Processed Food Additive Microbial Transglutaminase and Its Cross-Linked Gliadin Complexes Are Potential Public Health Concerns in Celiac Disease

Abstract

Microbial transglutaminase (mTG) is a survival factor for microbes, but yeasts, fungi, and plants also produce transglutaminase. mTG is a cross-linker that is heavily consumed as a protein glue in multiple processed food industries. According to the manufacturers' claims, microbial transglutaminase and its cross-linked products are safe, i.e., nonallergenic, nonimmunogenic, and nonpathogenic. The regulatory authorities declare it as "generally recognized as safe" for public users. However, scientific observations are accumulating concerning its undesirable effects on human health. Functionally, mTG imitates its family member, tissue transglutaminase, which is the autoantigen of celiac disease. Both these transglutaminases mediate cross-linked complexes, which are immunogenic in celiac patients. The enzyme enhances intestinal permeability, suppresses mechanical (mucus) and immunological (anti phagocytic) enteric protective barriers, stimulates luminal bacterial growth, and augments the uptake of gliadin peptide. mTG and gliadin molecules are cotranscytosed through the enterocytes and deposited subepithelially. Moreover, mucosal dendritic cell surface transglutaminase induces gliadin endocytosis, and the enzyme-treated wheat products are immunoreactive in CD patients. The present review summarizes and updates the potentially detrimental effects of mTG, aiming to stimulate scientific and regulatory debates on its safety, to protect the public from the enzyme's unwanted effects.

The temperature and pH repertoire of the transglutaminase family is expanding

“…[9]. It is related to the heavy use of mTG in processed food with the immunogenicity and potential pathogenicity of its cross‐linked protein complexes [2,5–7,10,12–14]. One wonders if by incorporating different TG genes with different temperature and pH range optimal activities into microbes, the actual detrimental Streptomyces mobaraensis ‐originated mTG will be cross‐linked in acidic and more extreme thermal environments.…”

“…Active amylase, lipase, and protease were detected, but, unfortunately, TG was not studied [15]. On a second thought, mTG, which is a survival factor for the bacteria that have unwanted side effects on human immune and physical protective barriers, intestinal permeability, and mucus quality [2,5–7,10,12], can be replaced for food processing, by a more friendly mammalian or other eukaryotic TG. If isolated and characterized from cold and hot habitats, the food industry might gain a friendlier and safer TG with a wider temperature and pH range of activity.…”

Lupin Protein Isolate Structure Diversity in Frozen-Cast Foams: Effects of Transglutaminases and Edible Fats

“…The demand for techno-functional properties of lupin proteins is of increasing interest, and here the enzymatic cross-linking of proteins using transglutaminase (TG, protein-glutamine γ-glutamyl-transferase E.C. 2.3.2.13) is commonly used to improve the techno-functional properties [ 11 , 12 , 13 ] and regarded as safe, although recent studies indicate concerns because the TG-treated wheat products can be immunoreactive patients with celiac disease [ 14 ]. Since TG catalyzes the acyl-transfer reaction between the γ-carboxylamide groups of protein (or peptide) bound glutamine and primary amines, the reaction outcome results into isopeptide bonded (inter- and intra- molecular) and cross-linked protein network.…”

Characterisation of a novel cold‐adapted calcium‐activated transglutaminase: implications for medicine and food processing

“…Microbial transglutaminase is widely used in various food processes: to manufacture cheese and other dairy products, in meat processing, and to manufacture bakery products. The use of microbial transglutaminase in the processed food has raised some concerns, since microbial transglutaminase is a potential inducer of coeliac disease . Microbial transglutaminase imitates functionally to the endogenous tissue transglutaminase, the autoantigen of coeliac disease, and may therefore represent an inducer of coeliac disease .…”

“…The use of microbial transglutaminase in the processed food has raised some concerns, since microbial transglutaminase is a potential inducer of coeliac disease . Microbial transglutaminase imitates functionally to the endogenous tissue transglutaminase, the autoantigen of coeliac disease, and may therefore represent an inducer of coeliac disease . Although microbial TGs have been extensively used, fish‐derived TGs are especially interesting for their application in food processing.…”