gut microbiome patterns associated wieh somatostatin in patients undergoing pancreaticoduodenectomy:a prospective study

Postoperative pancreatic fistula (POPF) is a common and dreaded complication after pancreaticoduodenectomy (PD). The relationship between gut microbiome and POPF has yet to be established. This prospective study aims to analyze the influences of somatostatin on gut microbiome and to characterize the microbial alterations following POPF. 45 Patients were randomly divided into PD group and additional somatostatin therapy group. One fecal sample per patient was preoperatively collected to determine the baseline gut microbiome. Another fecal sample was obtained to observe longitudinal changes. After fecal collection, 50 samples of 25 patients were analyzed by 16S-rRNA gene sequencing. Somatostatin therapy was independent risk factor for affecting the occurrence of POPF and reduced diversity and richness of the gut microbiome. The abundance levels of certain bacteria in the gut microbiome have significantly changed after somatostatin therapy. This phenomenon was also found in patients with or without POPF. Based on the LEfSe analysis, Bifidobacterium and could be used as preoperative valuable biomarkers of somatostatin therapy. In addition, Ruminococcaceae and Akkermansia are microbial predictors to POPF. This prospective study identifies the influence of somatostatin on gut microbiome and discovers the significant biomarkers related to somatostatin and POPF. Our study suggests that gut microbiome may become a potential therapeutic target and diagnostic biomarker of POPF patients.

术后胰瘘（Postoperative pancreatic fistula, POPF）是胰十二指肠切除术（pancreaticoduodenectomy, PD）后常见且极具危害性的手术并发症。目前肠道菌群与POPF之间的关联尚未明确。本项前瞻性研究旨在分析生长抑素对肠道菌群的影响，并阐明POPF发生后肠道菌群的特征性变化。研究共纳入45例患者，随机分为胰十二指肠切除术组（PD组）与联合生长抑素治疗组。所有患者术前均采集粪便样本，以确定其肠道菌群的基线特征；术后再次采集粪便样本以观察菌群的纵向动态变化。完成粪便样本采集后，对25例患者的50份粪便样本进行16S核糖体RNA（16S-rRNA）基因测序分析。结果显示，生长抑素治疗是影响POPF发生的独立危险因素，且可降低肠道菌群的多样性与丰富度；生长抑素治疗后，肠道菌群中特定细菌的丰度水平发生显著改变，该现象在伴或不伴POPF的患者中均存在。通过线性判别分析效应大小（Linear discriminant analysis Effect Size, LEfSe）分析，双歧杆菌属（Bifidobacterium）可作为术前评估生长抑素治疗效果的有价值生物标志物；此外，瘤胃球菌科（Ruminococcaceae）与阿克曼菌属（Akkermansia）可作为POPF的微生物预测标志物。本前瞻性研究明确了生长抑素对肠道菌群的影响，并发现了与生长抑素治疗及POPF相关的关键生物标志物。本研究提示，肠道菌群有望成为POPF患者潜在的治疗靶点与诊断生物标志物。