A Three-Arm, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety of ILactobacillus salivarius/I AP-32 and IBifidobacterium animalis/I CP-9 Used Individually in Healthy Infants

Probiotics are considered safe and beneficial to human health. However, the safety of Lactobacillus salivarius AP-32 and Bifidobacterium animalis CP-9 in infants has not been confirmed. This study was to assess the safety of long-term oral administration of L. salivarius AP-32 and B. animalis CP-9 in healthy infants compared with placebo. A three-arm, randomized, double-blind, placebo-controlled trial was conducted in healthy, full-term infants. Eighty-eight infants between 7 days and 2 months (60 ± 7 days) of age were selected and randomized to treatment with L. salivarius AP-32, B. animalis CP-9 or placebo for 4 months. The unblinding indicated subjects were randomized to receive B. animalis CP-9 (N = 28), L. salivarius AP-32 (N = 29), or placebo (N = 31). A total of 76 infants completed the 4-month treatment with fully compliance. The primary outcome was weight gain, with no significant difference in infant weight at 4 months when comparing AP-32 or CP-9 group with the placebo group, either. The head circumference and recumbent length of the CP-9 group were not significantly different from those of the placebo group. The recumbent length of the AP-32 group was slightly lower than that in the placebo group at month 4, but there was no difference between the two groups in head circumference. Overall, the growth trend of all treatments was similar without significant difference. Furthermore, there were no apparent differences between each group in digestive tolerance, the occurrence of adverse events, crying/fussing time and episodes, alpha diversity, and beta diversity. The CP-9 group showed a significant increase in the abundance of the Bacteroides genus, while the AP-32 group demonstrated a significant increase in the abundance of the Lactobacillus genus when comparing the two probiotic groups. Our study findings indicate that the oral administration of both AP-32 and CP-9 strains has a positive impact on the maintenance of a healthy gut flora in infants. Long-term use of L. salivarius AP-32 or B. animalis CP-9 is safe for infants from 7 days to 6 months of age.