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The gut microbiome regulates the increases in depressive-type behaviors and in inflammatory processes in the ventral hippocampus of stress vulnerable rats
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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“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].”
From Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review (2020) · cites this paper as [24]
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Metadata
- 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
- ORCID
- 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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