MP07-14 METABOLIC REDUNDANCY AND COOPERATION FACILITATE OXALATE METABOLISM IN THE GUT MICROBIOTA

Abstract

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology (MP07)1 Sep 2021MP07-14 METABOLIC REDUNDANCY AND COOPERATION FACILITATE OXALATE METABOLISM IN THE GUT MICROBIOTA Carlos Batagello, Anna Zampini, Andrew Nguyen, Ava Adler, Jose Agudelo, Manoj Monga, and Aaron Miller Carlos BatagelloCarlos Batagello More articles by this author , Anna ZampiniAnna Zampini More articles by this author , Andrew NguyenAndrew Nguyen More articles by this author , Ava AdlerAva Adler More articles by this author , Jose AgudeloJose Agudelo More articles by this author , Manoj MongaManoj Monga More articles by this author , and Aaron MillerAaron Miller More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000001980.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Calcium oxalate (CaOx) is a primary constituent in approximately 80% of kidney stones and hyperoxaluria is a risk factor for the onset of CaOx stones. Oxalate-degrading bacteria in the gut can reduce the levels of oxalate absorbed into the bloodstream and potentially reduce CaOx stone burden. How oxalate is processed within a complex microbial assemblage is poorly understood, as are the factors that facilitate the persistence of oxalate-degrading bacteria in the gut environment. In the current study, we aimed to determine what factors lead to persistent oxalate metabolism within the complex gut microbiota. METHODS: Through comparative metagenomic and metabolomic approaches, key bacteria and metabolic pathways stimulated by oxalate exposure were identified in mice. Bacteria that engaged in the identified metabolic pathways were isolated de novo from rodents. Mice with microbial transplants that included oxalate-degrading bacteria alone or the isolated bacteria were followed longitudinally to assess changes in urinary oxalate and formate, inflammatory cytokines, and colonization by transplanted bacteria. Additionally, levels of renal crystallization were assessed. RESULTS: Exposure to dietary oxalate benefitted the known oxalate specialist, Oxalobacter formigenes, most in a mouse model. However, oxalate-degrading genes were prevalent among diverse taxa in the gut. Besides oxalate-degrading pathways, others such as acetogenesis, methanogenesis, and sulfate reduction, were stimulated by exposure to oxalate. By including either a complete microbiome with a high capacity for oxalate metabolism or an assemblage of bacteria that included the isolated bacteria in addition to oxalate degraders, renal crystallization was significantly lowered compared to mice that received either oxalate degraders alone or those that did not receive any oxalate-degrading bacteria. CONCLUSIONS: Our results reveal that both metabolic redundancy relative to oxalate degradation and metabolic cooperation are needed to reduce calcium oxalate stone burden. These data may help to explain the limited results from clinical and animal studies that use oxalate-degrading bacteria alone and why there is a strong association between antibiotic use and the future onset of stones. Source of Funding: NIH_NOA_1R01DK121689-01A1 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e144-e145 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Carlos Batagello More articles by this author Anna Zampini More articles by this author Andrew Nguyen More articles by this author Ava Adler More articles by this author Jose Agudelo More articles by this author Manoj Monga More articles by this author Aaron Miller More articles by this author Expand All Advertisement Loading ...