Different Protein Sources Can Change the Gut Microbiome

Dietary protein sources – whether animal or plant-based – have previously been linked to differences in mortality rates. However, the mechanisms through which these protein sources influence human health and longevity remain poorly understood.

A new study from researchers at North Carolina State University, published in The ISME Journal, reveals that different protein sources can significantly alter the gut microbiome. These findings may lead to improved prevention and treatment strategies for gastrointestinal diseases, which currently impact the quality of life for millions worldwide.

The unknown impact of dietary protein on the gut microbiome

Dietary protein is a vital macronutrient needed for human health and critical to maintaining musculoskeletal health and maintaining metabolic functions. Protein stimulates muscle protein synthesis (MPS), allowing for muscle maintenance, growth and repair – an even more important consideration as we get older due to the impact of sarcopenia, the age-related decline in muscle mass and function.

When exploring differences between protein sources, animal proteins (e.g., eggs, milk, chicken, whey protein, etc.,) tend to stimulate MPS to a greater extent compared to plant proteins. For individuals who are vegetarian or vegan, it is vitally important they are aware of what non-animal-based foods provide sufficient dietary protein to support muscle health.

However, protein sources can also impact human health. Research has shown higher mortality rates in those who consume high amounts of animal protein, compared to those consuming mostly plant-based protein.

“There’s something wrong with what we’re eating today and we are not close to knowing what that is,” said Dr. Alfredo Blakeley-Ruiz, a postdoctoral researcher and co-corresponding author of the paper.

Despite the unknown, the gut microbiota – the microorganisms that live in the digestive tracts of animals – is thought to play a major role in impacting health from differing protein sources. In both mice and humans, diet has been shown to change the gut microbiota’s composition and function in ways that can be detrimental and beneficial to health.

Blakely-Ruiz and the team were specifically interested in how the source of protein in the diet (e.g., proteins found in milk, eggs and different plants like pea or soy) impacts the gut microbiomes of mice.

“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,” he said.

Functional changes in the gut microbiome occur in different protein sources

The researchers fed mice diets that contained just one protein source for a week at a time, including egg whites, brown rice, soy and yeast.

Using an integrated metagenomics-metaproteomics approach requiring high-resolution mass spectrometry, the researchers found that the mice gut microbiome changed considerably throughout the study, with some protein sources showing extreme effects.

“The composition of the gut microbiome significantly changed every time we changed the protein source,” Blakeley-Ruiz said. “The protein sources with the biggest functional effects were brown rice, yeast and egg whites.”

Blakeley-Ruiz and team examined the functional changes of the gut microbiome in response to the differing protein diets. They found that the two largest effects of the different protein sources were on amino acid metabolism and complex sugar degradation, with the latter coming as a surprise.

“Brown rice and egg white diets increased amino acid degradation in the mouse gut microbiome, meaning that the microbes were breaking down those proteins instead of making their own amino acids from scratch,” Blakeley-Ruiz said. “This is something we want to dig into more. Some amino acids can degrade into toxins and others can impact the gut-brain axis, so there are potential health implications from these diets.”

Glycans – long chains of sugars attached to proteins – also played a role in altering gut microbiome function, changing the production of enzymes that break them down.

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“This could be really meaningful, health-wise,” Blakeley-Ruiz said. “In the egg white diet, in particular, one bacterium took over and activated a bunch of glycan-degrading enzymes. We then grew this bacterium in the lab and found the glycan-degrading enzymes produced in media containing egg white protein were similar to those produced in media containing mucin.”

Mucin – a substance that lines the inside of the gut – protects the digestive system from acid and pathogens. If the bacteria produce enzymes that break down mucin, damage to the intestinal lining could occur, causing negative impacts on gut health – an area the researchers want to explore further.

Findings prompt deeper investigation into protein–microbiome links

Although this study provides an important foundation for future investigations into the relationship between dietary protein sources and gut microbiota composition, the authors acknowledge several limitations.

“One of the limitations of our study is that, of course, the diets are very artificial and could lead to amplified results,” said Dr. Manuel Kleiner, associate professor of plant and microbial biology and co-corresponding author of the paper. “But we now show that egg white has extreme effects on the microbiome. For the future, we’re very interested in understanding what the mechanism of this effect is in a mixed protein diet in mice.”

Despite the artificial nature of the dietary models used, the research highlights a shift in the microbiome driven by protein type, particularly egg white. Kleiner emphasized that while simplified diets may not directly reflect real-world eating patterns, they enable a controlled environment to isolate specific effects of individual proteins.

“Our study not only identifies which bacterial species are present in the gut microbiome and their relative abundance but also reveals their functional roles,” he added. “In this case, we see that the microbes are actively digesting glycans, giving us a very detailed picture of how diet influences microbial activity and metabolic outcomes.”

Reference: Blakeley-Ruiz JA, Bartlett A, McMillan AS, et al. Dietary protein source alters gut microbiota composition and function. The ISME Journal. 2025. doi: 10.1093/ismejo/wraf048

This article is a rework of a press release issued by North Carolina State University. Material has been edited for length and content.