Perioperative Oral Immunonutrient Regulation of Intestinal Barrier and Gut Microbiota in Patients with Gastric...

Background and Objectives: Perioperative enteral and parenteral nutrition have been increasingly used to treat malnutrition in patients with gastric cancer. Immunonutrients have been suggested to reduce postoperative inflammatory responses and enhance immune function compared to conventional nutritional formulas. However, the insufficiency of evidence and unclear specific mechanism limit the recommendation level of immunonutrients in clinical guidelines. This study aimed to investigate the effects of immunonutrients on intestinal barrier function and to explore potential mechanisms through gut microbiota modulation. Methods: A total of 58 patients who underwent gastric cancer surgery participated in this randomized controlled trial. The immunonutrients group (n = 29) was additionally supplemented with 282 mg of omega-3 fatty acids, 1.2 g of arginine, and 128 mg of nucleotides per 100 kilocalories compared to the standard nutrients group (n = 29). Perioperative serum immune, nutritional parameters, and intestinal barrier markers (diamine oxidase, D-lactate, endotoxin) were evaluated. Fecal microbiota structure and functional pathways were analyzed via metagenomic sequencing. Results: Postoperative immune and nutritional parameters showed no statistically significant intergroup differences, though mean value curves suggested a protective trend in the immunonutrients group. The immunonutrients group exhibited significantly lower postoperative diamine oxidase (p = 0.043) and endotoxin levels (p = 0.043), alongside a substantial increase in microbiota α-diversity (p = 0.0005). Probiotic genera such as Akkermansia (3.26%) and Bifidobacterium longum (2.31%) were enriched in the immunonutrients group. Functional pathway analysis suggested that immunonutrients enhanced intestinal barrier protection. Conclusions: Immunonutrients may attenuate surgery-induced intestinal barrier damage in gastric cancer patients by modulating gut microbiota diversity, enriching beneficial taxa, and suppressing pathogenic bacteria.