Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
Clin Transl Gastroenterol. 2020 Sep;11(9):e00232. doi: 10.14309/ctg.0000000000000232.
Exocrine pancreatic function is a critical host factor in determining the intestinal microbiota composition. Diseases affecting the exocrine pancreas could therefore influence the gut microbiome. We investigated the changes in gut microbiota of patients with chronic pancreatitis (CP).
Patients with clinical and imaging evidence of CP (n = 51) were prospectively recruited and compared with twice the number of nonpancreatic disease controls matched for distribution in age, sex, body mass index, smoking, diabetes mellitus, and exocrine pancreatic function (stool elastase). From stool samples of these 153 subjects, DNA was extracted, and intestinal microbiota composition was determined by bacterial 16S ribosomal RNA gene sequencing.
Patients with CP exhibited severely reduced microbial diversity (Shannon diversity index and Simpson diversity number, P < 0.001) with an increased abundance of facultative pathogenic organisms (P < 0.001) such as Enterococcus (q < 0.001), Streptococcus (q < 0.001), and Escherichia.Shigella (q = 0.002). The CP-associated changes were independent of exocrine pancreatic insufficiency. Short-chain fatty acid producers, considered protective for epithelia such as Faecalibacterium (q < 0.001), showed reduced abundance in patients with CP. Of 4 additional patients with CP previously treated with antibiotics (ceftriaxone and metronidazole), 3 patients were characterized by distinct Enterococcus overgrowth.
CP is associated with marked gut microbiota dysbiosis, greatly reduced diversity, and increased abundance of opportunistic pathogens, specifically those previously isolated from infected pancreatic necrosis. Taxa with a potentially beneficial role in intestinal barrier function are depleted. These changes can increase the probability of complications from pancreatitis such as infected fluid collections or small intestinal bacterial overgrowth (see Graphical Abstract, Supplementary Digital Content 1, http://links.lww.com/CTG/A383).
外分泌胰腺功能是决定肠道微生物群落组成的关键宿主因素。因此，影响外分泌胰腺的疾病可能会影响肠道微生物组。我们研究了慢性胰腺炎（CP）患者肠道微生物群的变化。
前瞻性招募了 51 例具有临床和影像学证据的 CP 患者，并与年龄、性别、体重指数、吸烟、糖尿病和外分泌胰腺功能（粪便弹性蛋白酶）分布相匹配的两倍数量的非胰腺疾病对照进行比较。从这 153 名受试者的粪便样本中提取 DNA，并通过细菌 16S 核糖体 RNA 基因测序确定肠道微生物群落组成。
CP 患者表现出严重降低的微生物多样性（Shannon 多样性指数和 Simpson 多样性数量，P < 0.001），兼性致病生物（如肠球菌（q < 0.001）、链球菌（q < 0.001）和大肠杆菌/志贺氏菌）的丰度增加（q = 0.002）。CP 相关变化与外分泌胰腺功能不全无关。短链脂肪酸产生菌，被认为对上皮有保护作用，如粪杆菌（q < 0.001），在 CP 患者中的丰度降低。在另外 4 例先前接受过抗生素（头孢曲松和甲硝唑）治疗的 CP 患者中，3 例表现为明显的肠球菌过度生长。
CP 与明显的肠道微生物失调、多样性大大降低和机会性病原体的丰度增加有关，特别是那些以前从感染性胰腺坏死中分离出来的病原体。对肠道屏障功能具有潜在有益作用的分类群被耗尽。这些变化会增加胰腺炎并发症的可能性，如感染性积液或小肠细菌过度生长（见图，补充数字内容 1，http://links.lww.com/CTG/A383）。
