A synbiotic medical food improves gut barrier function, reduces immune responses, and inhibits osteoclast activity in models of postmenopausal bone loss aligned with clinical outcomes

Abstract

Over half of women above age 50 are affected by osteopenia or osteoporosis, boneloss conditions influenced by estrogen decline, inflammation, and the intestinal microbiota. Probiotic-based interventions have shown promise in preclinical osteoporosis models. In a recent randomized, double-blind, placebo-controlled clinical trial of postmenopausal women, dietary intervention with SBD111, a synbiotic medical food combining plant-derived probiotics and prebiotic fibers, reduced bone loss in women with osteopenia, elevated body mass index (BMI), and/or elevated body fat. To investigate potential mechanisms underlying these outcomes, we examined intestinal epithelial, immune, and osteoclast responses to SBD111 in vitro. SBD111 administration improved intestinal barrier integrity, reduced immune cell cytokine secretion, and inhibited osteoclast activity. These effects align with clinically observed reductions in severe gastrointestinal symptoms and bone resorption markers. Together, these findings suggest that SBD111 modulates the gut-bone axis via barrier, immune, and antiresorptive pathways, supporting its role in maintaining skeletal health in postmenopausal women. IRB StatementsThe study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of MaineHealth under protocol 1689738-1 (approved 12/29/2020) and 958914 (approved 05/31/2005). Human peripheral blood mononuclear cells (PBMCs) were purchased from Charles River Laboratories and collected under their IRB-approved protocol with informed consent for commercial research use. Informed Consent Statements Informed consent was obtained from all participants involved in the study. HighlightsO_LISBD111 synbiotic medical food improves intestinal barrier function C_LIO_LISBD111 reduces cytokine release from inflamed immune cells C_LIO_LIThis synbiotic medical food inhibits osteoclast activity in vitro C_LIO_LIIn vitro SBD111 effects align with clinical reductions in bone loss and CTX-1 C_LI Graphical Abstract. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=128 SRC="FIGDIR/small/669142v1_ufig1.gif" ALT="Figure 1000"> View larger version (30K): org.highwire.dtl.DTLVardef@13b16dcorg.highwire.dtl.DTLVardef@59dfcaorg.highwire.dtl.DTLVardef@737e59org.highwire.dtl.DTLVardef@6c054a_HPS_FORMAT_FIGEXP M_FIG SBD111 synbiotic medical food reduces bone loss via barrier improvement, anti-inflammation, and osteoclast inhibition. (A) SBD111 improves barrier integrity in vitro. Visualized in the left panel, inflammation reduces intestinal epithelial barrier function, resulting in the influx of inflammatory mediators, thereby activating the immune system. The addition of SBD111, shown in purple (right), improves barrier function, reducing the ability of inflammatory mediators to cross the epithelial barrier. (B) SBD111 reduces inflammatory responses of inflamed immune cells in a concentration-dependent manner. Low concentrations of SBD111 induce inflammatory responses. At higher concentrations, fewer inflammatory cytokines are secreted. (C) SBD111-derived components/metabolites inhibit the activity of bone-resorbing osteoclasts and reduce their ability to degrade bone. Image created in https://BioRender.com C_FIG