Gut-brain axis modulation by sudachi peel extract enhances resilience to chronic social defeat stress in mice

J Affect Disord. 2025 Apr 4:S0165-0327(25)00588-9. doi: 10.1016/j.jad.2025.04.027. Online ahead of print.

ABSTRACT

BACKGROUND: Sudachitin, an anti-inflammatory compound from Citrus sudachi peel, may influence stress resilience. We examined whether sudachi peel extract affects depression-like behaviors and gut microbiota dysbiosis in mice subjected to chronic social defeat stress (CSDS).

METHODS: First, we examined the effect of sudachitin on depression-like behavior and plasma interleukin-6 (IL-6) levels following lipopolysaccharide (LPS, 0.5 mg/kg) administration. Next, we investigated whether supplementation with sudachi peel extract could modulate the gut microbiota dysbiosis induced by CSDS.

RESULTS: Sudachitin prevented LPS-induced depression-like behavior and the rise in plasma IL-6. In control mice, CSDS increased IL-6, induced splenomegaly, and caused anhedonia-like behavior. These changes were absent in the sudachi peel extract group. Although alpha-diversity of the gut microbiota remained abnormal under CSDS, beta-diversity was significantly altered by sudachi peel extract. Moreover, plasma IL-6 levels and Iba1 expression in the prefrontal cortex correlated with the relative abundance of certain gut bacteria.

LIMITATIONS: The exact mechanisms behind the resilience-promoting effects of sudachi peel extract remain unclear.

CONCLUSION: Sudachi peel extract supplementation improves resilience to CSDS by preventing anhedonia, reducing plasma IL-6 levels and splenomegaly, and modulating gut microbiota composition. Further research is needed to clarify these anti-inflammatory pathways and the roles of additional pro-inflammatory cytokines.

PMID:40189061 | DOI:10.1016/j.jad.2025.04.027