Research indicates significant alterations in the gut microbiota of chronic spontaneous urticaria patients, characterized by reduced diversity, lower levels of SCFA-producing bacteria, and increased pathogenic bacteria.
Chronic spontaneous urticaria (CSU) is the most common type of chronic urticaria (CU), often lasting for a few years despite intensive medical treatment. Moreover, relapse rates for the condition are exceptionally high. More than half of CSU patients do not respond to antihistamines, and many even do not respond to anti-monoclonal antibodies like omalizumab. One of the challenges in finding effective treatments for the condition is that the pathology of CU is still poorly understood.
Nonetheless, CU is known to be a disorder caused by immune dysregulation. The gut microbiome plays an important role in maintaining intestinal integrity and immune responses. Short-chain fatty acids (SCFAs) are also known to have anti-inflammatory action. Hence, it is likely that gut microbiome changes contribute to CSU/CU pathogenesis.
A study published in the journal Nature Communications explored the possible role of altered gut microbiomes in CSU.
CSU Patients Show Microbiota Shift: SCFA Decrease, Pathogen Increase
The study investigated the role of gut microbiota in CSU by analyzing the microbiome composition and metabolic profiles of CSU patients compared to healthy controls. The results revealed distinct differences in the gut microbiota of CSU patients, characterized by reduced diversity and significantly lower levels of SCFA-producing bacteria. Microbiome analysis using metagenomic sequencing of stool samples from CSU patients and healthy controls showed a decrease in α-diversity and a lower abundance of major SCFA producers such as Rikenellaceae, Alistipes, and Roseburia hominis in CSU patients. Additionally, 10 core SCFA-producing bacterial species were found to be lower in CSU patients compared to healthy controls.
Moreover, CSU patients exhibited higher levels of opportunistic pathogenic bacteria, such as Klebsiella pneumoniae and Escherichia coli, and increased blood levels of lipopolysaccharide (LPS), a marker of bacterial infection. The study identified a negative correlation between SCFA-producing bacteria and LPS levels, further suggesting the potential impact of gut microbiota on CSU. A longitudinal follow-up of CSU patients revealed a link between the remission and relapse of symptoms and the levels of SCFA-producing and opportunistic pathogenic bacteria. Specifically, patients experiencing relapse had lower levels of SCFA-producing bacteria and higher levels of opportunistic pathogens.
To understand the functional implications, the study performed fecal microbial transplantation (FMT) experiments in mice, transferring the microbiome of CSU patients or healthy controls. The results demonstrated that the CSU microbiome increased mast cell-driven skin inflammation, elevated intestinal permeability, and higher blood LPS levels in the recipient mice. Further experiments with specific bacteria showed that the SCFA producer Roseburia hominis attenuated mast cell-driven skin inflammation, while the opportunistic pathogen Klebsiella pneumoniae and LPS exacerbated these inflammatory responses.
The Bottom Line
This study highlights the significant alterations in gut microbiota composition and function in CSU patients, indicating a potential link between the microbiome, systemic inflammation, and the development or exacerbation of chronic urticaria symptoms.
Source:
Li, Z., Jian, X., Zhou, B., Li, J., Muñoz, M., Sun, W., Xie, L., Chen, X., Peng, C., Maurer, M., & Li, J. (2024). Gut microbiota facilitate chronic spontaneous urticaria. Nature Communications, 15(1). https://doi.org/10.1038/s41467-023-44373-x
