S2134 The Interplay of Psychoneuroimmunology and Gut Microbiota Modulation in Colorectal Cancer Treatment: A Systematic Review of Probiotic Interventions and Chemotherapy/Immunotherapy Outcomes

Introduction: Colorectal cancers (CRCs) found to be complicated by chemotherapy-induced gastrointestinal (GI) toxicity, systemic inflammation, and psychological distress can be managed by targeting the psychoneuroimmunological (PNI) axis and the gut microbiota. This systematic review and meta-analysis attempt to evaluate the effects of probiotics/synbiotics and PNI-based interventions (e.g., mindfulness, cognitive behavioral therapy, yoga) on outcomes in CRC. Methods: Following PRISMA 2020 guidelines, we thoroughly searched PubMed, Scopus, and Web of Science databases from 2007-2023 for randomized controlled trials (RCTs) focusing on probiotics, synbiotics, or psychosocial interventions in adults with CRC. Our main outcomes were chemotherapy-induced GI toxicity, along with anxiety and depression-related impacts. We looked into quality of life (QoL), inflammatory biomarkers like IL-6, CRP and NK cell activity as secondary outcomes. To evaluate the risk of bias, we employed the Cochrane RoB 2 tool. For the meta-analysis, we utilized a random-effects model and assessed heterogeneity through I² statistics. Results: Eighteen RCTs (n = 1029) were included: 9 on probiotic/synbiotic interventions (n ≈ 248) and 9 on PNI interventions (n = 781). Probiotic/synbiotic meta-analysis: Significantly reduced risk of grade ≥3 diarrhea as per National Cancer Institute classification (risk ratio [RR] = 0.56; 95% confidence interval [CI]: 0.42–0.75; P = 0.003). QoL improvements and reduced abdominal symptoms noted in 3 studies. One study showed decreased inflammatory markers (IL-6, TNF-α). PNI intervention meta-analysis: Reduced scores of anxiety (SMD = -0.72; 95% CI: -0.96 to -0.49; P< 0.001). Reduced depression scores (SMD = -0.68; 95% CI: -0.91 to -0.45; P < 0.001). Improved QoL in 4 studies. Biomarker improvements (↓CRP, ↑NK cells, ↓cortisol) in 3 studies. Heterogeneity ranged from low to moderate (I² = 35%–58%). No major adverse events were reported for either intervention category. Conclusion: PNI-based and probiotic/synbiotic interventions showed significant improvement in psychological symptoms while reducing GI toxicity and modulating inflammation in patients with CRC, which support their integration into comprehensive cancer care. Future studies could focus on standardization protocols, biomarker personalization, and their potential in enhancing response to therapy.