Distinct Gut Microbiome Signatures of Complete Responders to Omalizumab in Chronic Spontaneous Urticaria.

Fourteen antihistamine-refractory CSU patients were enrolled and divided into complete responders (CRs) and non-complete responders (NCRs) based on weekly urticarial activity score after three omalizumab injections.

• Total sample size was 14 patients
• Patients were classified as CRs or NCRs based on treatment response to omalizumab
• Three injections of omalizumab were administered
• Faecal specimens underwent bacterial 16S ribosomal RNA sequencing to determine gut bacterial microbiome
• Demographic data, blood samples, and faecal specimens were collected before, during, and after omalizumab treatment

At baseline, alpha-diversity indices of the CR group were higher than those of the NCR group.

• Alpha-diversity was measured before omalizumab treatment began
• Higher alpha-diversity was observed in CRs compared to NCRs at baseline
• These microbiome differences between the groups became less obvious after omalizumab treatment
• Bacterial microbiota composition was different between the two groups at baseline

Seven bacterial genera were more abundant in the CR group at baseline compared to the NCR group.

• The genera Bacteroides, Lactobacillus, Prevotella_9, Butyricimonas, Dialister, Megasphaera, and Ruminococcaceae_UCG-002 were more abundant in the CR group at baseline
• These differences in bacterial microbiota composition became less obvious after omalizumab treatment
• The findings suggest a pre-treatment microbiome signature characteristic of complete responders

Changes in IL-33 levels after omalizumab treatment were positively correlated with changes in the relative abundance of Dialister.

• Correlation coefficient r = 0.929, p = 0.003
• IL-33 levels were measured using enzyme-linked immunosorbent assay (ELISA)
• This correlation was measured between changes occurring after omalizumab treatment

Changes in IL-17 levels after omalizumab treatment were negatively correlated with changes in the relative abundance of Ruminococcaceae_UCG-002.

• Correlation coefficient r = -0.828, p = 0.022
• IL-17 levels were measured using enzyme-linked immunosorbent assay (ELISA)
• This inverse correlation was measured between changes occurring after omalizumab treatment

The gut microbiota composition of CSU patients differs from healthy controls, and gut microbiome differences exist between CSU patients with different treatment responses to omalizumab.

• Prior literature has established that gut microbiota composition of CSU patients differs from healthy controls
• Whether gut microbiome differs between CSU patients with different omalizumab treatment responses was previously seldom examined and largely unknown
• This study provides evidence that pre-treatment gut microbiome composition is associated with omalizumab treatment response