Oxalate-Degrading <named-content content-type="genus-species">Bacillus subtilis</named-content> Mitigates Urolithiasis in a <named-content content-type="genus-species">Drosophila melanogaster</named-content> Model

ABSTRACT Kidney stones affect nearly 10% of the population in North America and are associated with high morbidity and recurrence, yet novel prevention strategies are lacking. Recent evidence suggests that the human gut microbiota can influence the development of nephrolithiasis, although clinical t...

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Autores principales:	Kait F. Al, Brendan A. Daisley, Ryan M. Chanyi, Jennifer Bjazevic, Hassan Razvi, Gregor Reid, Jeremy P. Burton
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Bacillus subtilis Drosophila calcium oxalate host-microbe interactions microbiota nephrolithiasis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/fe1c51091bb642da89dd235f290d9173
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spelling	oai:doaj.org-article:fe1c51091bb642da89dd235f290d91732021-11-15T15:30:58ZOxalate-Degrading <named-content content-type="genus-species">Bacillus subtilis</named-content> Mitigates Urolithiasis in a <named-content content-type="genus-species">Drosophila melanogaster</named-content> Model10.1128/mSphere.00498-202379-5042https://doaj.org/article/fe1c51091bb642da89dd235f290d91732020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00498-20https://doaj.org/toc/2379-5042ABSTRACT Kidney stones affect nearly 10% of the population in North America and are associated with high morbidity and recurrence, yet novel prevention strategies are lacking. Recent evidence suggests that the human gut microbiota can influence the development of nephrolithiasis, although clinical trials have been limited and inconclusive in determining the potential for microbially based interventions. Here, we used an established Drosophila melanogaster model of urolithiasis as a high-throughput screening platform for evaluation of the therapeutic potential of oxalate-degrading bacteria in calcium oxalate (CaOx) nephrolithiasis. The results demonstrated that Bacillus subtilis 168 (BS168) is a promising candidate based on its preferential growth in high oxalate concentrations, its ability to stably colonize the D. melanogaster intestinal tract for as long as 5 days, and its prevention of oxalate-induced microbiota dysbiosis. Single-dose BS168 supplementation exerted beneficial effects on D. melanogaster for as long as 14 days, decreasing stone burden in dissected Malpighian tubules and fecal excreta while increasing survival and behavioral markers of health over those of nonsupplemented lithogenic controls. These findings were complemented by in vitro experiments using the established MDCK renal cell line, which demonstrated that BS168 pretreatment prevented increased CaOx crystal adhesion and aggregation. Taking our results together, this study supports the notion that BS168 can functionally reduce CaOx stone burden in vivo through its capacity for oxalate degradation. Given the favorable safety profile of many B. subtilis strains already used as digestive aids and in fermented foods, these findings suggest that BS168 could represent a novel therapeutic adjunct to reduce the incidence of recurrent CaOx nephrolithiasis in high-risk patients. IMPORTANCE Kidney stone disease is a morbid condition that is increasing in prevalence, with few nonsurgical treatment options. The majority of stones are composed of calcium oxalate. Unlike humans, some microbes can break down oxalate, suggesting that microbial therapeutics may provide a novel treatment for kidney stone patients. This study demonstrated that Bacillus subtilis 168 (BS168) decreased stone burden, improved health, and complemented the microbiota in a Drosophila melanogaster urolithiasis model, while not exacerbating calcium oxalate aggregation or adhesion to renal cells in vitro. These results identify this bacterium as a candidate for ameliorating stone formation; given that other strains of B. subtilis are components of fermented foods and are used as probiotics for digestive health, strain 168 warrants testing in humans. With the severe burden that recurrent kidney stone disease imposes on patients and the health care system, this microbial therapeutic approach could provide an inexpensive therapeutic adjunct.Kait F. AlBrendan A. DaisleyRyan M. ChanyiJennifer BjazevicHassan RazviGregor ReidJeremy P. BurtonAmerican Society for MicrobiologyarticleBacillus subtilisDrosophilacalcium oxalatehost-microbe interactionsmicrobiotanephrolithiasisMicrobiologyQR1-502ENmSphere, Vol 5, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bacillus subtilis Drosophila calcium oxalate host-microbe interactions microbiota nephrolithiasis Microbiology QR1-502
spellingShingle	Bacillus subtilis Drosophila calcium oxalate host-microbe interactions microbiota nephrolithiasis Microbiology QR1-502 Kait F. Al Brendan A. Daisley Ryan M. Chanyi Jennifer Bjazevic Hassan Razvi Gregor Reid Jeremy P. Burton Oxalate-Degrading <named-content content-type="genus-species">Bacillus subtilis</named-content> Mitigates Urolithiasis in a <named-content content-type="genus-species">Drosophila melanogaster</named-content> Model
description	ABSTRACT Kidney stones affect nearly 10% of the population in North America and are associated with high morbidity and recurrence, yet novel prevention strategies are lacking. Recent evidence suggests that the human gut microbiota can influence the development of nephrolithiasis, although clinical trials have been limited and inconclusive in determining the potential for microbially based interventions. Here, we used an established Drosophila melanogaster model of urolithiasis as a high-throughput screening platform for evaluation of the therapeutic potential of oxalate-degrading bacteria in calcium oxalate (CaOx) nephrolithiasis. The results demonstrated that Bacillus subtilis 168 (BS168) is a promising candidate based on its preferential growth in high oxalate concentrations, its ability to stably colonize the D. melanogaster intestinal tract for as long as 5 days, and its prevention of oxalate-induced microbiota dysbiosis. Single-dose BS168 supplementation exerted beneficial effects on D. melanogaster for as long as 14 days, decreasing stone burden in dissected Malpighian tubules and fecal excreta while increasing survival and behavioral markers of health over those of nonsupplemented lithogenic controls. These findings were complemented by in vitro experiments using the established MDCK renal cell line, which demonstrated that BS168 pretreatment prevented increased CaOx crystal adhesion and aggregation. Taking our results together, this study supports the notion that BS168 can functionally reduce CaOx stone burden in vivo through its capacity for oxalate degradation. Given the favorable safety profile of many B. subtilis strains already used as digestive aids and in fermented foods, these findings suggest that BS168 could represent a novel therapeutic adjunct to reduce the incidence of recurrent CaOx nephrolithiasis in high-risk patients. IMPORTANCE Kidney stone disease is a morbid condition that is increasing in prevalence, with few nonsurgical treatment options. The majority of stones are composed of calcium oxalate. Unlike humans, some microbes can break down oxalate, suggesting that microbial therapeutics may provide a novel treatment for kidney stone patients. This study demonstrated that Bacillus subtilis 168 (BS168) decreased stone burden, improved health, and complemented the microbiota in a Drosophila melanogaster urolithiasis model, while not exacerbating calcium oxalate aggregation or adhesion to renal cells in vitro. These results identify this bacterium as a candidate for ameliorating stone formation; given that other strains of B. subtilis are components of fermented foods and are used as probiotics for digestive health, strain 168 warrants testing in humans. With the severe burden that recurrent kidney stone disease imposes on patients and the health care system, this microbial therapeutic approach could provide an inexpensive therapeutic adjunct.
format	article
author	Kait F. Al Brendan A. Daisley Ryan M. Chanyi Jennifer Bjazevic Hassan Razvi Gregor Reid Jeremy P. Burton
author_facet	Kait F. Al Brendan A. Daisley Ryan M. Chanyi Jennifer Bjazevic Hassan Razvi Gregor Reid Jeremy P. Burton
author_sort	Kait F. Al
title	Oxalate-Degrading <named-content content-type="genus-species">Bacillus subtilis</named-content> Mitigates Urolithiasis in a <named-content content-type="genus-species">Drosophila melanogaster</named-content> Model
title_short	Oxalate-Degrading <named-content content-type="genus-species">Bacillus subtilis</named-content> Mitigates Urolithiasis in a <named-content content-type="genus-species">Drosophila melanogaster</named-content> Model
title_full	Oxalate-Degrading <named-content content-type="genus-species">Bacillus subtilis</named-content> Mitigates Urolithiasis in a <named-content content-type="genus-species">Drosophila melanogaster</named-content> Model
title_fullStr	Oxalate-Degrading <named-content content-type="genus-species">Bacillus subtilis</named-content> Mitigates Urolithiasis in a <named-content content-type="genus-species">Drosophila melanogaster</named-content> Model
title_full_unstemmed	Oxalate-Degrading <named-content content-type="genus-species">Bacillus subtilis</named-content> Mitigates Urolithiasis in a <named-content content-type="genus-species">Drosophila melanogaster</named-content> Model
title_sort	oxalate-degrading <named-content content-type="genus-species">bacillus subtilis</named-content> mitigates urolithiasis in a <named-content content-type="genus-species">drosophila melanogaster</named-content> model
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/fe1c51091bb642da89dd235f290d9173
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Oxalate-Degrading <named-content content-type="genus-species">Bacillus subtilis</named-content> Mitigates Urolithiasis in a <named-content content-type="genus-species">Drosophila melanogaster</named-content> Model

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