{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T10:55:47Z","timestamp":1791543347068,"version":"4.3.4"},"reference-count":10,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T00:00:00Z","timestamp":1791504000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["W2433079"],"award-info":[{"award-number":["W2433079"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32350010"],"award-info":[{"award-number":["32350010"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Calcium oxalate nephrolithiasis is commonly viewed as a consequence of urinary supersaturation, although crystal retention and renal injury are also influenced by gut microbiota dysbiosis and local tissue environment. In a recent study by Li\n                    <jats:italic>et al<\/jats:italic>\n                    , published in\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    , the authors integrated human metagenomic and metabolomic analyses with mouse and tubular cell models to identify indole\u20103\u2010propionic acid (IPA) as a key gut\u2010derived metabolite associated with kidney stone disease. Patients with calcium oxalate stones showed altered gut microbial composition and reduced serum IPA levels, which were inversely related to stone burden. In experimental models, IPA supplementation reduced renal crystal deposition, preserved kidney function, and limited tubular injury and apoptosis. Mechanistic studies showed that IPA activated aryl hydrocarbon receptor (AhR) in tubular epithelial cells, increased suppressor of cytokine signaling 3 (SOCS3) expression, and suppressed signal transducer and activator of transcription 1 (STAT1) phosphorylation and nuclear accumulation. These findings were supported by complementary activation, inhibition, knockdown, and overexpression experiments. Collectively, the data suggest that IPA protects renal epithelial cells through the AhR\u2013SOCS3\u2013STAT1 signaling pathway and may offer a potential therapeutic approach for calcium oxalate nephropathy. \u00a9 2026 The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.70134","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T10:31:13Z","timestamp":1791541873000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From microbial tryptophan metabolism to crystal injury: an\n                    <scp>IPA<\/scp>\n                    \u2013\n                    <scp>AhR<\/scp>\n                    checkpoint in calcium oxalate nephropathy"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2636-4430","authenticated-orcid":false,"given":"Lin","family":"Zhong","sequence":"first","affiliation":[{"name":"Institute of Synthetic Biology Industry, Hunan University of Arts and Science  Changde PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhagyalakshmi","family":"Purushothaman","sequence":"additional","affiliation":[{"name":"Institute of Synthetic Biology Industry, Hunan University of Arts and Science  Changde PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Tu","sequence":"additional","affiliation":[{"name":"Institute of Synthetic Biology Industry, Hunan University of Arts and Science  Changde PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3537-9340","authenticated-orcid":false,"given":"Seenivasan","family":"Boopathi","sequence":"additional","affiliation":[{"name":"Institute of Synthetic Biology Industry, Hunan University of Arts and Science  Changde PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"16008","DOI":"10.1038\/nrdp.2016.8","article-title":"Kidney stones","volume":"2","author":"Khan SR","year":"2016","journal-title":"Nat Rev Dis Primers"},{"key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41581-020-00392-1","article-title":"Randall's plaque and calcium oxalate stone formation: role for immunity and inflammation","volume":"17","author":"Khan SR","year":"2021","journal-title":"Nat Rev Nephrol"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","DOI":"10.1002\/path.70135","article-title":"Gut microbiota\u2010derived tryptophan metabolite attenuates calcium oxalate nephropathy by suppressing renal tubular cell apoptosis through the AhR\/SOCS3\/STAT1 axis","author":"Li Y","year":"2026","journal-title":"J Pathol"},{"key":"e_1_2_9_5_1","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1136\/gutjnl-2017-315734","article-title":"Understanding the gut\u2013kidney axis in nephrolithiasis: an analysis of the gut microbiota composition and functionality of stone formers","volume":"67","author":"Ticinesi A","year":"2018","journal-title":"Gut"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/nature24661","article-title":"A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites","volume":"551","author":"Dodd D","year":"2017","journal-title":"Nature"},{"key":"e_1_2_9_7_1","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.jare.2024.08.018","article-title":"Gut microbiota\u2010derived indole\u20103\u2010propionic acid alleviates diabetic kidney disease through its mitochondrial protective effect via reducing ubiquitination mediated\u2010degradation of SIRT1","volume":"73","author":"Zeng Y","year":"2025","journal-title":"J Adv Res"},{"key":"e_1_2_9_8_1","doi-asserted-by":"crossref","DOI":"10.4014\/jmb.2503.03045","article-title":"Indole propionic acid regulates gut immunity: mechanisms of metabolite\u2010driven immunomodulation and barrier integrity","volume":"35","author":"Ren T","year":"2025","journal-title":"J Microbiol Biotechnol"},{"key":"e_1_2_9_9_1","doi-asserted-by":"crossref","DOI":"10.1007\/s00240-025-01779-0","article-title":"Gut microbiota\u2010derived indole\u20103\u2010acetic acid ameliorates calcium oxalate renal stone formation via AHR\/NF\u2010\u03baB axis","volume":"53","author":"Jing J","year":"2025","journal-title":"Urolithiasis"},{"key":"e_1_2_9_10_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.micres.2025.128293","article-title":"Gut microbiota\u2013indole\u20103\u2010acetic acid axis in cancer: dual functions, mechanistic insights, and therapeutic potential","volume":"300","author":"Zhong L","year":"2025","journal-title":"Microbiol Res"},{"key":"e_1_2_9_11_1","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1016\/j.juro.2014.11.093","article-title":"Activation of the NLRP3 inflammasome in association with calcium oxalate crystal induced reactive oxygen species in kidneys","volume":"193","author":"Joshi S","year":"2015","journal-title":"J Urol"}],"container-title":["The Journal of Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.70134","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/path.70134","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/path.70134","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T10:31:15Z","timestamp":1791541875000},"score":1,"resource":{"primary":{"URL":"https:\/\/pathsocjournals.onlinelibrary.wiley.com\/doi\/10.1002\/path.70134"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,9]]},"references-count":10,"alternative-id":["10.1002\/path.70134"],"URL":"https:\/\/doi.org\/10.1002\/path.70134","archive":["Portico"],"relation":{},"ISSN":["0022-3417","1096-9896"],"issn-type":[{"value":"0022-3417","type":"print"},{"value":"1096-9896","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,9]]},"assertion":[{"value":"2026-07-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"path.70134"}}