The Role Walnuts May Play in Gut Health and Personalized, Precision Health Benefits

Now new evidence suggests that walnuts may have prebiotic potential.⁶ Prebiotics have been shown to promote the growth of beneficial gut bacteria.⁷ This evidence was reported in two recently published review papers in Nutrients and Antioxidants, which explored the relationship between walnuts and a compound called urolithin A (UA). UA is produced by gut bacteria and may play a role in the gut microbiome and personalized, precision health benefits. UA is a gut microbiome-derived natural compound produced by gut bacteria after they digest plant-based substances called ellagitannins (ETs) and ellagic acid (EA), which are complex polyphenols abundant in foods such as pomegranates, berries, and nuts, including walnuts.

In a 2023 review published in Nutrients, researchers summarized findings surrounding nut consumption and its impact on the gastrointestinal system. Specific to walnuts, the review showed a beneficial role this nut may play in supporting beneficial gut bacteria, related to composition and diversity. While the findings are promising, the review ultimately showed inconsistent results associated with improved health benefits related to critical gut bacteria such as microbial alpha- and beta-diversity.⁸

A second 2023 review, published in Antioxidants and comprised of 33 studies, investigated the evidence supporting the benefits of walnuts in relation to inflammation and overall disease risk. The findings suggest that walnuts, as part of a healthy diet, may help reduce inflammation and promote normal digestive function, due in part to their unique nutrient matrix and metabolites produced during digestion. This paper suggests much of the beneficial properties of walnuts associated with anti-inflammatory effects are linked to ellagitannins, or polyphenols found in walnuts which are ultimately metabolized by gut microbiota to bioactive, anti-inflammatory urolithins as discussed above.⁶

While additional research is needed to fully explore the relationship between UA and cellular function, researchers suggest UAs may enhance cellular health by increasing how our cells function and stay working their best, while also reducing inflammation within the intestinal mucosa. As it relates to gut health, it appears UA may alter the gut microbiota by improving its diversity.^6,8 To more accurately assess the health benefits and functionality associated with consumption of foods, such as walnuts and UA, further studies are needed to better define the mechanisms responsible for their extraction during digestion, and how foods, like walnuts, may ultimately affect bioavailability.

When considered together, both reviews illuminate impactful findings from pre-clinical and human studies suggesting that when walnuts are digested there is a process that takes place converting walnut-derived ellagitannins into a complex family of anti-inflammatory urolithins that may influence the growth of “good” bacteria in the gut.^6,8,~ However, they’re narrative reviews that involved animal studies, cellular studies, and some promising human trials. These narrative reviews do have systematic searching which could offer a comprehensive look at findings among patients of various backgrounds; however, it can be limited by the methods, reported outcomes and quality of the individual studies involved. Future clinical studies are needed in other research settings and populations to better understand how walnuts impact gut health and at what amounts.

Researcher and Professor of Medicine at the University of Connecticut School of Medicine, Dr. Daniel W. Rosenberg, Ph.D. shares, “Evidence that microbial metabolism of walnut-derived ellagitannins is highly patient-dependent has prompted our NIH-funded clinical trial to study ellagic acid metabolism in subjects at elevated risk of colorectal cancer. Our goal is to better understand how two ounces per day of walnuts added to the regular diet may affect an individual’s microbiome and to define the specific microbes responsible for these metabolic reactions required to form urolithins.”

Emerging Research Around Walnut Consumption, Gut Health and Potential Heart Health Benefits

In a randomized, crossover, controlled-feeding study published in Clinical Nutrition (2023), 35 otherwise healthy adults with overweight or obesity and elevated LDL cholesterol who were randomly selected to eat approximately 57 grams of walnuts per day for 3 weeks had increased activity of two genes from gut bacteria. ⁹ Past research suggests the two genes activated in this study, glycine amidinotransferase (K00613) and arginine deiminase (K01478) are involved in various metabolic roles in the body, including potential benefits related to heart health.^10,11

Researchers implemented 3-weeks of various diets with a two-week washout period beginning with the initial Standardized Western Diet (SWD) which included 50% kcal carbohydrate, 16% protein, 34% fat, 12% saturated fatty acids and then in random sequence order:

• Walnut Diet (WD) which included 18% of energy from walnuts (57g/d/2100kcal)
• Fatty acid-matched diet devoid of walnuts (WFMD)
• Diet where oleic acid replaces alpha-linolenic acid (ORAD)
• *Liquid non-tropical plant oils were included in the WFMD and ORAD diets

Scientists found the walnut-enriched diet affected ⍺-and b-diversity of the genes expressed compared to the other study diets where they are suggesting the whole walnut matrix modulates gut microbiome functionality. Specifically, following the walnut diet, researchers did observe greater expression of two metabolism-related genes, glycine amidinotransferase (K00613) and arginine deiminase (K01478) that are involved in metabolic pathways that may impact cardiovascular health.^10,11

It is important to understand that this study included participants from one geographical location with limited racial and ethnic diversity and therefore further research should be conducted in a more representative cohort to ensure external validity.  This work is exploratory and should be interpreted with caution as it needs to be replicated in other human clinical trials to assess how walnuts might impact risk of disease through interactions with the gut bacteria.  

To learn more about walnuts and the emerging gut health research check out this Gut Health Research Summary or this Digest the Latest on Gut Health and Walnuts blog post. You can also watch the latest video from Dr. Daniel W. Rosenberg, Ph.D. entitled, “Science In Seconds: The Wonders of Walnuts,” published on the UConn Today website.

Walnuts offer a simple, cost-effective (and delicious!) strategy for providing a wide range of potential health benefits that may improve gut bacteria and overall gut health. As research continues to evolve in this space, it can’t hurt to give your gut some love with walnuts!

For simple ways to incorporate walnuts in your eating pattern try gut health-promoting recipes like this fiber-rich Toasted Walnut, Black Bean, Corn and Tomato Salad or this Steak Sandwich with Walnut Kimchi Slaw.