State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
Signal Transduct Target Ther. 2023 Jan 30;8(1):40. doi: 10.1038/s41392-022-01219-0.
The intestinal microbiota has been associated with host immunity as well as psoriasis; however, the mechanism of intestinal microbiota regulating psoriasis needs to be demonstrated systematically. Here, we sought to examine its role and mechanism of action in the pathogenesis of psoriasis. We found that the severity of psoriasis-like skin phenotype was accompanied by changes in the composition of the intestinal microbiota. We performed co-housing and fecal microbial transplantation (FMT) experiments using the K14-VEGF transgenic mouse model of psoriasis and demonstrated that the transfer of intestinal microbiota from mice with severe psoriasis-like skin phenotype exacerbated psoriasiform skin inflammation in mice with mild symptoms, including increasing the infiltration and differentiation of Th17, and increased the abundance of Prevotella, while decreasing that of Parabacteroides distasonis, in the colon. These alterations affected fatty acid metabolism, increasing the abundance of oleic and stearic acids. Meanwhile, gentamicin treatment significantly reduced the abundance of Prevotella and alleviated the psoriasis-like symptoms in both K14-VEGF mice and imiquimod (IMQ)-induced psoriasis-like mice. Indeed, administration of oleic and stearic acids exacerbated psoriasis-like symptoms and increased Th17 and monocyte-derived dendritic cell infiltration in the skin lesion areas in vivo, as well as increased the secretion of IL-23 by stimulating DCs in vitro. At last, we found that, treatment of PDE-4 inhibitor alleviated psoriasis-like phenotype of K14-VEGF mice accompanied by the recovery of intestinal microbiota, including the decrease of Prevotella and increase of Parabacteroides distasonis. Overall, our findings reveal that the intestinal microbiota modulates host metabolism and psoriasis-like skin inflammation in mice, suggesting a new target for the clinical diagnosis and treatment of psoriasis.
肠道微生物群与宿主免疫以及银屑病有关；然而，肠道微生物群调节银屑病的机制需要系统地证明。在这里，我们试图研究其在银屑病发病机制中的作用和机制。我们发现，银屑病样皮肤表型的严重程度伴随着肠道微生物群组成的变化。我们使用 K14-VEGF 转基因银屑病小鼠模型进行了共饲养和粪便微生物移植（FMT）实验，证明了从严重银屑病样皮肤表型小鼠中转移肠道微生物群会加剧轻度症状小鼠的银屑病样皮肤炎症，包括增加 Th17 的浸润和分化，并增加结肠中普雷沃氏菌的丰度，而减少拟杆菌的丰度。这些改变影响了脂肪酸代谢，增加了油酸和硬脂酸的丰度。同时，庆大霉素治疗显著降低了普雷沃氏菌的丰度，并缓解了 K14-VEGF 小鼠和咪喹莫特（IMQ）诱导的银屑病样小鼠的银屑病样症状。事实上，给予油酸和硬脂酸会加剧银屑病样症状，并增加皮肤损伤区域 Th17 和单核细胞衍生树突状细胞的浸润，以及体外刺激 DC 增加 IL-23 的分泌。最后，我们发现 PDE-4 抑制剂的治疗缓解了 K14-VEGF 小鼠的银屑病样表型，同时恢复了肠道微生物群，包括普雷沃氏菌的减少和拟杆菌的增加。总的来说，我们的发现表明，肠道微生物群调节了小鼠的宿主代谢和银屑病样皮肤炎症，为银屑病的临床诊断和治疗提供了一个新的靶点。
