Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Hunan Key Laboratory of Skin Cancer and Psoriasis, Furong Labratory, Changsha, Hunan, China.
Nat Commun. 2024 Jan 2;15(1):112. doi: 10.1038/s41467-023-44373-x.
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）伴有肠道菌群失调，但相关性仍难以捉摸。在这里，我们使用宏基因组测序和短链脂肪酸代谢组学，并评估人类 CSU 粪便微生物移植、肺炎克雷伯菌、罗氏菌和体内代谢物的影响。CSU 肠道微生物群显示出低多样性和短链脂肪酸产生，但高水平的肠道肺炎克雷伯菌与血液短链脂肪酸水平呈负相关，并与高疾病活动度相关。血液内毒素水平升高，与快速疾病复发和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内毒素积累。移植罗氏菌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，我们表明 CSU 中的肠道微生物组改变可能分别降低短链脂肪酸水平和增加内毒素水平，并促进 MC 驱动的皮肤炎症。
