Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice

Nobuyuki Sudo, Yoichi Chida, Yuji Aiba, Junko Sonoda, Naomi Oyama, Xiao Nian Yu, Chiharu Kubo, Yasuhiro Koga

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870 Citations (Scopus)

Abstract

Indigenous microbiota have several beneficial effects on host physiological functions; however, little is known about whether or not postnatal microbial colonization can affect the development of brain plasticity and a subsequent physiological system response. To test the idea that such microbes may affect the development of neural systems that govern the endocrine response to stress, we investigated hypothalamic-pituitary-adrenal (HPA) reaction to stress by comparing germfree (GF), specific pathogen free (SPF) and gnotobiotic mice. Plasma ACTH and corticosterone elevation in response to restraint stress was substantially higher in GF mice than in SPF mice, but not in response to stimulation with ether. Moreover, GF mice also exhibited reduced brain-derived neurotrophic factor expression levels in the cortex and hippocampus relative to SPF mice. The exaggerated HPA stress response by GF mice was reversed by reconstitution with Bifidobacterium infantis. In contrast, monoassociation with enteropathogenic Escherichia coli, but not with its mutant strain devoid of the translocated intimin receptor gene, enhanced the response to stress. Importantly, the enhanced HPA response of GF mice was partly corrected by reconstitution with SPF faeces at an early stage, but not by any reconstitution exerted at a later stage, which therefore indicates that exposure to microbes at an early developmental stage is required for the HPA system to become fully susceptible to inhibitory neural regulation. These results suggest that commensal microbiota can affect the postnatal development of the HPA stress response in mice.

Original languageEnglish
Pages (from-to)263-275
Number of pages13
JournalJournal of Physiology
Volume558
Issue number1
DOIs
Publication statusPublished - Jul 1 2004

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Pituitary-Adrenal System
Specific Pathogen-Free Organisms
Microbiota
Germ-Free Life
Enteropathogenic Escherichia coli
Endocrine System
Brain-Derived Neurotrophic Factor
Corticosterone
Feces
Ether
Adrenocorticotropic Hormone
Hippocampus

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. / Sudo, Nobuyuki; Chida, Yoichi; Aiba, Yuji; Sonoda, Junko; Oyama, Naomi; Yu, Xiao Nian; Kubo, Chiharu; Koga, Yasuhiro.

In: Journal of Physiology, Vol. 558, No. 1, 01.07.2004, p. 263-275.

Research output: Contribution to journalArticle

Sudo, Nobuyuki ; Chida, Yoichi ; Aiba, Yuji ; Sonoda, Junko ; Oyama, Naomi ; Yu, Xiao Nian ; Kubo, Chiharu ; Koga, Yasuhiro. / Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. In: Journal of Physiology. 2004 ; Vol. 558, No. 1. pp. 263-275.
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