Ewart, DVM, PhD, , , , , ,
RATIONALE: We hypothesized that particular microbiotas enhance risk for allergic diseases. Our goal was to provide proof-of-concept that C57BL/6 mice transplanted with young adult human microbiota (Humice) that enhances Th2 immunity had higher responses to house dust mite allergen (HDM) than C57BL/6 mice with mouse microbiota (Momice) and that colonization with Campylobacter jejuni 260.94 would further amplify Th2 responses.

METHODS: Groups of Humice and Momice were administered C. jejuni or sham gavage on ~day -30 and HDM intranasally on days 0, 2, 5, 7, 9 and 12. On day 14 lung function was measured and blood, bronchoalveolar lavage (BAL), lung, feces, and gastrointestinal tissues were collected. Lung inflammation, lung function parameters, and immune responses were assessed.

RESULTS: In Humice, either HDM or C. jejuni alone was sufficient to increase plasma IgE, while Momice required both HDM and C. jejuni to increase IgE. The greatest lung function declines occurred in HDM-exposed Humice given C. jejuni. Respiratory system resistance (Rrs) was significantly increased in HDM-exposed, uninfected mice carrying either microbiota. Respiratory system compliance (Crs) decreased in HDM-exposed Humice regardless of C. jejuni infection, while increases in tissue resistance (G), tissue elastance (H), and respiratory system elastance (Ers) following HDM exposure in Humice required C. jejuni infection. Although increased G in HDM-exposed Humice required C. jejuni infection, this parameter was increased in HDM-exposed Momice regardless of C. jejuni infection. Multiple interactions occurred among factors.

CONCLUSIONS: Human microbiota, with or without concurrent C. jejuni infection, enhanced allergic responses to HDM in mice.