A Pilot Controlled Feeding Trial Modifying Protein Intake in Healthy Subjects to Assess Adherence and the Metabolome

Abstract

Dietary protein has been shown to impact physiology and pathophysiology, including inflammation and cancer, effects believed to occur through host and microbe-mediated mechanisms. However, the majority of studies investigating this concept have been conducted in animal models, with less information on the optimal approach, tolerability and biologic effects of modifying protein intake in humans. The current study presents a longitudinal controlled feeding trial carried out in healthy humans to acutely modulate protein intake using individualized diets. Adherence to study diets was monitored through subject-reported electronic picture-based assessments and global metabolomic analysis was performed on serum and stool, following each diet stage. Subjects exhibited strong adherence to study diets, with macronutrient intake meeting study goals during each stage. Metabolomic analysis revealed shifts in both serum and feces in association with modifying protein intake, including reciprocal changes in the abundance of amino acids and amino-acid related compounds, when comparing high to reduced protein stages. Additional fecal metabolite changes consisted of reduced microbial fermentation products following the reduced protein diet stage. Collectively, this study provides a robust method to precisely modify and monitor protein intake in humans, as well as assess corresponding metabolomic alterations.

Acknowledgements

The authors thank Ms. Sharon Schmidt for assistance in administering several aspects of this trial, Student Health Services of Stony Brook University for assistance with collecting blood samples and Ms. Kathleen Carrozza for facilitating food storage.

Conflicts of Interest

Brian Ingram is an employee of Metabolon Inc.

Authors’ Contributions

JCS and LD conceptualized the study, formulated diets, supervised personnel, analyzed data and wrote the manuscript. MB and EMS formulated, prepared and provided study diets and consented subjects. LCC and BI analyzed and assisted with the display of metabolomic data. SA and MS carried out data analysis. DCM conceptualized the study, supervised personnel, performed data analysis and wrote the manuscript.

Additional information

Funding

This work was supported by startup funds from the Stony Brook Cancer Center and Bahl Center for Metabolomics and Imaging (D.C.M) and R25CA214272.