Review calls for allergen assessment of precision-fermented proteins in finished foods

The review focuses on comparison with known milk and egg allergens

A review published in Foods on 5 September 2026 argues for assessing precision-fermented milk and egg proteins in their final food formulations, after realistic processing, alongside their native counterparts. The authors at Kyung Hee University examine existing evidence on how production and processing can affect protein structure and recognition by IgE antibodies, which are involved in allergic reactions.

The review focuses on recombinant milk and egg-white proteins, including established allergens such as β-lactoglobulin and ovalbumin. Its central question is whether the fermentation-derived protein behaves like the corresponding native protein. The authors argue that an identical amino-acid sequence does not by itself establish that equivalence, because production can affect other molecular properties and leave residual material in the ingredient.

Production-related differences are supported by different levels of evidence

The production organism can affect sugar modifications on the protein, processing of its ends and the host-cell material remaining after purification. The review describes observed glycosylation differences in particular fermentation-derived milk and egg proteins. It also discusses documented extensions at the beginning of some yeast-produced proteins, while noting that their prevalence across products and effects on IgE recognition have not been systematically established.

Other proposed differences, including altered disulfide pairing and susceptibility to protein breakdown in commercially relevant yeast and fungal products, remain mechanistic possibilities in the evidence reviewed. The authors distinguish these possibilities from demonstrated effects. They also state that available controlled comparisons are insufficient to rank production organisms or culture media by allergenic risk.

Food processing can change antibody recognition in either direction

Heat, high pressure, enzymatic hydrolysis and reactions with sugars can destroy, hide or expose the protein regions recognised by IgE, or create new regions for recognition. The direction depends on the protein, treatment and food matrix. The authors therefore argue that findings for conventional milk or egg ingredients cannot automatically be transferred to a fermentation-derived ingredient in a different formulation.

The review distinguishes glycosylation, in which sugars are attached enzymatically within the producing cell, from glycation, a non-enzymatic reaction with sugars during processing or storage. It reports that glycosylation differences have been observed, but direct comparisons of glycation products and resulting immune reactivity between precision-fermented and native proteins remain missing.

Each assessment method answers a different question

The authors retain the established tiered framework: review of known allergenicity and consumption history, sequence comparison with allergen databases, laboratory digestion tests, serum IgE-binding assays and clinical studies where warranted. For proteins designed to reproduce known allergens, they argue that sequence analysis is most informative where the recombinant sequence differs from the native one. Digestion tests should contribute comparative evidence rather than a simple pass-or-fail classification.

IgE binding measures antibody recognition and does not by itself establish whether a food causes clinical symptoms. The review recommends interpreting it alongside functional immune-response tests and other evidence. It describes clinical food challenges as a way to assess reactions directly, while emphasising their risk of severe allergic reactions and the need for strict supervision when lower-tier findings warrant them.

The review also separates cross-reactivity in people already sensitised to a protein from new allergic sensitisation in previously nonallergic people. The authors note that methods using antibodies from already sensitised patients cannot establish whether a new protein region can initiate sensitisation. They report that validated, internationally agreed predictive methods for new sensitisation are still lacking.

A lactoferrin example illustrates the limits of the published evidence

The review discusses a published assessment of recombinant human lactoferrin, whose native counterpart is not a major food allergen. It also cites a subsequent 28-day trial involving 66 healthy adults that measured anti-lactoferrin antibodies. That trial did not recruit allergic participants and measured total antibody rather than IgE; the review therefore states that it does not address IgE-mediated reactivity.

The authors call for direct comparisons under matched processing conditions, criteria for interpreting differences and monitoring of relevant properties across routine manufacturing batches. Human-based experimental models and computational approaches also require further validation. The review reports no newly created or analysed data, acknowledges funding from South Korea's Ministry of Food and Drug Safety and declares no conflicts of interest.