The Surprising Ways Your Proteins Slip Past Digestion

Protein has a reputation for being simple: eat more of it, build muscle, feel full. But new research from North Carolina State University suggests that the story is far messier. Even highly regarded proteins like egg white don’t always dissolve neatly into amino acids. Instead, a surprising share slips through undigested, landing in the colon where microbes get the first pick.

The study, published in *Food & Function*, tracked six protein sources—soy, casein, brown rice, yeast, pea and egg white—through the digestive systems of mice. Using high-resolution mass spectrometry, researchers mapped which proteins broke down in the small intestine and which persisted to the large intestine, where gut microbes take over. The results challenge the tidy dichotomy of animal versus plant protein.

Beyond the Animal-Plant Divide

“Oftentimes what people think about is animal protein versus plant protein,” said Manuel Kleiner, associate professor of plant and microbial biology at NC State and co-corresponding author. “What we are finding is really it’s much more about the specific protein source and not about an animal-plant dichotomy.”

That distinction matters because undigested proteins don’t just pass through harmlessly. They become raw material for the gut microbiota, fueling microbial metabolism that can produce beneficial compounds like short-chain fatty acids—or less welcome byproducts such as ammonia or hydrogen sulfide.

Eggs, Rice, and Unexpected Survivors

Lead author Ayesha Awan, a Ph.D. candidate at NC State, was struck by the persistence of proteins once thought highly digestible.

“Egg white is often thought of as a highly digestible protein source, but our study showed that a notable portion escapes digestion,” Awan explained. “Also, brown rice protein constituted about 50% of the fecal proteins and was not very efficiently digested by the host or by the gut microbiota.”

That means your pricey egg-white omelet may be feeding bacteria as much as it feeds you. Brown rice protein, popular in plant-based supplements, fared even worse, lingering in both germ-free and conventional mice without much breakdown.

When Proteins Keep Their Edge

Perhaps the most surprising finding was that certain functional proteins—enzyme inhibitors, lectins, antimicrobial proteins—retained their structure all the way to the colon. Soy’s Kunitz trypsin inhibitor and egg white’s avidin and lysozyme were among those still intact, raising the question of whether they remain active inside the gut.

“Dietary proteins have a major impact on host physiology,” Kleiner noted. “We still need to understand if these proteins are intact or active when they make it to the colon.”

If they are, it could help explain links between diet and conditions like inflammatory bowel disease. Proteins that block digestive enzymes or alter microbial communities could tip the balance toward either resilience or dysfunction.

Following the Proteins, Step by Step

The researchers didn’t just look at feces, as most studies do. They sampled multiple sections of the gut, confirming that digestion in the small intestine looked similar regardless of whether microbes were present. It was only in the large intestine where differences emerged. The gut microbiota either degraded proteins further or allowed them to persist in altered forms.

That nuance could shift how nutritionists and food companies talk about protein. Marketing often leans on digestibility scores like PDCAAS, but those measures may not capture what happens once proteins meet a living microbiome.

Uncomfortable Questions Ahead

Protein powders and high-protein diets are booming, but this work underscores that not all grams are created equal. For some, protein might be nourishing gut microbes in ways that support health. For others, it could stoke inflammation or deprive the host of nutrients. And it’s not yet clear how much of this mouse biology translates directly to humans.

For now, the message is cautionary: more protein isn’t always better, and the source matters in ways far beyond “plant” or “animal.” The researchers plan to explore next how these source-specific differences affect metabolic and inflammatory outcomes.

Journal: Food & Function
DOI: 10.1039/D5FO01132A