Nasal-spray Bacillus probiotics reduce mild respiratory infections and the risk of new infections in preschool children

Abstract Respiratory tract infections are a leading cause of morbidity and antibiotic overuse. Nasal-spray probiotics offer a promising non-specific preventive strategy when pathogen-targeted interventions are ineffective, with rapid local effects at the respiratory mucosa. Here, we conducted a randomized placebo-controlled trial (ClinicalTrials.gov: NCT06148194) in two preschools in Vietnam. A total of 400 children aged 2–5 years were randomly assigned to receive either LiveSpo Navax ( B. subtilis ANA4 and B. clausii ANA39, ≥ 1 × 10⁹ CFU/mL) or saline placebo nasal sprays administered daily for 28 days ( n = 200 each). The trial was completed without any treatment-related side effects. By day 28, the Navax group showed significantly greater reductions in respiratory symptoms (1.74-3.83-fold) and medication use (1.40-3.00-fold). Viral infections decreased 3.25-fold, with new infections among children who were infection-free at baseline reduced ~ 6-fold (95% CI: 1.91–19.82; p = 0.002). Bacterial co-infections decreased 1.55-2.00-fold, with a ~ 2-fold reduction in newly acquired bacterial infections (95% CI: 1.023–4.122; p = 0.047). Nasal microbiota analysis revealed enrichment of beneficial genera ( Brevibacillus and Bacillus ) and suppression of pathogens ( Moraxella catarrhalis , Streptococcus pneumoniae , and Haemophilus influenzae ). These findings indicate that nasal-spray Bacillus probiotics are safe and associated with reduced respiratory symptom burden and lower detection rates of common viral and bacterial pathogens. Trial registration : ClinicalTrials.gov Identifier NCT06148194, posted on 28/11/2023.