Akkermansia Muciniphila vs. Fluoxetine: Amelioration of Depression-like Behaviors and Cognitive Dysfunction Through Distinct Neurobiological Mechanisms.

Authors

Wan-Jiun Ma, Pei-Jui Hung, Fang Chih Chang, Marion Leclerc, Andrew Chih Wei Huang

Published in

Probiotics and antimicrobial proteins. Volume 18. Issue 4. Pages 5793-5817. Epub Nov 25, 2025.

Abstract

To date, no research has directly compared the potential of Akkermansia muciniphila (AKK) and the selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX) in alleviating depression-like behaviors and thier neural mechanisms. This study addressed this gap by examining the effects of chronic mild stress (CMS) on depression-like behavior and recognition memory deficits in rats. The results showed that both AKK and FLX reduced CMS-induced depression-like behaviors and restored recognition memory in a rat model. Both AKK and FLX increased serum 5-HT levels; however, only AKK reduced corticosterone (CORT) levels. Notably, AKK increased c-Fos expression in cognition-related regions of the medial prefrontal cortex (mPFC, such as the Cg1, PrL, and IL), emotion-related regions of the amygdala (BLA and CeA), and spatial learning-associated regions of the hippocampus (CA1, CA2, CA3, and DG). In contrast, FLX increased c-Fos expression only in the Cg1 and PrL. AKK significantly reduced IL-1β expression across all target brain regions, whereas FLX only reduced IL-1β in the CeA. Regarding apoptotic and neuroplasticity-related markers, AKK decreased p-ERK expression in all examined regions, while FLX increased p-ERK expression in the Cg1, PrL, IL, BLA, CA1, and DG. Both AKK and FLX reduced Caspase-3 expression in all target regions. Overall, AKK demonstrated a broader and more effective impact on CORT and 5-HT regulation, c-Fos activation, and IL-1β and p-ERK modulation. This study highlights the therapeutic potential of live A. muciniphila (administered for 28 days at 5.10 × 108 CFU/day) for treating depression-like behaviors and cognitive dysfunction in the neural mechanisms. These findings provide valuable insights for future clinical applications.
The online version contains supplementary material available at 10.1007/s12602-025-10850-6.

PMID:
41288961
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

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