The effects of autologous fecal microbiota transplantation on fear memory and anxiety abnormalities induced by single prolonged stress – Implication of gut-brain axis regulation

Increasing evidence suggests that alterations in the gut microbiota play a crucial role in the pathophysiology of psychiatric disorders, including post-traumatic stress disorder (PTSD). This implies that restoring gut microbiota might serve as a therapeutic strategy, with autologous fecal microbiota...

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Main Authors: Yu-Yen Cheng, Chen-Cheng Lin, Che-Se Tung, Cheng-Che Liu, Yia-Ping Liu
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Brain Research Bulletin
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Online Access:http://www.sciencedirect.com/science/article/pii/S0361923025002849
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author Yu-Yen Cheng
Chen-Cheng Lin
Che-Se Tung
Cheng-Che Liu
Yia-Ping Liu
author_facet Yu-Yen Cheng
Chen-Cheng Lin
Che-Se Tung
Cheng-Che Liu
Yia-Ping Liu
author_sort Yu-Yen Cheng
collection DOAJ
description Increasing evidence suggests that alterations in the gut microbiota play a crucial role in the pathophysiology of psychiatric disorders, including post-traumatic stress disorder (PTSD). This implies that restoring gut microbiota might serve as a therapeutic strategy, with autologous fecal microbiota transplantation (FMT) being the most promising treatment due to its effectiveness and fewer pharmacological side effects. However, the hypothesis that adjusting gut microbiota may help to restore the impairment of fear memory is still less examined. To evaluate this hypothesis, we employed single prolonged stress (SPS) rat model to examine the impact of autologous FMT on PTSD-related fear memory extinction retention deficits and increased anxiety, and to investigate changes in the levels of gut microbiota, central monoamines, and plasma corticosterone. The correlations between gut microbiota and central serotonin (5-HT) with fear extinction retention deficits and anxiety were analyzed. Note that littermates were used in the gut microbiota analysis to minimize individual differences. Our results demonstrated that autologous FMT significantly ameliorated SPS-induced deficits in fear extinction retention and conditioned anxiety but did not mitigate unconditioned anxiety. These improvements were significantly correlated with the restoration of 5-HT levels in the medial prefrontal cortex (mPFC), dorsal hippocampus (dHPC), and hypothalamus (HT). Autologous FMT also reversed SPS-induced reductions in plasma corticosterone level. Additionally, fecal microbiota analysis revealed significant changes at the genus level, with the relative abundance of the Prevotellaceae Ga6A1 group reduced after SPS, and Intestinimonas increased by FMT, as well as some taxa significantly correlated with fear extinction retention deficits. This study suggests that autologous FMT offers potential as a novel therapeutic strategy for PTSD.
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spelling doaj-art-63d3acd1af4a43e8a644fc4f3df5188f2025-08-20T03:42:34ZengElsevierBrain Research Bulletin1873-27472025-09-0122911147210.1016/j.brainresbull.2025.111472The effects of autologous fecal microbiota transplantation on fear memory and anxiety abnormalities induced by single prolonged stress – Implication of gut-brain axis regulationYu-Yen Cheng0Chen-Cheng Lin1Che-Se Tung2Cheng-Che Liu3Yia-Ping Liu4Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan; Laboratory of Cognitive Neuroscience, Department of Physiology, National Defense Medical Center, Taipei 11490, TaiwanLaboratory of Cognitive Neuroscience, Department of Physiology, National Defense Medical Center, Taipei 11490, Taiwan; Department of Physiology, National Defense Medical Center, Taipei 11490, TaiwanDepartment of Physiology, National Defense Medical Center, Taipei 11490, TaiwanGraduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan; Department of Physiology, National Defense Medical Center, Taipei 11490, Taiwan; Correspondence to: Department of Physiology, National Defense Medical Center, No.161, Section 6, Min-Chuan East Road, Taipei 114, Taiwan.Laboratory of Cognitive Neuroscience, Department of Physiology, National Defense Medical Center, Taipei 11490, Taiwan; Department of Physiology, National Defense Medical Center, Taipei 11490, Taiwan; Department of Psychiatry, Cheng Hsin General Hospital, Taipei 112, Taiwan; Correspondence to: Department of psychiatry, Cheng Hsin General Hospital.45, Cheng Hsin St., Beitou, Taipei 112, TaiwanIncreasing evidence suggests that alterations in the gut microbiota play a crucial role in the pathophysiology of psychiatric disorders, including post-traumatic stress disorder (PTSD). This implies that restoring gut microbiota might serve as a therapeutic strategy, with autologous fecal microbiota transplantation (FMT) being the most promising treatment due to its effectiveness and fewer pharmacological side effects. However, the hypothesis that adjusting gut microbiota may help to restore the impairment of fear memory is still less examined. To evaluate this hypothesis, we employed single prolonged stress (SPS) rat model to examine the impact of autologous FMT on PTSD-related fear memory extinction retention deficits and increased anxiety, and to investigate changes in the levels of gut microbiota, central monoamines, and plasma corticosterone. The correlations between gut microbiota and central serotonin (5-HT) with fear extinction retention deficits and anxiety were analyzed. Note that littermates were used in the gut microbiota analysis to minimize individual differences. Our results demonstrated that autologous FMT significantly ameliorated SPS-induced deficits in fear extinction retention and conditioned anxiety but did not mitigate unconditioned anxiety. These improvements were significantly correlated with the restoration of 5-HT levels in the medial prefrontal cortex (mPFC), dorsal hippocampus (dHPC), and hypothalamus (HT). Autologous FMT also reversed SPS-induced reductions in plasma corticosterone level. Additionally, fecal microbiota analysis revealed significant changes at the genus level, with the relative abundance of the Prevotellaceae Ga6A1 group reduced after SPS, and Intestinimonas increased by FMT, as well as some taxa significantly correlated with fear extinction retention deficits. This study suggests that autologous FMT offers potential as a novel therapeutic strategy for PTSD.http://www.sciencedirect.com/science/article/pii/S0361923025002849AnxietyFear extinction retentionFecal microbiota transplantationGut microbiotaGut-brain axisPost-traumatic stress disorder
spellingShingle Yu-Yen Cheng
Chen-Cheng Lin
Che-Se Tung
Cheng-Che Liu
Yia-Ping Liu
The effects of autologous fecal microbiota transplantation on fear memory and anxiety abnormalities induced by single prolonged stress – Implication of gut-brain axis regulation
Brain Research Bulletin
Anxiety
Fear extinction retention
Fecal microbiota transplantation
Gut microbiota
Gut-brain axis
Post-traumatic stress disorder
title The effects of autologous fecal microbiota transplantation on fear memory and anxiety abnormalities induced by single prolonged stress – Implication of gut-brain axis regulation
title_full The effects of autologous fecal microbiota transplantation on fear memory and anxiety abnormalities induced by single prolonged stress – Implication of gut-brain axis regulation
title_fullStr The effects of autologous fecal microbiota transplantation on fear memory and anxiety abnormalities induced by single prolonged stress – Implication of gut-brain axis regulation
title_full_unstemmed The effects of autologous fecal microbiota transplantation on fear memory and anxiety abnormalities induced by single prolonged stress – Implication of gut-brain axis regulation
title_short The effects of autologous fecal microbiota transplantation on fear memory and anxiety abnormalities induced by single prolonged stress – Implication of gut-brain axis regulation
title_sort effects of autologous fecal microbiota transplantation on fear memory and anxiety abnormalities induced by single prolonged stress implication of gut brain axis regulation
topic Anxiety
Fear extinction retention
Fecal microbiota transplantation
Gut microbiota
Gut-brain axis
Post-traumatic stress disorder
url http://www.sciencedirect.com/science/article/pii/S0361923025002849
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