Understanding the Enzymes That Break Down Oxalates

December 10, 2025 •

4 min read

While the human body does not produce its own enzymes to break down oxalates, specific microorganisms in our gut are equipped to do so. These microbial-derived enzymes are vital for metabolizing dietary oxalates and preventing their accumulation, a process central to reducing the risk of kidney stones and other health issues.

Quick Summary

Several enzymes, primarily from gut bacteria, are responsible for breaking down oxalates. The most prominent are oxalyl-CoA decarboxylase and formyl-CoA transferase, produced mainly by the bacterium Oxalobacter formigenes and other species like Lactobacillus and Bifidobacterium.

Key Points

Microbial origin: The human body does not produce its own oxalate-degrading enzymes; this function is performed by microorganisms in the gut.
Primary enzymes: The main enzymes are oxalyl-CoA decarboxylase (Oxc) and formyl-CoA transferase (Frc), which work together in a two-step process.
Key bacterium: The specialized gut bacterium Oxalobacter formigenes is the most well-known producer of these enzymes and uses oxalate as its sole energy source.
Gut microbiome network: Several other bacteria, including strains of Lactobacillus and Bifidobacterium, also contribute to oxalate degradation, forming a crucial microbial network.
Antibiotic impact: Antibiotics can disrupt the gut microbiome and kill oxalate-degrading bacteria like O. formigenes, increasing the risk of kidney stones.
Hyperoxaluria link: The absence or reduction of oxalate-degrading microbial activity is a significant risk factor for hyperoxaluria and calcium oxalate kidney stones.
Therapeutic potential: Therapeutic strategies involve using probiotics to restore oxalate-degrading bacteria or administering recombinant oxalate-degrading enzymes directly.

Key Enzymes and Microorganisms Involved in Oxalate Breakdown

The breakdown of oxalates, particularly in the human digestive system, is a function primarily performed by the gut microbiota, not by human enzymes. This process is crucial for maintaining oxalate homeostasis and preventing conditions like hyperoxaluria and calcium oxalate kidney stones. Several enzymes and the microbes that produce them play a significant role.

Oxalyl-CoA Decarboxylase (Oxc) and Formyl-CoA Transferase (Frc)

In humans, the two most critical enzymes for oxalate degradation are oxalyl-CoA decarboxylase (Oxc) and formyl-CoA transferase (Frc). These enzymes work in tandem within specific gut bacteria, such as the specialized anaerobe Oxalobacter formigenes. The two-step process involves:

Step 1: The Frc enzyme facilitates the transfer of a CoA moiety to oxalate, converting it into oxalyl-CoA.
Step 2: The Oxc enzyme then decarboxylates the oxalyl-CoA, yielding carbon dioxide and formyl-CoA.

This two-enzyme system allows bacteria like O. formigenes to use oxalate as their sole source of energy.

The Critical Role of Oxalobacter formigenes

Oxalobacter formigenes is a key player in oxalate metabolism and is particularly efficient at breaking down dietary oxalates in the large intestine. It is considered a 'specialist' oxalotroph because it uniquely relies on oxalate for its survival. Studies have consistently shown that the presence of O. formigenes in the gut is associated with lower urinary oxalate excretion, a protective factor against kidney stone formation. The bacterium also appears to stimulate the colon to secrete endogenous oxalate back into the gut lumen, where it can be degraded. However, the colonization of O. formigenes is often transient and can be eliminated by common antibiotics, which is linked to an increased risk of kidney stones.

Other Oxalate-Degrading Bacteria

While O. formigenes is the most studied, a complex network of other gut bacteria also contributes to oxalate degradation. These include 'generalist' oxalotrophs that can metabolize other nutrients besides oxalate. Notable examples include strains from the following genera:

Lactobacillus spp.: Various strains of this probiotic bacteria, including L. acidophilus and L. gasseri, possess the oxc and frc genes and have demonstrated oxalate-degrading abilities. Their effectiveness, however, can be species- and strain-specific.
Bifidobacterium spp.: Certain strains, such as Bifidobacterium animalis and B. infantis, also harbor oxalate-degrading enzymes. Like Lactobacillus, their oxalate-degrading capacity depends on the specific species and strain.
Enterococcus spp.: Species like Enterococcus faecalis have shown the ability to degrade oxalates, sometimes using them as an energy source in nutrient-poor conditions.

The Importance of the Microbiome and the Gut-Kidney Axis

The overall oxalate-degrading activity of the gut microbiome is more critical than the presence of a single bacterial species. This is due to the complex, interacting network of microbes that collectively influence oxalate handling. This relationship forms a 'gut-kidney axis,' where the health of the gut microbiome directly impacts kidney function and the risk of developing conditions like hyperoxaluria and calcium oxalate kidney stones. Disturbances to this microbial balance, or 'dysbiosis,' can severely impair oxalate degradation and lead to increased oxalate absorption.

Comparison of Oxalate-Degrading Enzymes


Feature	Oxalyl-CoA Decarboxylase (Oxc) & Formyl-CoA Transferase (Frc)	Oxalate Oxidase (OxO)	Oxalate Decarboxylase (OxDC)
Source	Primarily bacterial (e.g., O. formigenes, Lactobacillus, Bifidobacterium)	Primarily plants (e.g., wheat, azalea) and some fungi	Fungi (e.g., Trametes hirsuta) and some bacteria (e.g., Bacillus subtilis)
Mechanism	Two-step, anaerobic process using CoA and thiamine pyrophosphate	Aerobic process that splits oxalate into two CO2 and H2O2	Manganese-dependent, aerobic process that splits oxalate into formate and CO2
Location	Intracellular, within gut microbiota in mammals	Mostly in plant cell walls	Intracellular, within fungi and certain bacteria
Relevance for Human Health	Highly relevant for gut microbiome-mediated oxalate metabolism; crucial for reducing dietary oxalate absorption	Used primarily in diagnostic kits and research; not naturally present in humans	Found in some bacteria and fungi; recombinant versions have been studied for therapeutic use
Cofactor	Thiamine pyrophosphate, magnesium ion	Manganese	Manganese, oxygen

Therapeutic Implications

The knowledge of these enzymes and the bacteria that produce them has opened new avenues for therapeutic intervention, particularly for hyperoxaluria. Oral administration of recombinant oxalate-degrading enzymes, such as reloxaliase, has been developed to treat enteric hyperoxaluria by breaking down oxalate in the gastrointestinal tract. Additionally, targeting the gut microbiome through probiotics is another promising strategy. Research is ongoing to develop and improve these strategies.

Conclusion

In summary, the human body does not produce its own enzymes to break down oxalates. This critical function is performed by a network of specialized enzymes, most notably oxalyl-CoA decarboxylase and formyl-CoA transferase, which are produced by microorganisms within the gut, such as Oxalobacter formigenes and certain species of Lactobacillus and Bifidobacterium. The activity of these enzymes is a crucial aspect of maintaining oxalate homeostasis, and their presence is strongly linked to a reduced risk of kidney stones. Disruptions to this gut microbial network, often caused by antibiotic use, can lead to increased oxalate absorption and a higher risk of developing oxalate-related health issues. Efforts to restore or augment this microbial function through probiotics or recombinant enzymes hold promise for managing hyperoxaluria. For further reading, an authoritative source on oxalate homeostasis is available in this publication: Oxalate homeostasis - PubMed Central.

Frequently Asked Questions

No, the human body does not produce its own enzymes to break down oxalates. We rely on the enzymes produced by certain bacteria living in our gut to perform this function.

Oxalobacter formigenes is a specific type of anaerobic bacterium that lives in the human gut and uses oxalate as its primary source of energy. It is highly efficient at degrading oxalate and is considered a key species for maintaining proper oxalate balance.

Certain strains of Lactobacillus and Bifidobacterium are also capable of degrading oxalates, although they are not specialists like O. formigenes and can use other energy sources. They contain the necessary genes, oxc and frc, to aid in oxalate metabolism within the gut.

The loss of these beneficial bacteria, often due to antibiotic use, can reduce the gut's ability to break down dietary oxalate. This can lead to increased absorption of oxalate into the bloodstream, increasing the risk of hyperoxaluria and kidney stone formation.

Oxalate oxidase is primarily found in plants and converts oxalate into carbon dioxide and hydrogen peroxide. Oxalyl-CoA decarboxylase, typically found in gut bacteria, works with formyl-CoA transferase to convert oxalate into carbon dioxide and formate within a two-step anaerobic process.

While some dietary supplements contain probiotic strains of oxalate-degrading bacteria, their effectiveness can be variable. The overall activity of the microbiome and other dietary factors can influence their success. Recombinant enzyme supplements, such as reloxaliase, are also being developed for therapeutic use.

The gut-kidney axis refers to the communication and functional relationship between the gut and the kidneys. The gut microbiome's ability to degrade oxalates directly impacts the amount of oxalate that reaches the kidneys, thus influencing kidney health and function.