Abstract
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.
Highlights
Maternal separation (MS) has been established as a model to investigate early life stress (ELS) induced neurobiological and behavioral disorders later in life (Bian et al, 2015; Feifel et al, 2017; Wang et al, 2017)
Compared to MS + S−M, a significantly lower diversity was estimated in the MS group (P < 0.001) than in the MS group, but there were no significant differences between the control and the M + P + S group (P = 0.932)
When we analyzed the time spent in the central square, we found that there were no significant differences between the control and control + Pro groups (P = 0.739) and, in parallel, there were no significant differences between the M + P + S and M+P+S + Pro groups (P = 0.335)
Summary
Maternal separation (MS) has been established as a model to investigate early life stress (ELS) induced neurobiological and behavioral disorders later in life (Bian et al, 2015; Feifel et al, 2017; Wang et al, 2017). Previous studies reported that the impact of ELS on the hypothalamic-pituitary-adrenal (HPA) axis induces changes in adrenocorticotropic hormone (ACTH), corticosterone (CORT), glucocorticoid receptor (GR), neurotransmitters (Lai and Huang, 2011; Clarke et al, 2013; Chen and Baram, 2016), diversity of the gut microbiota (O’Mahony et al, 2011; Fukui et al, 2018) and associated molecules (Martisova et al, 2012; Clos-Garcia et al, 2019). Subsequent studies have indicated that supplementation with probiotics such as Lactobacilli positively influence the gut microbiota and restore the HPA axis (Bercik et al, 2012), attenuating emotional behavior and cognitive impairment against stress (Bravo et al, 2011; Liang et al, 2015; McVey Neufeld et al, 2019)
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