New research reveals how dietary proteins alter the gut microbiome and metabolic pathways

Protein sources can significantly affect gut microbiota, which may have implications for human health and disease prevention, according to recent research. Based on the study, egg white protein may negatively affect gut health by promoting mucin-degrading bacteria, brown rice was shown to be less harmful and more compatible with maintaining microbial balance, and yeast was in the middle, offering beneficial shifts but risking mucosal degradation. 

Protein sources most strongly influenced microbial pathways involved in amino acid metabolism and glycan (complex sugar) degradation. Long chains of sugars attached to proteins — glycans — changed the gut microbiome’s function. 

The researchers from North Carolina State University, US, believe their findings could help prevent and treat gastrointestinal diseases, which affect millions of people’s quality of life.

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

“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.”

Egg white protein may negatively affect gut health by promoting mucin-degrading bacteria.The paper cites previous research showing that consuming high animal protein, such as eggs and red meat, is associated with higher mortality rates than those who consume mostly plant-based protein. However, it notes a lack of understanding of underlying causes, such as in the gut.

Examining protein breakdown 

The study, published in the ISME Journal, examined how proteins in milk, eggs, and different plants like brown rice, peas, yeast, or soy affected mice’s gut microbiome. Researchers fed mice one protein source for a week and studied differences using an integrated metagenomics-metaproteomics approach.

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

They report that proteins had the most significant impact on amino acid metabolism, as expected, including complex sugar degradation, which was surprising.

“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 explains. 

“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.”

Glycans pave way for future research

The researchers observed that glycans affected the production of enzymes that break down glycans. “This could be really meaningful, healthwise,” Blakeley-Ruiz adds. 

Brown rice was less harmful and more compatible with maintaining microbial balance.“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.”

The gut is lined with mucin, protecting the digestive system from acid and pathogens. Therefore, if gut bacteria produce enzymes that break down mucin, they can damage the lining, harming 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, associate professor of plant and microbial biology and co-corresponding author of the paper, believes the study sets the foundation for future research on 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 says. “But we now show that egg white has extreme effects on the microbiome. In the future, we’re very interested in understanding the mechanism of this effect in mice with a mixed protein diet.”

“Our study shows not only which bacterial 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.”