Background/Objectives: Neoadjuvant chemotherapy (NAC) followed by radical gastrectomy is the current standard approach for locally advanced gastric cancer (GC) in the West. Both NAC and gastrectomy can significantly influence the gut microbiome, potentially leading to clinically significant changes. However, no longitudinal studies to date support this hypothesis. This study investigates gut microbiome changes throughout GC treatment, including NAC and gastrectomy. Methods: This longitudinal observational study included GC patients undergoing NAC followed by gastrectomy. Fecal microbiome composition, intestinal inflammation (fecal calprotectin), and gut permeability (LBP, sCD14) markers were investigated at baseline, after NAC, and after gastrectomy. Results: A total of 38 patients were included in the study. The results showed that NAC did not affect the gut microbiome composition at the phylum level. In contrast, radical gastrectomy led to an increased abundance of Bacteroidetes and Proteobacteria and a decreased abundance of Firmicutes and Actinobacteria. Furthermore, NAC alone did not impact alpha or beta diversity, while a combination of NAC and gastrectomy significantly influenced both. After gastrectomy, the gut microbiome composition analysis also revealed enrichment of oralization-associated bacterial species such asEscherichia-Shigella,Streptococcus equinus, unculturedStreptococcusspecies, and species from the Enterobacteriaceae family. Intestinal inflammation and gut permeability markers did not significantly change throughout the treatment. Conclusions: The radical treatment of advanced GC with NAC and radical surgery has long-term effects on the gut microbiome, characterized by gut microbiome oralization. These sustained alterations primarily stem from the radical gastrectomy rather than the NAC. Since previous studies have linked oralization-associated dysbiosis to various gastrointestinal symptoms, this study highlights the gut microbiome as a potential therapeutic target to enhance the quality of life in long-term survivors following gastrectomy.
背景/目的：新辅助化疗（NAC）联合根治性胃切除术是目前西方局部进展期胃癌（GC）的标准治疗方案。NAC与胃切除术均可能显著影响肠道微生物组，并可能导致具有临床意义的变化。然而，目前尚无纵向研究支持这一假设。本研究旨在探究胃癌治疗全程（包括NAC与胃切除术）中肠道微生物组的变化。方法：本纵向观察性研究纳入了接受NAC后行胃切除术的胃癌患者。分别在基线期、NAC后及胃切除术后，对粪便微生物组组成、肠道炎症标志物（粪便钙卫蛋白）及肠道通透性标志物（LBP、sCD14）进行了检测。结果：研究共纳入38例患者。结果显示，NAC在门水平上未影响肠道微生物组组成。相比之下，根治性胃切除术导致拟杆菌门和变形菌门丰度增加，而厚壁菌门和放线菌门丰度减少。此外，单独NAC对α或β多样性无影响，而NAC联合胃切除术则对两者均有显著影响。胃切除术后，肠道微生物组组成分析还揭示了口腔化相关细菌物种的富集，如埃希氏菌-志贺氏菌、马链球菌、未培养链球菌属物种以及肠杆菌科物种。肠道炎症和肠道通透性标志物在整个治疗过程中未发生显著变化。结论：采用NAC联合根治性手术治疗进展期胃癌对肠道微生物组具有长期影响，其特征表现为肠道微生物组的口腔化。这些持续性的改变主要源于根治性胃切除术，而非NAC。由于既往研究已将口腔化相关的菌群失调与多种胃肠道症状联系起来，本研究强调肠道微生物组可作为改善胃切除术后长期生存者生活质量的潜在治疗靶点。
Gut Microbiome Changes After Neoadjuvant Chemotherapy and Surgery in Patients with Gastric Cancer
肿瘤(癌症)患者之家