Abstract
Introduction: Phenylacetylglutamine (PAGln) has been recently discovered as a gut-microbiota-related metabolite, and circulating PAGln may be related to risks of cardiometabolic abnormalities. Gut microbiota-related dietary intakes and high-protein foods may affect circulating PAGln levels. Hypothesis: We assessed whether circulating PAGln levels may be related to intakes of gut-microbiota-related food intakes, and higher levels of PAGln may be associated with greater degrees of cardiometabolic abnormalities. We also tested a hypothesis that higher levels of circulating PAGln may be related to higher risk of the incident coronary heart disease (CHD). Methods: Circulating levels of PAGln, diet assessed using 7-day dietary records, and cardiometabolic abnormalities were assessed in the Women's Lifestyle Validation Study (WLVS) (n=723). The associations between plasma PAGln levels and risk of incident CHD were analyzed in a prospective nested case-control of 1520 women (760 incident cases of fatal CHD and nonfatal myocardial infarction and 760 controls) from the Nurses’ Health Study (NHS). We identified incident cases of CHD over 10-14 years of follow-up time. Results: Higher levels of PAGln were associated with higher levels of circulating insulin, triglycerides, as well as lower levels of HDL cholesterol. We found that greater intakes of red meat and processed meat (p=0.01), but not of poultry or fish (p >0.05), and lower intakes of vegetables (p=0.03) were significant factors associated with higher levels of circulating PAGln. In the prospective nested case-control study setting, higher levels of PAGln were associated with higher risk of the incident CHD. Every 1 unit increment of log-transformed PAGln was associated with a relative risk of 1.21 (95% CI: 1.01, 1.45) for the incident CHD. Conclusions: Gut-microbiota-affecting diet quality were related to circulating levels of PAGln. Circulating PAGln levels may be associated with cardiometabolic abnormalities and risk of incident CHD among women.
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