# Fecal Metabolomic Insights into Memory-Associated Pathways Modulated by Bacopa monnieri, Mixed Thai Berry, and Combined Extracts in Rats Under Chronic Unpredictable Mild Stress

## TL;DR

This study explores how different herbal extracts affect cognitive function and gut metabolism in stressed rats, revealing shared and unique metabolic changes linked to improved memory.

## Contribution

The study introduces fecal metabolomics as a tool to uncover distinct metabolic signatures of herbal treatments on cognitive improvement under chronic stress.

## Key findings

- Herbal treatments improved cognitive performance in stressed rats.
- Lipid remodeling, particularly unsaturated fatty acid biosynthesis, was a shared metabolic feature across treatments.
- Treatment-specific metabolite changes were observed, including bile acid signaling and amino-acid-derived metabolites.

## Abstract

Chronic stress impairs cognition through gut–brain axis dysregulation and metabolic imbalance. This study applied untargeted fecal metabolomics to investigate the cognitive and metabolic effects of Bacopa monnieri (L.) Wettst (Brahmi), mixed Thai berry, and their combined extracts in rats exposed to chronic unpredictable mild stress. Cognitive performance was evaluated using the novel object recognition test. Fecal metabolites were profiled using LC-ESI-QTOF-MS, followed by data preprocessing and multivariate statistical analysis. Orthogonal partial least squares regression was applied to identify metabolites associated with the recognition index, and pathway enrichment analysis was subsequently performed to interpret biological relevance. All interventions were associated with improved recognition performance and treatment-related metabolic modulation. Biosynthesis of unsaturated fatty acids was consistently enriched across treatment groups, indicating a shared involvement of lipid remodeling. Treatment-specific responses were also observed: Brahmi was associated with linoleic and alpha-linolenic acid metabolism; mixed Thai berry extract demonstrated dose-dependent modulation of lipid metabolism, with low-dose supplementation additionally yielding amino-acid-derived metabolites; and bile acid-related signaling was uniquely detected in the low-dose combined extract group. These findings demonstrate that fecal metabolomics can capture distinct metabolic signatures associated with herbal extract-induced cognitive improvement and highlight lipid remodeling as a shared metabolic feature across interventions under chronic stress.