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Characterization of Early Life Stress-Affected Gut Microbiota.

ABSTRACT: Early life stress (ELS), such as neglect and maltreatment, exhibits a strong impact on the mental and brain development of children. However, it is not fully understood how ELS affects the body and behavior of children. Therefore, in this study, we performed social isolation on weaned pre-adolescent mice and investigated how ELS could affect gut microbiota and mouse behavior. Using the metagenomics approach, we detected an overall ELS-related change in the gut microbiota and identified Bacteroidales and Clostridiales as significantly altered bacterial groups. These metagenomic alterations impaired social behavior in ELS mice, which also correlated with the abundance of Bacteroidales and Clostridiales. Our results demonstrate that ELS alters the gut microbiota and reduces social behavior in adolescent mice.

SUBMITTER: Usui N

PROVIDER: S-EPMC8306161 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Characterization of Early Life Stress-Affected Gut Microbiota.

Usui Noriyoshi N Matsuzaki Hideo H Shimada Shoichi S

Brain sciences 20210710 7

Early life stress (ELS), such as neglect and maltreatment, exhibits a strong impact on the mental and brain development of children. However, it is not fully understood how ELS affects the body and behavior of children. Therefore, in this study, we performed social isolation on weaned pre-adolescent mice and investigated how ELS could affect gut microbiota and mouse behavior. Using the metagenomics approach, we detected an overall ELS-related change in the gut microbiota and identified <i>Bacter ...[more]

PMID: 34356147

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Project description:The neurotransmitter serotonin (5-HT) plays a vital regulatory role in both the brain and gut. 5-HT is crucial for regulating mood in the brain as well as gastrointestinal motility and secretion peripherally. Alterations in 5-HT transmission have been linked to pathological symptoms in both intestinal and psychiatric disorders and selective 5-HT transporter (5-HTT) inhibitors, affecting the 5-HT system by blocking the 5-HT transporter (5-HTT) have been successfully used to treat CNS- and intestinal disorders. Humans that carry the short allele of the 5-HTT-linked polymorphic region (5-HTTLPR) are more vulnerable to adverse environmental stressors, in particular early life stress. Although, early life stress has been shown to alter the composition of the gut microbiota, it is not known whether a lower 5-HTT expression is also associated with an altered microbiome composition. To investigate this, male and female wild type (5-HTT+/+), heterozygous (5-HTT+/-), and knockout (5-HTT-/-) 5-HT transporter rats were maternally separated for 6 h a day from postnatal day 2 till 15. On postnatal day 21, fecal samples were collected and the impact of 5-HTT genotype and maternal separation (MS) on the microbiome was analyzed using high-throughput sequencing of the bacterial 16S rRNA gene. MS showed a shift in the ratio between the two main bacterial phyla characterized by a decrease in Bacteroidetes and an increase in Firmicutes. Interestingly, the 5-HTT genotype caused a greater microbal dysbiosis (microbial imbalance) compared with MS. A significant difference in microbiota composition was found segregating 5-HTT-/- apart from 5-HTT+/- and 5-HTT+/+ rats. Moreover, exposure of rats with 5-HTT diminished expression to MS swayed the balance of their microbiota away from homeostasis to 'inflammatory' type microbiota characterized by higher abundance of members of the gut microbiome including Desulfovibrio, Mucispirillum, and Fusobacterium, all of which are previously reported to be associated with a state of intestinal inflammation, including inflammation associated with MS and brain disorders like multiple depressive disorders. Overall, our data show for the first time that altered expression of 5-HTT induces disruptions in male and female rat gut microbes and these 5-HTT genotype-related disruptions are augmented when combined with early life stress.

Dataset Information

Characterization of Early Life Stress-Affected Gut Microbiota.

Publications

Characterization of Early Life Stress-Affected Gut Microbiota.

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