Published online Jul 19, 2025. doi: 10.5498/wjp.v15.i7.104921
Revised: March 18, 2025
Accepted: May 16, 2025
Published online: July 19, 2025
Processing time: 152 Days and 19 Hours
The association between hypothyroidism and depression is well established, but the underlying mechanisms remain unclear.
To explore the potential role of the gut microbiota in depressive-like behaviors in a mouse model of hypothyroidism, with a focus on bacterial composition.
Hypothyroidism was induced in mice using propylthiouracil. Depressive-like behaviors were assessed using the sucrose preference test (SPT), forced swimming test (FST), tail suspension test (TST), and open field test (OFT). Inflammatory cytokines, including interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α, and IL-10, were quantified, together with colon histopathology scores, brain-derived neurotrophic factor, nuclear factor κB, inhibitor of nuclear factor κB, and tight junction proteins (occludin, claudin-1, zonula occludens-1). Gut microbial composition was determined by 16S rRNA gene sequencing of fecal samples.
Propylthiouracil-treated mice exhibited pronounced depressive-like behaviors, intestinal barrier dysfunction, elevated peripheral and central inflammation, and gut microbiota dysbiosis. Pearson correlation analysis showed that Bilophila and Psychrobacter abundance positively correlated with sucrose preference in the SPT and locomotor activity in the OFT, and negatively correlated with immobility times in the FST and TST. Gordonibacter abundance was positively correlated with locomotion in the OFT and negatively correlated with immobility in the FST and TST. Prevotellaceae_UCG_001 was inversely correlated with immobility in the FST and TST. Streptococcus was positively associated with sucrose preference in the SPT.
The observed associations between specific bacterial taxa and behavioral indices support a potential connection between gut microbiota composition and depressive symptoms in mice with hypothyroidism.
Core Tip: Our research has found that hypothyroidism-induced depression is associated with gut microbiota dysbiosis, and the intestinal barrier dysfunction and the activation of peripheral and central inflammation play important roles between the two. Furthermore, through Pearson correlation analysis, we found that specific bacterial genera including Bilophila and Gordonibacter, correlate with depressive-like behaviors, suggesting that microbiota-targeted interventions may offer therapeutic benefits for depression associated with hypothyroidism.