Associations of NOD2 polymorphisms with Erysipelotrichaceae in stool of in healthy first degree relatives of Crohn’s disease subjects

BMC Medical Genetics

David S. Guttman¹  Paul Moayyedi²  Larbi Bedrani³  Michelle I. Smith³  Kenneth Croitoru⁴  Sun-Ho Lee⁴  Williams Turpin⁴  Juan Antonio Raygoza Garay⁴  Hillary A. Steinhart⁴  Hien Huynh⁵  Dan Turner⁶  Wei Xu⁷  Andrew D. Paterson⁸  Levinus A. Dieleman⁹  Anne Griffiths^1,10  Guy Aumais^1,11  Remo Panaccione^1,12  Osvaldo Espin-Garcia^1,13  Mark S. Silverberg^1,14 

[1] Department of Cell & Systems Biology, University of Toronto, Toronto, Ontario, Canada;Centre for the Analysis of Genome Evolution & Function, University of Toronto, Toronto, Ontario, Canada;Department of Medicine, McMaster University, Hamilton, Ontario, Canada;Department of Medicine, University of Toronto, Toronto, ON, Canada;Department of Medicine, University of Toronto, Toronto, ON, Canada;Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, 600 University Avenue Room 437, M5G 1X5, Toronto, Ontario, Canada;Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada;Department of pediatric GI, Shaare Zedek Medical Center, 91031, Jerusalem, Israel;Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada;Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada;Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada;Genetics and Genome Biology, The Hospital for Sick Children Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada;Division of Gastroenterology and CEGIIR, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada;Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada;Hôpital Maisonneuve-Rosemont, Department of Medicine, Montreal University, Montreal, Quebec, Canada;Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology of Gastroenterology, University of Calgary, Calgary, Alberta, Canada;Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada;Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada;Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, 600 University Avenue Room 437, M5G 1X5, Toronto, Ontario, Canada;

关键词: Fecal microbiota;    Healthy human;    Microbiome;    rs2066844;    rs2066845;    rs2066847;    NOD2;    Inflammatory bowel disease;   

DOI  :  10.1186/s12881-020-01115-w

来源: Springer

【 摘 要 】

BackgroundGenetic 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.MethodsBased 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.ResultsOur 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.ConclusionsThis 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.

【 授权许可】

CC BY