ArticleCellular and molecular life sciences : CMLS2024
Trimethylamine-N-oxide accelerates osteoporosis by PERK activation of ATF5 unfolding.
Article in Cellular and molecular life sciences : CMLS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- The gut-bone axis: microbial metabolism and nutritional interventions for bone health.Gut microbes · 2026Review
- Extracts of okra mucilage protect intestinal homeostasis through gut microbiota and immune responses.Journal of natural medicines · 2026Article
- Trimethylamine-N-oxide: the microbial cue in immune-mediated disorders.Trends in endocrinology and metabolism: TEM · 2026Review
- Exercise is associated with attenuated aging-related osteoporosis through TMAO alpha Klotho inflammasome signaling.iScience · 2026Article
- Pathophysiology and Molecular Signalling in Osteoporosis: Linking Risk Factors to Bone Loss.Journal of cellular and molecular medicine · 2026Review
- Roles of gut metabolites on bone mineralization and remodeling: impact of metabolic dysregulation on the gut-immune-bone axis.Frontiers in endocrinology · 2026Review
- Gut Microbial Metabolites as a Bridge in Osteoporotic Rehabilitation for the Elderly: From Aging-Related Dysbiosis to Precision Non-Pharmacological Strategies.International journal of general medicine · 2026Review
- Greening Bone Healing: The Emerging Role of Plant-Derived Exosome-Like Nanoparticles in Osteoporosis and Osteoarthritis Therapy.International journal of nanomedicine · 2026Review
- Gut microbiota in chronic kidney disease-mineral and bone disorder: shared mechanisms, disease-specific signatures, and therapeutic prospects.Frontiers in endocrinology · 2026Review
- Gut microbiota-derived TMAO drives the kidney-bone-vascular axis in chronic kidney disease complications.Renal failure · 2025Review
- Correlation of gut microbiota metabolite trimethylamine N-oxide with inflammatory levels and osteoporosis in patients with diabetic nephropathy.World journal of diabetes · 2025Article
- High-fat diet, intestinal microecology and bone loss.Nutrition & metabolism · 2025Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Imbalances in gut microbiota and their metabolites have been implicated in osteoporotic disorders. Trimethylamine-n-oxide (TMAO), a metabolite of L-carnitine produced by gut microorganisms and flavin-containing monooxygenase-3, is known to accelerate tissue metabolism and remodeling; however, its role in bone loss remained unexplored. This study investigates the relationship between gut microbiota dysbiosis, TMAO production, and osteoporosis development. We further demonstrate that the loss of beneficial gut microbiota is associated with the development of murine osteoporosis and alterations in the serum metabolome, particularly affecting L-carnitine metabolism. TMAO emerges as a functional metabolite detrimental to bone homeostasis. Notably, transplantation of mouse gut microbiota counteracts obesity- or estrogen deficiency-induced TMAO overproduction and mitigates key features of osteoporosis. Mechanistically, excessive TMAO intake augments bone mass loss by inhibiting bone mineral acquisition and osteogenic differentiation. TMAO activates the PERK and ATF4-dependent disruption of endoplasmic reticulum autophagy and suppresses the folding of ATF5, hindering mitochondrial unfolding protein response (UPR
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.