Psoriasis has long been associated with inflammatory bowel disease (IBD); however, a causal link is yet to be established. Here, we demonstrate that imiquimod-induced psoriasis (IMQ-pso) in mice disrupts gut homeostasis, characterized by increased proportions of colonic CX3CR1hi macrophages, altered cytokine production, and bacterial dysbiosis. Gut microbiota from these mice produce higher levels of succinate, which induce de novo proliferation of CX3CR1hi macrophages ex vivo, while disrupted gut homeostasis primes IMQ-pso mice for more severe colitis with dextran sulfate sodium (DSS) challenge. These results demonstrate that changes in the gut environment in psoriasis lead to greater susceptibility to IBD in mice, suggesting a two-hit requirement, that is, psoriasis-induced altered gut homeostasis and a secondary environmental challenge. This may explain the increased prevalence of IBD in patients with psoriasis. Display omitted •Imiquimod-induced psoriasis (IMQ-pso) induces gut microbiota dysbiosis•Gut microbiota in IMQ-pso secretes high levels of succinate•High succinate in IMQ-pso induces proliferation of colonic CX3CR1hi macrophages•Impaired gut homeostasis in IMQ-pso aggravates DSS-induced colitis in mice Patients with psoriasis often develop inflammatory bowel disease. Pinget et al. show that psoriasis disrupts the gut microbiota, increasing microbial production of succinate and pro-inflammatory ligands, inducing the proliferation and activation of colonic CX3CR1hi macrophages. The authors propose a model linking psoriasis and inflammatory bowel disease.