Modulation of gut microbiota composition due to early weaning stress induces depressive behavior during the juvenile period in mice.

BACKGROUND: 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. RESULTS: 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. CONCLUSION: Our results suggest that EW-induced alterations in the gut microbiota cause depressive behaviors and modulate the immune system.

Intergenerational transmission of maternal behavioral traits in mice: involvement of the gut microbiota.

The matrilineal transmission of maternal behavior has been reported in several species. Studies, primarily on rats, have suggested the importance of postnatal experience and the involvement of epigenetic mechanisms in mediating these transmissions. This study aims to determine whether the matrilineal transmission of maternal behavior occurs in mice and whether the microbiota is involved. We first observed that early weaned (EW) female mice showed lower levels of maternal behavior, particularly licking/grooming (LG) of their own pups, than normally weaned (NW) female mice. This difference in maternal behavioral traits was also observed in the second generation, even though all mice were weaned normally. In the subsequent cross-fostering experiment, the levels of LG were influenced by the nurturing mother but not the biological mother. Finally, we transplanted the fecal microbiota from EW or NW mice into germ-free (GF) mice raising pups. The maternal behaviors that the pups exhibited toward their own offspring after growth were analyzed, and the levels of LG in GF mice colonized with microbiota from EW mice were lower than those in GF mice colonized with microbiota from NW mice. These results clearly indicate that, among maternal behavioral traits, LG is intergenerationally transmitted in mice and suggest that the vertical transmission of microbiota is involved in this process. This study demonstrates the universality of the intergenerational transmission of maternal behavioral traits and provides new insights into the role of microbiota.

Microbial colonization history modulates anxiety-like and complex social behavior in mice.

Microbiome composition has a pivotal role in neurobehavioral development. However, there is limited information about the role of the microbiome in sociability of mice in complex social contexts. Germ-free (GF) mice were reared in a microbiota-free environment until postnatal day 21 and then transferred to a room containing specific pathogen free (SPF) mice. At 9 weeks old, group social behaviors were measured for three GF mice and three SPF mice unfamiliar to each other. GF mice spent less time in the center area of the arena and there were longer inter-individual distances compared with SPF mice. GF mice also had decreased brain-derived neurotrophic factor (BDNF) and increased ΔFosB mRNA in the prefrontal cortex compared to SPF mice. There were differences in the gut microbiome composition between GF and SPF mice; however, if cohabitating after weaning, then their microbiome composition became equivalent and group differences in behavior and BDNF and ΔFosB mRNA expression disappeared. These results demonstrate that the bacterial community can modulate neural systems that are involved in sociability and anxiety during the developmental period and suggest that sociability and anxiety can be shaped depending on the microbiome environment through interaction with conspecifics.

Dog and Cat Ownership Predicts Adolescents' Mental Well-Being: A Population-Based Longitudinal Study.

A potential association between pet ownership and mental well-being is suggested, but there is a shortage of high-quality longitudinal studies that consider probable differences among different species. We aimed to examine whether ownership of the most popular pets (dogs and cats) would predict mental well-being. The Tokyo Teen Cohort (TTC), a prospective population-based birth cohort study, had dog and cat ownership data at age 10 and mental well-being score at ages 10 and 12 from 2584 adolescents. Linear regression analysis with adjusting for covariates showed that dog ownership had a positive effect on mental well-being compared to no dog ownership, however, cat ownership had a negative effect compared to no cat ownership. Two-factor mixed-design analysis of variance showed that dog ownership predicted maintained mental well-being, while cat ownership predicted progressing decline of mental well-being. Thus, dog and cat ownership may have different effects on adolescents' mental well-being, implying that the underlying mechanisms that are activated by these types of ownership may differ.

Gonadal steroid hormone secretion during the juvenile period depends on host-specific microbiota and contributes to the development of odor preference.

The host microbial community is thought to have an important role in the host endocrine system and behavioral phenotype. We investigated chronological changes of levels of gonadal hormones and corticosterone in the feces of 4- to 8-week-old female germ-free (GF) mice, and conducted odor preference test at 8 weeks of age. We further evaluated the developmental impact of the microbial community by analyzing 4-week-old GF mice orally administered the fecal microbiota of specific pathogen-free (SPF) mice or guinea pigs (GF-SPF mice or GF-Guinea pig mice). The fecal estradiol, progesterone, and corticosterone levels of GF mice were lower than those of SPF mice. Furthermore, the increased levels in GF mice were suggested to be caused by colonization of microbiota of SPF mice or guinea pigs. However, the degree of recovery of progesterone and corticosterone by microbiota of guinea pigs was lower than that by SPF mice. In odor preference tests, interestingly, female GF mice preferred female odors to male odors, although this preference was not seen in other mice. These findings suggested that the microbial community plays an important role in the development of the host endocrine system for gonadal hormones and corticosterone, and odor preference in mice.