Oxalate-Degrading Bacillus subtilis Mitigates Urolithiasis in a Drosophila melanogaster Model.

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dc.citation.issue5
dc.citation.volume5
dc.contributor.authorAl KF
dc.contributor.authorDaisley BA
dc.contributor.authorChanyi RM
dc.contributor.authorBjazevic J
dc.contributor.authorRazvi H
dc.contributor.authorReid G
dc.contributor.authorBurton JP
dc.coverage.spatialUnited States
dc.date.accessioned2024-11-14T01:57:01Z
dc.date.available2024-11-14T01:57:01Z
dc.date.issued2020-10-01
dc.description.abstractKidney 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.
dc.description.confidentialfalse
dc.edition.editionOctober 2020
dc.format.paginatione00498-e00420
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/32907948
dc.identifier.citationAl KF, Daisley BA, Chanyi RM, Bjazevic J, Razvi H, Reid G, Burton JP. (2020). Oxalate-Degrading Bacillus subtilis Mitigates Urolithiasis in a Drosophila melanogaster Model.. mSphere. 5. 5. (pp. e00498-e00420).
dc.identifier.doi10.1128/mSphere.00498-20
dc.identifier.eissn2379-5042
dc.identifier.elements-typejournal-article
dc.identifier.issn2379-5042
dc.identifier.number00498
dc.identifier.pii5/5/e00498-20
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/72000
dc.languageeng
dc.publisherAmerican Society for Microbiology
dc.publisher.urihttps://journals.asm.org/doi/10.1128/msphere.00498-20
dc.relation.isPartOfmSphere
dc.rights(c) 2020 The Author/s
dc.rightsCC BY 4.0
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectBacillus subtilis
dc.subjectDrosophila
dc.subjectcalcium oxalate
dc.subjecthost-microbe interactions
dc.subjectmicrobiota
dc.subjectnephrolithiasis
dc.subjectprobiotics
dc.subjectAnimals
dc.subjectBacillus subtilis
dc.subjectCalcium Oxalate
dc.subjectDisease Models, Animal
dc.subjectDogs
dc.subjectDrosophila melanogaster
dc.subjectFemale
dc.subjectHigh-Throughput Screening Assays
dc.subjectIntestines
dc.subjectMadin Darby Canine Kidney Cells
dc.subjectMale
dc.subjectUrolithiasis
dc.titleOxalate-Degrading Bacillus subtilis Mitigates Urolithiasis in a Drosophila melanogaster Model.
dc.typeJournal article
pubs.elements-id454660
pubs.organisational-groupOther
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