A Rationally Designed Microbial Consortium Attenuates Allergic Asthma in a Murine Model

S A T U R D A Y Nikole E. Kimes, PhD, Ricardo B. Valladares, PhD, Din L. Lin, PhD, Susan V. Lynch, PhD; University of California, San Francisco. RATIONALE: Lactobacillus supplementation provides partial attenuation of allergic responses in the airway and alters the composition of the gastrointestinal microbiota. Using microbial profiling data from clinical studies, we designed a bacterial consortium based on enriched taxa and functional pathways associated with Lactobacillussupplementation. We hypothesized that intervention using a microbial consortium would provide improved protection against allergic asthma due to the functional synergism of the consortium members. METHODS: To investigate the protective effects of supplementation, C57BL/6 mice were intratracheally sensitized and challenged with cockroach allergen (CRA). The mice were concurrently supplemented with Lactobacillus johnsonii, the microbial consortium, or both over a three-week period. We evaluated allergic responses and potential mechanisms of protection using flow cytometry, qPCR, 16S rRNA gene sequencing, and histology. RESULTS: Supplementation with the microbial consortium and L. johnsoniicombined provided themost robust protection against allergic asthma, including significant decreases in lung mucin hyperplasia and Muc5 gene expression, as well as decreases in Th2-related cytokines. These responses were correlated with systemic increases in IL-17 secreting leukocytes. CONCLUSIONS: The gut microbiota forms a complex functional network that influences both individual microbial members and host immune responses. Here we show that a rationally designed microbial consortium can provide greater attenuation of allergic asthma than an individual probiotic species. Future research will be aimed at characterizing functional interactions and determining the mechanism of improved protection.