Cited by 206Gut microbiota and healthTryptophan and brain disordersStress Responses and Cortisol

The gut microbiome regulates the increases in depressive-type behaviors and in inflammatory processes in the ventral hippocampus of stress vulnerable rats

Pearson-Leary, Jiah, Zhao, Chunyu, Bittinger, Kyle, Eacret, Darrell, Luz, Sandra, Vigderman, Abigail S., Dayanim, Gabriel, Bhatnagar, Seema·2020·Molecular Psychiatry

Abstract

Chronic exposure to stress is associated with increased incidence of depression, generalized anxiety, and PTSD. However, stress induces vulnerability to such disorders only in a sub-population of individuals, as others remain resilient. Inflammation has emerged as a putative mechanism for promoting stress vulnerability. Using a rodent model of social defeat, we have previously shown that rats with short-defeat latencies (SL/vulnerable rats) show increased anxiety- and depression-like behaviors, and these behaviors are mediated by inflammation in the ventral hippocampus. The other half of socially defeated rats show long-latencies to defeat (LL/resilient) and are similar to controls. Because gut microbiota are important activators of inflammatory substances, we assessed the role of the gut microbiome in mediating vulnerability to repeated social defeat stress. We analyzed the fecal microbiome of control, SL/vulnerable, and LL/resilient rats using shotgun metagenome sequencing and observed increased expression of immune-modulating microbiota, such as Clostridia, in SL/vulnerable rats. We then tested the importance of gut microbiota to the SL/vulnerable phenotype. In otherwise naive rats treated with microbiota from SL/vulnerable rats, there was higher microglial density and IL-1β expression in the vHPC, and higher depression-like behaviors relative to rats that received microbiota from LL/resilient rats, non-stressed control rats, or vehicle-treated rats. However, anxiety-like behavior during social interaction was not altered by transplant of the microbiome of SL/vulnerable rats into non-stressed rats. Taken together, the results suggest the gut microbiome contributes to the depression-like behavior and inflammatory processes in the vHPC of stress vulnerable individuals.

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Crossref · 10.1038/s41380-019-0380-x

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  • Rats receiving FMT from SL/vulnerable rats displayed depressive-like behaviours in the forced swim test, while LL/resilient recipients were not significantly different from control.

    “It was found that rats receiving FMT from the SL/vulnerable group displayed depressive-like behaviours when asses with the forced swim test while the LL/resilient group was not significantly different than control [24].”

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Authors
Pearson-Leary, J., Zhao, C., Bittinger, K., Eacret, D., Luz, S., Vigderman, A. S., Dayanim, G., & Bhatnagar, S.
Affiliations
Children's Hospital of Philadelphia (US)
Corresponding author
Bhatnagar, Seema
Venue
Molecular Psychiatry
Published
2019-03-04
Volume
25
Issue
5
Pages
1068-1079
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
OpenAlex
W2918256091
Cited by
206
References
82
Citations by year
2026: 12 · 2025: 24 · 2024: 30 · 2023: 25 · 2022: 33 · 2021: 37 · 2020: 30 · 2019: 15
FWCI
9.52
Type
journal article
Language
en
Open access
closed
Locations
  • Molecular Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Funders
Army Research Office
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords
gut microbiota, depression-like behavior, anxiety-like behavior, social defeat stress, stress vulnerability, ventral hippocampus, neuroinflammation, microglia, IL-1β, Clostridia, fecal microbiota transplantation, resilience
MeSH terms
Gastrointestinal Microbiome, Animals, Anxiety, Behavior, Animal, Depression, Hippocampus, Stress, Psychological, Rats

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