Bacterial metabolite may link irritable bowel syndrome to mood disorders

04.09.2026

The findings highlight TnAse producing gut microbiota, indole, and AhR as promising therapeutic targets for IBS-associated affective disturbances.

What is already known

Conditions such as depression and anxiety are common, and previous research has shown that the gut-brain connection—through microbes, diet, or fecal transplants—can influence mood. Irritable bowel syndrome (IBS), which alters gut bacteria and often co-occurs with anxiety or depression, illustrates this link, with microbial metabolites offering promising targets for therapies.

What this research adds

Researchers found that people and mice with IBS have reduced levels of the microbe Alistipes shahii, which lowers production of a molecule called indole. Indole reduction disrupts signaling through AhR, a receptor that regulates neuron activity in the ventral dentate gyrus—a part of the hippocampus that plays a key role in regulating emotions and mood. This leads to weaker neuronal function and anxiety- and depression-like behaviors. Restoring A. shahii, indole, or activating neurons in the ventral dentate gyrus reversed these symptoms. Diosmin, a clinically approved AhR activator, also reversed emotional behaviors and neuron activity in mice with IBS.

Conclusions

The findings suggest that targeting the gut-brain connection offers a promising strategy to treat mood disorders associated with IBS.

Irritable bowel syndrome (IBS) is a condition that not only affects the gut but is also linked to mood disorders, as changes in the gut microbiota can influence brain function. Now, researchers have found that gut bacteria regulate mood in IBS by producing the metabolite indole, which activates a receptor that regulates neuron activity in a brain region important for emotional control.

The findings, published in Cell Metabolism, suggest that targeting the gut-brain connection offers a promising strategy to treat mood disorders associated with IBS.

Conditions such as depression and anxiety are common and often resistant to treatment, and previous research has shown that the gut-brain connection—through microbes, diet, or fecal transplants—can influence mood. IBS, which alters gut bacteria and often co-occurs with anxiety or depression, illustrates this link, with microbial metabolites offering promising targets for therapies.

Researchers led by Ting-Ting Wang at Shanghai Jiao Tong University School of Medicine in China studied how gut bacteria affect mood in people and mice with IBS.

Neuronal activity

Transferring gut bacteria from people or mice with IBS into germ-free mice caused the animals to develop anxiety- and depression-like behaviors. Further analyses identified a specific bacterium, Alistipes shahii, which was reduced in both people and mice with IBS.

Lower levels of A. shahii led to reduced levels of the enzyme TnAse, which is essential for producing indole. This drop in indole was associated with anxiety and depression in both people and mice with IBS. Restoring A. shahii in mice increased indole levels and improved emotional behaviors. Giving mice indole also relieved anxiety- and depression-like behaviors.

The researchers found that indole binds to AhR, a receptor that regulates neuron activity in the ventral dentate gyrus—a part of the hippocampus that plays a key role in regulating emotions and mood. Lower gut levels of indole reduced AhR signaling, which weakened the activity of neurons in the ventral dentate gyrus, leading to anxiety- and depression-like behaviors in mice.

Reversing symptoms

Further experiments showed that restoring indole levels or activating neurons in the ventral dentate gyrus reversed these emotional symptoms, whereas blocking neuron activity in the ventral dentate gyrus prevented indole’s benefits.

Diosmin, a clinically approved AhR activator, reversed emotional behaviors and neuron activity in mice with IBS. Diosmin also improved emotional symptoms in germ-free mice that received gut bacteria from people with IBS, the researchers found.

The findings, they say, “establish gut-derived indole as a key modulator of emotional behavior in IBS via the A. shahii-TnAse-indole-AhR-[ventral dentate gyrus] signaling pathway and highlight TnAse producing gut microbiota, indole, and AhR as promising therapeutic targets for IBS-associated affective disturbances.”