Walnut consumption and gut microbial metabolism: Results of an exploratory analysis from a randomized, crossover, controlled-feeding study.

Clinical nutrition (Edinburgh, Scotland). 2023;42(11):2258-2269
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Poor diet is a significant contributor to the development of heart disease. Dietary intake also affects gut microbiota composition as it serves as a substrate source for their growth and development. Nut intake has been shown to beneficially modulate the composition of gut microbiota and may be of help in the prevention of heart disease. This randomised control trial of 45 individuals aimed to determine the effect of a walnut-rich diet compared to a fatty-acid matched diet without walnuts and a diet rich where omega-9 replaces omega-3 fats on gut microbiota composition. The results showed that the walnut-enriched diet altered the functionality of the gut and increased the expression of genes responsible for producing an enzyme known as GATM. Walnut consumption did not alter the gut microbiota composition compared to the other diets. It was concluded that walnut intake may increase the production of GATM, which is responsible for the production of homoarginine. This amino acid has been shown to lower heart disease risk. This study could be used by healthcare professionals to understand one of the mechanisms through which walnuts may lower heart disease risk.


BACKGROUND & AIMS 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. METHODS A 3-period, randomized, crossover, controlled-feeding study was conducted. Participants were provided a 2-week run-in standard western diet (SWD; 50% kcal carbohydrate, 16% protein, 34% fat, 12% SFA). Following the SWD in random sequence order, participants were provided the WD, WFMD, and ORAD (48% carbohydrate; 17% protein; fat 35%; 7% SFA). The WD contained 18% of energy from walnuts (57 g/d/2100 kcal). The WFMD and ORAD were devoid of walnuts; liquid non-tropical plant oils were included in these diets. Metatranscriptomic analyses were performed as an exploratory outcome. RESULTS The analytical sample included 35 participants (40% female) with a mean ± SD age of 43 ± 10 y and BMI of 30.3 ± 4.9 kg/m2. The ⍺-diversity of taxa actively expressing genes, assessed by observed species (p = 0.27) and Pielou's Evenness (p = 0.09), did not differ 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 (p < 0.05). β-Diversity of the actively expressed genes differed following the WD compared to the WFMD (p = 0.001) and ORAD (p = 0.001); β-diversity did not differ between the WFMD and ORAD. Active composition analyses showed increased Gordonibacter (p < 0.001) 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. CONCLUSION Our results suggest walnut intake may increase endogenous production of homoarginine through gut microbiota-mediated upregulation of GATM, which is a novel mechanism by which walnuts may lower cardiovascular disease risk. However, given the exploratory nature replication is needed. CLINICAL TRIAL REGISTRATION Clinicaltrials.gov (NCT02210767).

Lifestyle medicine

Fundamental Clinical Imbalances : Digestive, absorptive and microbiological
Patient Centred Factors : Mediators/Gut microbiota
Environmental Inputs : Diet ; Nutrients
Personal Lifestyle Factors : Nutrition
Functional Laboratory Testing : Blood ; Stool

Methodological quality

Jadad score : 3
Allocation concealment : No


Nutrition Evidence keywords : Glycine amidinotransferase ; Homoarginine