# 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

**Authors:** Ryan S. Green, Tyler Roy, Daniela Diaz-Infante Morales, Claire Morrow, Ryan Neilson, Eric M. Schott, Mark R. Charbonneau, Alicia E. Ballok, Katherine J. Motyl, Gerardo V. Toledo

PMC · DOI: 10.1016/j.jff.2025.107114 · Journal of functional foods · 2026-01-24

## TL;DR

A synbiotic food improves gut health and reduces bone loss in postmenopausal women by reducing inflammation and inhibiting bone-degrading cells.

## Contribution

This study identifies a synbiotic medical food that modulates the gut–bone axis to reduce postmenopausal bone loss in clinical and preclinical models.

## Key findings

- SBD111 improves intestinal barrier integrity and reduces immune cell cytokine secretion in vitro.
- SBD111 inhibits osteoclast activity and bone resorption in postmenopausal models.
- Clinical outcomes align with reduced gastrointestinal symptoms and bone loss markers.

## Abstract

Over half of women above age 50 are affected by osteopenia or osteoporosis, bone-loss 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 microbes 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.

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 (seen in red) 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. Green, R. (2025) https://BioRender.com/agmo9s8.

## Linked entities

- **Diseases:** osteoporosis (MONDO:0005298)

## Full-text entities

- **Genes:** AHR (aryl hydrocarbon receptor) [NCBI Gene 196] {aka FVH3, RP85, bHLHe76}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, Tnfsf11 (tumor necrosis factor (ligand) superfamily, member 11) [NCBI Gene 21943] {aka Ly109l, ODF, OPGL, RANKL, Trance}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, Galt (galactose-1-phosphate uridyl transferase) [NCBI Gene 14430], IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, TNFSF11 (TNF superfamily member 11) [NCBI Gene 8600] {aka CD254, ODF, OPGL, OPTB2, RANKL, TNLG6B}, CAT (catalase) [NCBI Gene 847], Hp (haptoglobin) [NCBI Gene 15439] {aka HP-1, preHP2}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, IL23A (interleukin 23 subunit alpha) [NCBI Gene 51561] {aka IL-23, IL-23A, IL23P19, P19, SGRF}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TRAP [NCBI Gene 100187907], CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, GALT (galactose-1-phosphate uridylyltransferase) [NCBI Gene 2592], Acp5 (acid phosphatase 5, tartrate resistant) [NCBI Gene 11433] {aka TRACP, TRAP}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, CXCL1 (C-X-C motif chemokine ligand 1) [NCBI Gene 2919] {aka FSP, GRO1, GROa, MGSA, MGSA-a, NAP-3}, TNFRSF11B (TNF receptor superfamily member 11b) [NCBI Gene 4982] {aka OCIF, OPG, PDB5, TR1}, CSF1 (colony stimulating factor 1) [NCBI Gene 1435] {aka CSF-1, MCSF, PG-M-CSF}
- **Diseases:** osteoporosis (MESH:D010024), menopausalbone loss (MESH:D016388), osteonecrosis of the jaw (MESH:D059266), hip fracture (MESH:D006620), adenocarcinoma (MESH:D000230), BMD (MESH:D001851), resorption (MESH:D014091), cancers (MESH:D009369), gastrointestinal symptoms (MESH:D012817), systemic (MESH:D015619), obesity (MESH:D009765), tissue damage (MESH:D017695), fracture (MESH:D050723), Inflammation (MESH:D007249), osteoclast (MESH:D001862), adiposity (MESH:D018205), CTX (MESH:D019294), GI (MESH:D005767), bone loss (MESH:D001847), Menopause (MESH:D008594)
- **Chemicals:** Zeocin (MESH:C105427), short chain fatty acids (MESH:D005232), DMEM (-), FBS (MESH:C523711), Glutamax (MESH:C054122), oligofructose (MESH:C120489), glutaraldehyde (MESH:D005976), phenol red (MESH:D010637), butyrate (MESH:D002087), LPS (MESH:D008070), cellulose-acetate (MESH:C005062), HEPES (MESH:D006531), charcoal (MESH:D002606), CO2 (MESH:D002245), bisphosphonates (MESH:D004164), PBS (MESH:D007854), Vitamin K2 (MESH:D024482), alphaMEM (MESH:C420642), EDTA (MESH:D004492), acetate (MESH:D000085)
- **Species:** Levilactobacillus brevis (species) [taxon 1580], Lactiplantibacillus plantarum (species) [taxon 1590], Pichia kudriavzevii (species) [taxon 4909], Leuconostoc mesenteroides (species) [taxon 1245], Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090], Pseudomonas fluorescens (species) [taxon 294], Escherichia coli (E. coli, species) [taxon 562]
- **Cell lines:** SBD111 — Bos taurus (Bovine), Hybrid cell line (CVCL_J079), RAW264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), Caco-2 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0025), HT29-Lucia — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_A8BX), HT29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320)

## Full text

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## Figures

22 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12829910/full.md

## References

77 references — full list in the complete paper: https://tomesphere.com/paper/PMC12829910/full.md

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Source: https://tomesphere.com/paper/PMC12829910