Study Reveals Diverse Digestion of Proteins Impacts Gut Health

A recent study conducted by researchers at North Carolina State University challenges conventional views on dietary proteins, revealing that not all proteins are digested uniformly. As protein-rich diets gain popularity, this research highlights the significant variations in how different protein sources interact with the gut microbiota, potentially influencing overall health.

Using advanced high-resolution mass spectrometry, the study examined purified proteins from six distinct sources: soy, casein, brown rice, yeast, pea, and egg white. Researchers assessed the fate of these proteins in both germ-free mice—which lack gut microbiota—and mice with a conventional microbiota. This approach allowed for a detailed analysis of how much protein was digested by the host and which proteins escaped digestion to interact with gut microbes.

Ayesha Awan, a Ph.D. candidate at NC State and the study’s lead author, emphasized the importance of understanding these interactions. “Protein that isn’t fully digested makes its way to the colon, where it can interact with gut microbes,” Awan noted. “Those interactions may not always have the effect you’re aiming for in your diet.”

The findings revealed that proteins from all sources were present in the fecal samples of both groups of mice. Surprisingly, even proteins considered highly digestible, such as those from egg whites, showed significant portions escaping digestion. “Egg white is often thought of as a highly digestible protein source, but our study showed that a notable portion escapes digestion,” Awan explained. Furthermore, the study found that brown rice protein constituted about 50% of the fecal proteins, indicating it was not efficiently digested by either the host or gut microbiota.

The research also underscored the influence of gut microbiota on protein digestion. Manuel Kleiner, an associate professor of plant and microbial biology at NC State and co-author of the study, pointed out that the focus should shift from a simple animal-plant dichotomy to a deeper analysis of specific protein sources. “What we are finding is really it’s much more about the specific protein source,” he said.

In addition to digestion efficiency, the study identified specific proteins that were differentially abundant based on the presence of gut microbes. Certain proteins, particularly those linked to host health, were found to degrade more in the presence of gut microbiota, while others were enriched. Notably, antinutritional factors, such as the Kunitz trypsin inhibitor found in soy and several antimicrobial proteins from egg whites, escaped digestion and were available to gut microbes.

The research is significant for its comprehensive examination of multiple regions of the digestive tract. Unlike previous studies that focused solely on fecal matter, this study tracked proteins throughout the gut. It found that digestion in the small intestine remained largely consistent, whether or not the mice had gut microbes. “Most of the digestion is happening the same at the start in the small intestine,” Kleiner noted. The main differences were observed in the large intestine, where the microbiota had more opportunity to interact with the proteins.

These interactions could potentially influence the production of various metabolites, such as short-chain fatty acids and indoles, which are known to impact host health. The inefficient digestion of functional proteins, including enzyme inhibitors and antimicrobial compounds, raises questions about their roles in gut physiology and microbial composition.

The implications of this research extend to understanding diet-related health outcomes, such as inflammatory bowel conditions and metabolic disorders. As Awan stated, “Future work will focus on how different sources of dietary proteins and their interactions with the gut microbiota affect host health.”

The study’s findings have been published in the journal Food & Function on September 3, 2025. The research was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R35GM138362. Co-authors of the paper include Alexandria Bartlett, J. Alfredo Blakeley-Ruiz, Tanner Richie, and Casey M. Theriot, all from NC State. This investigation not only enhances the understanding of dietary proteins but also opens new avenues for research into their health implications.