Oxalobacter sp. reduces urinary oxalate excretion by promoting enteric oxalate secretion

Hatch, Marguerite; Cornelius, Janet G.; Allison, Milton J.; Sidhu, H.; Peck, Ammon B.; Freel, Robert W.

doi:10.1038/sj.ki.5000162

Cited by 216 publications

(213 citation statements)

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“…Subsequently, using various approaches in rats, we demonstrated that Oxalobacter can modulate intestinal oxalate transport by inducing colonic oxalate excretion, and a consistent and beneficial consequence of this bacterial-enterocyte interaction was a significant reduction in urinary oxalate excretion due to this enteric oxalate shunt (15). These results are especially encouraging in the context of enteric oxalate elimination in PH1, where a deficiency in the liver enzyme alanine-glyoxylate aminotransferase (AGT) results in an enhanced endogenous burden of oxalate, leading to hyperoxaluria, oxalosis, and renal failure (5).…”

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Enteric oxalate elimination is induced and oxalate is normalized in a mouse model of primary hyperoxaluria following intestinal colonization withOxalobacter

Hatch

Gjymishka

Salido

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

129

143

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Hatch M, Gjymishka A, Salido EC, Allison MJ, Freel RW. 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, 2011. First published December 16, 2010; doi:10.1152/ajpgi.00434.2010.-Oxalobacter colonization of rat intestine was previously shown to promote enteric oxalate secretion and elimination, leading to significant reductions in urinary oxalate excretion (Hatch et al. Kidney Int 69: 691-698, 2006). The main goal of the present study, using a mouse model of primary hyperoxaluria type 1 (PH1), was to test the hypothesis that colonization of the mouse gut by Oxalobacter formigenes could enhance enteric oxalate secretion and effectively reduce the hyperoxaluria associated with this genetic disease. Wild-type (WT) mice and mice deficient in liver alanine-glyoxylate aminotransferase (Agxt) exhibiting hyperoxalemia and hyperoxaluria were used in these studies. We compared the unidirectional and net fluxes of oxalate across isolated, short-circuited large intestine of artificially colonized and noncolonized mice. In addition, plasma and urinary oxalate was determined. Our results demonstrate that the cecum and distal colon contribute significantly to enteric oxalate excretion in Oxalobacter-colonized Agxt and WT mice. In colonized Agxt mice, urinary oxalate excretion was reduced 50% (to within the normal range observed for WT mice). Moreover, plasma oxalate concentrations in Agxt mice were also normalized (reduced 50%). Colonization of WT mice was also associated with marked (up to 95%) reductions in urinary oxalate excretion. We conclude that segment-specific effects of Oxalobacter on intestinal oxalate transport in the PH1 mouse model are associated with a normalization of plasma oxalate and urinary oxalate excretion in otherwise hyperoxalemic and hyperoxaluric animals. cecum; proximal colon; distal colon; slc26a6 CONSIDERABLE EVIDENCE HAS emerged from human and animal studies suggesting that colonization of the intestinal tract by the anaerobic bacterium Oxalobacter formigenes plays an important role in degrading dietary sources of oxalate in the intestine, leading to reduced intestinal oxalate absorption and, consequently, a lower urinary oxalate excretion (9, 10, 15, 18 -20, 22, 25-27, 29). Importantly, these bacteria, discovered by Allison et al.(1) in 1985, use oxalate as a sole carbon and energy source. In most of the studies involving human subjects, the approach has been to determine whether the lack of Oxalobacter colonization is associated with increased urinary oxalate excretion and stone formation (9, 10, 18 -20, 22, 26, 29). Clinical findings suggest a direct correlation between the complete absence or decreased activity of luminal Oxalobacter and the development of recurrent oxalate stone disease (18), as well as the hyperoxaluria associated with conditions such as inflammatory bowel disease, jejunoileal bypass, and cystic fibrosis (9,10,2...

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confidence: 97%

Enteric oxalate elimination is induced and oxalate is normalized in a mouse model of primary hyperoxaluria following intestinal colonization withOxalobacter

Hatch

Gjymishka

Salido

et al. 2011

American Journal of Physiology-Gastrointestinal and Liver Physi

129

143

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“…[17][18][19][20][21][22][23][24][25][26] The bacterium is known to be susceptible to some antibiotics, 27 although the sensitivity pattern is incompletely characterized. The absence of O. formigenes could permit more absorption of dietary oxalate in the colon and decreased secretion from endogenous sources, 28 resulting in higher oxalate excretion in the urine and thus predisposition to CaOx calculus formation. Data from a number of relatively small studies show that patients with renal calculi and some conditions related to hyperoxaluria have a lower prevalence of O. formigenes in the stool than control subjects.…”

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confidence: 99%

Oxalobacter formigenes May Reduce the Risk of Calcium Oxalate Kidney Stones

Kaufman

Kelly²,

Curhan³

et al. 2008

Journal of the American Society of Nephrology

258

181

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Most kidney stones are composed primarily of calcium oxalate. Oxalobacter formigenes is a Gramnegative, anaerobic bacterium that metabolizes oxalate in the intestinal tract and is present in a large proportion of the normal adult population. It was hypothesized that the absence of O. formigenes could lead to increased colonic absorption of oxalate, and the subsequent increase in urinary oxalate could favor the development of stones. To test this hypothesis, a case-control study involving 247 adult patients with recurrent calcium oxalate stones and 259 age-, gender-, and region-matched control subjects was performed. The prevalence of O. formigenes, determined by stool culture, was 17% among case patients and 38% among control subjects; on the basis of multivariate analysis controlling demographic factors, dietary oxalate, and antibiotic use, the odds ratio for colonization was 0.3 (95% confidence interval 0.2 to 0.5). The inverse association was consistently present within strata of age, gender, race/ethnicity, region, and antibiotic use. Among the subset of participants who completed a 24-h urine collection, the risk for kidney stones was directly proportional to urinary oxalate, but when urinary factors were included in the multivariable model, the odds ratio for O. formigenes remained 0.3 (95% confidence interval 0.1 to 0.7). Surprisingly, median urinary oxalate excretion did not differ with the presence or absence of O. formigenes colonization. In conclusion, these results suggest that colonization with O. formigenes is associated with a 70% reduction in the risk for being a recurrent calcium oxalate stone former.

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“…Oxalobacter formigenes (O. formigenes) is an aerobic gram negative bacterium that uses oxalate as its energy source and decreases intestinal absorption of oxalate and thus reduces urinary oxalate excretion [34,35] . This has been well documented in both human and animal experiments [36,37] .…”

Section: Role Of Oxalobacter Formigenesmentioning

confidence: 99%