Gut microbiota-driven pathogenic Th17 cells mediated autoimmune epididymo-orchitis in a mouse model of colitis

Inflammatory bowel disease (IBD) is linked to male fertility disorders, yet the role of gut microbiota dysbiosis remains underexplored. Here, we investigated how dysbiosis contributes to autoimmune epididymo-orchitis in a colitis mouse model induced by CD4⁺ T cell transfer. We transferred wild-type CD4⁺ T cells into male <i>Rag1</i> ^-/- mice, with some groups pretreated with antibiotics or receiving <i>Il-17a</i> ^-/- or <i>Ccr6</i> ^-/- CD4⁺ T cells. Through gut microbiota profiling, histopathology evaluation, immune cell infiltration assessments in the reproductive tissues, and sperm analysis, we observed severe gut dysbiosis, colon inflammation, and reproductive impairments characterized by leukocyte infiltration in mice transferred with wild-type T cells. Interestingly, these impairments were mitigated in groups pretreated with antibiotics or receiving <i>Il-17a</i> ^-/- cells but not <i>Ccr6</i> ^-/- CD4⁺ T cells. These findings highlight that gut microbiota dysbiosis can initiate Th17 cell-mediated reproductive disorders, offering insights for potential therapeutic interventions in IBD-related male infertility.