Gluten has long been blamed for digestive upset, but a new review uncovers its surprising health potential, from antioxidant peptides to blood pressure benefits, while exploring cutting-edge ways to make wheat safer for sensitive eaters.
Study: Gluten Proteins: Beneficial Factors and Toxic Triggers in Human Health. Image credit: baibaz/Shutterstock.com
Gluten is often linked to adverse health outcomes, but new evidence shows gluten-derived peptides can have antioxidant, antihypertensive, hypocholesterolemic, antidiabetic, and even protective effects against drug-induced oxidative damage, in addition to immune-modulatory functions. A recent review in Foods examined gluten proteins, highlighting their role in gluten-related disorders and their release of beneficial bioactive peptides during digestion and fermentation.
The two sides of gluten
Gluten is a group of storage proteins primarily found in wheat, with smaller amounts also present in barley and rye. It is valued for giving dough elasticity, structure, and texture, making it essential in bread, pasta, and baked goods. However, gluten is also linked to health issues in sensitive individuals.
Celiac disease (CD) affects about 1% of people. It is an autoimmune disorder triggered when people with specific genes eat gluten. Non-celiac gluten sensitivity (NCGS) and wheat allergy also cause gut and body symptoms, but through different mechanisms. For NCGS, experts increasingly use the term “non-celiac wheat/gluten sensitivity” since other wheat components, such as amylase-trypsin inhibitors (ATIs) and fermentable carbohydrates (FODMAPs), are also recognized as frequent symptom triggers.
At the same time, gluten is not purely harmful. Digestion, fermentation, or microbial activity can release bioactive peptides that support antioxidant defense, blood pressure regulation, and immune function. The review emphasizes that their effectiveness depends on bioavailability and whether these peptides remain intact, absorbed, and biologically active after digestion. The dual nature highlights gluten’s complex role in human nutrition.
Structure and composition
Gluten comprises gliadins (soluble proteins) and glutenins (insoluble polymers). Gliadins, rich in glutamine and proline, resist digestion and can provoke immune reactions. Glutenins, composed of high- and low-molecular-weight subunits linked by disulfide bonds, provide dough elasticity and strength.
Gluten-like proteins also occur in barley (hordeins), rye (secalins), and oats (avenins). While rye and barley often trigger CD, oats are generally less immunogenic but problematic for some patients. Gluten’s molecular complexity explains its desirable baking properties and its persistence in the gut, where resistant peptides can activate immune responses.
Gluten toxicity
In CD, incomplete digestion leaves gluten peptides intact. Modified by tissue transglutaminase, these peptides strongly bind immune receptors, triggering inflammation, intestinal injury, and symptoms such as diarrhea, anemia, and weight loss. Other factors, such as innate peptides (p31-43), gut microbiota imbalances, or viral infections, may influence disease onset. The only treatment is a lifelong gluten-free diet.
NCGS remains poorly defined. Symptoms such as bloating, abdominal pain, and fatigue improve with wheat or gluten reduction, but the triggers may include other components like amylase–trypsin inhibitors. Unlike CD, NCGS does not cause lasting intestinal damage.
Wheat allergy can provoke baker’s asthma, food-induced anaphylaxis, or other allergic symptoms. Numerous wheat proteins act as allergens; strict avoidance is the only effective management.
Gluten-linked benefits
Alongside its risks, gluten is a source of peptides with health-promoting potential. These are released during digestion, germination, or microbial fermentation. Many come from gliadins and glutenins, though other wheat proteins contribute.
Antioxidant peptides neutralize free radicals, reducing oxidative stress linked to chronic disease. Some also lower blood pressure by inhibiting angiotensin-converting enzyme. Other peptides demonstrate immunomodulatory, hypocholesterolemic, or antidiabetic activity by influencing cytokine signaling and enzyme function.
Gluten exorphins (opioid-like peptides) may affect mood, appetite, and gut function, though their role in humans is still debated. Some researchers even suggest possible links to neurological or neurodevelopmental disorders such as autism or schizophrenia, but the evidence remains inconclusive. Their clinical significance remains unclear, but targeted hydrolysis could enhance peptide release, supporting the development of functional wheat-based foods.
Reducing gluten toxicity
Fermentation with bacterial strains, particularly lactic acid bacteria, can break down gluten proteins and release beneficial peptides. When combined with fungal proteases, this process can substantially reduce immunogenic fragments. It also improves bread’s nutritional profile by enhancing mineral bioavailability and antioxidant activity. However, results in celiac patients are inconsistent, as not all harmful peptides are eliminated.
Enzymatic strategies use targeted proteases, such as prolyl endopeptidases, to cleave resistant gluten sequences. Enzyme cocktails or combinations with other treatments can neutralize highly toxic peptides. These have been applied in baking and brewing, producing lower-gluten foods, though ensuring complete safety remains difficult.
Oral enzyme therapy delivers proteases directly to the digestive tract to degrade gluten before it triggers immune responses. Products like latiglutenase and engineered proteases show potential for reducing damage from accidental gluten exposure. Still, the review stresses that these therapies are unreliable replacements for a strict gluten-free diet and that clinical trial results have been mixed and limited.
Genetic and breeding approaches aim to derive wheat with fewer immunogenic proteins through gene editing or crossbreeding. While effective in reducing harmful peptides, these methods face technical and consumer acceptance challenges.
Conclusions
Gluten-derived peptides hold promise as nutraceuticals, with antioxidant, antihypertensive, hypocholesterolemic, and antidiabetic properties. However, research remains limited, especially on their real-world health effects and whether they remain active and available after digestion. Rigorous animal and human studies are needed to validate their benefits.
For CD, a gluten-free diet is still the only proven treatment, though innovative strategies may ease restrictions and improve quality of life. Similar work is underway for NCGS, though its mechanisms and biomarkers are unclear.
Crucially, gluten is not inherently harmful for most people. For most, wheat-based foods can form part of balanced diets and may even provide health benefits. The challenge is harnessing gluten’s benefits while minimizing risks for sensitive individuals, guiding personalized nutrition and future therapeutic strategies.
Download your PDF copy now!
Precision probiotics lower blood sugar and cholesterol in mice