ObjectiveBehçet’s Disease (BD) is an intractable systemic vasculitis. When accompanied by intestinal symptoms, the prognosis is usually poor. 5-Aminosalicylic acid (5-ASA), corticosteroids, immunosuppressive drugs, and anti-tumor necrosis factor-α (anti-TNF-α) biologics are standard therapies to induce or maintain remission for intestinal BD. However, they might not be effective in refractory cases. Safety should also be considered when patients have an oncology history. Regarding the pathogenesis of intestinal BD and the specific targeting effect of vedolizumab (VDZ) on the inflammation of the ileum tract, previous case reports suggested that VDZ might be a potential treatment for refractory intestinal BD.MethodsWe report a 50-year-old woman patient with intestinal BD who had oral and genital ulcers, joint pain, and intestinal involvement for about 20 years. The patient responds well to anti-TNF-α biologics but not to conventional drugs. However, biologics treatment was discontinued due to the occurrence of colon cancer.ResultsVDZ was intravenously administered at a dose of 300 mg at 0, 2, and 6 weeks and then every eight weeks. At the 6-month follow-up, the patient reported significant improvement in abdominal pain and arthralgia. We observed complete healing of intestinal mucosal ulcers under endoscopy. However, her oral and vulvar ulcers remained unresolved, which disappeared after adding thalidomide.ConclusionVDZ may be a safe and effective option for refractory intestinal BD patients who do not respond well to conventional treatments, especially those with an oncology history.

Uncovering the mechanism underlying the pathogenesis of Edwardsiella piscicida-induced enteritis is essential for global aquaculture. In the present study, we identified E. piscicida as a lethal pathogen of the big-belly seahorse (Hippocampus abdominalis) and revealed its pathogenic pattern and characteristics by updating our established bacterial enteritis model and evaluation system. Conjoint analysis of metagenomic and metabolomic data showed that 15 core virulence factors could mutually coordinate the remodeling of intestinal microorganisms and host metabolism and induce enteritis in the big-belly seahorse. Specifically, the Flagella, Type IV pili, and Lap could significantly increase the activities of the representative functional pathways of both flagella assembly and bacterial chemotaxis in the intestinal microbiota (P < 0.01) to promote pathogen motility, adherence, and invasion. Legiobactin, IraAB, and Hpt could increase ABC transporter activity (P < 0.01) to compete for host nutrition and promote self-replication. Capsule1, HP-NAP, and FarAB could help the pathogen to avoid phagocytosis. Upon entering epithelial cells and phagocytes, Bsa T3SS and Dot/Icm could significantly increase bacterial secretion system activity (P < 0.01) to promote the intracellular survival and replication of the pathogen and the subsequent invasion of the neighboring tissues. Finally, LPS3 could significantly increase lipopolysaccharide biosynthesis (P < 0.01) to release toxins and kill the host. Throughout the pathogenic process, BopD, PhoP, and BfmRS significantly activated the two-component system (P < 0.01) to coordinate with other VFs to promote deep invasion. In addition, the levels of seven key metabolic biomarkers, Taurine, L-Proline, Uridine, L-Glutamate, Glutathione, Xanthosine, and L-Malic acid, significantly decreased (P < 0.01), and they can be used for characterizing E. piscicida infection. Overall, the present study systematically revealed how a combination of virulence factors mediate E. piscicida-induced enteritis in fish for the first time, providing a theoretical reference for preventing and controlling this disease in the aquaculture of seahorses and other fishes.