Indole-3-propionic acid function through PXR and AhR, molecular signaling pathways, and antitoxic role in underlying diseases

Oct 15, 2025The Journal of steroid biochemistry and molecular biology

Indole-3-propionic acid's role in reducing toxicity through PXR and AhR molecular pathways in diseases

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Abstract

Microbial metabolites, such as Indole-3-Propionic Acid (IPA), are produced by gut bacteria from dietary tryptophan.

IPA is absorbed by intestinal cells and enters the bloodstream, impacting multiple organ systems.
It interacts with the Pregnane X receptor (PXR) and aryl hydrocarbon receptor (AhR), leading to varied gene expression and biological pathways.
IPA may inhibit oxidative stress injury and reduce the production of proinflammatory cytokines.
Research suggests IPA has antioxidant, anti-inflammatory, anti-cancer, and neuroprotective properties.
Dysbiosis affecting IPA levels is associated with metabolic syndromes, inflammatory conditions, cancer, and neuropsychiatric diseases.

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The host organism's balance within the body relies on its crucial symbiotic relationship with gut microbiota. This balance, known as homeostasis, can be influenced by various factors. One significant factor is the role of bacterial metabolites from different substrates, such as tryptophan. Recent research has revealed that these metabolites impact many biological processes. Microbial metabolites, such as Indole-3-Propionic Acid (IPA), are produced by the intestinal microbiota by converting dietary tryptophan. IPA is absorbed by intestinal epithelial cells, transported via the portal circulation, undergoes minimal hepatic metabolism, and is subsequently released into the systemic circulation to reach peripheral tissues and exert its biological effects. The Pregnane X receptor (PXR) and aryl hydrocarbon receptor (AhR) are the two main receptors of IPA which induce different gene expression profiles and subsequently diverse biological pathways in different tissues. Once absorbed by intestinal epithelial cells, IPA is released into the circulatory system and can significantly affect the immune, cardiovascular, nervous, and gastrointestinal systems. Furthermore, IPA has been found to have positive effects on a cellular level by inhibiting oxidative stress injury and preventing the synthesis of proinflammatory cytokines. Numerous studies have highlighted IPA's antioxidant, anti-inflammatory, anti-cancer, and neuroprotective effects. Therefore, dysbiosis of IPA contributes to disorders such as metabolic syndromes, inflammatory conditions, cancer, and neuropsychiatric diseases. This review provides a detailed examination of the most recent studies on indole-3-propionic acid function through PXR and AhR, outlining its molecular signaling pathways and correlation with various diseases.

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Indole-3-propionic acid function through PXR and AhR, molecular signaling pathways, and antitoxic role in underlying diseases

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