BRIEF RESEARCH REPORT article
Front. Pharmacol.
Sec. Gastrointestinal and Hepatic Pharmacology
This article is part of the Research TopicThe Pharmacological Effects and Mechanisms of Drugs Against Human Diseases by Modulating Redox Homeostasis - Volume IIIView all articles
Salivary oxidative stress persists in Inflammatory Bowel Disease regardless of biological treatment response
Provisionally accepted
Elisabetta Bigagli1,2*
Tommaso Innocenti3
Gabriele Dragoni3Francesco Pindozzi3
Andrea Galli3
Maura Lodovici2
Cristina Luceri2- 1University of Florence, Florence, Italy
- 2Department of Neurosciences, Psychology, Drug Research and Child Health (NEUROFARBA),, Florence, Italy
- 3Azienda Ospedaliero Universitaria Careggi, Florence, Italy
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Background: Uncontrolled oxidative stress contributes to the pathogenesis of inflammatory bowel disease (IBD), yet its association with disease activity and response to biological therapy, has never been studied in saliva. We investigated whether salivary oxidative stress markers could predict therapeutic response to biologics in IBD patients. Methods: Seventy-three IBD patients (46 ulcerative colitis (UC), 27 Crohn’s disease (CD)) eligible for infliximab or vedolizumab and 56 healthy controls (HC) were enrolled. Salivary advanced oxidation protein products (AOPPs), advanced glycated end-products (AGEs), and ferric reducing antioxidant power (FRAS) were measured at baseline and at week 26. Clinical response was assessed at weeks 26 and 52, and endoscopic activity at baseline and week 52. Results: Baseline AOPPs and AGEs were higher in IBD than HC (p < 0.0001), but only AOPPs distinguished mild from moderate-severe endoscopic activity (AUC 0.72; p < 0.05). Clinical response at week 26 was 77.8% in CD and 69.6% in UC, yet AOPPs remained stable from baseline. Endoscopic remission at week 52 occurred in 40.7% of CD and 23.9% of UC patients. Neither baseline nor 26-week AOPPs or AGEs predicted endoscopic improvement or remission. Conclusions: Salivary AOPPs reflect baseline disease severity but do not predict response to biologics. Persistent AOPPs accumulation despite clinical control suggests a decoupling between clinical remission and oxidative homeostasis. Understanding the drivers and clinical relevance of persistent AOPPs is needed before considering potential therapeutic applications, such as antioxidant-based adjunctive strategies or interventions targeting AOPP-mediated damage, to improve remission rates in IBD patients receiving advanced treatments.
Keywords: IBD, Biological Therapy, Oxidative Stress, infliximab, Vedolizumab, biomarkers
Received: 04 Sep 2025; Accepted: 23 Oct 2025.
Copyright: © 2025 Bigagli, Innocenti, Dragoni, Pindozzi, Galli, Lodovici and Luceri. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Elisabetta Bigagli, elisabetta.bigagli@unifi.it
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