scholarly journals Early-Life Stress Modulates Gut Microbiota and Peripheral and Central Inflammation in a Sex-Dependent Manner

2021 ◽  
Vol 22 (4) ◽  
pp. 1899 ◽  
Author(s):  
Hae Jeong Park ◽  
Sang A. Kim ◽  
Won Sub Kang ◽  
Jong Woo Kim
Keyword(s):  
Gut Microbiota ◽  
Relative Abundance ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Female Rats ◽  
Rrna Gene ◽  
Dependent Manner ◽  
Male And Female Rats

Recent studies have reported that changes in gut microbiota composition could induce neuropsychiatric problems. In this study, we investigated alterations in gut microbiota induced by early-life stress (ELS) in rats subjected to maternal separation (MS; 6 h a day, postnatal days (PNDs) 1–21), along with changes in inflammatory cytokines and tryptophan-kynurenine (TRP-KYN) metabolism, and assessed the differences between sexes. High-throughput sequencing of the bacterial 16S rRNA gene showed that the relative abundance of the Bacteroides genus was increased and that of the Lachnospiraceae family was decreased in the feces of MS rats of both sexes (PND 56). By comparison, MS increased the relative abundance of the Streptococcus genus and decreased that of the Staphylococcus genus only in males, whereas the abundance of the Sporobacter genus was enhanced and that of the Mucispirillum genus was reduced by MS only in females. In addition, the levels of proinflammatory cytokines were increased in the colons (IFN-γ and IL-6) and sera (IL-1β) of the male MS rats, together with the elevation of the KYN/TRP ratio in the sera, but not in females. In the hippocampus, MS elevated the level of IL-1β and the KYN/TRP ratio in both male and female rats. These results indicate that MS induces peripheral and central inflammation and TRP-KYN metabolism in a sex-dependent manner, together with sex-specific changes in gut microbes.

Early life stress in mice alters gut microbiota independent of maternal microbiota inheritance

2021 ◽  
Vol 320 (5) ◽  
pp. R663-R674
Author(s):  
Keri M. Kemp ◽  
Jackson Colson ◽  
Robin G. Lorenz ◽  
Craig L. Maynard ◽  
Jennifer S. Pollock
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Disease ◽  
Gut Microbiota ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Microbial Community Composition ◽  
Early Life Stress ◽  
Alpha Diversity ◽  
Disease Development

Exposure to early life stress (ELS) is associated with a greater risk of chronic disease development including depression and cardiovascular disease. Altered gut microbiota has been linked to both depression and cardiovascular disease in mice and humans. Rodent models of early life neglect are used to characterize the mechanistic links between early life stress (ELS) and the risk of disease later in life. However, little is understood about ELS exposure and the gut microbiota in the young mice and the influence of the maternal inheritance of the gut microbiota. We used a mouse model of ELS, maternal separation with early weaning (MSEW), and normally reared mice to determine whether the neonate microbiota is altered, and if so, are the differences attributable to changes in dam microbiota that are then transmitted to their offspring. Individual amplicon sequence variants (ASVs) displayed differential abundance in the microbiota of MSEW compared with normally reared pups at postnatal day ( PD) 28. Additionally, ELS exposure reduced the alpha diversity and altered microbial community composition at PD28. The composition, levels of alpha diversity, and abundance of individual ASVs in the microbiota of dams were similar from MSEW or normally reared cohorts. Thus, the observed shifts in the abundance of individual bacterial ASVs in the neonates and young pups are likely driven by endogenous effects of MSEW in the offspring host and are not due to inherited differences from the dam. This knowledge suggests that exposure to ELS has a direct effect on microbial factors on the risk of chronic disease development.

scholarly journals Maternal Separation Induces Sex-Specific Differences in Sensitivity to Traumatic Stress

2021 ◽  
Vol 15 ◽  
Author(s):  
Dayan Knox ◽  
Stephanie A. Stout-Oswald ◽  
Melissa Tan ◽  
Sophie A. George ◽  
Israel Liberzon
Keyword(s):  
Risk Factors ◽  
Sex Differences ◽  
Animal Models ◽  
Traumatic Stress ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Female Rats ◽  
Male Rats

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric disorder with a high economic burden. Two risk factors for increasing the chances of developing PTSD are sex (being female) and early life stress. These risk factors suggest that early life stress-induced changes and sex differences in emotional circuits and neuroendocrinological systems lead to susceptibility to traumatic stress. Exploring mechanisms via which stress leads to specific effects can be accomplished in animal models, but reliable animal models that allow for an examination of how early life stress interacts with sex to increase susceptibility to traumatic stress is lacking. To address this, we examined the effects of early life stress [using the maternal separation (MS) model] and late adolescence/early adult traumatic stress [using the single prolonged stress (SPS) model] on startle reactivity, anxiety-like behavior in the open field (OF), and basal corticosterone levels in male and female rats. Female rats exposed to MS and SPS (MS/SPS) showed enhanced startle reactivity relative to MS/control female rats. Enhanced startle reactivity was not observed in MS/SPS male rats. Instead, non-maternally separated male rats that were exposed to SPS showed enhanced startle reactivity relative to controls. Female rats had enhanced locomotor activity in the OF and higher basal corticosterone levels in comparison to males, but measures in the OF and basal corticosterone were not affected by MS or SPS. Overall the results suggest that the combined MS and SPS models can be used to explore how changes in maternal care during infancy lead to sex differences in sensitivity to the effects of traumatic stress as adolescents and adults.

scholarly journals Early-life stress induces genome-wide sex-dependent miRNA expression and correlation across limbic brain areas in rats

Epigenomics ◽  
2021 ◽  
Author(s):  
Lauren A McKibben ◽  
Yogesh Dwivedi
Keyword(s):  
Prefrontal Cortex ◽  
Mirna Expression ◽  
Life Stress ◽  
Early Life ◽  
Target Genes ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Small Rna Sequencing ◽  
Dependent Manner ◽  
Genome Wide

Aims: The aim of this study was to assess regional- and sex-dependent changes in miRNA expression resulting from early-life stress (ELS). Materials and methods: Small RNA sequencing was used to determine sex-dependent changes in miRNAs after maternal separation, a rodent model of ELS, across the prefrontal cortex, amygdala and hippocampus. Results: Maternal separation induced anhedonia and altered miRNA expression in a sex-dependent manner, particularly in the prefrontal cortex and hippocampus. Gene ontology revealed that these miRNAs target genes with brain-specific biological functions. Conclusions: Using a network approach to explore miRNA signaling across the brain after ELS, regional differences were highlighted as key to studying the brain’s stress response, which indicates that sex is critical for understanding miRNA-mediated ELS-induced behavior.

Antidepressant-like effects of URB597 and JZL184 in male and female rats exposed to early life stress

2020 ◽  
Vol 39 ◽  
pp. 70-86 ◽  
Author(s):  
Shirley Alteba ◽  
Tomer Mizrachi Zer-Aviv ◽  
Adi Tenenhaus ◽  
Gilad Ben David ◽  
Jacob Adelman ◽  
...  
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats

Adolescent oxytocin administration reduces depression-like behaviour induced by early life stress in adult male and female rats

2021 ◽  
Vol 110 ◽  
pp. 110279
Author(s):  
Jade L. Thornton ◽  
Nicholas A. Everett ◽  
Paige Webb ◽  
Anita J. Turner ◽  
Jennifer L. Cornish ◽  
...  
Keyword(s):  
Adult Male ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats

Early life stress impairs fear conditioning in adult male and female rats

2006 ◽  
Vol 1087 (1) ◽  
pp. 142-150 ◽  
Author(s):  
Therese A. Kosten ◽  
Hongjoo J. Lee ◽  
Jeansok J. Kim
Keyword(s):  
Fear Conditioning ◽  
Adult Male ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats

scholarly journals Effects of Early Life Stress on Synaptic Plasticity in the Developing Hippocampus of Male and Female Rats

PLoS ONE ◽  
2016 ◽  
Vol 11 (10) ◽  
pp. e0164551 ◽  
Author(s):  
Nienke A. V. Derks ◽  
Harm J. Krugers ◽  
Casper C. Hoogenraad ◽  
Marian Joëls ◽  
R. Angela Sarabdjitsingh
Keyword(s):  
Synaptic Plasticity ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Female Rats ◽  
Male And Female ◽  
Male And Female Rats

scholarly journals Lactobacillus paracasei Supplementation Prevents Early Life Stress-Induced Anxiety and Depressive-Like Behavior in Maternal Separation Model-Possible Involvement of Microbiota-Gut-Brain Axis in Differential Regulation of MicroRNA124a/132 and Glutamate Receptors

2021 ◽  
Vol 15 ◽  
Author(s):  
Christopher Karen ◽  
Douglas J. H. Shyu ◽  
Koilmani Emmanuvel Rajan
Keyword(s):  
Gut Microbiota ◽  
Glutamate Receptors ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Stress Hormones ◽  
Early Life Stress ◽  
Metabolite Profile ◽  
Lactobacillus Paracasei ◽  
Beneficial Effects

This study was designed to investigate stressful social experience (SSE) in early life by examining how it can induce alterations in the microbiota-gut-brain axis. To test this, different experimental groups of pups experienced the presence of either a stranger (S) with mother (M+P+S) or without their mother (MS+S−M). Animals were assessed for anxiety-like behavior and high-throughput bacterial 16s rRNA sequencing was performed to analyze the structure of the gut microbiota. Our analysis revealed that early life SSE induced anxiety-like behavior and reduced the diversity and richness of gut microbiota. In the second experiment, all groups were supplemented with Lactobacillus paracasei HT6. The findings indicated that Lactobacillus supplementation had a significant beneficial effect on anxiety-like behavior in stressed rats (MS, M+P+S, and MS + S−M) accompanied by normalized levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), glucocorticoid receptor (GR), serotonin (5-HT), dopamine (DA), and noradrenaline (NA). Concomitantly, the expression of microRNA (miR)-124a was down-regulated and miR-132, caspase-3, glutamate receptors (GluR1, GluR 2; NR2A, and NR2B) were up-regulated in stressed groups but remained unchanged by Lactobacillus supplementation in stressed individuals. This indicates that stress-associated GluR1-GR altered interactions can be significantly prevented by Lactobacillus supplementation. Analysis of the fecal metabolite profile was undertaken to analyze the effect of Lactobacillus, revealing that five predicted neuroactive microbial metabolites were reduced by early life SSE. Our results showed a potential link between Lactobacillus supplementation and beneficial effects on anxiety-like behavior, the mechanism of which could be potentially mediated through stress hormones, neurotransmitters, and expression of miRNAs, glutamate receptors, and the microbiota-gut-brain axis.

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