Gut microbiota facilitate chronic spontaneous urticaria

Area of Science:

• Microbiology
• Immunology
• Gastroenterology

Background:

• Chronic spontaneous urticaria (CSU) is associated with gut dysbiosis, but the specific mechanisms and clinical relevance are not fully understood.
• Gut microbiota alterations may influence systemic inflammation and disease activity in CSU patients.

Purpose of the Study:

• To investigate the role of gut dysbiosis, specifically short-chain fatty acid (SCFA) production and bacterial composition, in CSU pathogenesis.
• To assess the impact of CSU-associated gut microbiota and specific bacteria on mast cell-driven skin inflammation and intestinal permeability.

Main Methods:

• Metagenomics sequencing and SCFA metabolomics were employed to analyze the gut microbiota of CSU patients.
• Human CSU fecal microbial transplantation and specific bacterial (Klebsiella pneumoniae, Roseburia hominis) transplantation were performed in mouse models.
• Effects on skin inflammation, intestinal permeability, and lipopolysaccharide (LPS) levels were evaluated.

Main Results:

• CSU gut microbiota exhibited low diversity, reduced SCFA production, and elevated Klebsiella pneumoniae levels, correlating with disease activity and lower blood SCFA levels.
• Elevated blood LPS levels were observed in CSU patients, linked to rapid relapse and high levels of gut conditional pathogens.
• CSU microbiome transfer and K. pneumoniae transplantation exacerbated IgE-mediated mast cell-driven skin inflammation and increased intestinal permeability and LPS accumulation in mice.

Conclusions:

• Gut dysbiosis in CSU is characterized by decreased SCFAs and increased LPS, contributing to mast cell-driven skin inflammation.
• Transplantation of Roseburia hominis and administration of caproate demonstrated protective effects against skin inflammation in recipient mice.
• Targeting gut microbiota and metabolites like SCFAs presents a potential therapeutic strategy for CSU.