# Integrated Untargeted and Targeted Metabolomics Reveals Distinct Bioactive Metabolite Profiles Between Probiotic Supplements and Yogurt

## TL;DR

This study compares the biochemical profiles of probiotic supplements and yogurt, identifying distinct metabolites and their potential health benefits.

## Contribution

The study introduces a novel integrated metabolomics approach to compare bioactive metabolite profiles of probiotic supplements and yogurt.

## Key findings

- Probiotic supplements have higher levels of amino acids, lysophospholipids, and indole derivatives compared to yogurt.
- Yogurt contains more carbohydrates, acylcarnitines, and sphingolipids, with specific bioactive metabolites like butyrate and creatine.
- PS-specific indole derivatives showed significant antiglycation activity, suggesting their role in health benefits.

## Abstract

Probiotics are widely consumed as health-promoting agents, with probiotic supplements (PS) and yogurt (YG) representing formulated products and fermented foods, respectively. Despite their broad consumption, systematic comparisons of their biochemical characteristics remain limited. In this study, integrated untargeted and targeted metabolomics approaches were applied to compare the comprehensive metabolite profiles of PS and YG. PS exhibited relatively higher levels of amino acids, dicarboxylic acids, and lysophospholipids, along with short-chain fatty acids such as acetate and propionate, and amino acid-derived bioactive metabolites, including γ-aminobutyric acid, branched-chain hydroxy acids, indole derivatives, and γ-glutamylpeptides. In contrast, YG showed higher relative abundances of carbohydrates, acylcarnitines, sphingolipids, and bioactive metabolites such as butyrate, creatine, carnitine, and orotic acid. Based on these metabolomic differences, 27 PS-specific and 17 YG-specific marker metabolites were identified. To explore their functional relevance, in vitro antioxidant and antiglycation activities were evaluated. PS exhibited significantly higher antioxidant and antiglycation activities than YG, which were positively correlated with amino acids and indole derivatives. Indole-3-acrylic acid, indole-3-acetic acid, and indole-3-propionic acid showed antiglycation activity and were identified as PS-specific bioactive marker metabolites. These findings reveal the distinct biochemical characteristics of PS and YG and highlight potential bioactive candidate metabolites that may contribute to their functional differences.