Researchers studied how eating too much protein affects the gut health of males and females differently. They fed young pigs either a high-protein diet or a normal-protein diet for four weeks and measured changes in gut bacteria and the protective lining of the intestines. They found that high-protein diets caused bacteria to produce more of a harmful substance called p-cresol, which weakened the gut’s protective barrier. Interestingly, females seemed to be affected more than males. While this study was done in pigs, it suggests that men and women might need different amounts of protein in their diets to keep their guts healthy.
The Quick Take
- What they studied: Whether eating high amounts of protein damages the gut’s protective barrier, and if this damage happens differently in males versus females
- Who participated: 20 young piglets (10 males and 10 females) that were siblings, fed either a high-protein diet (28% protein) or a standard diet (18% protein) for four weeks
- Key finding: High-protein diets increased harmful bacterial byproducts and weakened the gut’s protective proteins, with females showing greater damage than males
- What it means for you: If these findings apply to humans, it may suggest that women and men should eat different amounts of protein to maintain healthy guts. However, this is early research in animals, so don’t change your diet yet without talking to a doctor
The Research Details
Researchers conducted a controlled experiment using 20 young piglets that were matched siblings (10 males and 10 females). They divided each sex into two groups: one eating a high-protein diet (28% of calories from protein) and one eating a standard-protein diet (18% of calories from protein). Both groups ate their assigned diet for exactly four weeks. The researchers then measured three main things: what bacteria lived in the pigs’ colons using genetic testing, what harmful substances the bacteria produced (measured in urine), and how strong the protective lining of the gut was by looking at specific proteins under a microscope.
This type of study is called a controlled experiment because the researchers controlled what the animals ate and measured the results carefully. Using pigs is common in nutrition research because their digestive systems are similar to humans’ in many ways. By using sibling pairs, the researchers reduced differences caused by genetics, making it easier to see the effects of diet alone.
The study measured several important markers of gut health. The main focus was on a toxic substance called p-cresol that bacteria produce when they break down protein. The researchers also looked at specific proteins in the gut lining that act like glue holding cells together, which are important for keeping harmful substances out of the bloodstream.
Understanding how protein affects gut health is important because protein is essential for our bodies, but too much might cause problems. The gut lining acts like a protective barrier—it lets good nutrients in but keeps harmful substances out. If this barrier gets damaged, it can lead to inflammation and other health problems. This study is important because it suggests that the amount of protein we eat might affect this barrier differently depending on whether we’re male or female, which could mean one-size-fits-all nutrition advice isn’t the best approach.
This study has some strengths and limitations to consider. The strength is that it was a controlled experiment where researchers carefully controlled the diet and measured specific outcomes. Using sibling pairs helped reduce genetic differences. However, the sample size was relatively small (20 animals total), and it was done in pigs, not humans. The results are interesting but need to be confirmed in human studies before we can be confident they apply to people. The study was published in a peer-reviewed journal, which means other experts reviewed it before publication.
What the Results Show
The main finding was that pigs eating the high-protein diet produced more p-cresol, a toxic substance made by gut bacteria when they break down excess protein. This harmful substance was found in higher amounts in the urine of pigs on the high-protein diet. Additionally, the high-protein diet weakened the protective proteins in the gut lining—specifically proteins called E-cadherin and CD45 that help seal the intestinal barrier. These changes suggest the gut’s protective wall became less effective at keeping harmful substances out.
The most striking finding was that females responded differently than males. Female pigs on the high-protein diet had even higher levels of p-cresol and showed greater damage to their gut barrier proteins, particularly a protein called ZO-1. Female pigs also had different bacterial populations, with more of certain bacteria types (Staphylococcus and Chryseobacterium) compared to males on the same diet.
Interestingly, the high-protein diet didn’t change the overall types of bacteria present in the gut—the bacterial communities looked similar between groups. Instead, the diet changed what these bacteria produced and how they affected the gut lining. This suggests that it’s not about having different bacteria, but rather that the same bacteria behave differently when there’s more protein to break down.
The study found that the specific bacterial species that increased in females on high-protein diets (Staphylococcus and Chryseobacterium) are bacteria that are known to produce p-cresol. This connection between which bacteria increased and which harmful substances increased suggests a direct link between diet, bacterial behavior, and gut damage. The fact that these changes happened without major shifts in overall bacterial populations suggests that high protein doesn’t kill off good bacteria or allow bad bacteria to take over—instead, it changes how existing bacteria function.
This research builds on earlier work by the same team that showed in laboratory experiments (outside the body) that protein fermentation by bacteria affects males and females differently. This new study confirms those laboratory findings actually happen in living animals. The finding that high-protein diets can damage gut barrier function aligns with other research suggesting that excess protein may have downsides, though most nutrition research has focused on protein’s benefits. The sex-specific differences are relatively novel and suggest that previous research not considering sex differences may have missed important patterns.
Several limitations should be considered. First, this study was conducted in pigs, not humans, so we can’t be certain the results apply to people. Second, the sample size was small (only 10 animals per sex), which means the results might not be as reliable as studies with more participants. Third, the study only lasted four weeks, so we don’t know if these effects continue longer or if the body adapts over time. Fourth, the study used young piglets, so results might differ in adult animals or older humans. Finally, the study measured p-cresol in urine, which is an indirect measure—it doesn’t directly show how much is affecting the gut itself. The researchers also didn’t measure all possible outcomes that high protein might affect, so there could be other important effects they didn’t detect.
The Bottom Line
Based on this research alone, there’s not enough evidence to change protein recommendations for most people. However, if you’re a woman experiencing digestive issues and eating very high amounts of protein, it might be worth discussing with a doctor whether reducing protein intake could help. For men, the evidence of harm was less clear in this study. General recommendations remain that protein is essential and most people should eat adequate amounts—this study suggests that extremely high amounts might have downsides, particularly for women. Confidence level: Low to Moderate (this is animal research that needs human confirmation).
This research is most relevant to women who consume very high-protein diets (such as athletes or people doing high-protein weight loss diets). It’s also relevant to nutritionists and doctors who create personalized diet plans. People with existing gut health issues might want to discuss protein intake with their healthcare provider. This research is less immediately relevant to people eating normal amounts of protein as part of a balanced diet. Men may be less affected based on this study, but more research is needed to confirm this.
In the pig study, changes to the gut barrier happened within four weeks. If similar effects occur in humans, you might expect to see changes in that timeframe, though individual variation would likely be significant. However, this is speculative since the study was in animals. If you made dietary changes based on these findings, you’d want to monitor how you feel and work with a healthcare provider to assess any changes in digestive health over several weeks to months.
Want to Apply This Research?
- Track daily protein intake in grams and correlate with digestive symptoms (bloating, gas, changes in bowel movements, energy levels). Log these daily for at least 2-4 weeks to identify patterns, especially if you’re female and consuming high amounts of protein.
- If you’re consuming very high protein (above 1.6-2.0 grams per kilogram of body weight daily), consider gradually reducing to moderate levels (1.2-1.6 grams per kilogram) and track how your digestive symptoms change. This is particularly relevant for women. Make changes gradually over 1-2 weeks rather than all at once.
- Create a simple daily log tracking: (1) grams of protein consumed, (2) digestive comfort on a scale of 1-10, (3) energy levels, and (4) any digestive symptoms. Review weekly trends to see if reducing protein correlates with improved digestion. Share this data with a healthcare provider to make informed decisions about your protein intake.
This research was conducted in pigs and has not been confirmed in humans. The findings are preliminary and should not be used to make major dietary changes without consulting a healthcare provider or registered dietitian. Protein is an essential nutrient, and most people should not significantly reduce their protein intake based on this single animal study. If you have existing digestive issues or are considering major dietary changes, please discuss with your doctor first. This summary is for educational purposes and does not constitute medical advice.