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

Christopher Karen; Douglas J H Shyu; Koilmani Emmanuvel Rajan

doi:10.3389/fnins.2021.719933

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

Front Neurosci. 2021 Aug 31:15:719933. doi: 10.3389/fnins.2021.719933. eCollection 2021.

Authors

Christopher Karen¹, Douglas J H Shyu², Koilmani Emmanuvel Rajan¹

Affiliations

¹ Behavioural Neuroscience Laboratory, Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, India.
² Functional Genomics Laboratory, Department of Biological Science and Technology, National Pingtung University of Science and Technology, Neipu, Taiwan.

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.

Keywords: Lactobacillus; anxiety/depression-like behavior; early-life social stress; maternal separation; microbiota-gut-brain-axis; probiotics.