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This study implicates indole\u20103\u2010propionic acid (IPA), a gut microbiota\u2010derived tryptophan metabolite, in the maintenance of skeletal homeostasis under diabetic conditions. Circulating IPA was lower in diabetic mice and in a small exploratory cohort of patients with diabetic osteoporosis. IPA concentrations were positively associated with bone mass. Metagenomic profiling linked lower IPA to impaired microbial tryptophan metabolism and reduced Clostridium abundance. In diabetic mice, IPA supplementation improved trabecular microarchitecture and bone formation. In bone marrow mesenchymal stem cells subjected to high glucose and palmitate, IPA also restored GPX4 and SLC7A11 expression and was associated with recovery of Nrf2\u2010mediated antioxidant signaling. Pharmacological inhibition of Nrf2 substantially attenuated these anti\u2010ferroptosis and pro\u2010osteogenic effects. Together, these findings support a gut microbiota\u2010IPA\u2010Nrf2\u2010ferroptosis pathway linking altered microbial tryptophan metabolism to impaired osteogenesis. They provide a rationale for evaluating IPA as a potential therapeutic strategy for diabetic osteoporosis.<\/jats:p>","DOI":"10.1002\/advs.77649","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:04:50Z","timestamp":1788930290000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut Microbiota\u2010Derived Indole\u20103\u2010Propionic Acid Alleviates Diabetic Osteoporosis Through Nrf2\u2010Mediated Ferroptosis Suppression"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9485-3562","authenticated-orcid":false,"given":"Jinwu","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Orthopedics Peking University Third Hospital  Beijing China"},{"name":"Beijing Key Laboratory of Advanced Bioadaptable Orthopedic Implants Peking University Third Hospital  Beijing 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