Not All Proteins Are Equal for Gut Health, Study Suggests

Protein has become something of an obsession lately. Food companies have quadrupled the number of high-protein products they sell worldwide because they generate significant revenue, according to the BBC Science Focus. Major news outlets, including NPR, The Wall Street Journal and The New York Times, have also discussed the high-protein diet as an obsession or “craze.”

But at NC State University, our researchers go beyond the hype. In a new study, the research team explores different forms of protein in our diets and their impact on the gut’s microbiome — and, consequently, our overall life expectancy. 

The gut microbiome is a community of microorganisms living in the digestive tract that breaks down food and makes nutrients available to our bodies. Diet is known to influence the functioning of the gut microbiome and has a significant impact on human health. 

Currently, the impact of proteins on human health is not well understood. For this reason, NC State researchers are analyzing how proteins are metabolized to build new proteins, produce energy or perform other processes that can impact various aspects of our health. This study is part of a push to prevent and treat gastrointestinal diseases, which affect at least 60-70 million Americans, according to NIH data.

“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 the paper on 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 analyzed the effects of seven different sources of dietary protein on the gut microbiota of mice. They were specifically interested in how the source of protein in the diet — for example, proteins found in milk, eggs, chicken and plants like pea or soy — impacted the gut microbiomes of mice. For a week at a time, the mice were fed diets containing just one protein source, including egg whites, brown rice, soy and yeast.

The researchers used an integrated metagenomics-metaproteomics approach, which measures the abundance of gut microorganism species and how proteins affect the microbiota’s metabolic and physiological processes, such as their ability to utilize nutrients. The researchers found that the mice’s gut microbiome changed significantly 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,” said Blakeley-Ruiz, whose research is part of the plant and microbiology department and a collaboration between NC State’s College of Agriculture and Life Sciences and College of Sciences. 

The researchers expected the study to show that dietary protein has an impact on amino acid metabolism. Brown rice and egg white diets appeared to cause microbes to break down those proteins instead of making their own 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,” said Blakeley-Ruiz. Some amino acids can degrade into toxins and affect local tissues, or potentially impact health along the gut-brain axis. 

“So there are potential health implications from these diets.”

They hadn’t expected to see how dietary protein caused complex sugars to degrade, however. Long chains of sugars attached to dietary proteins, known as glycans, appeared to alter 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.

Blakeley-Ruiz explained that in the egg white diet, one bacterium took over and activated glycan-degrading enzymes. The research team then grew this bacterium in the lab and found that the glycan-degrading enzymes it produced were similar to those found in mucin.

Mucin lines the stomach and intestines, forming a protective barrier that aids digestion. But the bacterium activated by egg whites could break down mucin, which could damage the intestinal lining and negatively impact 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,” said Blakeley-Ruiz.

So does that mean we should avoid egg whites? Not necessarily.

If anything, the mice’s controlled protein diets are nothing like how we usually eat — and therefore, we can’t jump to any conclusions. More research is needed. 

“One of the limitations of our study is that, of course, the diets are very artificial and could lead to amplified results,” said Manuel Kleiner, an NC State associate professor of plant and microbial biology and co-corresponding author of the paper. The research, however, has laid the necessary groundwork for future investigations into how the gut’s microbiome reacts to different protein sources.

“But we now show that egg white has extreme effects on the microbiome,” Kleiner said. “For the future, we’re very interested in understanding what the mechanism of this effect is in a mixed protein diet in mice.”

Understanding how different proteins affect our gut microbiota — and potentially gastrointestinal diseases — is a crucial step in moving beyond diet fads and toward long-term health. 

“This could be really meaningful, health-wise,” Blakeley-Ruiz said. 

The research paper, “Dietary protein source alters gut microbiota composition and function,” is published in The ISME Journal. Co-authors of the paper include Alexandria Bartlett, Arthur S. McMillan, Ayesha Awan, Molly Vanhoy Walsh, Alissa K. Meyerhoffer, Simina Vintila, Jessie L. Maier, Tanner Richie and Casey M. Theriot — all from NC State University.

This article is based on a news release from NC State University.