Procyanidins and Bifidobacterium infantis alleviate anxiety and depression-like behavior in alcohol use disorder withdrawal mice via the gut-immune-brain axis.

Authors

Wei Wei, Chongchong Xu, Shixu Wang, Yue Wang, Jiahui Peng, Jinlin Li, Xinjian Zheng, Yuxi Huang, Rugang Chen, Shurong Zhong

Published in

Brain, behavior, and immunity. Pages 107035. Sep 28, 2026. Epub Sep 28, 2026.

Abstract

Alcohol use disorder (AUD) is frequently comorbid with anxiety and depression, conditions closely tied to gut microbiota dysbiosis, systemic inflammation, and immune imbalance-particularly between pro-inflammatory Th17 cells and regulatory T (Treg) cells. These peripheral immune perturbations can propagate neuroinflammation and disrupt central myelination, but the precise gut-immune-brain myelin cascade in AUD remains poorly defined.
This study investigated whether a combination of procyanidins (PC) and Bifidobacterium infantis (B. infantis)-administered either individually or as a symbiotic- could ameliorate anxiety and depression-like behaviors in an AUD withdrawal mouse model. We hypothesized that these interventions would restore peripheral Treg/Th17 balance, reduce systemic and central neuroinflammation, and promote remyelination in the prefrontal cortex (PFC) and hippocampus (HIP).
An AUD withdrawal model was established using a 6-week ethanol "drinking-in-the-dark" paradigm. After withdrawal, mice received daily oral administration of procyanidins (50 mg/kg),B. infantis(1 × 10⁷ CFU), their synbiotic combination, or saline for 28 days; a normal control group was included. Anxiety and depression-like behaviors were assessed by open field, elevated plus maze, tail suspension, and forced swim tests.
Peripheral Treg (CD4⁺CD25⁺Foxp3⁺) and Th17 (CD4⁺IL-17A⁺) cell proportions and serum cytokines (IL-10, TGF-β, IL-17A) were quantified. Central cytokines and Treg/Th17 transcription factor (FoxP3,RORγt) mRNA levels were measured in the PFC and hippocampus. Myelin proteins (MAG, MOG, MBP) were analyzed by western blotting, and PFC myelin ultrastructure was examined by electron microscopy. Gut microbiota composition was profiled by 16S rRNA sequencing, and intestinal permeability markers (Zonulin, iFABP) were detected by immunohistochemistry. Integrative multi-system correlation analyses were conducted.
Mice receiving PC,B. infantis, or their synbiotic combination all showed reduced anxiety and depression-like behaviors, with comparable efficacy among the three treatment groups. This improvement coincided with a restored peripheral immune profile: Treg cells and IL-10/TGF-β increased, while Th17 cells and IL-17A decreased. In the PFC and HIP, IL-10 and TGF-β were elevated, while IL-17A decreased. Importantly, each intervention upregulated PFC myelin proteins (MAG, MOG, MBP) and increased myelin density.
Interventions with procyanidins,B. infantis, or their synbiotic combination ameliorate anxiety and depression-like behaviors in AUD withdrawal mice, likely through modulation of the gut-immune-brain axis. These treatments restore gut microbial ecology and barrier function, rebalance peripheral Treg/Th17 immunity, and enhance IL-10-mediated central anti-inflammatory signaling, thereby facilitating remyelination in the PFC. The integrated gut-immune-myelin-behavior correlations highlight a novel gut targeted strategy for treating AUD associated affective disorders.

PMID:
42805421
Bibliographic data and abstract were imported from PubMed on 29 Sep 2026.

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