New Study Reveals Diverse Digestive Paths for Dietary Proteins

A recent study by researchers at North Carolina State University reveals that dietary proteins, whether from animal or plant sources, are not all digested in the same manner. This research highlights important differences in the composition, digestive efficiency, and interactions of various proteins with gut microbiota. The findings, published on September 3, 2025, in the journal Food & Function, challenge the simplistic classification of proteins and offer new insights into how different types of protein influence gut health.

Using advanced high-resolution mass spectrometry, the study analyzed purified proteins from six distinct sources: soy, casein, brown rice, yeast, pea, and egg white. Researchers conducted experiments on both germ-free mice, which lack gut microbiota, and conventional mice with a typical gut microbial population. This methodology enabled the team to track which proteins evade digestion and interact with gut microbes in the large intestine.

Lead author and Ph.D. candidate Ayesha Awan emphasized the significance of these findings. “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,” Awan explained. “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.”

Strikingly, the study detected dietary proteins from all sources in the fecal samples of both mouse groups. This suggests that even proteins commonly regarded as highly digestible, such as those from egg white, can still reach the colon and serve as a food source for gut microbiota. Awan noted, “Egg white is often thought of as a highly digestible protein source, but our study showed that a notable portion escapes digestion.”

Another key finding revealed that brown rice protein constituted roughly 50% of the fecal proteins, indicating it was not efficiently digested by either the host or gut microbiota. Manuel Kleiner, an associate professor of plant and microbial biology at NC State and co-author of the study, emphasized that the impact of protein sources is more nuanced than the binary of animal versus plant proteins. “What we are finding is really it’s much more about the specific protein source and not about an animal-plant dichotomy,” Kleiner stated.

The gut microbiota’s influence on protein digestion was also significant. The study observed that certain proteins either degraded more in the presence of gut microbes or were enriched in specific conditions. Notably, proteins with potential health implications, such as anti-nutritional factors from soy and antimicrobial proteins from egg whites, were found to escape digestion and interact with gut microbiota.

Kleiner remarked, “Dietary proteins have a major impact on host physiology. We still need to understand if these proteins are intact or active when they make it to the colon.” The study distinguished itself by examining multiple regions of the digestive tract, rather than focusing solely on fecal matter. Researchers found minimal differences in digestion within the small intestine, regardless of the presence of gut microbes. The notable changes occurred in the large intestine and feces, underscoring the role of gut microbiota in shaping the fate of dietary proteins.

“The main differences we’re seeing are in the large intestine, where the microbiota has more interaction with the protein and can modify or degrade it,” Awan explained. These interactions may influence the production of metabolites, which can significantly affect host health. The study suggests that the inefficient digestion of functional proteins, including enzyme inhibitors and antimicrobial proteins, may have roles in modulating gut physiology and microbial composition.

The implications of this research extend to diet-associated health outcomes, particularly concerning inflammatory bowel conditions and metabolic disorders. Kleiner concluded, “Future work will focus on how different sources of dietary proteins and their interactions with the gut microbiota affect host health.”

This comprehensive study, which received support from the National Institutes of Health, marks a significant advancement in understanding the complex relationships between dietary proteins and gut health. Researchers hope that their findings will pave the way for more tailored dietary recommendations that consider the specific protein sources and their effects on gut microbiota.