Maastricht University tests how fermentation-made milk proteins behave in the gut

Maastricht University researchers are developing animal-free methods to assess the safety and nutritional value of milk proteins made through precision fermentation, as a Dutch research program approaches its conclusion. The work focuses on what happens to these proteins during digestion and the evidence manufacturers need before bringing them to the European market. Separate research at the university has explored producing silk proteins in tobacco plant cells for potential medical applications.

‍• Researchers are using simulated digestion to investigate lactoferrin produced in bacteria.
• The dairy protein research forms part of Protein Transition 2.0, a national project running from 2022 to 2026.
• A separate doctoral project has developed a method for producing silk proteins in tobacco plant cells.

Vaios Fytsilis, based in the university’s Pharmacology and Toxicology research group, is studying lactoferrin produced in bacteria by a project partner. His colleague Miriam Urlings, at the Food Claims Research Centre in Venlo, is investigating the regulatory questions surrounding market access.

Their work forms part of Protein Transition 2.0, led by Wageningen University. The project examines several production approaches, including tissue-engineered milk, precision fermentation-derived milk proteins and microbial biomass. Its research covers protein quality, processing, scalability, food applications and safety.

According to Maastricht University, producing milk from cultured udder cells proved too difficult within the project, while precision fermentation offered a promising route to individual milk proteins.

For Fytsilis, the connection to Maastricht began with the cultivated burger unveiled in 2013.

“When I heard about that hamburger as a student, I was fascinated. Now I'm working in the very same field in Maastricht!” he said.

His current work addresses a question that cannot be answered simply by showing that a microorganism can produce a particular protein: how will that protein behave when someone eats it?

The lactoferrin sample in his laboratory is a light-brown powder. Assessing it requires attention to the protein’s structure as well as its chemical identity.

“Chemically, the cultivated protein is identical to that of a cow, but such a long molecule also has a three-dimensional shape,” Fytsilis said. “The way in which the protein acquires that 3D shape differs from one organism to another. A cow does it differently from a bacterium. That's why you can't be certain that our body can digest the protein or even tolerate it. That's the kind of thing you have to demonstrate in the lab.”

Fytsilis uses an animal-free method that reproduces digestion through the mouth, stomach and gut in sequence. He then analyzes the resulting breakdown products.

“This gives us a quick and relatively inexpensive insight into the protein's safety and nutritional value, which helps with the registration of such a novel food,” he said.

Urlings is examining how that evidence fits into the European assessment process. She is interviewing representatives from industry and the European Food Safety Authority to better understand the procedure and the questions applicants encounter.

“Answering the safety question is a search for everyone, because these cultivated proteins are so new,” she said.

Exposure is part of that assessment. Urlings emphasized that safety depends on the amount consumed, with assessors considering high consumption when evaluating proposed uses.

The Protein Brewery, another Protein Transition 2.0 participant, has already secured EU authorization for its Fermotein mycelium ingredient. That product is fungal biomass suitable for applications including dairy alternatives, distinct from the milk proteins produced through precision fermentation in the Maastricht research.

Urlings plans to investigate labeling next, including the names available to manufacturers selling ingredients intended to replace dairy proteins.

At the university’s Aachen-Maastricht Institute for Biobased Materials, Lara Bitar has investigated another animal protein: silk. Her doctoral research developed a method for producing silk proteins in tobacco plant cells.

Silk is of interest for medical applications because it is biodegradable and well tolerated in the body. Conventional production requires large numbers of silkworms, while variation in the resulting material presents a further challenge. The university said Bitar’s approach could offer a route to medical silk after further development. Her thesis, Silk fibroin produced in tobacco for biomedical applications, was published in September 2026.

Fytsilis and Urlings hope to continue their research after Protein Transition 2.0 ends.

“We've developed unique knowledge in a niche field, knowledge that isn't available anywhere else,” Fytsilis said. “It would be nice if the industry continued to work with us rather than trying to reinvent the wheel themselves.”

(Main photo shows Vaios Fytsilis in the laboratory at Maastricht University, where he is developing animal-free methods to assess the digestion and safety of fermentation-made milk proteins)

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