What Can Break Down Gluten? Understanding the Mechanisms of Gluten Degradation

October 28, 2025 •

5 min read

Human digestive enzymes, like proteases, are not fully equipped to break down the specific proline- and glutamine-rich peptides found in gluten. Understanding what can break down gluten is crucial for those with sensitivities and for innovations in food science.

Quick Summary

This article explores the biological mechanisms, from microbial and plant-based enzymes to fermentation, that break down gluten proteins. It also examines the role of supplemental enzymes and their efficacy in managing gluten sensitivities and celiac disease.

Key Points

Limited Human Capability: Human digestive enzymes are largely ineffective against the tough proline and glutamine peptide bonds in gluten.
Microbial Enzymes are Key: Enzymes known as glutenases, produced by certain bacteria and fungi, are capable of breaking down the problematic peptides in gluten.
Sourdough's Partial Breakdown: While long-fermented sourdough can reduce gluten content, it does not remove it entirely and is not safe for individuals with celiac disease.
Engineered Therapies are Promising: Novel oral enzyme supplements and pharmaceuticals are being developed to help manage accidental gluten exposure for those with celiac disease.
Gut Health Plays a Role: A healthy gut microbiome can produce its own gluten-degrading enzymes and influence the immune response to undigested gluten peptides.
Oral Supplements Vary Widely: Over-the-counter enzyme supplements should not be considered a treatment for celiac disease and are not a substitute for dietary avoidance.

The Challenge of Gluten Digestion

Gluten is a complex protein network found in wheat, barley, and rye, consisting primarily of gliadins and glutenins. Its unique structure, particularly its high content of the amino acids proline and glutamine, makes it resistant to complete degradation by normal human digestive enzymes. While most people can process gluten without issue, this incomplete digestion is the root cause of problems for those with gluten-related disorders like celiac disease (CD) and non-celiac gluten sensitivity (NCGS).

In individuals with CD, these undigested peptides trigger a severe autoimmune response in the small intestine, leading to inflammation and damage to the villi. For those with NCGS, the peptides can cause various gastrointestinal and other symptoms without the same level of intestinal damage. This resistance to digestion has driven research into alternative ways to break down gluten, both in food processing and therapeutically.

Methods and Agents for Gluten Degradation

Microbial and Plant-Based Enzymes

Beyond the human body's limited capacity, various enzymes produced by microbes and plants have shown an ability to degrade gluten proteins. These are often referred to as "glutenases".

Prolyl Endopeptidases (PEPs): This is a class of enzymes that specifically targets the peptide bonds involving proline residues, which are abundant and problematic in gluten. PEPs are produced by various bacteria and fungi. An example is AN-PEP from Aspergillus niger, which can function in the stomach's acidic environment and significantly break down gluten before it reaches the small intestine. Other bacterial sources include Sphingomonas capsulata and Myxococcus xanthus.
Cysteine Endopeptidases: Found in germinating cereals like barley, these enzymes, such as EP-B2, can break down gluten proteins, particularly cleaving after glutamine residues.
Subtilisins: Certain bacteria, including Rothia species from the human mouth and Bacillus licheniformis, produce subtilisin enzymes that can cleave immunogenic gluten peptides.

Fermentation and Food Processing

Traditional food preparation methods also influence gluten structure, though their effectiveness varies.

Sourdough Fermentation: The slow fermentation process in sourdough bread involves wild yeast and lactic acid bacteria, which produce enzymes that partially break down gluten proteins. This can make the bread more digestible for some individuals with mild gluten sensitivity. It is not, however, a safe option for individuals with celiac disease, as the remaining gluten content is still too high.
Commercial Hydrolysis: Some food products are specially processed using food-grade microbial peptidases to remove gluten or reduce it to legally mandated trace levels (below 20 ppm). This creates genuinely gluten-free products from gluten-containing ingredients.

The Role of Gut Microbiome and Intestinal Permeability

Research highlights the intricate relationship between gluten, the gut microbiome, and intestinal permeability.

Microbiota's Influence: The balance of bacteria in the gut can affect how gluten is processed. A diverse, healthy microbiome with specific bacteria like Lactobacillus has been shown to assist in breaking down gluten peptides. In contrast, dysbiosis (an imbalance in the gut flora) seen in some celiac patients may allow opportunistic pathogens like Pseudomonas to produce enzymes that can worsen the inflammatory response.
Intestinal Permeability (Leaky Gut): Undigested gluten peptides can activate zonulin, a protein that regulates the tight junctions between intestinal cells. This can lead to increased intestinal permeability, or "leaky gut," where larger molecules pass into the bloodstream, potentially triggering systemic inflammation. This effect is particularly pronounced in those with celiac disease. Read more about this at Healthline's article on leaky gut.

Oral Enzymes and Adjunctive Therapies

For individuals with gluten sensitivities, managing accidental gluten exposure is a significant concern. Oral enzyme supplements, sometimes marketed as "glutenase" products, are available, but their effectiveness can vary significantly.

Dietary Supplements: Many over-the-counter supplements contain enzymes like fungal prolyl endopeptidases (e.g., AN-PEP). While some studies show they may help reduce symptoms in cases of non-celiac gluten sensitivity, they are not a cure or reliable treatment for celiac disease. They have not been approved by the FDA as a celiac treatment and should not replace a strict gluten-free diet.
Pharmaceutical Approaches: For celiac disease, researchers are developing more robust and potent oral enzymes, like TAK-062 and Latiglutenase. These are designed to survive stomach acidity and efficiently degrade gluten peptides to provide protection against accidental exposure for patients following a gluten-free diet. These are undergoing clinical trials and are not yet widely available.

Conclusion

The human digestive system is inherently limited in its ability to break down gluten completely, which is the root of health issues for individuals with gluten-related disorders. However, a range of agents, from naturally occurring microbial and plant enzymes to engineered pharmaceutical and supplemental products, can assist in this process. While sourdough fermentation offers some reduction in gluten content, it remains unsafe for celiac patients due to incomplete degradation. The most promising current and future approaches involve targeted enzyme therapies that can effectively break down the problematic gluten peptides in the digestive tract. For those with celiac disease, a lifelong, strict gluten-free diet remains the only proven treatment. Any exploration of enzyme therapy should be done in consultation with a healthcare provider and should not be seen as a substitute for dietary avoidance. Furthermore, nurturing a healthy gut microbiome can play a supportive role in overall digestive wellness, regardless of gluten sensitivity.

Comparison of Gluten Digestion Methods


Method/Agent	Source	Mechanism	Effectiveness for Celiac Disease	General Use/Implication
Human Digestive Enzymes	Stomach, Pancreas	Proteases break down most proteins, but not fully effective on proline/glutamine-rich gluten peptides.	Ineffective; leaves immunogenic peptides.	Baseline digestion; insufficient for gluten-sensitive individuals.
Microbial Enzymes (e.g., PEP)	Bacteria (Aspergillus niger, Sphingomonas capsulata)	Cleaves peptide bonds at proline residues, breaking down gluten.	Not a replacement for GFD; potential for accidental exposure management.	Used in some dietary supplements; promising for adjunct therapy.
Sourdough Fermentation	Lactic acid bacteria, wild yeast	Bacteria break down gluten during long fermentation.	Unsafe; does not remove all gluten.	Can improve digestibility for those with mild non-celiac sensitivities.
Engineered Oral Enzymes	Pharmaceutical research (TAK-062, Latiglutenase)	Potent enzymes designed to survive gastric acid and break down immunogenic peptides.	Potential adjunct therapy to protect against cross-contamination.	Still under clinical trial; not a cure for CD.
Probiotics	Fermented foods, supplements	Certain strains (Lactobacillus) can aid in breaking down gluten peptides.	Supportive role; not a treatment.	Supports overall gut health; can complement a gluten-free diet.
Gut Microbiota	Intestinal bacteria	The balance of bacteria affects gluten processing and inflammation.	Dysbiosis can worsen inflammation.	Modulating microbiota through diet can improve overall gut health.

Frequently Asked Questions

No, digestive enzyme supplements currently available over-the-counter cannot break down enough gluten to effectively treat or cure celiac disease. A lifelong, strict gluten-free diet remains the only proven therapy.

No, fermentation does not make sourdough bread safe for people with celiac disease. While the process reduces some gluten content, it does not eliminate it completely, and even trace amounts can cause a harmful reaction.

The gut microbiome plays a supportive role, with some bacteria like certain Lactobacillus strains possessing enzymes that can further break down residual gluten peptides. However, an unhealthy microbiome can contribute to inflammation in response to gluten.

These are potent enzymes designed to be orally administered and work in the stomach and small intestine to break down the specific immunogenic gluten peptides that trigger immune responses. They are intended as a safeguard against accidental gluten ingestion for celiac patients and are currently under clinical investigation.

For those with non-celiac gluten sensitivity, some anecdotal evidence and small studies suggest certain enzyme supplements may help ease symptoms from minor gluten exposure. However, they should not be used as a license to consume gluten regularly and should be discussed with a healthcare provider.

Yes, some plants and microorganisms naturally produce enzymes (glutenases) that can degrade gluten. Examples include enzymes from germinating barley and certain fungi, which have been used in food processing or studied for therapeutic potential.

The unique protein structure of gluten is rich in proline and glutamine residues. Human proteases are unable to effectively cleave the peptide bonds at these amino acids, allowing immunogenic peptides to persist and cause problems in sensitive individuals.