Balanced Lifestyle

As gut health continues to be a topic of conversation surrounding health and wellness, consumers are looking for simple ways to support their gut and ultimately their overall health. While there is still so much we don’t know about the gut microbiome, one thing is relatively certain: the foods we eat have an impact on the health and diversity of the community of beneficial bacteria living in our gut, otherwise known as the gut microbiome.

Fiber, probiotics, prebiotics, and a variety of other nutrients help promote overall gut health. Fiber stimulates beneficial fermentation and progression of diversity in the gut. Prebiotics are a subset of fibers that are non-digestible and ultimately “feed” the good bacteria found in the gut. Probiotics are the “good” bacteria found in the gut that can also be consumed through food or supplements. A newer concept in the gut health realm is postbiotics which are inactivated microbial cells or gut bacteria, or what is left behind after prebiotics and probiotics are digested.

When it comes to food, research has shown that consuming walnuts may help support gut health. A study from the USDA and University of Illinois found that among a small sample of 18 healthy adults (ages 35-68), those participants who ate 42 grams (about 1.5 ounces) of walnuts each day for three weeks experienced a decrease in secondary bile acids, which may play a role in colon cancer, inflammation, and gastrointestinal diseases. The study also found that eating walnuts seemed to result in an increase in gut bacteria thought to be beneficial for health.1 While these results are promising, more research is needed to explore the relationship between cause and effect.

Research Explores the Role Walnuts May Play in the Production of Urolithin A and Potential Health Benefits

The latest evidence suggests that walnuts may have prebiotic potential.2 Prebiotics have been shown to promote the growth of beneficial gut bacteria.3 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.4

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.2

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.2,4 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.2,4 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, which would also strengthen further reviews on this topic.

 It is important to understand that these are narrative reviews of animal, cellular, and some human studies. While they could offer a comprehensive look at findings, they can be limited by the methods, reported outcomes and quality of the individual studies involved.

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.”

Dr. Rosenberg has continued to explore walnut consumption and UA. His latest study published in BMC Microbiology, further investigates the impact of two ounces per day of walnut consumption on markers of urolithin metabolites.

A longitudinal study of 39 healthy adults was done to understand the impact of walnut consumption (2 oz per day for 21 days) on intestine microbiota and urine levels of UA. Researchers found significant differences in the fecal microbial composition at the end of the intervention, compared to baseline. Among these differences, several genera were found to be significantly associated with urolithin metabolites. This suggests that walnut supplementation positively altered the gut microbiome and increased the amount of urolithin metabolites.5

While this study is novel and offers promise of walnuts’ impact on the gut microbiome, it is not without limitations. This was a longitudinal study and did not have a control group. Further randomized controlled trials are needed to confirm the results and draw further conclusions about the functional impact of these microbiome changes.5

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

In a randomized, crossover, controlled-feeding study published in Clinical Nutrition, 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.6 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.7,8

Researchers implemented three 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, 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.7,8

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 disease risk through interactions with the gut bacteria. 

To learn more about walnuts and the emerging gut health research check out this 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.  Walnuts also provide a variety of other nutrients per one ounce serving. They are the only nut to provide an excellent source of the anti-inflammatory omega-3 alpha-linolenic acid, or ALA (2.5g/oz), plus 2 grams of fiber and a mix of tocopherols (5.91mg/oz) and antioxidant polyphenols (69.3 ± 16.5 µmol catechin equivalents/g).9-12,*

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.

References:
1. Holscher HD, Guetterman HM, Swanson KS, et al. Walnut Consumption Alters the Gastrointestinal Microbiota, Microbially Derived Secondary Bile Acids, and Health Markers in Healthy Adults: A Randomized Controlled Trial. J Nutr. 2018, 148, 861
2. Fan N, Fusco JL, Rosenberg DW. Antioxidant and anti-inflammatory properties of walnut constituents: Focus on personalized cancer prevention and the microbiome. Antioxidants. 2023;12(5):982.
3. Davani-Davari D, Negahdaripour M, Karimzadeh I, Seifan M, Mohkam M, Masoumi SJ, Berenjian A, Ghasemi Y. Prebiotics: Definition, Types, Sources, Mechanisms, and Clinical Applications. Foods. 2019 Mar 9;8(3):92. doi: 10.3390/foods8030092.
4. Mandalari G, Gervasi T, Rosenberg DW, Lapsley KG, Baer DJ. Effect of nuts on gastrointestinal health. Nutrients. 2023;15(7):1733.
5. Liu H, Birk JW, Provatas AA, et al. Correlation between intestinal microbiota and urolithin metabolism in a human walnut dietary intervention. BMC Microbiology. 2024;24:476.
6. Petersen KS, Chandra M, Chen See JR, Leister J, Jafari F, Tindall A, Kris-Etherton PM, Lamendella R. Walnut consumption and gut microbial metabolism: Results of an exploratory analysis from a randomized, crossover, controlled-feeding study. Clin Nutr. 2023 Nov;42(11):2258-2269. doi: 10.1016/j.clnu.2023.09.023. Epub 2023 Sep 28. PMID: 37826992.
7. Smith J, Johnson A, Brown K. Elevated expression of the Arginine:Glycine Amidinotransferase Gene in heart failure and its normalization after recovery. Circulation. 2006;113(10):1344-1351. doi: 10.1161/CIRCULATIONAHA.105.000448.
8. Mao L, Mostafa R, Ibili E, Fert-Bober J. Role of protein deimination in cardiovascular diseases: potential new avenues for diagnostic and prognostic biomarkers. Expert Rev Proteomics. 2021 Dec;18(12):1059-1071. doi: 10.1080/14789450.2021.2018303. Epub 2022 Jan 12. PMID: 34929115.
9. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (Macronutrients) (2005) NAS. IOM. Food and Nutrition Board.
10. Prior R. Oxygen radical absorbance capacity (ORAC): New horizons in relating dietary antioxidants/bioactives and health benefits. J of Functional Foods. 2015;18(B):797-810
11. U.S. Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 2020-2025. 9th Edition. December 2020. Available at DietaryGuidelines.gov.
12. Halvorsen BL, Carlsen MH, Phillips KM, et al. Content of redox-active compounds (ie, antioxidants) in foods consumed in the United States. Am J Clin Nutr. 2006;84:95-135.
 
* The data for antioxidant capacity of foods generated by test-tube methods cannot be extrapolated to human effects. Clinical trials to test benefits of dietary antioxidants have produced mixed results.
~ Animal studies are valuable for providing background information and can be used as a basis for additional research. Since mice have different microbiota than humans, more research is needed to determine how these results may translate to humans.
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