Gut Microbiome and Metabonomic Profile Predict Early Remission to Anti-Integrin Therapy in Patients with Moderate to Severe Ulcerative Colitis

Abstract

ABSTRACT Patients with ulcerative colitis (UC) have low response rates to anti-integrin medications, necessitating the identification of noninvasive biomarkers for predicting remission to anti-integrin therapy. In this study, patients with moderate to severe UC commencing anti-integrin therapy (n = 29), inactive to mild UC patients (n = 13), and healthy controls (n = 11) were selected. Besides clinical evaluation, fecal samples were collected at baseline and week 14 from moderate to severe UC patients. The clinical remission was defined based on the Mayo score. Fecal samples were assessed with 16S rRNA gene sequencing, liquid chromatography-tandem mass spectrometry, and gas chromatography-mass spectrometry (GC-MS). We identified that Verrucomicrobiota was significantly more abundant in the remission group (P < 0.001) than that of nonremission group at phylum level for patients commencing vedolizumab. GC-MS analysis revealed that the concentrations of butyric acid (P = 0.024) and isobutyric acid (P = 0.042) were significantly higher in the remission group compared to the nonremission group at baseline. Finally, the combination of Verrucomicrobiota, butyric acid, and isobutyric acid improved the diagnosis of early remission to anti-integrin therapy (area under the concentration-time curve = 0.961). We identified significantly higher phylum level diversity of Verrucomicrobiota in remission than the nonremission groups at baseline. Notably, the combination of gut microbiome and metabonomic profiles improved the diagnosis of early remission to anti-integrin therapy. IMPORTANCE It is reported that patients with ulcerative colitis (UC) have low response rates to anti-integrin medications in the latest VARSITY study. Therefore, our primary goals were to discover differences in the gut microbiome and metabonomics patterns between early remission and nonremission patients and to explore the diagnostic value in predicting clinical remission to anti-integrin therapy accurately. In this study, we found that Verrucomicrobiota was significantly more abundant in the remission group (P < 0.001) than that of nonremission group at phylum level for patients commencing vedolizumab. Gas chromatography-mass spectrometry analysis revealed that the concentrations of butyric acid (P = 0.024) and isobutyric acid (P = 0.042) were significantly higher in the remission group compared with the nonremission group at baseline. Notably, the combination of Verrucomicrobiota, butyric acid, and isobutyric acid improved the diagnosis of early remission to anti-integrin therapy (area under the concentration-time curve = 0.961).

Keywords

• anti-integrin therapy
• metabonomics
• microbiology
• ulcerative colitis