Gut-Microbiota-Related Metabolite Phenylacetylglutamine and Risk of Incident Coronary Heart Disease Among Women

Abstract Context Phenylacetylglutamine (PAGln) is a novel metabolite derived from gut microbial metabolism of dietary proteins, specifically phenylalanine, which may be linked to risks of adverse cardiovascular events. Objective We investigated whether higher plasma levels of PAGln were associated with a greater risk of incident coronary heart disease (CHD) and tested whether adherence to a plant-based diet, which characterizes habitual dietary patterns of animal and plant food intake, modified the associations. Methods We examined associations between plasma PAGln and risk of incident CHD over 11 to 16 years in a nested case-control study of 1520 women (760 incident cases and 760 controls) from the Nurses’ Health Study. Separately, we analyzed relations between PAGln and dietary intakes measured through dietary records in the Women's Lifestyle Validation Study (n = 725). Results Higher PAGln levels were related to a greater risk of CHD (P < .05 for dose-response relationship). Higher PAGln was associated with greater red/processed meat intake and lower vegetable intake (P < .05 for all). We found a significant interaction between PAGln and adherence to plant-based diet index (PDI) on CHD (Pinteraction = .008); higher PAGln levels were associated with an increased risk of CHD (relative risk per 1 SD: 1.22 [95% CI: 1.05, 1.41]) among women with low PDI but not among those with high PDI. Conclusion Higher PAGln was associated with higher risk of CHD, particularly in women with dietary patterns of eating more animal foods and fewer plant-based foods. Adherence to plant-based diets might attenuate unfavorable associations between a novel microbial metabolite and CHD risk.