Bifidobacterium animalis subsp. lactis BLa80 for preventing allergic, respiratory, and gastrointestinal diseases in young children in China: a randomized double-blind placebo-controlled trial.

BACKGROUND: Respiratory, gastrointestinal, and allergic diseases can significantly affect children's physical and mental health and quality of life. PURPOSE: This study aimed to assess the safety of Bifidobacterium animalis subsp. lactis BLa80, its preventive effects on morbidities related to respiratory, gastrointestinal, and allergic diseases, and its impact on the gut microbiome of children during the study period. METHODS: Healthy children aged 0-3 years were randomly assigned to an intervention group (IG; n=180) or control group (CG; n=180). Participants received probiotics or placebo for 3 months, followed by a 3-month follow-up period. Children in the IG received one oral probiotic sachet daily for 90 consecutive days starting on the first day of the intervention. Each sachet contained maltodextrin and the BLa80 strain at 5×109 colony-forming units (CFUs). Children in the CG received placebo sachets containing maltodextrin only. The primary outcome measure was eczema morbidity during the 6-month study period. Secondary outcomes included acute upper respiratory tract infections (URTIs) and acute tracheitis/bronchitis. Fecal gut microbiota profiles were assessed by 16S rRNA sequencing. Fecal immune biomarkers including calprotectin, human beta-defensin-2 (HBD-2), cathelicidin (LL-37), and secretory immunoglobulin A were also determined. This study was registered with the China Clinical Trial Center (ChiCTR2300074956). RESULTS: Per-protocol analyses were conducted of 156 and 164 subjects in the IG and CG, respectively. The morbidity rate of eczema during the 6-month period was significantly lower in the IG versus CG (intention-to-treat analysis: 26.1% [47 of 180] vs. 66.7% [120 of 180], P<0.01; per-protocol analysis: 30.1% [47 of 156] vs. 73.2% [120 of 164], P<0.01). Probiotic supplementation was also associated with a lower risk of URTIs (IG vs. CG: 40.3% vs. 20.7%; risk ratio [RR], 0.752; 95% confidence interval [CI], 0.653-0.866) and acute tracheitis/bronchitis (18.8% vs. 9.5%; RR, 0.897; 95% CI, 0.825-0.977). Bla80 intervention increased the relative abundance of Bifidobacterium bifidum, Bifidobacterium kashiwanohense PV20-2, Bifidobacterium longum, and Enterococcus dispar ATCC (American Type Culture Collection) 51266 while decreasing the abundance of Bacteroides thetaiotaomicron. Postintervention, the IG had significantly lower concentrations of LL-37 (3,509.31±587.89 pg/g vs. 3,720.82±614.90 pg/g, P=0.006) and HBD-2 (202.36±56.35 pg/g vs. 222.65±56.23 pg/g, P=0.005) than the CG. No serious adverse events were reported in either group. CONCLUSION: The daily administration of BLa80 at 5×109 CFU for 3 months in children aged 0-3 years reduced therisk of eczema, URTIs, and acute tracheitis/bronchitis and beneficially altered the gut microbiome composition, fecal immune biomarkers, and functional gene composition without any adverse effects.