INTERMITTENT FASTING IMPROVES COLITIS OUTCOMES IN PRECLINICAL IBD MODELS: A META-ANALYSIS TO GUIDE HUMAN TRIALS

Abstract INTRODUCTION Inflammatory Bowel Disease (IBD), including Crohn’s disease and ulcerative colitis, is a lifelong disorder marked by immune dysregulation, mucosal injury, and microbiome imbalance. While pharmacologic therapies dominate current treatment algorithms, non-drug strategies like intermittent fasting (IF) remain underexplored. This reflects increasing interest in holistic, low-toxicity adjuncts for IBD. Despite emerging animal data, no consolidated evidence exists to guide translational research. Our Aim Was To evaluate the impact of IF on inflammatory, histologic, microbial, and clinical outcomes in preclinical IBD models and assess readiness for human study design. METHODS Following PRISMA guidelines, we conducted a systematic review and meta-analysis across PubMed, Embase, Cochrane Library, ScienceDirect, Google Scholar, and ClinicalTrials.gov (2000–2024) for preclinical and clinical studies evaluating IF in chemically induced colitis. Inclusion criteria required measurement of histologic inflammation, cytokines (e.g., TNF-α, IL-6), microbiota composition, and/or behavioral indicators. Seven murine studies met criteria. Data extraction was independently performed by two reviewers; pooled standardized mean differences (SMD) and qualitative synthesis were used where feasible. RESULTS Histologic improvement observed in 5/7 studies (pooled SMD: –1.13). Pro-inflammatory cytokines (e.g., TNF-α, IL-6) were consistently reduced (SMD range: –1.09 to –1.77). Microbial shifts included increased alpha diversity and enrichment of SCFA-producing genera (e.g., Lactobacillus, Bacteroides). Behavioral metrics (e.g., weight stabilization, disease activity index) improved across studies. No eligible human RCTs were identified, underscoring a critical translational gap. Protocol heterogeneity (fasting type, duration) limits uniformity but not reproducibility. DISCUSSION Intermittent fasting confers reproducible anti-inflammatory, mucosal, and microbial benefits in preclinical IBD models. The absence of human trials highlights the urgent need for clinical evaluation. These findings offer a mechanistically sound, non-pharmacologic rationale to inform first-in-human studies for IBD remission and adjunctive maintenance.