A Comprehensive Metabolomic and Microbial Analysis Following Dietary Amino Acid Reduction in Mice

Nutritional metabolomics provides a comprehensive overview of the biochemical processes that are induced by dietary intake through the measurement of metabolite profiles in biological samples. However, there is a lack of deep phenotypic analysis that shows how dietary interventions influence the metabolic state across multiple physiologic sites. Dietary amino acids have emerged as important nutrients for physiology and pathophysiology given their ability to impact cell metabolism. The aim of the current study is to evaluate the effect of modulating amino acids in diet on the metabolome and microbiome of mice. Here, we report a comprehensive metabolite profiling across serum, liver, and feces, in addition to gut microbial analyses, following a reduction in either total dietary protein or diet-derived non-essential amino acids in mice. We observed both distinct and overlapping patterns in the metabolic profile changes across the three sample types, with the strongest signals observed in liver and serum. Although amino acids and related molecules were the most commonly and strongly altered group of metabolites, additional small molecule changes included those related to glycolysis and the tricarboxylic acid cycle. Microbial profiling of feces showed significant differences in the abundance of select species across groups of mice. Our results demonstrate how changes in dietary amino acids influence the metabolic profiles across organ systems and the utility of metabolomic profiling for assessing diet-induced alterations in metabolism.