P144 Changes of fecal metabolic and lipidomic features by anti-tumor necrosis factor treatment and prediction of clinical remission in patients with ulcerative colitis
ShinShin, S.(1);Kim, S.Y.(2);Park, S.J.(3);Im, J.P.(4);Kim, H.J.(5);Lee, K.M.(6); Kim, J.W.(7); Jung, S.A.(8);Lee, J.(9);Kang, S.B.(10); Shin, S.J.(11);Kim, E.S.(12); Kim, Y.S.(13);Kim, T.O.(14);Kim, H.S.(15);Park, D.I.(16);Kim, H.K.(17); Kim, E.S.(18); Kim, Y.H.(19);Teng, D.(20);Kim, J.H.(21);Kim, W.(21);Saeed, M.(2); Moon, J.M.(1);Kim, K.(1);Choi, C.H.(1);Choi, H.K.(2);
(1)Chung-Ang University College of Medicine, Department of Internal medicine, Seoul, Korea- Republic Of;(2)Chung-Ang University- College of Pharmacy, Pharmacy, Seoul, Korea- Republic Of;(3)Yonsei University College of Medicine, Department of Internal Medicine and Institute of Gastroenterology, Seoul, Korea- Republic Of;(4)Seoul National University College of Medicine, Department of Internal Medicine and Liver Research Institute, Seoul, Korea- Republic Of;(5)Kyung Hee University Hospital, Department of Gastroenterology, Seoul, Korea- Republic Of;(6)The Catholic University of Korea St. Vincent’s Hospital, Department of Gastroenterology, Suwon, Korea- Republic Of;(7)Seoul National University College of Medicine, Department of Internal Medicine and Liver Research, Seoul, Korea- Republic Of;(8)Ewha Woman's University College of Medicine, Department of Gastroenterology, Seoul, Korea- Republic Of;(9)College of Medicine- Chosun University, Department of Internal Medicine, Gwangju, Korea- Republic Of;(10)The Catholic University of Korea Daejeon St. Mary’s Hospital, Department of Gastroenterology, Daejeon, Korea- Republic Of;(11)Ajou University School of Medicine, Department of Gastroenterology, Suwon, Korea- Republic Of;(12)Korea University Anam Hospital, Department of Gastroenterology, Seoul, Korea- Republic Of;(13)Inje University Seoul Paik Hospital, Department of Gastroenterology, Seoul, Korea- Republic Of;(14)Inje University Haeundae Paik Hospital, Department of Gastroenterology, Busan, Korea- Republic Of;(15)Chonnam National University Hospital, Department of Gastroenterology, Gwangju, Korea- Republic Of;(16)Kangbuk Samsung Hospital- Sungkyunkwan University, Department of Internal Medicine, Seoul, Korea- Republic Of;(17)Inha University Hospital, Department of Gastroenterology, Incheon, Korea- Republic Of;(18)Kyungpook National University- School of Medicine, Department of Internal Medicine, Daegu, Korea- Republic Of;(19)Samsung Medical Center- Sungkyunkwan University School of Medicine, Department of Internal Medicine, Seoul, Korea- Republic Of;(20)AbbVie Pte. Ltd., AbbVie Pte. Ltd., Singapore, Singapore;(21)Chung-Ang University College of Medicine, Department of Microbiology, Seoul, Korea- Republic Of; The IBD Research Group of the Korean Association for the Study of Intestinal Diseases
Background
Tumor necrosis factor (TNF) antagonists are recommended for patients with ulcerative colitis (UC) for the effectiveness in inducing and maintaining clinical remission. We investigated the altered fecal metabolites and lipids by anti-TNF treatment and prediction model of remission in patients with UC.
Methods
A prospective, observational multicenter study was conducted at 17 academic hospitals in Korea. Fecal samples were collected from adult patients with moderately to severely active UC (n=116) before and after 8 and 56 weeks of adalimumab treatment and from healthy controls (HC, n=37). Clinical remission was assessed using Mayo score. Metabolome and lipidome analyses were performed using gas chromatography-, and nano electro spray ionization-mass spectrometry, respectively. Prediction models of remission were developed using baseline fecal samples by Fourier transform-infrared (FT-IR) spectroscopy combined with machine learning algorithms.
Results
Fecal metabolites and lipids in UC were different from HC at baseline and were changed similarly to HC during treatment. Fecal metabolites and lipids in remitters (RM) after treatment were more grouped and clustered with those of HC compared with non-remitters (NRM). In RM, 2-aminobutyric acid, galactose and dodecanoate levels which were previously decreased at baseline compared to HC increased to the levels of HC, whereas benzoate, stigmasterol, 3-hydroxybutyrate, diacylglycerol and triacylglycerol levels which were previously increased at baseline compared to HC decreased to the levels of HC after 56 weeks of treatment. The best model predicting short-term remission was developed by applying logistic regression (LR) and radial basis functions (rbf) support vector machine (SVM) with an accuracy of 0.99 (95% confidence interval [CI], 0.98-1.01). For long-term remission, the best prediction model was developed by rbf-SVM revealing 0.99 [CI 0.98-1.01]. LR and K-nearest neighbors also showed excellent performance for prediction of long-term remission (accuracy of 0.96 [CI 0.90-1.02] and 0.96 [CI 0.92-1.00], respectively.
Conclusion
Fecal characteristics in UC were changed after anti-TNF treatment and became similar to those of HC. Potential therapeutic target compounds were suggested to develop novel therapeutic strategies for UC. Novel remission prediction models by FT-IR spectroscopy were also established.