Kamimura Itsuka, Miyauchi Eiji, Takeuchi Tadashi, Tsuchiya Noriaki, Tamura Kanami, Uesugi Ayumi, Negishi Hiroki, Taida Takashi, Kato Tamotsu, Kawasumi Masami, Nagasawa Miho, Mogi Kazutaka, Ohno Hiroshi, Kikusui Takefumi
Laboratory for Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Laboratory for Intestinal Ecosystem, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan.
Anim Microbiome. 2024 Jun 20;6(1):33. doi: 10.1186/s42523-024-00322-7.
The gut microbiota plays an important role in the development of behavior and immunity in infants and juveniles. Early weaning (EW), a form of social stress in mice, leads to increased anxiety and an enhanced stress response in the hypothalamic-pituitary-adrenal axis during adulthood. Early life stress also modulates the immune system and increases vulnerability to infection. However, studies investigating the causal relationships among juvenile stress, microbiota changes, and immune and behavioral deficits are limited. Therefore, we hypothesized that EW alters gut microbiota composition and impairs the development of the nervous and immune systems.
EW mice moved longer distances in the marble-burying test and had longer immobility times in the tail suspension test than normal weaning (NW) mice. In parallel, the gut microbiome composition differed between NW and EW mice, and the abundance of Erysipelotrichacea in EW mice at 8 weeks of age was lower than that in NW mice. In an empirical study, germ-free mice colonized with the gut microbiota of EW mice (GF-EW mice) demonstrated higher depressive behavior than GF mice colonized with normal weaning microbiota (GF-NW mice). Immune cell profiles were also affected by the EW microbiota colonization; the number of CD4 + T cells in the spleen was reduced in GF-EW mice.
Our results suggest that EW-induced alterations in the gut microbiota cause depressive behaviors and modulate the immune system.
肠道微生物群在婴幼儿和青少年行为及免疫发育中发挥着重要作用。早期断奶（EW）是小鼠社会应激的一种形式，会导致成年期焦虑增加以及下丘脑 - 垂体 - 肾上腺轴应激反应增强。早期生活应激还会调节免疫系统并增加感染易感性。然而，研究青少年应激、微生物群变化与免疫及行为缺陷之间因果关系的研究有限。因此，我们推测早期断奶会改变肠道微生物群组成，并损害神经和免疫系统的发育。
在埋珠试验中，早期断奶小鼠移动的距离比正常断奶（NW）小鼠长，在尾悬测试中静止不动的时间也更长。同时，NW小鼠和EW小鼠的肠道微生物群组成不同，8周龄EW小鼠中丹毒丝菌科的丰度低于NW小鼠。在一项实证研究中，用EW小鼠肠道微生物群定殖的无菌小鼠（GF - EW小鼠）比用正常断奶微生物群定殖的无菌小鼠（GF - NW小鼠）表现出更高的抑郁行为。免疫细胞谱也受到EW微生物群定殖的影响；GF - EW小鼠脾脏中CD4 + T细胞数量减少。
我们的结果表明，早期断奶引起的肠道微生物群改变会导致抑郁行为并调节免疫系统。
