Mp63-07 the Butox Study: The Role of the Gut Microbiome and Butyrate in Calcium Oxalate Kidney Stone Disease

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology (MP63)1 May 2024MP63-07 THE BUTOX STUDY: THE ROLE OF THE GUT MICROBIOME AND BUTYRATE IN CALCIUM OXALATE KIDNEY STONE DISEASE Sarah Hanstock, Demian Ferreira, Hans Adomat, Felipe Eltit, Qiong Wang, Dalia Othman, Breanna Nelson, Roman Herout, Rizhi Wang, Genelle Lunken, Aaron Miller, Ben Chew, and Dirk Lange Sarah HanstockSarah Hanstock , Demian FerreiraDemian Ferreira , Hans AdomatHans Adomat , Felipe EltitFelipe Eltit , Qiong WangQiong Wang , Dalia OthmanDalia Othman , Breanna NelsonBreanna Nelson , Roman HeroutRoman Herout , Rizhi WangRizhi Wang , Genelle LunkenGenelle Lunken , Aaron MillerAaron Miller , Ben ChewBen Chew , and Dirk LangeDirk Lange View All Author Informationhttps://doi.org/10.1097/01.JU.0001009436.52988.91.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Kidney stones remain a global problem with limited effective treatments and high rates of recurrence. A primary cause of kidney stones is hyperoxaluria. Dietary oxalate (Ox) is absorbed through the intestinal tract. One factor that modulates intestinal Ox absorption is the intestinal microbiome. A few studies, including ours, reported a lower abundance of butyrate-producing bacteria in the intestines of stone formers. Here we examine the role of butyrate at the intestinal and distal sites and how this influences calcium oxalate (CaOx) nephrolithiasis. METHODS: We utilized a diet-induced hyperoxaluria murine model in which animals were fed diets supplemented with inulin (prebiotic) +\- sodium oxalate, or tributyrin (butyrate prodrug) +\- sodium oxalate. Urine, blood, and stool samples were collected for Ox measurements using isotope dilution high-performance liquid chromatography/mass spectrometry, the latter samples also being used for microbiome composition analysis (16S rRNA sequencing) and short chain fatty acid (SCFA) quantification. Renal and intestinal tissues were collected to measure expression of oxalate transporters and inflammatory markers, and histology for the presence of CaOx crystals. RESULTS: Supplementation of tributyrin in animals fed a high Ox diet resulted in a significant decrease in CaOx crystal formation versus animals on the Ox diet alone (p<0.001). Tributyrin supplementation was not found to impact Ox excretion, as stool and urinary oxalate levels remained unchanged compared to the Ox only group. Inulin supplementation did not have this same protective effect in animals on the high oxalate diet. Butyrate levels were elevated in animals fed the inulin only diet (p<0.001), an effect the disappeared on a combination inulin+oxalate diet. Ox alone was shown to lead to significant microbiome dysbiosis. CONCLUSIONS: Intestinal butyrate production by the intestinal microbiome plays a significant role in the development of CaOx nephrolithiasis. Elevating intestinal butyrate levels via dietary tributyrin supplementation appears to be an effective way to attenuate renal CaOx crystal formation. The specific mechanisms involved warrant further investigation. Source of Funding: None © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1033 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Sarah Hanstock More articles by this author Demian Ferreira More articles by this author Hans Adomat More articles by this author Felipe Eltit More articles by this author Qiong Wang More articles by this author Dalia Othman More articles by this author Breanna Nelson More articles by this author Roman Herout More articles by this author Rizhi Wang More articles by this author Genelle Lunken More articles by this author Aaron Miller More articles by this author Ben Chew More articles by this author Dirk Lange More articles by this author Expand All Advertisement PDF downloadLoading ...