Desulfovibrio vulgaris trigger depression-like behavior in mice through dual disruption of colonic homeostasis and fatty acid metabolism.

Abstract

OBJECTIVE: Desulfovibrio is a genus of sulfate-reducing bacteria residing in the gut, and growing evidence has implicated it in the pathogenesis of depression. However, the exact association and intrinsic mechanisms between the two remain unelucidated. This study aims to investigate whether Desulfovibrio induces depression-like behaviors in mice via the Microbiota-Gut-Brain Axis and to preliminarily elucidate the underlying mechanisms. METHODS: A two-week Desulfovibrio-induced mouse model of depression was established in this study. Based on preliminary experimental results, a Desulfovibrio bacterial suspension concentration of 1 × 10^8 CFU/ml, which demonstrated a more pronounced impact on depression-like behaviors in mice, was selected to investigate the intervention effect of Desulfovibrio on depression and its underlying mechanisms. Behavioral changes in mice were assessed using the sucrose preference test (SPT), open field test (OFT), tail suspension test (TST), and forced swim test (FST) to evaluate the antidepressant effects. The abundance of Desulfovibrio in mouse intestines was quantified using quantitative polymerase chain reaction (q-PCR). Targeted metabolomic analysis of short-chain fatty acids (SCFAs) in mice was performed using GC-MS. Targeted metabolomic analysis of arachidonic acid (AA) in mice was conducted using LC-MS. Additionally, histopathological changes in mouse colon tissue were observed via HE staining. RESULTS: Q-PCR analysis revealed a significant increase in the abundance of Desulfovibrio in the intestinal tract of mice in the model group, indicating successful colonization of Desulfovibrio in these animals. Behavioral results indicated that intervention with Desulfovibrio significantly induced behavioral phenotypes of anhedonia, reduced spontaneous activity, and behavioral despair in mice, demonstrating its direct role in promoting depression-like phenotypes. Histological findings revealed disordered colonic gland structures, epithelial damage, and increased inflammatory cell infiltration in the model group, suggesting impaired intestinal barrier function. Metabolomic analysis showed that Desulfovibrio intervention reshaped the serum short-chain fatty acid profile, with butyrate decreased and propionate increased. Concurrently, arachidonic acid metabolism shifted toward a pro-inflammatory state, evidenced by elevated levels of pro-inflammatory mediators such as Prostaglandin E2 (PGE2) and Leukotriene B4 (LTB4), while the anti-inflammatory substance Docosahexaenoic Acid (DHA) was reduced. CONCLUSION: Desulfovibrio trigger depression-like behaviors in mice by disrupting the colonic barrier structure, perturbing the short-chain fatty acid metabolic profile, and activating the pro-inflammatory arachidonic acid metabolic pathway. To further explore the relationship between gut microbiota and the onset of depression, depression model animals were used, revealing that Desulfovibrio may serve as a potential intervention target for depression.