Abstract
Gut microbes are essential for the degradation of dietary oxalate, and this function may play a role in decreasing the incidence of kidney stones. However, many oxalate-degrading bacteria are susceptible to antibiotics and the use of oxalate-degrading probiotics has only led to an ephemeral reduction in urinary oxalate. The objective of the current study was to determine the efficacy of using whole-community microbial transplants from a wild mammalian herbivore, Neotoma albigula, to increase oxalate degradation over the long term in the laboratory rat, Rattus norvegicus. We quantified the change in total oxalate degradation in lab rats immediately after microbial transplants and at 2- and 9-month intervals following microbial transplants. Additionally, we tracked the fecal microbiota of the lab rats, with and without microbial transplants, using high-throughput Illumina sequencing of a hyper-variable region of the 16S rRNA gene. Microbial transplants resulted in a significant increase in oxalate degradation, an effect that persisted 9 months after the initial transplants. Functional persistence was corroborated by the transfer, and persistence of a group of bacteria previously correlated with oxalate consumption in N. albigula, including an anaerobic bacterium from the genus Oxalobacter known for its ability to use oxalate as a sole carbon source. The results of this study indicate that whole-community microbial transplants are an effective means for the persistent colonization of oxalate-degrading bacteria in the mammalian gut.
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References
James L, Butcher J (1972) Halogeton poisoning of sheep: effect of high level oxalate intake. J Anim Sci 35:1233–1238
Conyers RA, Bais R, Rofe AM (1990) The relation of clinical catastrophes, endogenous oxalate production, and urolithiasis. Clin Chem 36:1717–1730
Massey L, Roman-Smith H, Sutton R (1993) Effect of dietary oxalate and calcium on urinary oxalate and risk of formation of calcium oxalate kidney stones. J Am Diet Assoc 93:901–906
Coe F, Evan A, Worcester E (2005) Kidney stone disease. J Clin Invest 115:2598–2608
Franceschi VR, Nakata PA (2005) Calcium oxalate in plants: formation and function. Annu Rev Plant Biol 56:41–71
Taylor E, Curhan G (2008) Determinants of 24-hour urinary oxalate excretion. Clin J Am Soc Nephrol 3:1453–1460
Holmes RP, Goodman HO, Assimos DG (2001) Contribution of dietary oxalate to urinary oxalate excretion. Kidney Int 59:270–276
Dussol B, Berlan Y (1998) Urinary kidney stone inhibitors. what is the new? Urol Int 60:69–73
Khan S, Thamilselvan S (2000) Nephrolithiasis: a consequence of renal epithelial cell exposure to oxalate and calcium oxalate crystals. Mol Urol 4:305–312
Bihl G, Meyers A (2001) Recurrent renal stone disease—advances in pathogenesis and clinical management. Lancet 358:651–656
Asselman M, Verkoelen C (2002) Crystal-cell interaction in the pathogenesis of kidney stone disease. Curr Opin Nephrol 12:271–276
Barbas C, Garcías A, Saavedra L, Muros M (2002) Urinary analysis of nephrolithiasis markers. J Chromatogr B 781:433–455
Moe O (2006) Kidney stones: pathophysiology and medical management. Lancet 367:333–344
Ramello A, Vitale C, Marangella M (2000) Epidemiology of nephrolithiasis. J Nephrol 13:45–50
Alexander R, Hemmelgarn B, Wiebe N, Bello A, Morgan C, Samuel S, Klarenbach S, Curhan G, Tonelli M (2012) Kidney stones and kidney function loss: a cohort study. BMJ 345:e5287
Hodgkinson A (1977) Oxalic acid in biology and medicine. Academic Press, New York
Allison MJ, Cook HM, Milne DB, Gallagher S, Clayman RV (1986) Oxalate degradation by gastrointestinal bacteria from humans. J Nutr 116:455–460
Allison MJ, Dawson KA, Mayberry WR, Foss JG (1985) Oxalobacter formigenes gen. nov., sp. nov.: oxalate-degrading anaerobes that inhabit the gastrointestinal tract. Arch Microbiol 141:1–7
Hokama S, Honma Y, Toma C, Ogawa Y (2000) Oxalate-degrading Enterococcus faecalis. Microbiol Immunol 44:235–240
Ren Z, Pan C, Jiang L, Wu C, Liu Y, Zhong Z, Ran L, Ren F, Chen X, Wang Y (2011) Oxalate-degrading capacities of lactic acid bacteria in canine feces. Vet Microbiol 152:368–373
Daniel SL, Hartman PA, Allison MJ (1987) Intestinal colonization of laboratory rats with Oxalobacter formigenes. Appl Environ Microbiol 53:2767–2770
Turroni S, Vitali B, Bendazzoli C, Candela M, Gotti R, Federici F, Pirovano F, Brigidi P (2007) Oxalate consumption by lactobacilli: evaluation of oxalyl-CoA decarboxylase and formyl-CoA transferase activity in Lactobacillus acidophilus. J Appl Microbiol 103:1600–1609
Miller AW, Kohl KD, Dearing MD (2014) The gastrointestinal tract of the white-throated woodrat (Neotoma albigula) harbors distinct consortia of oxalate-degrading bacteria. Appl Environ Microbiol 80:1595–1601
Sidhu H, Holmes R, Allison M, Peck A (1999) Direct quantification of the enteric bacterium Oxalobacter formigenes in human fecal samples by quantitative competitive-template PCR. J Clin Microbiol 37:1503–1509
Kaufmann D, Kelly J, Curhan G, Anderson T, Dretler S, Preminger G, Cave D (2008) Oxalobacter formigenes may reduce the risk of calcium oxalate kidney stones. J Am Soc Nephrol 19:1197–1203
Campieri C, Campieri M, Bertuzzi V, Swennen E, Matteuzzi D, Stefoni S, Pirovano F, Centi C, Ulisse S, Famularo G (2001) Reduction of oxaluria after an oral course of lactic acid bacteria at high concentration. Kidney Int 60:1097–1105
Turroni S, Bendazzoli C, Dipalo SC, Candela M, Vitali B, Gotti R, Brigidi P (2010) Oxalate-degrading activity in Bifidobacterium animalis subsp. lactis: impact of acidic conditions on the transcriptional levels of the oxalyl coenzyme A (CoA) decarboxylase and formyl-CoA transferase genes. Appl Environ Microbiol 76:5609–5620
Lieske JC, Tremaine WJ, De Simone C, O’Connor HM, Li X, Bergstralh EJ, Goldfarb DS (2010) Diet, but not oral probiotics, effectively reduces urinary oxalate excretion and calcium oxalate supersaturation. Kidney Int 78:1178–1185
Sidhu H, Allison M, Peck A (1997) Identification and classification of Oxalobacter formigenes strains by using oligonucleotide probes and primers. J Clin Microbiol 35:350–353
Lange J, Wood K, Wong H, Otto R, Mufarrij P, Knight J, Akpinar H, Holmes R, Assimos D (2012) Sensitivity of human strains of Oxalobacter formigenes to commonly prescribed antibiotics. Urology 79:1286–1289
Kharlamb V, Schelker J, Francois F, Jiang J, Holmes RP, Goldfarb DS (2011) Oral antibiotic treatment of Helicobacter pylori leads to persistently reduced intestinal colonization rates with Oxalobacter formigenes. J Endourol 25:1781–1785
Duncan S, Richardson A, Kaul P, Holmes R, Allison M, Stewart C (2002) Oxalobacter formigenes and its potential role in human health. Appl Environ Microbiol 68:3841–3847
Hoppe B, Von Unruh G, Blank G, Rietschel E, Sidhu H, Laube N, Hesse A (2005) Absorptive hyperoxaluria leads to an increased risk for urolithiasis or nephrocalcinosis in cystic fibrosis. Am J Kidney Dis 46:440–445
Sidhu H, Allison M, May Chow J, Clark A, Peck A (2001) Rapid reversal of hyperoxaluria in a rat model after probiotic administration of Oxalobacter formigenes. J Urol 166:1487–1491
Hoppe B, Beck B, Gatter N, Von Unruh G, Tischer A, Hesse A, Laube N, Kaul P, Sidhu H (2006) Oxalobacter formigenes: a potential tool for the treatment of primary hyperoxaluria type 1. Kidney Int 70:1305–1311
Hatch M, Gjymishka A, Salido EC, Allison MJ, Freel RW (2011) Enteric oxalate elimination is induced and oxalate is normalized in a mouse model of primary hyperoxaluria following intestinal colonization with Oxalobacter. Am J Physiol Gastrointest Liver Physiol 300:G461–G469
Palgi N, Ronen Z, Pinshow B (2008) Oxalate balance in fat sand rats feeding on high and low calcium diets. J Comp Physiol B 178:617–622
Belenguer A, Ben Bati M, Hervás G, Toral PG, Yáñez-Ruiz DR, Frutos P (2013) Impact of oxalic acid on rumen function and bacterial community in sheep. Animal 7:940–947
Knight J, Deora R, Assimos DG, Holmes RP (2013) The genetic composition of Oxalobacter formigenes and its relationship to colonization and calcium oxalate stone disease. Urolithiasis 41:187–196
Chung J, Pamp SJ, Hill JA, Surana NK, Edelman SM, Troy EB, Reading NC, Villablanca EJ, Wang S, Mora JR, Umesaki Y, Mathis D, Benoist C, Relman DA, Kasper DL (2012) Gut immune maturation depends on colonization with a host-specific microbiota. Cell 149:1578–1593
Shirley EK, Schmidt-Nielsen K (1967) Oxalate metabolism in the pack rat, sand rat, hamster, and white rat. J Nutr 91:496–502
Miller A, Oakeson K, Dale C, Dearing M (2016) The effect of dietary oxalate on the gut microbiota of the mammalian herbivore Neotoma albigula. Appl Environ Microbiol. doi:10.1128/AEM.00216-16
Kohl KD, Weiss RB, Cox J, Dale C, Dearing MD (2014) Gut microbes of mammalian herbivores facilitate intake of plant toxins. Ecol Lett 17:1238–1246
Caporaso JG, Kuczynski J, Stombaugh J, Bittinger K, Bushman FD, Costello EK, Fierer N, Pena AG, Goodrich JK, Gordon JI (2010) QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7:335–336
Caporaso J, Lauber C, Walters W, Berg-Lyons D, Lozupone C, Turnbaugh P, Fierer N, Knight R (2011) Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample. PNAS 108:4516–4522
Bokulich N, Subramanian S, Faith J, Gevers D, Gordon J, Knight R, Mills D, Caporaso J (2012) Quality-filtering vastly improves diversity estimates from Illumina amplicon sequencing. Nat Methods 10:57–59
Edgar RC (2010) Search and clustering orders of magnitude faster than BLAST. Bioinformatics 26:2460–2461
Lozupone C, Hamady M, Knight R (2006) UniFrac—an online tool for comparing microbial community diversity in a phylogenetic context. BMC Bioinformatics 7:371
Kohl KD, Skopec MM, Dearing MD (2014) Captivity results in disparate loss of gut microbial diversity in closely related hosts. Conserv Physiol 2:cou009
Grehan M, Brody T, Leis S, Campbell J, Hazel M, Wettstein A (2010) Durable alteration of the colonic microbiota by the administration of donor fecal flora. J Clin Gastroenterol 44:551–561
Khoruts A, Dicksved J, Jansson J, Sadowsky M (2010) Changes in the composition of the human fecal microbiome after bacteriotherapy for recurrent Clostridium difficile-associated diarrhea. J Clin Gastroenterol 44:354–360
Manichanh C, Reeder J, Gibert P, Varela E, Llopis M, Antolin M, Guigo R, Knight R, Guarner F (2010) Reshaping the gut microbiome with bacterial transplantation and antibiotic intake. Genet Res 20:1411–1419
Song Y, Garg S, Girotra M, Maddox C, von Rosenvinge E, Dutta A, Dutta S, Fricke W (2013) Microbiota dynamics in patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection. PLoS One 8:e81330
Langille M, Meehan C, Koenig J, Dhanani A, Rose R, Howlett S, Beiko R (2014) Microbial shifts in the aging mouse gut. Microbiome 2:50
Germino G, Kirkali Z (2015) Urinary stone disease: research challenges and opportunities. NIDDK http://www.niddk.nih.gov/news/events-calendar/Pages/Urinary-Stone-Disease-Research-Challenges-Opportunities_04-2015.aspx#tab-minutes. Accessed 10 January 2016
Trinchieri A (2008) Epidemiology of urolithiasis: an update. Clin Cas Min Bone Metab 5:101–106
Acknowledgments
This project was funded by NSF (grant DEB-1342615 to M. Denise Dearing and Colin Dale) and NIH (grant 1F32DK102277-01A1 to Aaron W. Miller). We thank Kevin Kohl for help in collecting animals; Adam Schmidt, Caleb Felicetti, and Ky-Phuong Luong for help with diet trials; and Bob Weiss for feedback on the experiment.
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Miller, A.W., Oakeson, K.F., Dale, C. et al. Microbial Community Transplant Results in Increased and Long-Term Oxalate Degradation. Microb Ecol 72, 470–478 (2016). https://doi.org/10.1007/s00248-016-0800-2
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DOI: https://doi.org/10.1007/s00248-016-0800-2