Safety and Tolerability of SBD111 an Optimized Probiotic/Prebiotic Medical Food Combination Designed for the Dietary Management of Age-Related Bone Loss in Adults.

Abstract

ObjectivesTo determine the effect of a daily administration of 6.1 × 1010 CFU/d of SBD111 (an optimized probiotic/prebiotic combination) on safety and tolerability in adults in a randomized trial. MethodsParticipants (n = 32) were randomized to either SBD111 or placebo. The primary outcomes were the number, frequency and severity of adverse Gastrointestinal (GI) symptoms over 28-d. Secondary outcomes were the number and severity of all adverse events (AEs). Stool samples were collected at baseline and after 28-d to determine the impact of SBD111 on gut microbial engraftment, diversity and function using shotgun metagenomics. Groups were compared using Incidence Rate Ratios (negative binomial regression), Odds Ratios (logistic regression) and 95%CI (P< 0.05) using intention-to-treat approach. ResultsAt baseline, the mean age was 45(SD:18)y in SBD111 users (n = 5M, 10F) vs 42(SD:14)y in placebo users (n = 5M, 12F). The two groups did not significantly differ in age, BMI, blood pressure and screening labs. After 28-d, the presence of GI symptoms tended to be higher with SBD111 use vs placebo (P = 0.08). The total number, frequency/severity of GI symptoms did not significantly differ between groups and only 1 person withdrew from the placebo group due to side effects. The number of AEs possibly related to the study were significantly higher with SBD111 use vs placebo (P = 0.05), there were no significant differences in the mean number or severity of AEs. The majority of reported AEs were mild, some were moderate, but none were severe. There were no significant differences in Shannon diversity/microbial richness between the two groups at baseline or after 28-d. After 28-d, participants receiving SBD111 but not placebo showed a significant enrichment in metabolic pathways of menaquinone (vitamin K2) production including the superpathway of menaquinol-10. Fragment recruitment analysis identified the genomic signal of the strains comprising SBD111 after 28-d of SBD111 use, but not placebo. SBD111 strains were undetectable at baseline in either group. ConclusionsThe relatively low frequency and mild severity of GI symptoms and AEs suggests that SBD111 at the level tested is safe for human consumption and that SBD111 microbes are able to pass through the intestinal tract, be identified in stool and enrich microbial gene pathways related to bone health. Funding SourcesSolarea Bio Inc.