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Peer-reviewedCC BYScientific Reports

Combined metabolomics and microbiota analysis reveals the therapeutic effect of indole-3-propionic acid on ovariectomy-induced osteoporosis

  • Liang A.1
  • Na Gong2
  • Sheng Li1
  • Wenzheng Lv1
  • Yingnan Ji1
  1. 1Central Hospital Affiliated to Shenyang Medical College
  2. 2General Hospital of Northern Theater Command
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Abstract

Osteoporosis is a process of bone tissue destruction jointly caused by chronic inflammation and oxidative stress. Indole-3-propionic acid (IPA), as a metabolic molecule of the gut microbiota, exerts anti-inflammatory and antioxidant properties. However, the role of IPA in ovariectomy-induced osteoporosis in rats remains unclear. We utilized ELISA and qRT-PCR to measure cytokine levels in serum and the mRNA expression of bone metabolism-related genes, respectively. Meanwhile, bone microstructure was analyzed using CT scanning technology. Additionally, we conducted non-targeted metabolomics and 16 S rDNA gene sequencing studies on mouse fecal samples, employing multivariate statistical analysis for data visualization. IPA administration significantly attenuated the elevation of inflammatory mediators (TNF-α, IL-1β, IL-6) in OVX rats, while enhancing anti-inflammatory IL-10 levels. It could alter biochemical markers (Ca, P, ALP, CTX-1 and PINP) and suppress the expression of critical osteoclast differentiation genes (NFATc1, CTSK, ACP5, OSCAR), preventing OVX-induced bone loss. Additionally, the bone microstructure improved. Metabolomic profiling revealed IPA’s regulatory role in fatty acid and amino acid metabolic pathways. Phloretin may serve as biomarker for the bone-protective effects of IPA. Additionally, IPA restored the balance of the Bacteroidota/Firmicutes gut microbiota. These findings underscore IPA’s therapeutic potential, providing a scientific rationale for developing IPA-based interventions for osteoporosis management.

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Cite

BibTeXRIS
BibTeX
@article{liang2026combined,
  title = {{Combined metabolomics and microbiota analysis reveals the therapeutic effect of indole-3-propionic acid on ovariectomy-induced osteoporosis}},
  author = {Liang A. and Na Gong and Sheng Li and Wenzheng Lv and Yingnan Ji},
  journal = {Scientific Reports},
  year = {2026},
  month = aug,
  doi = {10.1038/s41598-026-61654-9},
  url = {https://doi.org/10.1038/s41598-026-61654-9},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Combined metabolomics and microbiota analysis reveals the therapeutic effect of indole-3-propionic acid on ovariectomy-induced osteoporosis
AU  - Liang A.
AU  - Na Gong
AU  - Sheng Li
AU  - Wenzheng Lv
AU  - Yingnan Ji
PY  - 2026
DA  - 2026/08/01
JO  - Scientific Reports
DO  - 10.1038/s41598-026-61654-9
UR  - https://doi.org/10.1038/s41598-026-61654-9
AB  - Osteoporosis is a process of bone tissue destruction jointly caused by chronic inflammation and oxidative stress. Indole-3-propionic acid (IPA), as a metabolic molecule of the gut microbiota, exerts anti-inflammatory and antioxidant properties. However, the role of IPA in ovariectomy-induced osteoporosis in rats remains unclear. We utilized ELISA and qRT-PCR to measure cytokine levels in serum and the mRNA expression of bone metabolism-related genes, respectively. Meanwhile, bone microstructure was analyzed using CT scanning technology. Additionally, we conducted non-targeted metabolomics and 16 S rDNA gene sequencing studies on mouse fecal samples, employing multivariate statistical analysis for data visualization. IPA administration significantly attenuated the elevation of inflammatory mediators (TNF-α, IL-1β, IL-6) in OVX rats, while enhancing anti-inflammatory IL-10 levels. It could alter biochemical markers (Ca, P, ALP, CTX-1 and PINP) and suppress the expression of critical osteoclast differentiation genes (NFATc1, CTSK, ACP5, OSCAR), preventing OVX-induced bone loss. Additionally, the bone microstructure improved. Metabolomic profiling revealed IPA’s regulatory role in fatty acid and amino acid metabolic pathways. Phloretin may serve as biomarker for the bone-protective effects of IPA. Additionally, IPA restored the balance of the Bacteroidota/Firmicutes gut microbiota. These findings underscore IPA’s therapeutic potential, providing a scientific rationale for developing IPA-based interventions for osteoporosis management.
SN  - 2045-2322
ER  -