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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2020-10-01
|
| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSphere.00498-20 |
| _version_ | 1818901096058322944 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-19T20:14:19Z |
| format | Article |
| id | doaj.art-fe1c51091bb642da89dd235f290d9173 |
| institution | Directory Open Access Journal |
| issn | 2379-5042 |
| language | English |
| last_indexed | 2024-12-19T20:14:19Z |
| publishDate | 2020-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj.art-fe1c51091bb642da89dd235f290d91732022-12-21T20:07:14ZengAmerican Society for MicrobiologymSphere2379-50422020-10-015510.1128/mSphere.00498-20Oxalate-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> ModelKait F. Al0Brendan A. Daisley1Ryan M. Chanyi2Jennifer Bjazevic3Hassan Razvi4Gregor Reid5Jeremy P. Burton6Canadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, Ontario, CanadaCanadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, Ontario, CanadaCanadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, Ontario, CanadaDivision of Urology, Department of Surgery, Western University, London, Ontario, CanadaDivision of Urology, Department of Surgery, Western University, London, Ontario, CanadaCanadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, Ontario, CanadaCanadian Centre for Human Microbiome and Probiotic Research, Lawson Health Research Institute, London, Ontario, CanadaABSTRACT 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.https://journals.asm.org/doi/10.1128/mSphere.00498-20Bacillus subtilisDrosophilacalcium oxalatehost-microbe interactionsmicrobiotanephrolithiasis |
| spellingShingle | 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 mSphere Bacillus subtilis Drosophila calcium oxalate host-microbe interactions microbiota nephrolithiasis |
| 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_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_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_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 |
| topic | Bacillus subtilis Drosophila calcium oxalate host-microbe interactions microbiota nephrolithiasis |
| url | https://journals.asm.org/doi/10.1128/mSphere.00498-20 |
| work_keys_str_mv | AT kaitfal oxalatedegradingnamedcontentcontenttypegenusspeciesbacillussubtilisnamedcontentmitigatesurolithiasisinanamedcontentcontenttypegenusspeciesdrosophilamelanogasternamedcontentmodel AT brendanadaisley oxalatedegradingnamedcontentcontenttypegenusspeciesbacillussubtilisnamedcontentmitigatesurolithiasisinanamedcontentcontenttypegenusspeciesdrosophilamelanogasternamedcontentmodel AT ryanmchanyi oxalatedegradingnamedcontentcontenttypegenusspeciesbacillussubtilisnamedcontentmitigatesurolithiasisinanamedcontentcontenttypegenusspeciesdrosophilamelanogasternamedcontentmodel AT jenniferbjazevic oxalatedegradingnamedcontentcontenttypegenusspeciesbacillussubtilisnamedcontentmitigatesurolithiasisinanamedcontentcontenttypegenusspeciesdrosophilamelanogasternamedcontentmodel AT hassanrazvi oxalatedegradingnamedcontentcontenttypegenusspeciesbacillussubtilisnamedcontentmitigatesurolithiasisinanamedcontentcontenttypegenusspeciesdrosophilamelanogasternamedcontentmodel AT gregorreid oxalatedegradingnamedcontentcontenttypegenusspeciesbacillussubtilisnamedcontentmitigatesurolithiasisinanamedcontentcontenttypegenusspeciesdrosophilamelanogasternamedcontentmodel AT jeremypburton oxalatedegradingnamedcontentcontenttypegenusspeciesbacillussubtilisnamedcontentmitigatesurolithiasisinanamedcontentcontenttypegenusspeciesdrosophilamelanogasternamedcontentmodel |