A recent study from North Carolina State University indicates that the way dietary proteins are digested varies significantly depending on their source, challenging the common categorization of proteins as simply animal- or plant-based. The research used high-resolution mass spectrometry to track purified proteins from soy, casein, brown rice, yeast, pea, and egg white in both germ-free mice and those with a conventional gut microbiota.
“We wanted to not only track how much protein is digested by the host, but also which specific proteins escape digestion to interact with the gut microbiota in the colon and ultimately which proteins make it out of the gut,” said Ayesha Awan, an NC State Ph.D. candidate and lead author of the paper. “This is especially important at a time when everyone is incorporating more protein in their diets.
“Protein that isn’t fully digested makes its way to the colon, where it can interact with gut microbes – and those interactions may not always have the effect you’re aiming for in your diet.”
The study found that dietary proteins from all sources appeared in fecal samples of both groups of mice. This result suggests even highly digestible proteins can reach the large intestine and become available for interaction with gut microbes.
“Egg white is often thought of as a highly digestible protein source, but our study showed that a notable portion escapes digestion,” Awan said. “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.”
Manuel Kleiner, associate professor at NC State and co-corresponding author on the paper, noted: “Oftentimes what people think about is animal protein versus plant protein. What we are finding is really it’s much more about the specific protein source and not about an animal-plant dichotomy.”
The presence or absence of gut microbes influenced which dietary proteins persisted through digestion. Some component proteins degraded more in mice with gut microbes than those without; others were enriched instead. Certain functional dietary proteins relevant to health—such as antinutritional factors like Kunitz trypsin inhibitor from soy or antimicrobial egg white components including lysozyme and avidin—were found to escape digestion and remain accessible to gut bacteria.
“Dietary proteins have a major impact on host physiology,” Kleiner said. “We still need to understand if these proteins are intact or active when they make it to the colon.”
Unlike previous studies focusing solely on feces, this research examined multiple digestive tract regions. Digestion in the small intestine did not differ between mice with or without microbiota; differences emerged mainly in the large intestine.
“This work follows proteins throughout the gut, not just at the very end,” Kleiner said. “Most of the digestion is happening the same at the start in the small intestine, whether the mice have a microbiota or not.”
“That means that in the small intestine, whether or not you have gut microbiota may not have much of an effect on how you’re processing that protein,” Awan said. “This makes sense since there are fewer microbes in the small intestine, and they don’t have much time to interact with dietary protein. The main differences we’re seeing are in the large intestine where microbiota has more interaction with protein and can modify or degrade it.”
These interactions could affect production of metabolites such as short-chain fatty acids or indoles linked to health outcomes.
Researchers suggest inefficient digestion of certain functional dietary proteins—including enzyme inhibitors and antimicrobial agents—could play roles influencing gut physiology and microbial composition. They conclude that considering specific sources of dietary protein may be important for understanding health effects related to diet such as inflammatory bowel conditions or metabolic disorders.
“Future work will focus on how different sources of dietary proteins and their interactions with gut microbiota affect host health,” Kleiner said.
The paper was published September 3rd in Food & Function (DOI: 10.1039/D5FO01132A) by authors from NC State University: Ayesha Awan, Alexandria Bartlett, J. Alfredo Blakeley-Ruiz, Tanner Richie, Casey M. Theriot, Manuel Kleiner.
Funding for this research came from National Institute of General Medical Sciences under award number R35GM138362.



