Self-Replenishable Metabolically Augmented Synbiotic Microspheres Remodel Gut-Bone Homeostasis.

Area of Science:

• Microbiology
• Biomaterials Science
• Bone Biology

Background:

• Gut microbiota dysbiosis and altered short-chain fatty acid (SCFA) metabolism are linked to postmenopausal osteoporosis (PMO).
• Existing probiotic therapies often overlook the role of SCFA metabolism in gut-bone homeostasis.

Purpose of the Study:

• To develop and evaluate a novel synbiotic microsphere (SMASM) for restoring gut-bone homeostasis in PMO.
• To investigate the impact of SMASMs on gut microbiota, SCFA production, and bone metabolism.

Main Methods:

• Fecal samples from PMO patients were sequenced.
• Synbiotic microspheres (SMASMs) were fabricated using Lactobacillus rhamnosus GG (LGG) and hyaluronic acid (HA).
• In vitro and in vivo (ovariectomized mice) studies assessed SMASM efficacy, gut barrier integrity, inflammation, and bone loss.

Main Results:

• SMASMs demonstrated biocompatibility, acid resistance, and mucosal adhesion in vitro.
• Oral SMASM administration in mice improved intestinal barrier integrity, reduced inflammation, and suppressed bone loss.
• SMASMs increased SCFA production (butyric, isobutyric, valeric acids) and supported microbial homeostasis.

Conclusions:

• SMASMs represent a promising strategy for addressing metabolic disorders in PMO via the gut-bone axis.
• Hyaluronic acid acts as a key prebiotic substrate, enhancing LGG function and SCFA production.
• This approach offers novel insights into restoring gut-bone homeostasis through in situ fermentation.