Fecal Microbiota Signatures Are Associated with Response to Ustekinumab Therapy among Crohn’s Disease Patients

• DOI: 10.1128/mbio.02120-17
• Publication Date: 2018-03-12T12:37:02Z
• Authors: Matthew K. Doherty; Tao Ding; Charlie Koumpouras; Shannon E. Telesco; Calixte Monast; Anuk Das; Carrie Brodmerkel; Patrick D. Schloss
• Keywords: Dysbiosis; Ustekinumab

The fecal microbiota is a rich source of biomarkers that have previously been shown to be predictive numerous disease states. Less well studied the effect immunomodulatory therapy on and its role in response therapy. This study explored associations between therapeutic Crohn's (CD) patients treated with ustekinumab (UST; Stelara) phase 2 CERTIFI study. Using stool samples collected over course 22 weeks, composition these subjects' bacterial communities was characterized by sequencing 16S rRNA gene. Subjects remission could distinguished from those active 6 weeks after treatment using random forest models trained baseline clinical data (area under curve [AUC] 0.844, specificity 0.831, sensitivity 0.774). most operational taxonomic units (OTUs) were ubiquitous among subjects affiliated Faecalibacterium Escherichia or Shigella median community diversity 1.7 times higher than (P = 0.020). Their structures also significantly different 0.017). Two OTUs 0.003) Bacteroides 0.022) more abundant at who CD. UST-treated responders increased study, contrast nonresponsive 0.012). observed differences changes due support potential for as biomarker.IMPORTANCE CD global health concern, increasing incidence prevalence, causing large economic care impacts. Finding prognostic give clinicians ability identify likely respond diagnosis will reduce time receive drugs are unlikely beneficial. associated induction, especially Faecalibacterium, successful UST anti-tumor necrosis factor alpha (anti-TNF-α) refractory patients. More broadly, results suggest useful noninvasive biomarker directing monitoring gastrointestinal diseases.