UNASSIGNED: A total of 36 CSU patients with VD3 insufficiency (VDI; serum 25(OH)VD3 <30 ng/mL) and 36 sex-, age-, and body mass index-matched CSU patients with non-VDI were enrolled. Fecal and serum bacteria were identified through 16S rRNA sequencing, and serum 25(OH)VD3 and inflammation biomarkers were assessed using ELISA kits. IFNI response was determined by measuring the stimulatory activity of serum on IFNI-stimulated response element in HEK293 cells in vitro with luciferase assays.
UNASSIGNED: Higher urticarial activity score over 7 days (UAS7), higher frequency of levocetirizine resistance, and more severe proinflammation but weaker IFNI response were observed in VDI than non-VDI patients (all P<0.05). IFNI response was strongly positively associated with serum 25(OH)VD3 level in both groups (P<0.001). Compared to non-VDI patients, abundance of the fecal genera Prevotella 9, Escherichia-Shigella, and Klebsiella was significantly increased, while Bacteroides, Faecalibacterium, and Agathobacter were remarkably reduced in VDI patients (all P<0.05). Burkholderia-Caballeronia-Paraburkholderia (40.95%), Acinetobacter (3.05%), and Aquabacterium (2.37%) were the top three bacteria in sera from VDI patients. Both serum 25(OH)VD3 level and IFNI response were positively associated with fecal Bacteroides in the two groups (P<0.05). In non-VDI patients, there were moderately positive associations between IFNI response and fecal Lachnoclostridium, unclassified_f__Lachnospiraceae, and Phascolarctobacterium and between serum 25(OH)VD3 level and fecal Lachnoclostridium (all P<0.01). Circulating microbiota in VDI patients was closely related only to proinflammation and UAS7 (both P<0.05).
UNASSIGNED: Changes in gut but not circulating microbiota composition are associated with serum 25(OH)VD3 insufficiency and impaired IFNI homeostasis, which points to greater disease severity (UAS7) and systemic proinflammation in CSU patients.
■共有36例CSU患者VD3功能不全(VDI;血清25(OH)VD3<30ng/mL)和36性别-,年龄-,纳入体重指数匹配的非VDICSU患者。通过16SrRNA测序鉴定粪便和血清细菌,使用ELISA试剂盒评估血清25(OH)VD3和炎症生物标志物。通过用荧光素酶测定法在体外测量HEK293细胞中血清对IFNI刺激的应答元件的刺激活性来确定IFNI应答。
■7天以上的荨麻疹活动得分较高(UAS7),左西替利嗪耐药的频率较高,与非VDI患者相比,VDI患者的促炎作用更严重,但IFNI反应更弱(均P<0.05)。两组IFNI反应与血清25(OH)VD3水平呈显著正相关(P<0.001)。与非VDI患者相比,粪便Prevotella9属的丰度,大肠杆菌-志贺氏菌,克雷伯菌显著增加,而拟杆菌,粪杆菌,VDI患者的Gaggathobacter明显减少(均P<0.05)。伯克霍尔德菌-卡波列菌-帕拉布尔霍尔德菌(40.95%),不动杆菌(3.05%),VDI患者血清中细菌居前3位的是水细菌(2.37%)。两组血清25(OH)VD3水平和IFNI反应均与粪便拟杆菌呈正相关(P<0.05)。在非VDI患者中,IFNI反应与粪便泪囊梭菌之间存在中度正相关,未分类,并在血清25(OH)VD3水平与粪便衣原体之间(均P<0.01)。VDI患者的循环菌群仅与促炎和UAS7密切相关(均P<0.05)。
■肠道而不是循环微生物群组成的变化与血清25(OH)VD3不足和IFNI稳态受损有关,这表明CSU患者的疾病严重程度(UAS7)和全身性促炎。