Broncho-Vaxom (BV) is known to attenuate allergic airway inflammation and chronic bronchitis in humans, but the underlying mechanism of this gut-mediated immunity remains unclear. This study investigated the effects of an oral BV on gut and systemic short-chain fatty acids (SCFAs) and immune responses. Oral BV was administered daily for 15 days prior to commencing the study in an asthma mouse model. Asthma was induced by ovalbumin (OVA) sensitization followed by a challenge with 1% OVA by inhalation. Asthmatic phenotypes, gut- and systemic- immune responses, and SCFAs in the cecum and blood were then investigated. Airway hyperresponsiveness, total immunoglobulin E production, and pulmonary inflammation were all significantly suppressed by BV. The interleukin-13 level was also suppressed, whereas TGF-β expression was increased, in the lungs of the BV-treated mice. The regulatory T (Treg) cell numbers were increased in the small intestine, and the acetate level was increased in the cecum and serum after BV treatment. The levels of acetate in the cecum and serum were negatively correlated with airway hyperresponsiveness and with the eosinophil numbers in the BAL fluid of the OVA-induced mice. There was a positive correlation between the acetate levels in the feces and serum and the lung expression of TGF-β in the asthma mice. Oral BV administration appears to prevent allergic inflammation by enhancing Treg cell proliferation and acetate production in an asthmatic mouse model.