Prediction of Response to Systemic Corticosteroids in Active UC by Microbial Composition-A Prospective Multicenter...

Area of Science:

• Gastroenterology
• Microbiome research
• Immunology

Background:

• Corticosteroids are a primary treatment for moderately to severely active ulcerative colitis (UC).
• A significant portion of UC patients (up to one-third) do not respond to corticosteroid therapy.
• Predicting response to corticosteroids is crucial for optimizing UC treatment strategies.

Purpose of the Study:

• To investigate the association between fecal microbial composition and metabolic capacity with systemic corticosteroid response in ulcerative colitis patients.
• To identify potential microbial biomarkers for predicting treatment outcomes in UC.

Main Methods:

• Prospective, multicenter study of 93 patients with active UC receiving systemic corticosteroids.
• Fecal samples collected pre-treatment and after 4 weeks; microbiome analyzed via 16S rRNA gene sequencing (QIIME 2).
• Microbial metabolic pathways predicted using parsimonious flux balance analysis; patients classified as responders or nonresponders based on symptom improvement.

Main Results:

• 74% of patients responded to corticosteroids. Baseline microbial diversity and composition did not reliably distinguish responders from nonresponders, except in biologic-naïve patients.
• Responders exhibited significant longitudinal changes in gut microbiome diversity and composition, with enrichment of beneficial taxa (e.g., Blautia, Anaerostipes, Bifidobacterium) and increased predicted butyrate synthesis.
• Nonresponders showed minimal taxonomic shifts, with an increase in Streptococcus salivarius and a microbiome profile diverging from responders.

Conclusions:

• Baseline fecal microbiome characteristics have limited predictive value for corticosteroid response in active UC.
• Longitudinal changes in microbial composition and metabolic function, particularly the restoration of beneficial bacteria and butyrate production, are associated with successful corticosteroid treatment in UC.