MON-829 - Gastrointestinal Kinetics, Metabolic Activity, and Anti-Inflammatory Activity of SBD111, A Synbiotic Medical Food for Postmenopausal Bone Loss

Non-hormonal options to preserve bone mass in postmenopausal women remain limited, and there is a dearth of solutions to address chronic inflammation that contributes to bone loss. SBD111 is a synbiotic medical food developed to mitigate postmenopausal bone loss. In a randomized, placebo-controlled clinical study, SBD111 significantly reduced bone loss in groups of postmenopausal women with osteopenia, with elevated BMI, or with elevated fat mass (Schott et al., 2025). In addition to skeletal benefits, SBD111 administraton was associated with a significant reduction in severe gastrointestinal (GI) symptoms, suggesting a gut-mediated mechanism that contributes to both tolerability and efficacy. Consistent with this observation, in vitro and ex vivo mechanistic studies demonstrated improved intestinal barrier function and reduced osteoclast activity following SBD111 exposure (Green et al., 2025), prompting further investigation into its activity and function within the gut.
To characterize gut engagement, we conducted an open label, short-term clinical kinetic study in healthy volunteers, evaluating the presence of SBD111 in stool samples over time using molecular and microbiological techniques. In parallel, activation of SBD111 microbes following capsule release was assessed in vitro under anaerobic conditions, and effects on epithelial inflammatory responses were evaluated using TNFα-stimulated HT29 cells treated with SBD111 at multiple concentrations.
SBD111 strains were rapidly detected in stool following administration using molecular methods, with viable strains also recoverable by culture, confirming survival through the gastrointestinal tract. Upon cessation of dosing, SBD111 washed out within days, consistent with transient gut persistence and a favorable safety profile. In vitro simulation of capsule release demonstrated prompt metabolic activation of SBD111, including increased microbial counts and media acidification. Consistent with functional engagement, SBD111 exposure significantly reduced TNFα-induced secretion of the pro-inflammatory chemokines IL-8 and CXCL1 from HT29 cells across tested concentrations.
Collectively, these data demonstrate that SBD111 becomes active early following administration, engages the intestinal epithelium, and modulates inflammatory signaling while remaining non-persistent. Together with clinical observations of reduced GI symptoms and bone-protective efficacy, these findings support a gut-mediated mechanism linking intestinal inflammation and skeletal health in postmenopausal women.

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