USA: In a recent study published in Clinical Nutrition, researchers from the US have discovered a novel mechanism by which walnuts may lower the risk of cardiovascular disease (CVD).
Results of the exploratory analysis from a crossover, randomized, controlled-feeding study suggest that walnut intake may increase endogenous homoarginine production through gut microbiota-mediated upregulation of glycine amidinotransferase (GATM).

The effect of walnut-related modulation of gut microbiota composition on microbiota functionality is unknown. The aim was to characterize the effect of a walnut-enriched diet (WD), compared to a fatty acid-matched diet devoid of walnuts (WFMD) and a diet where oleic acid replaces alpha-linolenic acid (ORAD), on bacterial gene expression.
Cardiovascular disease is the leading cause of death globally. Dietary factors are estimated to be associated with more than half of all CVD-related deaths. Recent studies have suggested that gut microbiome may contribute to CVD development. Dietary intake affects gut microbiota composition by serving as a substrate for microbial metabolism, and the resulting metabolites affect host health. Randomized controlled trials have revealed nut intake affects microbiota composition.
Strong evidence shows walnut consumption improves major risk factors for CVD. However, the effect of walnut-related modulation of gut microbiota composition on microbiota functionality is unknown. Therefore, Kristina S. Petersen, Department of Nutritional Sciences, Texas Tech University, Lubbock, TX, USA, and colleagues aimed to characterize the effect of a walnut-enriched diet (WD), versus a fatty acid-matched diet devoid of walnuts (WFMD) and a diet where oleic acid replaces alpha-linolenic acid (ORAD), on bacterial gene expression.
For this purpose, the researchers conducted a 3-period, randomized, crossover, controlled-feeding study. Participants were given a 2-week run-in standard western diet (SWD; 50% kcal carbohydrate, 16% protein, 34% fat, 12% SFA). After the SWD in random sequence order, the people were provided the WD, WFMD, and ORAD (48% carbohydrate; 17% protein; fat 35%; 7% SFA).
The walnut-enriched diet contained 18% energy from walnuts. The ORAD and WFMD were devoid of walnuts; these diets included liquid non-tropical plant oils. Metatranscriptomic analyses were performed as an exploratory outcome. The analytical sample comprised 35 participants (40% female) with a mean ± SD age of 43 ± 10 y and BMI of 30.3 ± 4.9 kg/m2.
The study led to the following findings:
There was no difference in the ⍺-diversity of taxa actively expressing genes, assessed by observed species and Pielou's Evenness, among the diets.
The ⍺-diversity of actively expressed genes was greater following the WD compared to the WFMD and ORAD as assessed by the observed genes and Pielou's Evenness metrics.
β-Diversity of the actively expressed genes differed following the WD compared to the WFMD and ORAD; β-diversity did not differ between the WFMD and ORAD.
Active composition analyses showed increased Gordonibacter activity following the WD vs. the ORAD.
Greater expression of many genes was observed following the WD compared to the WFMD and ORAD.
Following the WD, greater expression of metabolism-related genes encoding glycine amidinotransferase (GATM; K00613) and arginine deiminase (K01478) was observed compared to the WFMD.
Greater expression of glycine amidinotransferase (GATM; K00613) by Gordonibacter was also observed following the WD vs. the WFMD and ORAD.
"To our knowledge, metatranscriptomics has not been used before to assess the effect of walnut consumption on gut microbiota gene expression," the researchers wrote.
They observed substantial between- and within-individual variability in the expressed genes. They found a greater expression of two metabolism-related genes, glycine amidinotransferase (K00613) and arginine deiminase (K01478) following the walnut diet; these enzymes are involved in metabolic pathways that may confer cardioprotective.
"The results of these exploratory analyses contribute to further understanding the walnut-related modulation of gut microbiome.," the researchers concluded. "However, replication is needed given the exploratory nature of this research"
Reference:
Petersen, K. S., Chandra, M., Chen See, J. R., Leister, J., Jafari, F., Tindall, A., Kris-Etherton, P. M., & Lamendella, R. (2023). Walnut consumption and gut microbial metabolism: Results of an exploratory analysis from a randomized, crossover, controlled-feeding study. Clinical Nutrition, 42(11), 2258-2269. https://doi.org/10.1016/j.clnu.2023.09.023