Red and Processed Meat Effects on the Metabolome and Microbiome

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PROJECT SUMMARY Recent controversy has arisen concerning whether frequent intake of red and processed meat can be part of a healthy diet, or whether red and processed meat should be avoided or consumed only in moderation. Consumers and health care professionals are confused by these opposing views and research is needed to definitively guide dietary recommendations. Observational cohorts have found that those who self-report frequent red and processed meat intake have higher risk of several diet-related chronic diseases such as cardiovascular disease, type II diabetes and cancer compared to those with low or no intake of these foods. These findings are valuable, but self-reported diet without biological markers does not advance science towards understanding biological mechanisms. Some cohort studies have reported links between red and processed meat consumption and health related biomarkers such as lipids or food preparation-generated biomarkers such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HAs). However, many of these studies examined the associations of red and processed meat with blood or urine biomarkers in cross- sectional analyses, leaving the possibility for residual confounding and an inability to draw causal inference. Further, often only one pathway or one compound was measured in these studies, limiting insight into multiple pathways affected by red and processed meat consumption. And no studies have tested red and processed meat on systems-wide biomarkers using the metabolome and microbiome. To overcome these evidence gaps we will conduct a rigorous randomized cross-over feeding trial, which is a study design optimally suited for investigating mechanisms linking food intake with metabolic response due to the ability to carefully control food intake. This pilot, controlled feeding trial will enroll 20 heathy adult females and males. Participants will consume two diets, in random order: 1) Diet A is based on the Healthy Eating Index-2015 (HEI-2015) and includes no red or processed meat; 2) Diet B is based on the Healthy Eating Index-2015 and includes red and processed meat (HEI-2015-M) as primary protein sources. Both diet periods last 21 days and a 21-day washout period occurs between diets. All food is prepared in a metabolic kitchen and either picked up by participants or delivered by courier to their homes. Two types of mechanistic biomarkers are outcomes for this study, both reflecting systems-wide readouts: (1) metabolomics; and (2) gut microbiota. Blood, 24-hour urine and stool are collected before and after the experimental diets to test these specific aims: (1) Identify the extent and nature of shifts in the metabolome when consuming a standard HEI-2015 diet compared to a HEI-2015-M diet; and (2) Identify and characterize modulation of the gut microbial community when consuming a standard HEI-2015 diet compared to a HEI-2015-M diet. This pilot trial is expected to provide discovery, mechanistic data on the impact of red and processed meat intake on human metabolism that will be used to design and power a larger randomized controlled trial.