Inflammatory Bowel Diseases, 2021, 27, S63–S66 https://doi.org/10.1093/ibd/izab273 Supplement Article RAID Prediction: Pilot Study of Fecal Microbial Signature With Capacity to Predict Response to Anti-TNF Treatment David Busquets, MD,∗, Lia Oliver, MD, † Joan Amoedo, PhD, † Sara Ramió-Pujol, PhD, † Marta Malagón, PhD, † Marta Serrano, PhD, † Anna Bahí, PhD, ‡ Montse Capdevila, MD, ‡ Aleix Lluansí, MD, ‡ Leyanira Torrealba, MD, ∗ Laia Peries, MD, ∗ Rosa Chavero, MD, ∗ Pau Gilabert, MD, § Miriam Sàbat, PhD, ¶ Jordi Guardiola, PhD, § , Mariona Serra-Pagès, PhD, † Jesús Garcia-Gil, Prof, †,‖ and Xavier Aldeguer, PhD,∗ ,†,‡ From the ∗Servei Aparell Digestiu Hospital Universitari Dr. Josep Trueta, Girona, Spain † GoodGut S.L, Girona, Catalonia, Spain ‡ Institut d’Investigació Biomèdica de Girona (IdIBGi), Girona, Catalonia, Spain § Servei Aparell Digestiu Hospital Universitari de Bellvitge, Hospitalet de Llobregat, Spain ¶ Hospital de Santa Caterina, Girona, Catalonia, Spain ‖ Deparment of Biology, University of Girona, Girona, Catalonia, Spain Address correspondence to: Dr. David Busquets, Hospital Universitari Girona Dr. J Trueta, carretera França s/n, 17007 Girona, Catalonia, Spain (dbusquets. girona.ics@gencat.cat). Background and Aims: Crohn’s disease and ulcerative colitis evolve with alternate outbreaks and remissions of variable duration in both cases. Despite the advances, about 10-30% of patients do not respond to the treatment after the induction period. Besides, between 20% to 50% further patients need an optimization of the dose to respond the treatment. Recent studies have pointed gut microbiota can play a role in the anti-TNF treatment response. This study aimed to define a bacterial signature that could be used to predict the response of patients to anti-TNF treatment. Methods: There were obtained 38 stool samples from 38 IBD patients before starting anti-TNF treatments: Adalimumab, Golimumab or Infliximab. Patients were differentiated in 2 groups: responders and non-responders to biological treatment. From each sample, DNA was puri- fied and used in a qPCR for the quantification of the 8 microbial markers. Results: In this proof of concept, the predictive ability to identify anti-TNF treatment responders was analyzed. An algorithm consisting in the combination of 4 bacterial markers showed a high capacity to discriminate between responders and non- responders. The algorithm proved high sensitivity and specificity reporting values of 93.33% and 100% respectively, with a positive predictive value of 100% and a negative predictive value of 75% for predicting response to biologic treatment. Conclusions: A specific bacterial signature could beneficiate patients with inflammatory bowel disease predicting the therapeutic effective- ness of an anti-TNF treatment, leading to a personalized therapy, improving the patients’ quality of life, saving costs and gaining time in patient improvement. Lay Summary This study aimed to define a microbial signature that could be used to predict the response of patients to anti-TNF treatment in inflammatory bowel disease. An algorithm consisting in the combination of 4 bacterial markers showed a high capacity to discriminate between responders and nonresponders. Key Words: microbiota, prediction, anti-TNFα Introduction Infammatory bowel diseases (IBDs) are chronic diseases that share an immune-mediated pathogenesis and relapsing course. Crohn’s disease (CD) and ulcerative colitis (UC) are the 2 main IBD types that evolve with alternating outbreaks with remission of variable duration in both cases. Currently, one of the most effective therapies for treating refractory IBD is the suppression of tumour necrosis alpha factor function (anti-TNFα), improving patient’s quality of life by postponing the number of surgeries and hospitalization. However, therapeutic effcacy is hampered by primary and secondary loss of response. 1 Given the known side effects and associated costs of biological therapies, signifcant efforts have been channeled towards the discovery of biomarkers that enable the prediction of response prior to the initiation of treatment. The mucosa-associated microbiota plays an important role protecting and maintaining the optimal physiological condi- tions of the intestine besides shaping the immune response. 2 Regarding IBD patients, it has been described that they © 2021 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Received for publication: September 16, 2021. Editorial Decision: September 24, 2021 Downloaded from https://academic.oup.com/ibdjournal/article/27/Supplement_2/S63/6428471 by guest on 07 April 2022