(OR22-05-23) Walnut Consumption and Gut Microbial Metabolism Assessed by Metatranscriptomics: A Randomized, Crossover, Controlled-Feeding Study

Objectives: Prior research shows walnut consumption affects gut microbiota composition. The effect of walnuts on gut microbiota functionality remains unclear. We aimed to characterize the effect of a walnut-enriched diet (WD) on bacterial gene expression using metatranscriptomics compared to a fatty acid matched diet devoid of walnuts (WFMD) and a diet where oleic acid replaced alpha-linolenic acid (ORAD).

Methods: A 3-period, randomized, crossover, controlled-feeding study was conducted. Participants had a 2-week run-in on a standard western diet (SWD; 50% kcal carbohydrate, 16% protein, 34% fat, 12% SFA). Following the SWD, participants consumed the WD, WFMD and ORAD (48% carbohydrate; 17% protein; fat 35%; 7% SFA) in random sequence order. The WD contained 18% of kcal from walnuts (57g/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. The analytic sample for these analyses includes 35 participants with archived samples available.

Results: The alpha diversity of taxa actively expressing genes (active composition), assessed by observed species (p=0.27) and Pielou’s Evenness (p=0.09), was not different between the diets. However, the alpha diversity of actively expressed genes differed between the diets, as assessed by the observed genes (p=0.008) and Pielou’s Evenness (p=0.036) metrics. Active composition analyses showed increased Gordonibacter (p < 0.001) activity following the WD vs. the ORAD. Gene analyses showed greater expression of several genes following the WD compared to the WFMD and ORAD. Following the WD, greater expression of genes encoding glycine amidinotransferase (GATM; K00613) and nitrite reductase (cytochrome c-552; K03385) was observed compared to the ORAD. Greater expression of these genes by Gordonibacter was also observed.

Conclusions: 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 efforts are warranted.

Funding Sources: California Walnut Commission