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Gut microbiota dysbiosis and host metabolic dysregulation are recognized as pivotal drivers in disease pathogenesis, yet the underlying mechanisms remain incompletely understood. In this study, by integrating metagenomics and metabolomics, we identified dysregulation of tryptophan metabolites in patients with CaOx nephrolithiasis, with microbiota\u2010derived indole\u20103\u2010propionic acid (IPA) as the most discriminatory differential metabolite. Oral IPA supplementation markedly reduced renal CaOx crystal deposition and tubular injury in a CaOx nephropathy murine model. Mechanistically, IPA activated the aryl hydrocarbon receptor (AhR), which translocated to the nucleus and transcriptionally upregulated suppressor of cytokine signaling 3 (SOCS3)\u2014a negative regulator of signal transducer and activator of transcription 1 (STAT1)\u2014thereby suppressing STAT1 phosphorylation, alleviating oxalate\u2010induced tubular cell injury and apoptosis, and inhibiting CaOx crystal deposition. Our findings identify tryptophan metabolite alteration as a critical metabolic signature of CaOx nephropathy and demonstrate that microbiota\u2010derived IPA attenuates oxalate\u2010induced renal tubular cell injury and apoptosis via the AhR\u2013SOCS3\u2013STAT1 axis. \u00a9 2026 The Pathological Society of Great Britain and Ireland.<\/jats:p>","DOI":"10.1002\/path.70135","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T08:46:41Z","timestamp":1791535601000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gut microbiota\u2010derived tryptophan metabolite attenuates calcium oxalate nephropathy by suppressing renal tubular cell apoptosis through the\n                    <scp>AhR<\/scp>\n                    \u2013\n                    <scp>SOCS3<\/scp>\n                    \u2013\n                    <scp>STAT1<\/scp>\n                    axis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4795-3146","authenticated-orcid":false,"given":"Ya","family":"Li","sequence":"first","affiliation":[{"name":"Department of Urology and Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital, Sichuan University  Chengdu PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology and Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital, Sichuan University  Chengdu PR China"},{"name":"Department of Urology, Qilu Hospital of Shandong University Cheeloo College of Medicine Shandong University  Jinan PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lede","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Urology and Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital, Sichuan University  Chengdu PR China"},{"name":"Department of Anesthesiology West China Hospital of Sichuan University  Chengdu PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8532-9336","authenticated-orcid":false,"given":"Zhongyu","family":"Jian","sequence":"additional","affiliation":[{"name":"Department of Urology and Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital, Sichuan University  Chengdu PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linhu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Urology and Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital, Sichuan University  Chengdu PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menghua","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology and Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital, Sichuan University  Chengdu PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Urology and Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital, Sichuan University  Chengdu PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Chen","sequence":"additional","affiliation":[{"name":"Animal Experimental Center West China Hospital, Sichuan University  Chengdu PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengzhu","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Urology and Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital, Sichuan University  Chengdu PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology and Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital, Sichuan University  Chengdu PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyuan","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Urology and Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital, Sichuan University  Chengdu PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banghua","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Urology and Institute of Urology (Laboratory of Reconstructive Urology) West China Hospital, Sichuan University  Chengdu PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3700-3339","authenticated-orcid":false,"given":"Xi","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Urology and Institute of Urology (Laboratory of Reconstructive Urology) West China 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