Indole Acetic Acid Exerts Anti-Depressive Effects on an Animal Model of Chronic Mild Stress

Indole acetic acid (IAA), an intestinal bacteria-derived tryptophan metabolite, has been detected at abnormal concentrations in the cerebrospinal fluid and urine of depressed individuals. The effects of such altered IAA concentrations on mood regulation are not known. A mouse model of unpredictable...

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Main Authors: Ying Chen, Peijun Tian, Zheng Wang, Ruili Pan, Kexin Shang, Gang Wang, Jianxin Zhao, Wei Chen
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/14/23/5019
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author Ying Chen
Peijun Tian
Zheng Wang
Ruili Pan
Kexin Shang
Gang Wang
Jianxin Zhao
Wei Chen
author_facet Ying Chen
Peijun Tian
Zheng Wang
Ruili Pan
Kexin Shang
Gang Wang
Jianxin Zhao
Wei Chen
author_sort Ying Chen
collection DOAJ
description Indole acetic acid (IAA), an intestinal bacteria-derived tryptophan metabolite, has been detected at abnormal concentrations in the cerebrospinal fluid and urine of depressed individuals. The effects of such altered IAA concentrations on mood regulation are not known. A mouse model of unpredictable chronic mild stress (UCMS) was used to assess the effects of IAA administration (50 mg/kg). Treatment with IAA for 5 weeks attenuated depression and anxiety-like behaviours, improved hypothalamus–pituitary–adrenal axis dysfunction and increased brain-derived neurotrophic factor expression. IAA supplementation also enhanced the serotonin pathway in the brain and gut. UCMS caused an imbalance of microbial indole metabolites in the colon, whereas IAA treatment reversed this. However, IAA intake did not affect the concentrations of indoles in the brain. Intestinal bacteria in different sections of the gut were altered by IAA treatment, with the colon showing more changes than other segments. The gut microbiome in the colon had increased proportions of <i>Ruminococcaceae</i> UCG013, <i>Ruminiclostridium</i> 6, <i>Prevotella</i>, <i>Alloprevotella</i> and <i>Bacteroides</i> species, which can produce short-chain fatty acids and indole derivatives. Cumulatively, our study highlights the potential of IAA treatment to alleviate mood disorders and offers a theoretical basis for understanding the antidepressant effects of IAA.
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spelling doaj.art-ccc0316fbe1f4756a175a6a0a0cd6b8d2023-11-24T11:50:49ZengMDPI AGNutrients2072-66432022-11-011423501910.3390/nu14235019Indole Acetic Acid Exerts Anti-Depressive Effects on an Animal Model of Chronic Mild StressYing Chen0Peijun Tian1Zheng Wang2Ruili Pan3Kexin Shang4Gang Wang5Jianxin Zhao6Wei Chen7State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, ChinaIndole acetic acid (IAA), an intestinal bacteria-derived tryptophan metabolite, has been detected at abnormal concentrations in the cerebrospinal fluid and urine of depressed individuals. The effects of such altered IAA concentrations on mood regulation are not known. A mouse model of unpredictable chronic mild stress (UCMS) was used to assess the effects of IAA administration (50 mg/kg). Treatment with IAA for 5 weeks attenuated depression and anxiety-like behaviours, improved hypothalamus–pituitary–adrenal axis dysfunction and increased brain-derived neurotrophic factor expression. IAA supplementation also enhanced the serotonin pathway in the brain and gut. UCMS caused an imbalance of microbial indole metabolites in the colon, whereas IAA treatment reversed this. However, IAA intake did not affect the concentrations of indoles in the brain. Intestinal bacteria in different sections of the gut were altered by IAA treatment, with the colon showing more changes than other segments. The gut microbiome in the colon had increased proportions of <i>Ruminococcaceae</i> UCG013, <i>Ruminiclostridium</i> 6, <i>Prevotella</i>, <i>Alloprevotella</i> and <i>Bacteroides</i> species, which can produce short-chain fatty acids and indole derivatives. Cumulatively, our study highlights the potential of IAA treatment to alleviate mood disorders and offers a theoretical basis for understanding the antidepressant effects of IAA.https://www.mdpi.com/2072-6643/14/23/5019indole acetic aciddepressionHPA axisserotoningut microbiotaindole derivative
spellingShingle Ying Chen
Peijun Tian
Zheng Wang
Ruili Pan
Kexin Shang
Gang Wang
Jianxin Zhao
Wei Chen
Indole Acetic Acid Exerts Anti-Depressive Effects on an Animal Model of Chronic Mild Stress
Nutrients
indole acetic acid
depression
HPA axis
serotonin
gut microbiota
indole derivative
title Indole Acetic Acid Exerts Anti-Depressive Effects on an Animal Model of Chronic Mild Stress
title_full Indole Acetic Acid Exerts Anti-Depressive Effects on an Animal Model of Chronic Mild Stress
title_fullStr Indole Acetic Acid Exerts Anti-Depressive Effects on an Animal Model of Chronic Mild Stress
title_full_unstemmed Indole Acetic Acid Exerts Anti-Depressive Effects on an Animal Model of Chronic Mild Stress
title_short Indole Acetic Acid Exerts Anti-Depressive Effects on an Animal Model of Chronic Mild Stress
title_sort indole acetic acid exerts anti depressive effects on an animal model of chronic mild stress
topic indole acetic acid
depression
HPA axis
serotonin
gut microbiota
indole derivative
url https://www.mdpi.com/2072-6643/14/23/5019
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