Microbiota-derived acetate protects against UPEC-epididymo-orchitis by improving the phagocytosis of testicular macrophages.

The gut microbiota is intimately associated with maintaining a stable intestinal immune balance. However, it remains unclear whether gut dysbiosis affects the homeostasis within the testes. In our DSS-induced colitis mouse model, we observed increased inflammatory cell infiltration within the mouse testes. Analysis of the gut microbiota in the feces of DSS colitis mice and mice treated with antibiotics revealed a significant decrease in the number of bacteria related to cellulose decomposition in the gut, as well as a decrease in the content of short-chain fatty acid salts in the peripheral blood of mice. In vitro experiments found that acetate can significantly improve the outcome of UPEC-induced bacterial epididymo-orchitis. Further in vitro experiments demonstrated that acetate can enhance the bacterial phagocytic ability of testicular macrophages (TM), accelerate the early clearance of bacteria within the testes, and thus reduce the degree of testicular inflammation. This study provides a link to explain the progression of bacterial epididymo-orchitis in relation to gut microbiota dysbiosis and offers new insights for the treatment of bacterial epididymo-orchitis. Overall design: Transcriptome analysis of TM stimulated by UPEC and sodium acetate. Approximately 10^6 TM were isolated and inoculated into 6-well plates. Sodium acetate (10mM) was pre-treated for 30 minutes, followed by UPEC (MOI: 5) infection for 3 hours, after which the cells were collected for transcriptome sequencing; (C1-2: Control group. U1-2: UPEC infected. A1-2: UPEC infected + sodium acetate treatment).