Meta-analysis of Clinical Microbiome Studies in Urolithiasis Reveal Age, Stone Composition, and Study Location as the Predominant Factors in Urolithiasis-Associated Microbiome Composition

ABSTRACT To determine whether functionally relevant questions associated with the urinary or gut microbiome and urinary stone disease (USD) can be answered from metagenome-wide association studies (MWAS), we performed the most comprehensive meta-analysis of published clinical MWAS in USD to date, us...

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Autores principales:	Naveen Kachroo, Dirk Lange, Kristina L. Penniston, Joshua Stern, Gregory Tasian, Petar Bajic, Alan J. Wolfe, Mangesh Suryavanshi, Andrea Ticinesi, Tiziana Meschi, Manoj Monga, Aaron W. Miller
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2021
Materias:	urolithiasis metagenomics microbiome meta-analysis kidney stone clinical Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5919acc1487d47cab3c768325f77662e
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spelling	oai:doaj.org-article:5919acc1487d47cab3c768325f77662e2021-11-10T18:37:52ZMeta-analysis of Clinical Microbiome Studies in Urolithiasis Reveal Age, Stone Composition, and Study Location as the Predominant Factors in Urolithiasis-Associated Microbiome Composition10.1128/mBio.02007-212150-7511https://doaj.org/article/5919acc1487d47cab3c768325f77662e2021-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02007-21https://doaj.org/toc/2150-7511ABSTRACT To determine whether functionally relevant questions associated with the urinary or gut microbiome and urinary stone disease (USD) can be answered from metagenome-wide association studies (MWAS), we performed the most comprehensive meta-analysis of published clinical MWAS in USD to date, using publicly available data published prior to April 2021. Six relevant studies met inclusion criteria. For alpha-diversity, significant differences were noted between USD status, stone composition, sample type, study location, age, diet, and sex. For beta-diversity, significant differences were noted by USD status, stone composition, sample type, study location, antibiotic use (30 days and 12 months before sampling), sex, hypertension, water intake, body habitus, and age. Prevotella and Lactobacillus in the gut and urinary tract, respectively, were associated with healthy individuals, while Enterobacteriaceae was associated with USD in the urine and stones. Paradoxically, other Prevotella strains were also strongly associated with USD in the gut microbiome. When data were analyzed together, USD status, stone composition, age group, and study location were the predominant factors associated with microbiome composition. Meta-analysis showed significant microbiome differences based on USD status, stone composition, age group or study location. However, analyses were limited by a lack of public data from published studies, metadata collected, and differing study protocols. Results highlight the need for field-specific standardization of experimental protocols in terms of sample collection procedures and the anatomical niches to assess, as well as in defining clinically relevant metadata and subphenotypes such as stone composition. IMPORTANCE Studies focused on the microbiome broadly support the hypothesis that the microbiome influences the onset of chronic diseases such as urinary stone disease. However, it is unclear what environmental factors shape the microbiome in ways that increase the risk for chronic disease. In addition, it is unclear how differences in study methodology can impact the results of clinical metagenome-wide association studies. In the current meta-analysis, we show that age, stone composition, and study location are the predominant factors that associate with the microbiome and USD status. Furthermore, we reveal differences in results based on specific analytical protocols, which impacts the interpretation of any microbiome study.Naveen KachrooDirk LangeKristina L. PennistonJoshua SternGregory TasianPetar BajicAlan J. WolfeMangesh SuryavanshiAndrea TicinesiTiziana MeschiManoj MongaAaron W. MillerAmerican Society for Microbiologyarticleurolithiasismetagenomicsmicrobiomemeta-analysiskidney stoneclinicalMicrobiologyQR1-502ENmBio, Vol 12, Iss 4 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	urolithiasis metagenomics microbiome meta-analysis kidney stone clinical Microbiology QR1-502
spellingShingle	urolithiasis metagenomics microbiome meta-analysis kidney stone clinical Microbiology QR1-502 Naveen Kachroo Dirk Lange Kristina L. Penniston Joshua Stern Gregory Tasian Petar Bajic Alan J. Wolfe Mangesh Suryavanshi Andrea Ticinesi Tiziana Meschi Manoj Monga Aaron W. Miller Meta-analysis of Clinical Microbiome Studies in Urolithiasis Reveal Age, Stone Composition, and Study Location as the Predominant Factors in Urolithiasis-Associated Microbiome Composition
description	ABSTRACT To determine whether functionally relevant questions associated with the urinary or gut microbiome and urinary stone disease (USD) can be answered from metagenome-wide association studies (MWAS), we performed the most comprehensive meta-analysis of published clinical MWAS in USD to date, using publicly available data published prior to April 2021. Six relevant studies met inclusion criteria. For alpha-diversity, significant differences were noted between USD status, stone composition, sample type, study location, age, diet, and sex. For beta-diversity, significant differences were noted by USD status, stone composition, sample type, study location, antibiotic use (30 days and 12 months before sampling), sex, hypertension, water intake, body habitus, and age. Prevotella and Lactobacillus in the gut and urinary tract, respectively, were associated with healthy individuals, while Enterobacteriaceae was associated with USD in the urine and stones. Paradoxically, other Prevotella strains were also strongly associated with USD in the gut microbiome. When data were analyzed together, USD status, stone composition, age group, and study location were the predominant factors associated with microbiome composition. Meta-analysis showed significant microbiome differences based on USD status, stone composition, age group or study location. However, analyses were limited by a lack of public data from published studies, metadata collected, and differing study protocols. Results highlight the need for field-specific standardization of experimental protocols in terms of sample collection procedures and the anatomical niches to assess, as well as in defining clinically relevant metadata and subphenotypes such as stone composition. IMPORTANCE Studies focused on the microbiome broadly support the hypothesis that the microbiome influences the onset of chronic diseases such as urinary stone disease. However, it is unclear what environmental factors shape the microbiome in ways that increase the risk for chronic disease. In addition, it is unclear how differences in study methodology can impact the results of clinical metagenome-wide association studies. In the current meta-analysis, we show that age, stone composition, and study location are the predominant factors that associate with the microbiome and USD status. Furthermore, we reveal differences in results based on specific analytical protocols, which impacts the interpretation of any microbiome study.
format	article
author	Naveen Kachroo Dirk Lange Kristina L. Penniston Joshua Stern Gregory Tasian Petar Bajic Alan J. Wolfe Mangesh Suryavanshi Andrea Ticinesi Tiziana Meschi Manoj Monga Aaron W. Miller
author_facet	Naveen Kachroo Dirk Lange Kristina L. Penniston Joshua Stern Gregory Tasian Petar Bajic Alan J. Wolfe Mangesh Suryavanshi Andrea Ticinesi Tiziana Meschi Manoj Monga Aaron W. Miller
author_sort	Naveen Kachroo
title	Meta-analysis of Clinical Microbiome Studies in Urolithiasis Reveal Age, Stone Composition, and Study Location as the Predominant Factors in Urolithiasis-Associated Microbiome Composition
title_short	Meta-analysis of Clinical Microbiome Studies in Urolithiasis Reveal Age, Stone Composition, and Study Location as the Predominant Factors in Urolithiasis-Associated Microbiome Composition
title_full	Meta-analysis of Clinical Microbiome Studies in Urolithiasis Reveal Age, Stone Composition, and Study Location as the Predominant Factors in Urolithiasis-Associated Microbiome Composition
title_fullStr	Meta-analysis of Clinical Microbiome Studies in Urolithiasis Reveal Age, Stone Composition, and Study Location as the Predominant Factors in Urolithiasis-Associated Microbiome Composition
title_full_unstemmed	Meta-analysis of Clinical Microbiome Studies in Urolithiasis Reveal Age, Stone Composition, and Study Location as the Predominant Factors in Urolithiasis-Associated Microbiome Composition
title_sort	meta-analysis of clinical microbiome studies in urolithiasis reveal age, stone composition, and study location as the predominant factors in urolithiasis-associated microbiome composition
publisher	American Society for Microbiology
publishDate	2021
url	https://doaj.org/article/5919acc1487d47cab3c768325f77662e
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Meta-analysis of Clinical Microbiome Studies in Urolithiasis Reveal Age, Stone Composition, and Study Location as the Predominant Factors in Urolithiasis-Associated Microbiome Composition

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