Strategies to Improve Immune Function Before Surgery
Surgical procedures impose significant physiological strain on the body, often leading to temporary immune suppression, increased inflammation, and metabolic disruption. These changes can heighten vulnerability to postoperative complications, particularly infections and delayed recovery. In response, there has been growing interest in preoperative strategies designed to strengthen immune function before surgery, collectively known as prehabilitation. Current medical literature supports nutrition optimization, exercise, inflammation reduction, microbiome support, and targeted micronutrient therapy as key methods for improving immune readiness prior to surgery.
Nutritional prehabilitation remains a central focus in strategies for immune function optimization before surgery. Thorough nutritional screening allows clinicians to identify protein-energy malnutrition and micronutrient deficiencies that can impair immune cell activity. Immune-enhancing nutritional formulas—containing arginine, omega-3 fatty acids, glutamine, antioxidants, and nucleotides—have shown measurable benefits in surgical populations. Studies consistently report reduced postoperative infection rates, shortened hospital stays, and better wound healing outcomes in patients who receive these specialized nutritional supplements prior to surgery. Carbohydrate loading shortly before anesthesia (and before patients must stop eating) has also been shown to reduce insulin resistance and preserve metabolic stability, indirectly supporting immune competence during the perioperative period.
Beyond nutrition alone, multimodal prehabilitation programs have demonstrated substantial immune-modulating effects. These programs combine structured exercise, nutritional guidance, psychological support, and patient education to enhance global physiologic resilience. Exercise interventions improve lymphocyte function, regulate inflammatory signaling, and increase overall conditioning. Barberis et al found that personalized prehabilitation produced beneficial changes in immune signaling pathways and reduced postoperative complications compared with standard preparation, underscoring the physiologic impact of targeted preoperative interventions.
Reducing baseline inflammation is another essential component of immune preparation. Chronic low-grade inflammation weakens immune responsiveness and amplifies the physiologic stress response following surgery. Strategies such as mindfulness, improved sleep quality, stress-reduction techniques, and behavioral support can help decrease circulating inflammatory markers and promote a more balanced immune environment before surgery.
The role of the gut microbiome has also gained attention in recent years. Prebiotics and probiotics may enhance mucosal immunity, maintain gut barrier integrity, and reduce inflammation caused by bacterial translocation. Clinical trials in abdominal and bariatric surgery populations suggest that preoperative probiotic supplementation may reduce inflammatory markers and infection rates, making microbiome support a promising adjunct in prehabilitation.
An additional evidence-supported strategy involves targeted micronutrient optimization. Micronutrients such as vitamin D, zinc, selenium, and vitamins C and E are essential for immune cell activation, antioxidant defense, and tissue repair. Deficiencies are common, especially among patients with chronic illness. Literature suggests that correcting these deficiencies preoperatively may enhance innate immune responses, support collagen synthesis, and improve wound healing. Incorporating micronutrient assessment and supplementation into prehabilitation programs is increasingly recommended as a practical, low-cost strategy for immune enhancement.
Taken together, these approaches highlight the importance of personalized, multidisciplinary prehabilitation. By incorporating nutrition, exercise, inflammation control, microbiome support, and micronutrient optimization, clinicians can better prepare patients for the physiologic demands of surgery and improve overall outcomes.
References
1. Barberis L, Mancin S, Morales Palomares S, et al. Nutritional prehabilitation in patients undergoing cystectomy: a systematic review. Nutrients. 2024;16(11):1682. DOI: 10.3390/nu16111682
2. Barberis L, Mancin S, Morales Palomares S, et al. Immune modulation by personalized vs standard prehabilitation before major surgery: a randomized clinical trial. JAMA Netw Open. 2025. PMID: 36596634
3. Gillis C, Li C, Lee L, et al. Prehabilitation strategies: enhancing surgical resilience with a focus on nutritional optimization and multimodal interventions. Ann Surg. 2025.
4. Ham HJ, Kim J. Targeted nutritional strategies in postoperative care. Anesth Pain Med. 2025;20(1):34-45. DOI: 10.1016/j.advnut.2025.100392
5. Li C, Carli F, Lee L, et al. Prehabilitation and inflammation: molecular pathways and biomarkers. J Surg Res. 2024. DOI: 10.1159/000545181