New Study Reveals Diverse Digestive Paths for Dietary Proteins

A recent study from North Carolina State University has unveiled that dietary proteins are not all digested in the same way, challenging the traditional classification of proteins into animal and plant-based categories. This research indicates that the source of protein significantly affects its composition, digestive efficiency, and interaction with the gut microbiota.

The study employed high-resolution mass spectrometry to analyze purified proteins from six different sources: soy, casein, brown rice, yeast, pea, and egg white. Researchers observed the fate of these proteins in both germ-free mice, lacking gut microbiota, and conventional mice with a complete microbiota. The findings revealed that some proteins escape complete digestion and reach the large intestine, where they can influence gut microbial activity.

Ayesha Awan, a Ph.D. candidate at NC State and lead author of the study, emphasized the importance of understanding how proteins interact with gut microbes. “We wanted to track how much protein is digested by the host and which specific proteins escape digestion to interact with the gut microbiota in the colon,” Awan stated. She noted that undigested proteins can lead to unintended effects, especially as many people are increasing protein intake in their diets.

Interestingly, proteins from all tested sources were detected in the fecal samples of both groups of mice, suggesting that even those proteins typically regarded as easily digestible can arrive in the colon and serve as nutrients for gut microbes. For instance, while egg white is often viewed as a highly digestible protein, a significant portion was found to escape digestion. The study also highlighted that brown rice protein constituted approximately 50% of the fecal proteins, indicating it was not efficiently digested either by the host or by gut microbiota.

Manuel Kleiner, an associate professor of plant and microbial biology at NC State and co-corresponding author, noted that the research indicates that individual protein sources behave differently. “What we are finding is that it’s much more about the specific protein source and not just about an animal-plant dichotomy,” Kleiner explained.

The study also revealed that the gut microbiota plays a crucial role in determining which proteins persist in the intestinal tract. Some proteins were more degraded in the presence of gut microbes, while others were enriched. Notably, certain proteins relevant to host health, such as the Kunitz trypsin inhibitor from soy and various antimicrobial proteins from egg white, were found to escape digestion and become accessible to gut microbiota.

Kleiner remarked on the significant implications of these findings, stating, “Dietary proteins have a major impact on host physiology.” He pointed out the need for further research to determine whether the proteins reaching the colon are intact or still active.

The study is distinctive in that it examined various sections of the digestive tract, not merely focusing on fecal output. Researchers found that digestion in the small intestine was largely unaffected by the presence of gut microbes, with significant differences observed only in the large intestine and feces. Kleiner elaborated, “Most of the digestion is happening the same at the start in the small intestine, whether the mice have a microbiota or not.”

Awan added that the small intestine has fewer microbes and less time for interaction with dietary proteins, explaining why the primary differences emerged in the large intestine, where the microbiota can interact more extensively with proteins.

These interactions may influence the production of beneficial metabolites, such as short-chain fatty acids, which can have positive effects on host health. The inefficient digestion of functional proteins, including enzyme inhibitors and antimicrobial proteins, raises questions about their potential roles in shaping gut health and microbial composition.

The researchers concluded that the source of dietary protein should be a key consideration in understanding health outcomes related to diet, particularly concerning inflammatory bowel conditions and metabolic disorders. Kleiner stated, “Future work will focus on how different sources of dietary proteins and their interactions with the gut microbiota affect host health.”

The findings were published on September 3, 2025, in the journal Food & Function, and were supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R35GM138362. The research team included co-authors Alexandria Bartlett, J. Alfredo Blakeley-Ruiz, Tanner Richie, and Casey M. Theriot from NC State University.