Department of Oncology and Laparoscopy Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Thyroid Surgery, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
J Gastroenterol Hepatol. 2022 Mar;37(3):518-530. doi: 10.1111/jgh.15760. Epub 2022 Jan 22.
Patients undergoing abdominal surgery can develop postoperative ileus (POI). Inflammation of the intestinal muscularis following intestinal manipulation may be caused by displaced bacteria or lipopolysaccharide (LPS). The aim of this study was to investigate the relationship between gut microbiota, LPS, and POI in colorectal cancer (CRC) patients and explore underlying mechanisms of LPS-triggered POI.
Sixty CRC patients undergoing colorectal resection were included. Bacterial communities from fecal samples were characterized by 16S rRNA gene sequencing, and fecal LPS levels were determined by Limulus amebocyte lysate assay. Mice were used to mechanistically investigate the causal relationship between microbiota, LPS, and POI.
We discovered that CRC patients who developed prolonged POI (PPOI) had a unique pro-inflammatory gut microbial composition during the perioperative period. The highest proportions of Gram-negative bacteria at the genus level were Escherichia-Shigella and Bacteroides; the abundance of Escherichia-Shigella was higher throughout the perioperative period. Fecal LPS levels were significantly higher in patients with PPOI. In mice treated with an antibiotic cocktail, intestinal muscularis inflammation and intestinal dysfunction were significantly improved. Inflammation and dysfunction were significantly reduced in mice treated with polymyxin B, but were worsened by treatment with LPS. Moreover, LPS upregulated p38 phosphorylation in mice, and treatment with an inhibitor of p38 (SB203580) significantly alleviated intestinal inflammation and dysmotility.
Lipopolysaccharide increases intestinal muscularis inflammation via activation of p38 signaling, which aggravates POI. Removing bacterial sources of LPS during the perioperative period is promising for the prophylactic treatment of PPOI.
接受腹部手术的患者可能会发生术后肠梗阻（POI）。肠道操作后肠肌层的炎症可能是由移位细菌或脂多糖（LPS）引起的。本研究旨在探讨结直肠癌（CRC）患者肠道微生物群、LPS 与 POI 之间的关系，并探索 LPS 触发 POI 的潜在机制。
纳入 60 例行结直肠切除术的 CRC 患者。通过 16S rRNA 基因测序对粪便样本中的细菌群落进行特征分析，并通过鲎变形细胞溶解物试验测定粪便 LPS 水平。使用小鼠来对微生物群、LPS 和 POI 之间的因果关系进行机制研究。
我们发现，发生长时间 POI（PPOI）的 CRC 患者在围手术期具有独特的促炎肠道微生物组成。属水平革兰氏阴性菌的最高比例为大肠杆菌-志贺氏菌和拟杆菌；整个围手术期埃希氏菌-志贺氏菌的丰度更高。PPOI 患者的粪便 LPS 水平明显更高。在接受抗生素鸡尾酒治疗的小鼠中，肠道肌层炎症和肠道功能障碍明显改善。多粘菌素 B 治疗可显著减轻炎症和功能障碍，但 LPS 治疗会加重炎症和功能障碍。此外，LPS 上调了小鼠中 p38 的磷酸化，p38 抑制剂（SB203580）的治疗显著缓解了肠道炎症和运动障碍。
LPS 通过激活 p38 信号增加肠道肌层炎症，从而加重 POI。围手术期去除 LPS 的细菌来源有望成为预防 PPOI 的治疗方法。
