Chronic spontaneous urticaria (CSU) comes with gut dysbiosis, but its relevance remains elusive. Here we use metagenomics sequencing and short-chain fatty acids metabolomics and assess the effects of human CSU fecal microbial transplantation, Klebsiella pneumoniae, Roseburia hominis, and metabolites in vivo. CSU gut microbiota displays low diversity and short-chain fatty acids production, but high gut Klebsiella pneumoniae levels, negatively correlates with blood short-chain fatty acids levels and links to high disease activity. Blood lipopolysaccharide levels are elevated, link to rapid disease relapse, and high gut levels of conditional pathogenic bacteria. CSU microbiome transfer and Klebsiella pneumoniae transplantation facilitate IgE-mediated mast cell(MC)-driven skin inflammatory responses and increase intestinal permeability and blood lipopolysaccharide accumulation in recipient mice. Transplantation of Roseburia hominis and caproate administration protect recipient mice from MC-driven skin inflammation. Here, we show gut microbiome alterations, in CSU, may reduce short-chain fatty acids and increase lipopolysaccharide levels, respectively, and facilitate MC-driven skin inflammation.

慢性自发性荨麻疹（CSU）与肠道菌群失调有关，但其相关性仍然难以捉摸。在这里，我们使用宏基因组测序和短链脂肪酸代谢组学，评估人类 CSU 粪便微生物移植、肺炎克雷伯菌、人罗斯伯利亚菌和代谢物在体内的影响。 CSU 肠道微生物群的多样性和短链脂肪酸产量较低，但肠道肺炎克雷伯菌水平较高，与血液短链脂肪酸水平呈负相关，并与高疾病活动性相关。血液脂多糖水平升高，与疾病快速复发以及肠道条件致病菌水平升高有关。 CSU 微生物组转移和肺炎克雷伯菌移植促进 IgE 介导的肥大细胞 (MC) 驱动的皮肤炎症反应，并增加受体小鼠的肠道通透性和血液脂多糖积累。人罗斯伯利亚移植和己酸给药可保护受体小鼠免受 MC 驱动的皮肤炎症。在这里，我们发现 CSU 中肠道微生物组的改变可能分别减少短链脂肪酸和增加脂多糖水平，并促进 MC 驱动的皮肤炎症。