Combined microbiome and metabolome analysis of gut microbiota and metabolite interactions in chronic spontaneous urticaria

Abstract

BackgroundThe pathogenesis of chronic spontaneous urticaria (CSU) is unclear, and it turned out to be involved in biological processes, such as autoimmunity, autoallergy, inflammation, and coagulation. The gut microbiota plays an important role in immune and inflammatory diseases. However, the relationship between chronic spontaneous urticaria and the gut microbiota remains unknown.MethodsThe stool and serum samples were taken from 15 CSU patients and 15 normal controls. Changes in the composition of gut microbiota and serum metabolism in CSU patients and normal controls were analyzed by 16S ribosomal RNA (rRNA) gene sequencing and untargeted metabolomics.ResultsThe results of 16S rRNA gene sequencing showed that compared with normal controls, CSU patients had increased α-diversity of gut microbiota and significant differences in β-diversity. At the phylum level, the relative abundance of Firmicutes increased and the relative abundance of Bacteroidetes and Proteobacteria decreased in CSU patients compared with healthy controls. At the genus level, six kinds of bacteria were significantly enriched in CSU patients and five in normal controls. Metabolomic analysis revealed altered levels of metabolites such as unsaturated fatty acids and purines. Correlation analysis of gut microbiota and metabolites showed that Lachnospira was negatively correlated with arachidonic acid, and Gemmiger was also negatively correlated with (±)8-HETE.ConclusionThis study suggests that changes in gut microbiota and metabolites may play a role in immune and inflammatory pathways in the pathogenesis of CSU patients.

Current insights on gut microbiome and chronic urticaria: progress in the pathogenesis and opportunities for novel therapeutic approaches

“…In metabolomics analyses, SCFAs were the predominant metabolites, while unsaturated fatty acids may also be essential in the pathogenesis of CSU. Unsaturated fatty acids such as arachidonic acid and docosahexaenoic acid have been shown to stimulate the growth of Bacteroides and have anti-inflammatory effects, 72 supported by Wang et al and Luo et al 26 , 46 Lachnospira showed a negative correlation with arachidonic acid, while Gemmiger exhibited a negative correlation with (±) 8-HETE, a product of the enzymatic oxidation of arachidonic acid. 46 , 73 Furthermore, purine metabolites such as adenine and adenosine were also increased in the CSU group.…”

“…Unsaturated fatty acids such as arachidonic acid and docosahexaenoic acid have been shown to stimulate the growth of Bacteroides and have anti-inflammatory effects, 72 supported by Wang et al and Luo et al 26 , 46 Lachnospira showed a negative correlation with arachidonic acid, while Gemmiger exhibited a negative correlation with (±) 8-HETE, a product of the enzymatic oxidation of arachidonic acid. 46 , 73 Furthermore, purine metabolites such as adenine and adenosine were also increased in the CSU group. A mouse experiment found that inflammatory cells in allergic mice may result in increased levels of adenine and adenosine, providing further evidence that inflammation contributes to the pathogenesis of CSU.…”

“… 57 Luo et al found that the genus Prevotella was more abundant in the CSU group than in HCs and was shown to stimulate Th17 immune response and recruit neutrophils to trigger persistent inflammation in mouse experiments. 46 Zhang et al observed a notable rise in the relative abundance of the Proteobacteria phylum in CSU patients. 19 This increase in Proteobacteria is commonly seen in individuals with asthma and allergic conditions, potentially because Proteobacteria can induce allergic responses by upregulating the expression of Th17-related genes.…”

“… 45 Luo et al discovered that the abundance of phylum Bacteroidetes was lower in CSU patients compared to the HCs, suggesting a possible protective role of Bacteroidetes against CSU. 46 Research has shown that Bacteroides exerts a regulatory influence on human immunity, mainly by producing capsular polysaccharide A and SCFAs. Capsular polysaccharide A plays a role in maintaining and balancing immune system function, as well as in preventing bacterial and viral infections.…”