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Can a gut antibiotic ease stress depression in adolescent rats?

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In 56 adolescent rats, 150 mg/kg rifaximin during 4 weeks of CUMS restored sucrose preference, open-field and water-maze performance, raised Ruminococcaceae/Lachnospiraceae and brain butyrate, and shifted microglia toward anti-inflammatory functions.

Source

Rifaximin-mediated gut microbiota regulation modulates the function of microglia and protects against CUMS-induced depression-like behaviors in adolescent rat

Li H, Xiang Y, Zhu Z, et al. · Journal of neuroinflammation · 2021

doi.org/10.1186/s12974-021-02303-yRead the full paper ↗211 citationscc by

Study at a glance

Design
Animal / in-vitro — Adolescent rats: 4-week CUMS ± 150 mg/kg oral rifaximin; 16S microbiota, SCFAs, microglia, hippocampal neurogenesis, and depression-like tests
N
N=56 · 56 three-week-old rats; n = 14 in CON, CON+R, CUMS, and CUMS+R
Population
Adolescent rats (started at 3 weeks) under chronic unpredictable mild stress
Outcome
Depression-like and cognitive behavior, fecal microbiome, brain/serum SCFAs, microglial phenotype, hippocampal neurogenesis

Structured fields used in claim comparison tables when every cited study has a complete layer.

What they did

Randomized 3-week-old rats (n = 14/group) to control ± rifaximin or CUMS ± rifaximin for 4 weeks (150 mg/kg i.g.), then ran SPT, open field, and Morris water maze plus 16S, SCFAs, and hippocampal microglia/neurogenesis assays.

What they found

Rifaximin improved CUMS depression-like and maze behavior, increased Ruminococcaceae and Lachnospiraceae (positively correlated with brain butyrate), raised anti-inflammatory microglial factors, and prevented CUMS neurogenic abnormalities.

The limits

What it doesn't show

Rat CUMS plus a poorly absorbed antibiotic is not a clinical depression trial; rifaximin is not shown to treat human adolescent MDD, and n = 14/group is modest.

Key terms

Rifaximin
Poorly absorbed antibiotic given here at 150 mg/kg to remodel gut microbiota.
CUMS
Chronic unpredictable mild stress used to induce depression-like behavior.
Ruminococcaceae / Lachnospiraceae
Butyrate-associated gut families that rose with rifaximin.
SCFA / butyrate
Short-chain fatty acids; brain butyrate tracked the enriched taxa.
Microglia
CNS immune cells whose anti-inflammatory output increased with rifaximin.
Morris water maze
Spatial memory task improved alongside SPT and open field.

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Total rats numbered:

Common questions

How many rats?

56 (n = 14 in each of four groups).

Rifaximin dose/duration?

150 mg/kg intragastric during 4 weeks of CUMS.

Which taxa increased?

Ruminococcaceae and Lachnospiraceae.

Which SCFA tracked those taxa?

Brain butyrate.

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