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

Abstract

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.

Epigallocatechin Gallate (EGCG) Promotes the Immune Function of Ileum in High Fat Diet Fed Mice by Regulating Gut Microbiome Profiling and Immunoglobulin Production

“…Indeed, our results showed that the relative abundance of norank_Erysipelotrichaceae was positively correlated with the genes encoded IgA. This taxon can produce palmitic, stearic, oleic acid, and fatty acids, which could result in metabolism disorder, stimulate pro-inflammatory cytokine production and enhance the responses of T helper 17 cells (76,77). In the present study, the relative abundance of norank_f_Erysipelotrichaceae was significantly enriched with HFD, which was consistent with the previous report (78).…”

Diagnostic model for predicting hyperuricemia based on alterations of the gut microbiome in individuals with different serum uric acid levels

“…Certain Bacteroides species are considered biomarkers of IBD and their associated OmpW proteins can be used as targets for developing IBD immunotherapy ( 29 ). Shigella and Erysipelotrichaceae are considered opportunistic pathogens in the human gut and are significantly increased in Crohn’s disease ( 30 , 31 ). Erysipelotrichaceae can produce phenyl sulfate, which impairs glomerular function and is highly associated with diabetic nephropathy ( 32 ).…”

Linkage analysis identifies novel genetic modifiers of microbiome traits in families with inflammatory bowel disease

“…Against this background, it is interesting to note that a recent study by Turpin et al 32 , being specifically targeted at NOD2 , demonstrated an association between variants in this gene and the fecal microbiome composition in healthy first-degree relatives of CD patients. Notably, the authors also pointed out the advantages of their study design over traditional association studies of population-representative healthy individuals.…”

“…Notably, the authors also pointed out the advantages of their study design over traditional association studies of population-representative healthy individuals. In contrast to Turpin et al 32 however, our study (i) was not focused upon certain genetic variants, but covered all genomic regions implicated in IBD by GWAS before, and (ii) used a genetic linkage approach in IBD families to explore the possible joint role of genotype and microbiome in the etiology of the disease.…”