New research from NC State reveals that different protein sources in animal diets can dramatically alter the gut microbiome, both in composition and function.
A new study from researchers at <span class="glossaryLink" aria-describedby="tt" data-cmtooltip="
” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>North Carolina State University has found that the type of protein in an animal’s diet significantly influences both the composition and activity of the gut microbiome, the community of microorganisms living in the digestive tract.
These gut microbes play a crucial role in various aspects of health, and the study’s findings could contribute to improved strategies for preventing and treating gastrointestinal diseases that affect millions of people worldwide.
“There’s something wrong with what we’re eating today, and we are not close to knowing what that is,” said Alfredo Blakeley-Ruiz, an NC State postdoctoral researcher and co-corresponding author of a paper describing 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.”
In their experiment, the researchers examined the effects of specific dietary protein sources, such as those from milk, eggs, and plants like peas and soy, on the gut microbiomes of mice. The mice were each fed a diet consisting of a single protein source for one week. These sources included egg whites, brown rice, soy, and yeast, allowing the researchers to isolate the impact of each protein on the gut microbial ecosystem.
Shifts in Microbial Populations and Activity
Using an integrated metagenomics-metaproteomics approach requiring high resolution mass spectrometry, the researchers found that the mice gut microbiome changed a lot over the course of 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.”
In examining the functional changes in the gut microbiome, the study showed that the two largest effects of dietary protein were on amino <span class="glossaryLink" aria-describedby="tt" data-cmtooltip="
” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>acid metabolism, which was expected by the researchers, and complex sugar degradation, which was not.
“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 <span class="glossaryLink" aria-describedby="tt" data-cmtooltip="
<div class="text-wrapper"><br />Amino acids are a set of organic compounds used to build proteins. There are about 500 naturally occurring known amino acids, though only 20 appear in the genetic code. Proteins consist of one or more chains of amino acids called polypeptides. The sequence of the amino acid chain causes the polypeptide to fold into a shape that is biologically active. The amino acid sequences of proteins are encoded in the genes. Nine proteinogenic amino acids are called "essential" for humans because they cannot be produced from other compounds by the human body and so must be taken in as food.<br /></div>
</div>
” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>amino acids from scratch,” Blakeley-Ruiz said. “This makes intuitive sense because proteins are made of amino acids, but 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.”
The study also showed that long chains of sugars attached to the dietary proteins, called glycans, also play a role in changing gut microbiome function. Multiple dietary protein sources, including soy, rice, yeast, and egg white, caused microbes in the gut to change the production of enzymes that break down glycans, sometimes substantially.
“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 that the glycan-degrading enzymes it produced in media containing egg white protein were similar to those produced in media containing mucin.”
Potential Implications for Gut Health
Mucin is the substance that lines the inside of the gut, protecting the digestive system from things like acid and pathogens. So if bacteria are producing enzymes that, purposely or not, break down mucin, they could be damaging the intestinal lining and causing negative impacts on gut health.
“I’m excited to explore this potential connection between the expression of glycan degrading enzymes in the egg white diet and the breakdown of mucin by the gut microbiome in future studies,” says Blakeley-Ruiz.
Manuel Kleiner, an NC State associate professor of plant and microbial biology and co-corresponding author of the paper, said the study lays the groundwork for future investigation of the effects of protein sources on the gut microbiome.
“One of the limitations of our study is that, of course, the diets are very artificial and could lead to amplified results,” Kleiner said. “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.
“Our study shows not only which bacterial <span class="glossaryLink" aria-describedby="tt" data-cmtooltip="
” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>species are in the gut microbiome and their abundance, but also what they are actually doing. Here, they are specifically digesting the glycans. The result is a very comprehensive picture of what really matters in the gut in terms of diet and function.”
Reference: “Dietary protein source alters gut microbiota composition and function” by J Alfredo Blakeley-Ruiz, Alexandria Bartlett, Arthur S McMillan, Ayesha Awan, Molly Vanhoy Walsh, Alissa K Meyerhoffer, Simina Vintila, Jessie L Maier, Tanner G Richie, Casey M Theriot and Manuel Kleiner, 21 March 2025, The ISME Journal.
DOI: 10.1093/ismejo/wraf048
The study was supported by the <span class="glossaryLink" aria-describedby="tt" data-cmtooltip="
” data-gt-translate-attributes=”[{“attribute”:”data-cmtooltip”, “format”:”html”}]” tabindex=”0″ role=”link”>National Institutes of Health through awards R35GM138362, T32DK007737 and P30 DK034987, and by the USDA National Institute of Food and Agriculture, Hatch project 7002782.
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