Associations of NOD2 polymorphisms with Erysipelotrichaceae in stool of in healthy first degree relatives of Crohn's disease subjects.
Adolescent
Adult
Alleles
Child
Cohort Studies
Crohn Disease
/ diagnosis
Family
Feces
/ microbiology
Female
Firmicutes
/ classification
Gene Frequency
Genetic Predisposition to Disease
/ genetics
Genotype
Humans
Male
Microbiota
/ genetics
Nod2 Signaling Adaptor Protein
/ genetics
Polymorphism, Single Nucleotide
Young Adult
Fecal microbiota
Healthy human
Inflammatory bowel disease
Microbiome
NOD2
rs2066844
rs2066845
rs2066847
Journal
BMC medical genetics
ISSN: 1471-2350
Titre abrégé: BMC Med Genet
Pays: England
ID NLM: 100968552
Informations de publication
Date de publication:
15 10 2020
15 10 2020
Historique:
received:
06
01
2020
accepted:
31
08
2020
entrez:
16
10
2020
pubmed:
17
10
2020
medline:
3
11
2020
Statut:
epublish
Résumé
Genetic analyses have identified many variants associated with the risk of inflammatory bowel disease (IBD) development. Among these variants, the ones located within the NOD2 gene have the highest odds ratio of all IBD genetic risk variants. Also, patients with Crohn's disease (CD) have been shown to have an altered gut microbiome, which might be a reflection of inflammation itself or an effect of other parameters that contribute to the risk of the disease. Since NOD2 is an intracellular pattern recognition receptor that senses bacterial peptidoglycan in the cytosol and stimulates the host immune response (Al Nabhani et al., PLoS Pathog 13:e1006177, 2017), it is hypothesized that NOD2 variants represent perfect candidates for influencing host-microbiome interactions. We hypothesized that NOD2 risk variants affect the microbiome composition of healthy first degree relative (FDR) of CD patients and thus potentially contribute to an altered microbiome state before disease onset. Based on this, we studied a large cohort of 1546 healthy FDR of CD patients and performed a focused analysis of the association of three major CD SNPs in the coding region of the NOD2 gene, which are known to confer a 15-40-fold increased risk of developing CD in homozygous or compound heterozygous individuals. Our results show that carriers of the C allele at rs2066845 was significantly associated with an increase in relative abundance in the fecal bacterial family Erysipelotrichaceae. This result suggests that NOD2 polymorphisms contribute to fecal microbiome composition in asymptomatic individuals. Whether this modulation of the microbiome influences the future development of CD remains to be assessed.
Sections du résumé
BACKGROUND
Genetic analyses have identified many variants associated with the risk of inflammatory bowel disease (IBD) development. Among these variants, the ones located within the NOD2 gene have the highest odds ratio of all IBD genetic risk variants. Also, patients with Crohn's disease (CD) have been shown to have an altered gut microbiome, which might be a reflection of inflammation itself or an effect of other parameters that contribute to the risk of the disease. Since NOD2 is an intracellular pattern recognition receptor that senses bacterial peptidoglycan in the cytosol and stimulates the host immune response (Al Nabhani et al., PLoS Pathog 13:e1006177, 2017), it is hypothesized that NOD2 variants represent perfect candidates for influencing host-microbiome interactions. We hypothesized that NOD2 risk variants affect the microbiome composition of healthy first degree relative (FDR) of CD patients and thus potentially contribute to an altered microbiome state before disease onset.
METHODS
Based on this, we studied a large cohort of 1546 healthy FDR of CD patients and performed a focused analysis of the association of three major CD SNPs in the coding region of the NOD2 gene, which are known to confer a 15-40-fold increased risk of developing CD in homozygous or compound heterozygous individuals.
RESULTS
Our results show that carriers of the C allele at rs2066845 was significantly associated with an increase in relative abundance in the fecal bacterial family Erysipelotrichaceae.
CONCLUSIONS
This result suggests that NOD2 polymorphisms contribute to fecal microbiome composition in asymptomatic individuals. Whether this modulation of the microbiome influences the future development of CD remains to be assessed.
Identifiants
pubmed: 33059653
doi: 10.1186/s12881-020-01115-w
pii: 10.1186/s12881-020-01115-w
pmc: PMC7566148
doi:
Substances chimiques
NOD2 protein, human
0
Nod2 Signaling Adaptor Protein
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
204Subventions
Organisme : CIHR
ID : CMF108031
Pays : Canada
Organisme : Crohn's and Colitis Canada
ID : CCC-GEMIII
Pays : International
Investigateurs
Maria Abreu
(M)
Paul Beck
(P)
Charles Bernstein
(C)
Kenneth Croitoru
(K)
Levinus Dieleman
(L)
Brian Feagan
(B)
Anne Griffiths
(A)
David Guttman
(D)
Kevan Jacobson
(K)
Gilaad Kaplan
(G)
Denis O Krause
(DO)
Karen Madsen
(K)
John Marshall
(J)
Paul Moayyedi
(P)
Ernest Seidman
(E)
Mark Silverberg
(M)
Andy Stadnyk
(A)
A Hillary Steinhart
(AH)
Michael Surette
(M)
Dan Turner
(D)
Thomas Walters
(T)
Bruce Vallance
(B)
Guy Aumais
(G)
Alain Bitton
(A)
Maria Cino
(M)
Jeff Critch
(J)
Lee Denson
(L)
Colette Deslandres
(C)
Wael El-Matary
(W)
Hans Herfarth
(H)
Peter Higgins
(P)
Hien Huynh
(H)
Jeff Hyams
(J)
David Mack
(D)
Jerry McGrath
(J)
Anthony Otley
(A)
Remo Panancionne
(R)
Robert Baldassano
(R)
Anne M Griffiths
(AM)
Charlotte Hedin
(C)
Seamus Hussey
(S)
Hien Hyams
(H)
David Keljo
(D)
David Kevans
(D)
Charlie Lees
(C)
Sanjay Murthy
(S)
Remo Panaccione
(R)
Nimisha Parekh
(N)
Sophie Plamondon
(S)
Graham Radford-Smith
(G)
Mark Ropeleski
(M)
Joel Rosh
(J)
David Rubin
(D)
Michael Schultz
(M)
Corey Siegel
(C)
Scott Snapper
(S)
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