Probiotic acetate mitigates menopausal asthma exacerbation by modulating T2 inflammation and cDC1 levels in the lungs 3566

Abstract Description Asthma, an inflammatory lung disease, disproportionately affects women in adulthood, often worsening with estrogen decline during menopause. The mechanisms behind this exacerbation remain unclear. Using a mouse model of postmenopausal asthma via ovariectomy (OVx), we sensitized and challenged female mice with ovalbumin (OVA) to induce allergic responses. Re-challenging OVx-allergic mice led to heightened lung inflammation, mimicking clinical observations. Interestingly, acetate-producing probiotic treatment mitigated this inflammatory exacerbation. To explore acetate’s effects, mice received acetate intraperitoneally starting 15 days before sensitization, with treatment ending before challenge on days 21–24. OVx was performed 10 days later, followed by re-challenge. Acetate reduced airway T2 inflammation, including inflammatory cell infiltration, mucus production, BAL IL-5, and serum IgE levels, while increasing airway Treg cells. Lung profiles revealed a reduced percentage of cDC1 cells in OVx mice, which acetate treatment restored. Probiotic acetate treatment before estrogen decline protects sensitized, ovariectomized and challenged mice from airway inflammation by increasing cDC1 cells, potentially influencing Treg responses. Funding Sources AADCRC or P01 Center Affiliation: University of Chicago/University of Virginia (Ober/Sperling/Nobrega AADCRC) (U19 AI162310) and São Paulo Research Foundation 2021/06751-4 to CMF Topic Categories Immediate Hypersensitivity, Asthma, and Allergic Responses (HYP)