Probiotic Supplementation’s Influence on Low Bone Mineral Density (BMD)

L. reuteri probiotic supplementation elevated vital amino acids influencing bone metabolism in elderly females.

Metabolomics found biomarkers linking gut microbiota changes to bone metabolism in
aged women.

The challenge: Does Probiotic Supplementation Impact Gut Microbiome Metabolites in
Osteoporosis Treatment?

Osteoporosis, prevalent among the elderly, manifests as reduced bone mineral density
(BMD) elevating fracture vulnerability. Gut microbiota influences bone metabolism. L.
reuteri probiotic aids bone health, particularly in low BMD elderly women. Previous
studies highlighted benefits in mice, but human metabolomic response to probiotic
supplementation remained unexplored until now.

Metabolon Insight: Global and Specific Metabolic Changes Correlate with Higher Bone
Mineral Density.

This study involved 68 elderly women with osteopenia, divided into L. reuteri and
placebo groups. Metabolon Global Discovery Panel analysis detected 1,232 metabolites,
with 97 showing variation between the two groups. Some of these metabolites relate to
amino acid, peptide, and lipid metabolism. Isovalerylcarnitine (C5) exhibited a positive
correlation with volumetric BMD (vBMD) at both baseline and after 12 months.

In a cross-sectional study involving 240 women, divided by tibia vBMD, 104 differential
metabolites were identified. These metabolites impact pathways like amino acid
metabolism, steroid hormone biosynthesis, butanoate metabolism, and citrate-acid
cycle, with steroid hormones influencing bone metabolism regulation.

Insight: Amino acid and steroid hormone metabolism are critical for bone stimulation.
L. reuteri supplementation increases critical amino acids, particularly branched-chain
amino acids (BCAAs), perhaps influencing osteoblast development via the gammaglutamyl amino acid cycle and mTORC1 complex activation. There were differences in
BCAA and steroid hormone production between patients with high and low BMD,
indicating their role in bone metabolism.

In both metabolomic studies, 12 metabolites significantly differed, with
isovalerylcarnitine (C5), TMAP, and valine higher in high BMD subjects. Post L. reuteri
supplementation, these metabolites increased, correlating with total tibia vBMD at
baseline and after 12 months. Elevated butyrylcarnitine (C4) suggests its role in
providing essential energy for bone formation.

Result: Metabolomics Offers Potential Biomarkers and Osteoporosis Therapeutics.
Utilizing metabolomics, researchers identified crucial metabolites post L. reuteri
supplementation, potentially serving as future treatment biomarkers. Notably, a
significant rise in butyrylcarnitine (C4) supports a role for butyrate indicating in bone
metabolism, with other metabolites showing changes in amino acid, peptide, and lipid

Metabolomic analysis in elderly women with severe osteoporosis or high BMD revealed
correlated metabolite classes. Isovalerylcarnitine (C5) showed promise as a potential
bone loss biomarker, highlighting gut microbiota and metabolomics interplay in aging
women’s bone metabolism.

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