MXPA99010790A - Oxalate-degrading microorganisms or oxalate-degrading enzymes for preventing oxalate related disease - Google Patents

Abstract

La presente invención provee materiales y procedimientos para el suministro de cepas seleccionadas de bacterias y/o enzimas degradantes de oxalato al tracto intestinal de personas quienes tienen riesgo acrecentado de enfermedad relacionada a oxalato debido a que han perdido, o tienen concentraciones inadecuadas, de estas bacterias;la administración de estas bacterias y/o la enzima relevante remueve el oxalato del tracto intestinal, y reduce de esta manera la cantidad de oxalato disponible para absorción, y reduce el riesgo de enfermedad relaciona a oxalato.

Description

OXALATO DEGRADING MICROORGANISMS OR ENZYMES OXALATO DEGRADANTS TO PREVENT DISEASE RELATED TO OXALATO RECIPROCAL REFERENCE TO RELATED REQUEST This application claims the priority of provisional application USSN 60 / 047,473, filed on May 23, 1997.

BACKGROUND OF THE INVENTION The calculations of the genitourinary tract (urolithiasis) are a major health problem throughout the world. Most stones associated with urolithiasis are composed of calcium oxalate alone or calcium oxalate plus calcium phosphate. Other disease states have also been associated with excess oxalate. These include vulvodynia, oxalosis associated with end-stage renal disease and Crohn's disease, and other enteric disease states. Oxalic acid (and / or its salt oxalate) is found in a wide variety of foods, and is therefore a component of many constituents of the human diet. The increased oxalate absorption may occur after foods containing high amounts of oxalic acid are ingested. Foods such as spinach and rhubarb are well known to contain high amounts of oxalate, but a multitude of other foods and beverages also contain oxalate. Since oxalate is found in a wide variety of foods, diets that have low levels of oxalate and are also acceptable are difficult to formulate. Oxalate is also produced metabolically by normal tissue enzymes. Oxalate (the dietary oxalate that is absorbed, as well as the oxalate that is produced metabolically) is not further metabolized by tissue enzymes and, therefore, must be excreted. This excretion occurs mainly through the kidneys. The concentration of oxalate in kidney fluids is critical, since increased oxalate concentrations cause increased risk of calcium oxalate crystal formation, and thus the subsequent formation of kidney stones. The risk of kidney stone formation revolves around a number of factors that have not yet been fully understood. Renal stones of genitourinary treatment occur in approximately 2% of the population in western countries, and approximately 70% of these calculations are formed of calcium oxalate or calcium oxalate plus calcium phosphate. Some individuals (eg, patients with intestinal disease such as Crohn's disease, inflammatory bowel disease or steatorrhea, and also patients who have undergone jejunoileal bypass surgery), absorb most of the oxalate from their diets, than others. For these individuals, the incidence of urolithiasis by oxalate increases markedly. The incidence of increased disease is due to increased levels of oxalate in the kidneys and urine and this, the hyperoxaluric syndrome most common in man, is known as enteric hyperoxaluria. Oxalate is also a problem in patients with end-stage renal disease, and there is recent evidence (Solomons et al. [1991] "Calcium citrate for vulvar vestibulitis" Journal of Reproductive Medicine 36: 879-882) that elevated urinary oxalate intervenes also in vulvar vestibulitis (vulvodynia). Oxalate degrading bacteria have been isolated from human feces (Allison et al. [1986] "Oxalate degradation by gastrointestinal bacteria from humans" J. Nutr.1-16: 455-460). It was found that these bacteria are similar to oxalate degrading bacteria that have been isolated from the intestinal contents of a number of animal species (Dawson et al. [1980] "Isolation and some characteristics of anaerobic oxalate-degrading bacteria the rumen" Appl. Environ Microbiol 40: 833-839; Allison and Cook [1981] "Oxalate degradation by microbes of the large bowel of herbivores: the effect of dietary oxalate" Science 212: 675-676; Daniel et al. [1987] "Microbial degradation of oxalate in the gastrointestinal tracts of rats "Appl, Environ Microbiol 53: 1793-1797). These bacteria are different from any organism described above, and have been given a new name of species and genus, formigenes (Allison et al. [1985] "Oxalobacter formigenes gen. Nov., Sp. Nov .. oxalate-degrading anaerobes that inhabit the gastrointestinal tract "Arch Microbiol.141: 1-7).

Not all humans possess populations of O. formigenes in their intestinal tract (Allison et al. [1995] "Oxalate-degrading bacteria", in Khan, S. R (ed.), Calcium Qxalate in Biological Systems CRC Press, Doane et al. [1989] "Microbial oxalate degradation: effects on oxalate and calcium balance in humans" Nutrition Research 9: 957-964). There are very low concentrations or complete absence of oxalate-degrading bacteria in fecal samples from people who have undergone jejunoileal bypass surgery (Allison et al. [1986] "Oxalate degradation by gastrointestinal bacteria from humans" J. Nutr. 1 16: 455- 460).

BRIEF DESCRIPTION OF THE INVENTION The present invention pertains to materials and methods that reduce the risk of developing urolithiasis by limiting the amount of dietary oxalate absorbed from the intestinal tract. In one embodiment of the present invention, a reduction in oxalate absorption is achieved by supplying oxalate degrading bacteria to the intestinal tract. In a preferred embodiment, these bacteria are Oxalobacter formigenes. These bacteria only use oxalate as growth substrate. This use reduces the concentration of soluble oxalate in the intestine, and in this way the amount of oxalate available for absorption. In a specific embodiment, the present invention provides materials and methods for the delivery of O. formigenes to the intestinal tract of people who are at increased risk of oxalate-related disease. These bacteria and their progeny replicate in the intestine, and remove the oxalate from the intestinal tract, thereby reducing the amount of oxalate available for absorption and thus reducing the risk of oxalate-related disease. In a further embodiment of the present invention, a reduction in oxalate absorption is achieved by administering enzymes that function to degrade oxalate. These enzymes can be isolated and purified, or they can be administered as a lysate of Oxalobacter formigenes cells. In a specific embodiment, the enzymes that are administered are formyl-CoA transferase and oxalyl-CoA decarboxylase. In a preferred embodiment, additional factors that improve enzyme activity can be administered. These additional factors can be, for example, oxalyl CoA, MgCl2 and TPP (thiamine diphosphate, an active form of vitamin B ^.) Another aspect of the present invention pertains to pharmaceutical compositions for oral administration. Oxalate or oxalate-degrading enzymes in the small intestine of humans Preferably, the microorganisms and / or the enzymes are encapsulated in a dose delivery system that decreases the likelihood of release of the materials in the stomach, but which increases the probability of release in the small intestine Microorganisms and / or enzymes can also be administered as a constituent of foods such as milk, meats and yogurt.

BRIEF DESCRIPTION OF THE FIGURES Figure 1 a shows the results of a study evaluating the fate of dietary oxaiate when Oxalobacter formigenes cells are included in the diet. Figure 1b shows the results of a study evaluating the fate of dietary oxalate when Oxalobacter formigenes cells are included in the diet. Figure 2a shows the results of a study evaluating the fate of dietary oxalate when Oxalobacter formigenes cells are included in the diet. \ Figure 2b shows the results of a study evaluating the fate of dietary oxalate when Oxalobacter formigenes cells are included in the diet. Figure 2c shows the results of a study evaluating the fate of dietary oxalate when Oxalobacter formigenes cells are included in the diet.

DETAILED DESCRIPTION OF THE INVENTION The present invention pertains to the introduction of oxalate degrading bacteria and / or enzymes into the human intestinal tract, where the activity of these materials reduces the absorption of oxalate and reduces the risk of disease due to it. In a specific embodiment, the present invention pertains to the preparation and administration of cells of oxalate-degrading bacteria of the species Oxalobacter formigenes, to the human intestinal tract, where their metabolic activities reduce the amount of oxalate available for absorption from the intestine, and reduce in this way the oxalate concentrations in the kidney and other cellular fluids. The introduced cells degrade the oxalate and replicate in the intestinal habitat, so that the progeny of the initial cells colonize the intestine and continue to remove the oxalate. This activity reduces the risk of kidney stone formation, as well as other complications of disease caused by oxalic acid. In a preferred embodiment, the specific strains of O. formigenes used are strains isolated from human intestinal samples. The strains are thus part of the normal human intestinal bacterial flora. However, since they are not present in all people, the introduction of these organisms corrects a deficiency that exists in some humans. The enrichment of the contents of the small intestine with one or more species of oxalate-degrading bacteria causes a reduction of oxalate in the intestinal contents. Some of the bacteria carry out the degradation of oxalate at or near the absorption site. The activity of the bacteria decreases the level of absorption of dietary oxalate. Pharmaceutical compositions for the introduction of oxalate-degrading bacteria and / or enzymes into the small intestine, include bacteria and / or enzymes that have been lyophilized or frozen in the form of paste or liquid, and encapsulated in a gel capsule. The material of the gel capsule is preferably a polymeric material that forms a pill or delivery capsule that is resistant to degradation by gastric acidity and pepsin of the stomach, but which is degraded by the concomitant release of oxalate-degrading materials by the higher pH and bile acid contents in the proximal small intestine. The released material then converts the oxalate present in the small intestine to harmless products. You can also combine pharmaceutical vehicles with bacteria or enzymes. These would include saline-pH phosphate buffer. Bacteria and / or enzymes that will be administered can be supplied as capsules or microcapsules designed to protect the material from the adverse effects of the stomach acid. One or more of several enteric protective coating methods may be used. Descriptions of such enteric coatings include the use of phthalate-cellulose acetate (CAP) (Yacobí, A., E. H. Walega, 1988, Oral reissue forms: Dosing and evaluation, Pergammon Press). Other descriptions of encapsulation technology include the U.S. patent. No. 5,286,495, incorporated herein by reference. Other methods of administering these microorganisms and / or enzymes to the small intestine include the addition of the material directly to the food sources. The bacteria can be added as freshly harvested cells, freeze-dried cells, or other protected cells. The food can be complemented with oxalate degrading organisms, without affecting its taste or appearance. These foods can be, for example, yogurt, milk, peanut butter or chocolate. After ingestion, when the foodstuffs are being digested and absorbed by the small intestine, the microorganisms and / or the enzymes degrade the oxalate present in the small intestine, thus preventing the absorption thereof into the bloodstream. Food can be supplemented with oxalate-degrading microorganisms. Microbes can be grown in media, and be separated from them in the form of a paste by centrifugation. Traditional yogurt cultures obtained from any commercial dairy product can be mixed with the culture of oxalate degrading microbes. This culture mixture can then be added to the basic premix of dairy product - yogurt without affecting its flavor or consistency. The yogurt can then be produced and packaged by using traditional commercial procedures. In another example, oxalate-degrading bacteria can be added to already produced yogurts.

Another example is adding the microbes to milk after it has been homogenized and sterilized. This method is currently used by the dairy industry to add the organism Lactobacillus acidophilus. Any food source containing bacteria can be used, supplemented with oxalate-degrading bacteria, such as cheese or meat products that have selected microorganisms added during processing. Strains of bacteria (O. formigenes) used in accordance with the present invention are preferably pure cultures that are isolated from anerobic cultures that have been inoculated with dilutions of intestinal contents of normal humans. A special medium containing calcium oxalate can be used to detect oxalate-degrading colonies. The purity of each strain can be ensured by the use of at least two subsequent repetitive cloning steps. O. formigenes strains useful in accordance with the present invention have been characterized based on several tests including: cellular fatty acid patterns, cellular protein patterns, DNA and RNA (Jensen and Allison, 1995), and responses to probes of oligonucleotides (Sidhu et al., 1996). Two groups of these bacteria have been described (Groups I and II, both existing within the present description of the species). The strains used have been selected based on the degradation capacity of oxalate and the evidence of the ability to colonize the human intestinal tract. Selected strains include representative members of groups I and II of the species. One embodiment of the present invention encompasses methods for the selection, preparation and administration of oxalate-degrading bacteria appropriate for a variety of subjects. Prominently, but not exclusively, these are people who do not host these bacteria in their intestines. These uncolonized people are identified using tests that allow the rapid and definitive detection of O. formigenes even when the organisms are at relatively low concentrations in mixed bacterial populations, such as those found in the intestinal contents. The methods of the present invention can also be used to treat individuals whose oxalate degrading bacteria have been depleted due to, for example, antibiotic treatment or in post-operative situations. Bacteria that can be used according to the present invention can be identified by at least two methods: 1) Oligonucleotide probes specific for these bacteria can be used; and / or 2) A culture test, in which an anaerobic medium with 10 mM oxalate is inoculated, and after incubation at 37 ° C for 1 to 7 days, the oxalate loss is determined. Pure cultures of strains of O. formigenes can be grown in batch cultures in fermenters, and the cells can be harvested using techniques known to those skilled in the art. Cells of a selected individual strain, or mixtures of known strains, can be treated as needed (eg, by freeze-dehydration with trehalose or glycerol) to preserve their viability, and then placed in capsules designed to protect them at the same time. pass through the stomach acid (enteric coating capsules). The cells are ingested in quantities and at intervals determined by the needs of the individuals. In some cases, an individual or periodic use may be all that is needed and, in other cases, regular ingestion may be required (for example, with food). The invention also pertains to the administration to the human intestinal tract of oxalate-degrading products or enzymes prepared from O. formigenes cells. In one embodiment, the oxalate degrading enzymes can be purified and prepared as a pharmaceutical composition for oral consumption. In a preferred embodiment, these enzymes are produced recombinantly. The DNA sequences encoding these enzymes are known to those skilled in the art and are described, for example, in WO 98/16632. These sequences, or other sequences that code for oxalate degrading proteins, can be expressed in a suitable host. The host can be, for example, E. coli. The expressed protein can be isolated, purified and administered, as described herein. Alternatively, the recombinant host expressing the desired oxalate degrading proteins can be administered. The recombinant host can be administered in a viable or non-viable form. In another preferred embodiment, the enzymes are coated or otherwise formulated or modified to protect them, so that they are not inactivated in the stomach and are available to exert their oxalate degrading activity in the small intestine. Examples of such formulations are known to those skilled in the art and are described, for example, in the US patent. No. 5,286,495. Following are examples illustrating the procedures for practicing the invention. These examples should not be considered as limiting.

EXAMPLE 1 Treatment of high-risk patients O. formigenes cells coated with enteric coat, can be ingested by populations of patients at high risk of oxalate-related disease. These include: 1 .- People who have a history of uroiitíasis with multiple episodes of idiopathic calculations. 2.- People in risk of urolithiasis with high concentration of urinary oxalate due to enteric disease (enteric hyperoxaluria). 3.- People with high levels of oxalate in serum due to end-stage renal disease. 4.- People with vulvar vestibulitis.

. - People who have diets with high levels of oxalate, such as occurs in certain areas and stations in India and Saudi Arabia.

EXAMPLE 2 Treatment of low risk patients O. formigenes cells protected with an enteric layer can also be ingested by individuals in populations with less risk of oxalate-related disease. These include: 1. People who have lost populations of normal oxalate-degrading bacteria due to: oral antibiotic treatments or episodes of diarrheal disease. 2. Infants that will be inoculated, so that a normal protective population of Oxalobacter is established more easily than it is in the later case of life, when they operate principles of competitive exclusion. 3.- Other people not yet specified that may benefit.

EXAMPLE 3 Use of oxalolate-degrading enzymes of Oxalobacter formigenes to control hyperoxaluria A study was conducted to evaluate the efficacy of oxalolate degrading enzymes of Oxalobacter formigenes for the control of hyperoxaluria.

Animals used: Sprague Dawley male rats: body weight, 250-300 g. Diets used: Normal diet (N.D): Harían Teklad TD 89222; Ca at 0.5%, P at 0.4%. Drug used: lyophilized lysate mixture of Oxalobacter formigenes (enzyme source) with Oxalil CoA, MgCl2 and TPP. Drug delivery system (capsules): Capsule size 9 for previous clinical studies in rats (Capsu-Gel). Enteric coating Eudragit L-100-55 (Hulls America, Inc.). Basal collection of urine for 24 hours. Fecal analysis for Oxalobacter formigenes - rats were not colonized with Oxalobacter formigenes.

Experimental protocol: A. Long-term studies: Protocol for animals: Group I (n = 4): Oxalate diet was administered with the lysate. The rats were administered two capsules a day at 4: p.m., and an oxalate diet at night. The diet was removed during the day (8:00 a.m. to 4:00 p.m.). Group II (n = 4): Oxalate diet was administered as described for group I (hyperoxaluric controls). 24-hour urine samples were obtained on days 7 and 9 of the previous treatment. The data on the average concentration of urinary oxalate for the two groups of rats shown above, indicated that the Oxalobacter lysate supply decreased the concentration of urinary oxalate in the rats of group I, compared with the hyperoxaluric controls (group II). Enzymes can not be active for a long period in the gastrointestinal tract; therefore, short-term studies were carried out as described below.

B. Short-term studies: Protocol for animals: Group I (n = 4): One capsule was administered at 8:00 a.m .; oxalate diet for two hours (the rats were fasted overnight so that they will feed well during this period) and a capsule at 10:00 a.m. Group II (n = 4): Oxalate diet for two hours as in group I. The urine of all animals was collected for the following 5-hour period, and analyzed for the oxalate concentration. This was carried out on days 1 1, 12 and 15 of this study. The results of this study show that the oxalobacter lysate supply produces a significant decrease in urinary oxalate levels in a period of 5 hours after the administration of oxalate and drug in the rats of group I, compared to the hyperoxaluric control group (group II). At this point, a cross study between the two groups of rats was carried out.

C. Cross-over studies: Protocol for animals: Group I: Oxalate diet was administered twice a day at 8:00 - 10:00 a.m. and at 3:00 p.m. - 5:00 pm. Group II: One capsule was given twice daily before feeding the oxalate diet as in group I. Short-term studies were carried out for the effect of Oxalobacter's lysate delivery on urinary oxalate levels, as described in section B above, and on days 2 and 5 after the cross study. Cross-sectional studies show that the previously hyperoxaluric group II rats, which are now being fed with the Oxalobacter lysate, show a decrease in urinary oxalate levels. In contrast, group I rats revert to hyperoxaluria after withdrawal of the drug.

EXAMPLE 4 Treatment of rats with Oxalobacter formigenes cells A study was conducted to evaluate the fate of dietary oxalate when Oxalobacter formigenes cells are included in the diet.

Methods: Male Wistar rats were fed a diet of normal concentration of calcium (1%) and high concentration of oxalate (0.5%), or with a diet of low calcium concentration (0.02%) and high concentration of oxalate (0.5%) ) during two separate experiments. 14C-oxalate (2.0 uCi) was administered on day 1, and again on day 7 of the study. Oxalobacter formigenes cells (380 mg / day) were administered to the water that rats drank on days 5 to 1 1. The fate of oxalate 14C was measured based on the analysis of 14C in feces, urine and expired air. The rats served as self-controls, and measurements were made during the control period (before the Oxalobacter cells were delivered) during days 1 to 4; during the experimental period (when the bacterial cells were delivered), measurements were made on days 7 to 11.

Results: 1. When the rats were fed the normal calcium diet (1%), less than 1% of the administered dose of 14C of the oxalate in the expired air was recovered (such as carbon dioxide produced from oxalate 14C in the intestine, absorbed in the blood and then expired); however, in all cases, more than 14C was recovered during the period when the rats were fed with Oxalobacter cells (Figure 1 a). This contrasts with the results obtained when the diet had low levels of calcium (0.02%), when more than 50% of the 1 C of the oxalate recovered as carbon dioxide in the expired air during the experimental period, when the rats were fed with Oxalobacter cells (Figure 1b). These results are remarkably different from the very low amounts of 14C (less than 5%) recovered during the control period (prior to delivery of Oxalobacter cells). In this way, the supply of Oxalobacter formigenes cells to rats markedly increased the amount of dietary oxalate, which was degraded in the intestinal tract. 2. The supply of Oxalobacter cells also decreased the amount of 14C-oxalate that was excreted in the urine. The values for a collection of 4 days during the control and experimental periods, and for a single day in each of these periods, are shown in figures 2a and 2b, respectively. The amounts of oxalate recovered in the rat feces were also lower during the experimental period (when the Oxalobacter cells were delivered), than those found for the control period (Figure 2c). Most laboratory rats do not have Oxalobacter in their intestinal tract (that is, they are not colonized). The present results show that the determined administration of these oxalate-degrading bacteria to rats causes a large portion of the dietary oxalate to be degraded and, consequently, less dietary oxalate to be excreted in the urine. The effects of dietary calcium on oxalate degradation are remarkable. Calcium combines with oxalate, so that their solubility and availability to be attacked by Oxalobacter are limited, and the amount that is degraded when the rats are fed a diet of high calcium concentration, is much lower than the amounts degraded when the calcium in the diet is at a low concentration. It should be understood that the examples and embodiments described herein are for illustrative purposes only, and that various modifications or changes in light thereof will be suggested by those skilled in the art and will be included within the spirit and scope of the application. and the scope of the appended claims.

REFERENCES Allison, MJ, HM Cook (1981) Oxalate degradation by microbes of the large bowel of herbivores: the effect of dietary oxalate "Science 212: 675-676 Allison, MJ, Dawson KA, WR Mayberry, JG Foss (1985)" Oxalabacter formigenes gen. nov., sp. nov .: oxalate-degrading anaerobes that inhabit the gastrointestinal tract "Arch. Microbiol. 141: 1-7 Allison, MJ, HM Cook, DB Milne, S. Gallagher, RV Clayman (1986)" Oxalate degradation by gastrointestinal bacterium from humans "J. Nutr. 1 16: 455-460 Allison, MJ, SL Daniel, NA Cornick (1995)" Oxalate-degrading bacteria ", in Khan, SR (ed.), Calcium Oxalate in Bioloqical Systems CRC Press (in press Costello, J., M. Smith, MJ Allison "Manipulation of urinary oxalate by feeding Oxalobacter formigenes to rats and the possible significance of Oxalobacter in the extrarenal excretion of oxalate" (unpublished data) Daniel, SL, PA Hartman, MJ Allison (1987) "Microbial degradation of oxalate in the gastrointestinal tracts of rats." Appl. Environ Microbiol 53: 1793-1797 Daniel, SL, PA Hartman, MJ Allison (1993) "Intestinal colonization of laboratory rats by anaerobe oxalate-degrading bacterium: effects on the urinary and fecal excretion n of dietary oxalate "Microbial Ecology in Health and Disease 6: 277-283. Dawson, K.A., M.J. Allison, P.A. Hartman (1980) "Isolation and some characteristics of anaerobic oxalate-degrading bacteria the rumen" Appl. Environ. Microbiol. 40: 833-839. Doane, L. T., M. Liebman, D. R. Caldwell (1989) "Microbial oxalate degradation: effects on oxalate and calcium balance in humans" Nutrition Research 9: 957-964. Earnest, D. L. (1979) "Entéric hyperoxaluria", in Stollerman, G. H. (ed.), Advances in internal medicine, Year Book Medical Publisher, St. Louis, 25: 407-427. Hodgkinson, A. (1977) Oxalic Acid in Bioloqy and Medicine, Academic Press, New York. Ito, H., Miyake M., M. Noda "A new oxalate-degrading organism solated from human feces", Summary of the Annual Meeting of the Amer. Soc. Microbiol., Q-106. Jensen, N. S., M. J. Allison (1995) "Studies on the diversity among anaerobic oxaiate degrading bacteria now in the species Oxalobacter formigenes", Summary of the General Meeting of the Amer. Soc. Microbiol., 1- 29. Soiomons, C. C, M. H. Melmed, S. M. Heitler (1991) "Calcium citrate for vulvar vestibulitis" Journal of Reproductive Medicine 36: 879-882.

Claims (21)

NOVELTY OF THE INVENTION CLAIMS

1. A method for reducing the absorption of dietary oxalate, characterized in that said method comprises administering a composition comprising a material selected from the group consisting of oxalate degrading microbes and oxalate degrading enzymes.

2. The method according to claim 1, further characterized in that said method comprises the administration of oxalate-degrading enzymes.

3. The method according to claim 2, further characterized in that it comprises administering formyl-CoA transferase and oxalyl-CoA decarboxylase.

4. The method according to claim 3, further characterized in that said enzymes are produced in recombinant form.

5. The method according to claim 3, further characterized in that it comprises administering an additional factor selected from the group consisting of oxalyl CoA, MgCl2 and TPP.

6. The method according to claim 1, further characterized in that it comprises administering intact and intact oxalate degrading microbes.

7. - The method according to claim 6, further characterized in that said microbes are Oxalobacter formigenes.

8. The method according to claim 6, further characterized in that said microbes colonize the intestines.

9. The method according to claim 1, further characterized in that it is used to treat a patient whose intestines have insufficient numbers of oxalate-degrading bacteria.

10. The method according to claim 9, further characterized in that it is used to treat a patient whose natural intestinal bacteria have been depleted due to treatment with antibiotics. 1.

The method according to claim 1, further characterized in that said microbe or said enzyme is formulated to reduce the inactivation in the stomach.

12. The method according to claim 1, further characterized in that said formulation comprises a coating that dissolves preferably in the small intestine, comparatively with the stomach.

13. A composition for reducing the absorption of dietary oxalate from the intestines, characterized in that said composition comprises a material selected from the group consisting of oxalate degrading microbes and oxalate degrading enzymes.

14. The composition according to claim 13, further characterized in that said composition comprises viable and intact oxalate degrading bacteria.

15. The composition according to claim 13, further characterized in that said composition comprises lysate of cells of oxalate-degrading bacteria.

16. The composition according to claim 13, further characterized in that said bacteria are Oxalobacter formigenes.

17. The composition according to claim 13, further characterized in that said composition comprises oxalate degrading enzymes.

18. The composition according to claim 17, further characterized in that said enzymes are formyl-CoA transferase and oxalyl CoA decarboxylase.

19. The composition according to claim 18, further characterized in that it comprises a compound selected from the group consisting of oxalyl CoA, MgCl2 and TPP.

20. The composition according to claim 13, further characterized in that said composition is formulated to reduce deactivation in the stomach.

21. The composition according to claim 20, further characterized in that said composition is coated with a material that is preferably degraded in the small intestine.