Early Feeding After Gastrectomy Linked to Immune-Cell Preservation

Patients who received early enteral nutrition after surgery for gastric cancer retained more selected peripheral immune cells and experienced fewer complications than patients whose nutrition was delayed, according to a retrospective study of 120 adults undergoing radical gastrectomy. The investigation, conducted at the Affiliated Hospital of Qinghai University in China from January 2022 through December 2023, found that the primary immune measure—a peripheral CD4+/CD8+ T-cell ratio on postoperative day 7—was 1.42 ± 0.18 with early enteral nutrition and 1.26 ± 0.21 with traditional delayed nutrition. The estimated mean difference was 0.16, with a 95% confidence interval of 0.09 to 0.23 and P < 0.001. The association is promising but not proof that early feeding caused the immune and clinical differences, because treatment allocation followed institutional protocols rather than randomization.

The researchers divided the cohort into two groups of 60 patients. Those eligible under the hospital’s early enteral nutrition protocol began tube-administered nutrition within 24 hours of surgery, initially receiving glucose solution before progressing to standard enteral formula. By postoperative day 3, the target was 25–30 kcal/kg/day and 1.2–1.5 g/kg/day of protein. The comparison group began enteral nutrition on postoperative days 3–5, with parenteral nutrition predominating during the early recovery period. The groups did not have statistically significant differences in measured characteristics including age, sex, body-mass index, tumor location, TNM stage, operation type and duration, blood loss, or the frequencies of TP53 mutations, ERBB2 positivity and KRAS mutations. However, nonsignificant baseline tests do not prove that the groups were equivalent, and the nonrandom allocation left possible confounding by clinical suitability for early feeding.

Several immune-cell measures declined after surgery in both groups, but the early-nutrition group showed better preservation of selected phenotypes. On postoperative day 7, CD3+ T cells averaged 1,235 ± 152 cells/μL with early enteral nutrition, compared with 1,086 ± 168 cells/μL with delayed nutrition. CD4+ T-cell counts were 512 ± 68 versus 456 ± 72 cells/μL, while CD56+ natural killer cells numbered 285 ± 42 versus 248 ± 38 cells/μL; all three comparisons had P < 0.001. The higher CD4+/CD8+ ratio did not result from fewer CD8+ cells, which were similar between groups at 362 ± 48 and 365 ± 52 cells/μL, respectively, with P = 0.743. Instead, the difference primarily reflected higher CD4+ counts. Between-group differences in CD3+, CD4+ and natural killer cell counts, as well as the CD4+/CD8+ ratio, were also present on postoperative day 3, but complete longitudinal interaction statistics were unavailable and the trajectories could not be analysed with the same precision as the day-7 comparisons.

Clinical outcomes pointed in the same direction. Nine of 60 patients in the early-enteral-nutrition group experienced at least one postoperative complication within 30 days, compared with 19 of 60 in the delayed-nutrition group—15.0% versus 31.7%. The reported risk ratio was 0.47, with a 95% confidence interval of 0.23 to 0.96 and P = 0.031. Individual complications were numerically less frequent with early nutrition, including pulmonary infection in 3.3% versus 10.0%, wound infection in 3.3% versus 8.3%, and delayed gastric emptying in 5.0% versus 11.7%. Because some patients had more than one event, these category percentages were not mutually exclusive. The study did not measure specific inflammatory pathways, so the lower complication rate cannot be treated as direct evidence about NFKB1 or IL6 signaling. It instead records an association between nutritional timing, postoperative immune-cell counts and clinical complications.

The early-nutrition group also showed faster recovery of gastrointestinal function and better biochemical indicators of nutritional status. Time to first flatus averaged 2.8 ± 0.6 days with early enteral nutrition and 3.9 ± 0.8 days with delayed nutrition, while first defecation occurred after 3.5 ± 0.7 versus 5.2 ± 1.1 days. Oral intake resumed after 4.2 ± 0.8 versus 6.3 ± 1.2 days, and patients reached a full oral diet after 7.1 ± 1.3 versus 9.8 ± 1.8 days; all four comparisons had P < 0.001. On postoperative day 7, serum albumin was 38.5 ± 3.2 versus 35.8 ± 3.8 g/L, prealbumin was 245.3 ± 28.6 versus 218.7 ± 32.4 mg/L, and hemoglobin was 116.8 ± 12.4 versus 108.2 ± 14.6 g/L, again with P < 0.001 for each comparison. These were clinical nutritional and hematologic measurements, not assays of nutrient transport, MTOR signaling, intestinal-barrier genes or cytokine activity.

Hospital utilization also differed between the groups. Patients receiving early enteral nutrition had a postoperative hospital stay of 10.3 ± 2.1 days, compared with 13.8 ± 2.9 days among those receiving delayed nutrition, and total hospital stays were 15.8 ± 2.6 versus 19.2 ± 3.4 days; both comparisons had P < 0.001. Nutritional support cost more in the early-nutrition group, at 4,850 ± 680 Chinese yuan versus 3,620 ± 520 yuan, but total hospitalization cost was lower at 52,380 ± 8,250 yuan versus 61,240 ± 9,850 yuan, with P < 0.001 for both comparisons. Patients given early nutrition also reported higher global health-status scores on the European Organisation for Research and Treatment of Cancer quality-of-life instrument at discharge—65.8 ± 8.2 versus 58.3 ± 9.6—and one month after surgery—78.5 ± 7.4 versus 72.1 ± 8.8. Satisfaction scores for nutritional management and perceived recovery speed were also higher. These secondary outcomes were exploratory, and the investigators did not adjust for multiple comparisons, so their nominal P values should be interpreted cautiously.

For cancer immunologists, the peripheral blood findings raise a more ambitious question: could nutrition delivered during the stress of major surgery help preserve an immune profile favorable to later checkpoint blockade? The study itself does not answer that question. No patient received immune checkpoint inhibitor therapy as part of the investigation, and the researchers did not assay tumor immune gene expression, cytokine proteins or signaling pathways. A CD4+/CD8+ ratio describes the composition of circulating T cells but does not directly measure IFNG or IL2 expression, while a natural killer cell count does not establish cytotoxicity, interferon production or perforin and granzyme activity. Likewise, postoperative complications are clinical outcomes rather than validated molecular surrogates. Any connection between early feeding, intestinal biology, inflammation and later immunotherapy response therefore remains a hypothesis requiring prospective testing with direct molecular measurements and actual treatment outcomes.

The tumor-mutation results require similarly restrained interpretation. TP53 mutations were present in 51.7% of the early-nutrition group and 55.0% of the delayed-nutrition group, ERBB2 positivity occurred in 18.3% and 16.7%, and KRAS mutations in 15.0% and 13.3%. These frequencies described the clinical context of the cohort, but no mutation-stratified outcome analyses were performed. The ERBB2-positive and KRAS-mutant subgroups were also small, preventing reliable estimation of treatment effects within those categories. The data consequently cannot show whether the observed nutritional and immune associations were consistent across molecular subgroups, nor can they establish that a particular mutation altered the effect of early enteral nutrition.

Although the results make a coherent case for further investigation, the study has major constraints. It was retrospective, single-center and nonrandomized, creating opportunities for selection bias and residual confounding, particularly because clinicians selected early feeding according to tolerance criteria. Repeated-measures models could not be reconstructed from the aggregate data, so time-by-group interaction statistics were unavailable. Only one month of follow-up was available, leaving long-term immune recovery, survival and oncologic outcomes unknown. A stronger next phase would require randomized or otherwise rigorous multicentre comparison, complete serial immune profiling with prespecified longitudinal analyses, and integration of cytokine assays, transcriptomics, spatial tumor immune profiling and mutation-defined subgroups. If subsequent trials show that early nutritional support preserves immune phenotypes while improving recovery, testing whether those changes translate into better checkpoint-blockade responses would still be necessary. For now, the study offers an observational association between feeding within 24 hours and selected postoperative immune and clinical outcomes after gastrectomy, rather than evidence that timing itself caused the improvements or that either immune marker can guide immunotherapy selection.

Subject of Research: Early enteral nutrition and postoperative peripheral immune-cell outcomes after gastrectomy for gastric cancer

Article Title: Early enteral nutrition and perioperative peripheral immune-cell dynamics after gastrectomy for gastric cancer

Article References: Jiang, H., He, Y., Tian, M., Xu, Y., & Guo, X. (2026). Early enteral nutrition and perioperative peripheral immune-cell dynamics after gastrectomy for gastric cancer. Frontiers in Genetics, 17, Article 1931867. https://doi.org/10.3389/fgene.2026.1931867

Image Credits: AI Generated

DOI: 10.3389/fgene.2026.1931867

Keywords: gastric cancer, gastrectomy, enteral nutrition, postoperative recovery, CD4+ T cells, natural killer cells, immune phenotyping, postoperative complications, enhanced recovery, cancer immunology, Early, enteral