# Wuji Pill and Akkermansia muciniphila alleviates intestinal dysfunction and depression-like behavior in irritable bowel syndrome through the microbiota-gut-brain axis

## TL;DR

Wuji Pill and Akkermansia muciniphila improve IBS symptoms in rats by enhancing gut health and brain function through the microbiota-gut-brain axis.

## Contribution

Demonstrates that Wuji Pill alleviates IBS via modulation of Akkermansia muciniphila and regulation of the tryptophan metabolism pathway.

## Key findings

- Wuji Pill increased Akkermansia muciniphila abundance and improved IBS symptoms in rats.
- Fecal microbiota and A. muciniphila transplantation enhanced intestinal mucus secretion and short-chain fatty acids.
- Treatment suppressed microglia activation and inhibited the tryptophan-kynurenine pathway in the hippocampus.

## Abstract

Irritable bowel syndrome (IBS) is a typical disorder of gut-brain interaction (DGBI). The microbiota-gut-brain (MGB) axis is pivotal in preventing and treating IBS. Wuji Pill is a traditional Chinese medicine commonly used to treat IBS. This study aimed to investigate the mechanism by which Wuji Pill improves IBS via the MGB axis.

The visceral sensitivity and colonic motor function were evaluated using the abdominal wall withdrawal reflex test and the colonic motility curve. Depression-like behavior were evaluated using sucrose preference test, open field test, novelty-suppressed feeding test, and forced swimming tests. The intestinal mucus secretion and the activation status of microglia was detected using AB-PAS staining and immunofluorescence staining, respectively. The species composition and abundance of gut microbiota were detected through 16S rRNA sequencing and RT-qPCR. Targeted metabonomics and RT-qPCR were used for metabolites and metabolic enzymes analysis.

In this study, Wuji Pill improved the symptoms of IBS rats and increased the relative abundance of Akkermansia muciniphila in feces. Additionally, antibiotics affected the repair of intestinal mucus secretion and significantly reduced the level of short-chain fatty acids. Subsequently, fecal microbiota transplantation and A. muciniphila transplantation can improve the symptoms of IBS rat by increasing intestinal mucus secretion, elevating the levels of acetic acid and butyric acid in feces. Additionally, the microglia in the cortex were suppressed, and the tryptophan-kynurenine pathway in the hippocampus was inhibited, leading to the conversion of tryptophan into 5-HT.

This study highlights the Wuji Pill may alleviate IBS symptoms by modulating A. muciniphila and regulating the tryptophan metabolism pathway through MGB axis.

Diagram illustrating the impact of Wuji pill on IBS via the MGB axis. It shows two brain states: activated microglia with IBS and resting after Wuji pill treatment improves symptoms. Indicators include depression, visceral hypersensitivity, and SCFAs such as acetic, propionic, and butyric acids. The gut microbiota diversity includes Akkermansia and Prevotella, which affect mucus production and serotonin levels. Labels such as SCFAs, IBS rat model, and TPH1 pathway are highlighted, showing interactions between gut and brain functions.