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

BACKGROUNDSudachitin, 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).

METHODSFirst, 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.

RESULTSSudachitin 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.

LIMITATIONSThe exact mechanisms behind the resilience-promoting effects of sudachi peel extract remain unclear.

CONCLUSIONSudachi peel extract supplementation enhances 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.