Department of Surgery, Pennsylvania State University College of Medicine, Hershey, PA.
Department of Biology, Juniata College, Huntingdon, PA.
J Crohns Colitis. 2017 Oct 27;11(11):1393-1397. doi: 10.1093/ecco-jcc/jjx083.
Individuals with familial adenomatous polyposis (FAP) may undergo a total proctocolectomy with ileal pouch-anal anastomosis (IPAA) to surgically treat their disease. Inflammation of the ileal pouch, termed pouchitis, is uncommon in FAP patients but prevalent in patients who received IPAA for ulcerative colitis, a type of inflammatory bowel disease (IBD).
We report on two FAP siblings, living in the same household, who underwent IPAA surgery within one week of each other. Their mother also had an IPAA for FAP. One sibling developed pouchitis while his brother and mother have remained pouchitis-free. We investigated the genetic and microbial factors that might explain the development of pouchitis in the one sibling. We surveyed DNA isolated from the two brothers and their parents for NOD2 IBD risk variants by Sanger sequencing. The composition of mucosa-associated bacteria was analyzed by 16S rRNA gene sequencing on terminal ileum and rectal tissue collected at the time of surgical resection from the two brothers. The sibling with pouchitis inherited the IBD-associated risk alleles for NOD2 (rs17221417 and rs2076756) from his healthy father. Both the mother and unaffected brother lacked these variants. Microbiome sequencing of the terminal ileum and rectum found reduced levels of potentially 'beneficial' bacteria (Faecalibacterium prausnitzii, Bacteroides, and Ruminococcaceae) in the sibling with pouchitis relative to his brother.
These findings suggest that the NOD2 signaling pathway may contribute to intrinsic bacterial dysbiosis which is pre-existing and which may then predispose individuals to pouchitis after IPAA surgery.
家族性腺瘤性息肉病（FAP）患者可通过全直肠结肠切除加回肠贮袋肛管吻合术（IPAA）进行手术治疗。回肠贮袋炎是一种不常见于 FAP 患者但常见于溃疡性结肠炎（一种炎症性肠病，IBD）患者的贮袋炎症。
我们报告了 2 例 FAP 同胞，他们在一周内相继接受了 IPAA 手术。他们的母亲也因 FAP 接受了 IPAA。其中一位患者出现了贮袋炎，而他的兄弟和母亲则没有贮袋炎。我们调查了可能解释其中一位患者发生贮袋炎的遗传和微生物因素。我们通过 Sanger 测序调查了来自两位兄弟及其父母的 DNA 中 NOD2 IBD 风险变异。通过对两位兄弟在手术切除时收集的回肠末端和直肠组织进行 16S rRNA 基因测序，分析了粘膜相关细菌的组成。患有贮袋炎的患者从健康的父亲那里继承了 NOD2（rs17221417 和 rs2076756）的 IBD 相关风险等位基因。母亲和未受影响的兄弟都没有这些变体。回肠末端和直肠的微生物组测序发现，患有贮袋炎的患者的“有益”细菌（粪肠球菌、拟杆菌和真杆菌科）水平降低。
这些发现表明，NOD2 信号通路可能导致固有细菌失调，这种失调是预先存在的，可能使个体在接受 IPAA 手术后易患贮袋炎。
