NEW YORK, May 10: A new study by researchers at North Carolina State University has revealed that the type of protein in an animal's diet has a significant impact on both the composition and function of the gut microbiome — the complex community of microorganisms living in the digestive tract. These findings may help guide future approaches to prevent and treat gastrointestinal diseases that affect millions globally.

“There’s something wrong with what we’re eating today, and we are not close to knowing what that is,” said Alfredo Blakeley-Ruiz, a postdoctoral researcher at NC State and co-corresponding author of the study. “Our lab wanted to know how different diets impact what lives in the gut, and to learn something about what those microbes are doing, functionally, in response to that diet.”

The research team tested the effects of various dietary protein sources — including milk, eggs, and plant-based proteins such as peas, soy, brown rice, and yeast — on the gut microbiomes of mice. Each group of mice was fed a diet containing a single protein source for one week, allowing the researchers to isolate how each protein influenced the gut’s microbial ecosystem.

Using a combined metagenomics and metaproteomics approach, including high-resolution mass spectrometry, the team found that the microbial composition shifted dramatically with each protein source. According to Blakeley-Ruiz, the most pronounced functional effects came from diets based on brown rice, yeast, and egg whites.

“We observed significant changes in the gut microbiome composition every time we changed the protein source,” Blakeley-Ruiz said.

Two key functional changes emerged from the data: shifts in amino acid metabolism and in the degradation of complex sugars, also known as glycans. While the influence on amino acid metabolism was expected, the extent of the microbiome’s response to glycans was not.

“Brown rice and egg white diets increased amino acid degradation in the mouse gut microbiome, meaning the microbes were breaking down dietary proteins rather than synthesizing their own amino acids,” said Blakeley-Ruiz. “This has important health implications, as some amino acids can degrade into harmful toxins or influence the gut-brain axis.”

Additionally, proteins with glycan attachments triggered major changes in the activity of microbial enzymes that degrade these sugar chains. The researchers observed that diets based on soy, rice, yeast, and egg whites altered microbial enzyme production — with the egg white diet causing one bacterium in particular to dominate and ramp up production of glycan-degrading enzymes.

Further lab tests showed that this same bacterium produced glycan-degrading enzymes in the presence of egg white protein similar to those it produced when exposed to mucin — a protective substance that lines the gut wall.

“If bacteria begin breaking down mucin, they could compromise the gut lining and contribute to digestive issues or disease,” Blakeley-Ruiz explained. “I’m excited to explore this connection further in future research.”

Co-corresponding author Manuel Kleiner, associate professor of plant and microbial biology at NC State, noted that while the study’s diets were highly controlled and may exaggerate certain effects, the findings offer critical insights into how protein types influence gut health.

“One limitation is that the diets were very artificial, which could amplify the results,” Kleiner said. “But we now know that egg white protein has a particularly strong effect on the gut microbiome. Moving forward, we want to understand how this plays out in more realistic, mixed-protein diets.”

He added, “Our study not only shows which bacterial species are present and their abundance, but also reveals what they are actively doing. In this case, we see specific digestion of glycans, giving us a more complete picture of how diet affects gut function.”

The study paves the way for more targeted research into dietary impacts on the microbiome and could lead to more personalized dietary recommendations to support gut health.