Postoperative pancreatic fistula (POPF) is a common and dreaded complication after pancreaticoduodenectomy (PD). The gut microbiota has been considered as an crucial mediator of postoperative complications, however, the precise roles of gut microbiota in POPF are unclear. A prospective study was developed to explore the effects of somatostatin on gut microbiota and we aim to identify the microbial alterations in the process of POPF. A total of 45 patients were randomly divided into PD group or additional somatostatin therapy group. The fecal sample of each patient was collected preoperatively and postoperatively and the gut microbiota was analyzed by 16S rRNA sequencing. Our study found that somatostatin therapy was independent risk factor for the occurrence of POPF, and it reduced the microbial diversity and richness in patients. At genus level, somatostatin therapy led to a decreased abundance in Bifidobacterium, Subdoligranulum and Dubosiella, whereas the abundance of Akkermansia, Enterococcus and Enterobacter were increased. The abundance levels of certain bacteria in the gut microbiota have significantly shifted in patients with POPF. The LEfSe analysis revealed that Ruminococcaceae could be used as microbial markers for distinguishing patients with high risk of POPF. Furthermore, Verrucomicrobia and Akkermansia could be used as preoperative biomarkers for identifying patients without POPF. Our prospective study highlights the specific communities related with somatostatin therapy and discovers POPF-associated microbial marker, which suggests that gut microbiota may become a diagnostic biomarker and potential therapeutic target for POPF.

术后胰瘘（POPF）是胰十二指肠切除术（PD）后常见且可怕的并发症。肠道微生物群被认为是术后并发症的关键介质，然而肠道微生物群在 POPF 中的确切作用尚不清楚。我们开展了一项前瞻性研究来探讨生长抑素对肠道微生物群的影响，我们的目的是确定 POPF 过程中微生物的变化。共有45例患者随机分为PD组或加用生长抑素治疗组。术前和术后收集每位患者的粪便样本，并通过16S rRNA测序分析肠道微生物群。我们的研究发现生长抑素治疗是POPF发生的独立危险因素，并且降低了患者体内微生物的多样性和丰富度。在属水平上，生长抑素治疗导致双歧杆菌、Subdoligrinum和Dubosiella的丰度下降，而阿克曼氏菌、肠球菌和肠杆菌的丰度增加。POPF 患者肠道微生物群中某些细菌的丰度水平发生了显着变化。LEfSe 分析表明，瘤胃球菌科可用作区分 POPF 高风险患者的微生物标志物。此外，疣微菌属和阿克曼氏菌可用作术前生物标志物，用于识别无 POPF 的患者。我们的前瞻性研究强调了与生长抑素治疗相关的特定群落，并发现了 POPF 相关的微生物标志物，这表明肠道微生物群可能成为 POPF 的诊断生物标志物和潜在的治疗靶点。