NOD2 genetic variants predispose one of two familial adenomatous polyposis siblings to pouchitis through microbiome dysbiosis

Kathleen M. Schieffer, Justin R. Wright, Leonard R. Harris, Sue Deiling, Zhaohai Yang, Regina Lamendellab, Gregory S. Yochum, Walter A. Koltun

Research output: Contribution to journalArticle

Abstract

Background and Aims: 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). Methods and Results: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)1393-1397
Number of pages5
JournalJournal of Crohn's and Colitis
Volume11
Issue number11
DOIs
StatePublished - Nov 1 2017

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Dysbiosis
Pouchitis
Adenomatous Polyposis Coli
Microbiota
Siblings
Colonic Pouches
Bacteroides
Mothers
Ileum
Inflammatory Bowel Diseases
Microbial Genetics
Ulcerative Colitis
rRNA Genes
Rectum
Fathers
Mucous Membrane
Parents
Alleles

All Science Journal Classification (ASJC) codes

  • Gastroenterology

Cite this

Schieffer, Kathleen M. ; Wright, Justin R. ; Harris, Leonard R. ; Deiling, Sue ; Yang, Zhaohai ; Lamendellab, Regina ; Yochum, Gregory S. ; Koltun, Walter A. / NOD2 genetic variants predispose one of two familial adenomatous polyposis siblings to pouchitis through microbiome dysbiosis. In: Journal of Crohn's and Colitis. 2017 ; Vol. 11, No. 11. pp. 1393-1397.
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abstract = "Background and Aims: 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). Methods and Results: 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. Conclusion: 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.",
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NOD2 genetic variants predispose one of two familial adenomatous polyposis siblings to pouchitis through microbiome dysbiosis. / Schieffer, Kathleen M.; Wright, Justin R.; Harris, Leonard R.; Deiling, Sue; Yang, Zhaohai; Lamendellab, Regina; Yochum, Gregory S.; Koltun, Walter A.

In: Journal of Crohn's and Colitis, Vol. 11, No. 11, 01.11.2017, p. 1393-1397.

Research output: Contribution to journalArticle

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T1 - NOD2 genetic variants predispose one of two familial adenomatous polyposis siblings to pouchitis through microbiome dysbiosis

AU - Schieffer, Kathleen M.

AU - Wright, Justin R.

AU - Harris, Leonard R.

AU - Deiling, Sue

AU - Yang, Zhaohai

AU - Lamendellab, Regina

AU - Yochum, Gregory S.

AU - Koltun, Walter A.

PY - 2017/11/1

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N2 - Background and Aims: 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). Methods and Results: 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. Conclusion: 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.

AB - Background and Aims: 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). Methods and Results: 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. Conclusion: 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.

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