Abstract
Chronic urticaria (CU) is defined as the continuous or intermittent presence of urticaria for a period exceeding 6 weeks and sometimes occurring with angioedema. Between 66 and 93% of patients with CU have chronic spontaneous urticaria (CSU), the precise pathogenesis of which is largely unknown. The aim of this study was to determine the relationship between gut microbiota and serum metabolites and the possible pathogenesis underlying CSU. We collected feces and blood samples from CSU patients and healthy controls and the relationship between gut microbiota and serum metabolites was assessed using 16S rRNA gene sequencing and untargeted metabolomic analyses. The CSU group exhibited decreased alpha diversity of the microbial population compared to the control group. The abundance of unidentified Enterobacteriaceae was increased, while the abundance of Bacteroides, Faecalibacterium, Bifidobacterium, and unidentified Ruminococcaceae was significantly reduced in CSU patients. The serum metabolome analysis revealed altered levels of docosahexaenoic acid, arachidonic acid, glutamate, and succinic acid, suggesting changes in unsaturated fatty acids and the butanoate metabolism pathway. The combined serum metabolomics and gut microbiome datasets were correlated; specifically, docosahexaenoic acid, and arachidonic acid were positively correlated with Bacteroides. We speculate that alterations in gut microbes and metabolites may contribute to exacerbated inflammatory responses and dysregulated immune function with or without regulatory T cell dependence in the pathogenesis of CSU.
Highlights
Chronic urticaria (CU) is defined by the continuous or intermittent presence of urticaria for a period exceeding 6 weeks and sometimes occurring with angioedema
Compared with the healthy controls, univariate analysis showed that place of residence, whether or not antibiotics were used during pregnancy, mode of production, feeding mode, dietary habits, whether, or not antibiotics were used in the past year, whether or not surgery was performed in the last 6 months, mental trauma and other stress factors, and whether or not alcohol consumption were significantly related to the onset of chronic spontaneous urticaria (CSU) (P < 0.05) (Supplementary Table 1)
We demonstrated that antibiotic use during pregnancy, cesarean section, high-fat, low-carbohydrate diets, antibiotic use in the past year, and alcohol consumption are independent risk factors for CSU
Summary
Chronic urticaria (CU) is defined by the continuous or intermittent presence of urticaria for a period exceeding 6 weeks and sometimes occurring with angioedema. CU can be classified into chronic inducible urticaria (CINDU) and chronic spontaneous urticaria (CSU) based on the triggering factor (Bernstein et al, 2014; Zuberbier et al, 2014b). 20% of individuals experience acute urticaria at least once during their lifetime, and 0.1% will develop chronic symptoms (Greaves, 2000; Zuberbier et al, 2014a). The main treatment option for CSU is to control symptoms, which significantly affect the quality of life patients (Fine and Bernstein, 2016). Alterations in the gut microbiota has been shown to be associated with allergic diseases, including asthma (Arnold et al, 2011), food allergies (Ling et al, 2014), and atopic dermatitis (Hulshof et al, 2017). Several studies have suggested that the changes in gut microbiota composition are linked to CU, including Akkermansia muciniphila, Faecalibacterium prausnitzii, the Clostridium leptum group, the Enterobacteriaceae family (Nabizadeh et al, 2017), and the Lactobacillus, Bifidobacterium, and Bacteroides genera (Rezazadeh et al, 2018); there is no specific mechanism by which to explore the dysbiosis of gut microbiota in the pathogenesis of CSU
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