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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MDPI AG
2022-11-01
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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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