Abstract
Crohn's disease (CD) and Intestinal tuberculosis (ITB) are chronic inflammatory ulcero-constrictive intestinal diseases with similar phenotype. Although both are disease models of chronic inflammation and their clinical presentations, imaging, histological and endoscopic findings are very similar, yet their etiologies are diverse. Hence, we aimed to look at differences in the prevalence of pathobionts like adherent-invasive Escherichia coli (AIEC), Listeria monocytogenes, Campylobacter jejuni and Yersinia enterocolitica in CD and ITB as well as their associations with host-associated genetic polymorphisms in genes majorly involved in pathways of microbial handling and immune responses. The study cohort included 142 subjects (69 patients with CD, 32 with ITB and 41 controls). RT- PCR amplification was used to detect the presence of AIEC, L. monocytogenes, C. jejuni, and Y. enterocolitica DNA in colonic mucosal biopsies. Additionally, we tested three SNPs in IRGM (rs13361189, rs10065172, and rs4958847), one SNP in ATG16L1 (rs2241880) and one SNP in TNFRSF1A (rs4149570) by real-time PCR with SYBR green from peripheral blood samples in this cohort. In patients with CD, AIEC was most frequently present (16/ 69, 23.19%) followed by L. monocytogenes (14/69, 20.29%), C. jejuni (9/69, 13.04%), and Y. enterocolitica (7/69, 10.14%). Among them, L. monocytogenes and Y. enterocolitica were significantly associated with CD (p = 0.02). In addition, we identified all the three SNPs in IRGM (rs13361189, rs10065172, and rs4958847), one SNP in ATG16L1 (rs2241880) and TNFRSF1A (rs4149570) with a significant difference in frequency in patients with CD compared with ITB and controls (p<0.05). Higher prevalence of host gene polymorphisms, as well as the presence of pathobionts, was seen in the colonic mucosa of patients with CD as compared to ITB, although both are disease models of chronic inflammation.
Highlights
Crohn’s Disease (CD) is a chronic, relapsing, transmural, inflammatory disorder of gastrointestinal tract, which results from the prolonged, uncontrolled immune response to pathogenic or commensal microflora, in genetically susceptible individuals
We aimed to look at differences in the prevalence of pathobionts like adherent-invasive Escherichia coli (AIEC), Listeria monocytogenes, Campylobacter jejuni and Yersinia enterocolitica in CD and Intestinal tuberculosis (ITB) as well as their associations with host-associated genetic polymorphisms in genes majorly involved in pathways of microbial handling and immune responses
This study investigated the prevalence of these pathobionts and their association with single nucleotide genetic polymorphisms (SNPs) of immunity-related GTPase family M (IRGM), autophagy-related gene 16 like 1 (ATG16L1) and TNFRSF1A gene responsible for microbial sensing and handling in the CD and ITB patients and non-Inflammatory bowel disease (IBD) control
Summary
Crohn’s Disease (CD) is a chronic, relapsing, transmural, inflammatory disorder of gastrointestinal tract, which results from the prolonged, uncontrolled immune response to pathogenic or commensal microflora, in genetically susceptible individuals. Though the etiology remains elusive, CD results from the complex interplay of host genetics and alterations in lifestyle or host environment [1] These host-associated changes potentiate alterations in sensing and handling of gut commensals, which along with changes in structure and function of the gut microbial community, perpetuates the vicious cycle of gut dysbiosis and inflammation [2, 3]. The onset of toxic pro-inflammatory gut environment supports an overgrowth of enteropathogens and functionally altered and potentially pathogenic commensal flora called the ‘pathobionts’ Several of these pathogenic bacteria associated with CD, include adherent-invasive Escherichia coli (AIEC), Listeria monocytogenes, Campylobacter jejuni, Mycobacterium avium subspecies paratuberculosis (MAP) and Yersinia enterocolitica [7,8,9,10,11]. We aimed to look at differences in the prevalence of pathobionts like adherent-invasive Escherichia coli (AIEC), Listeria monocytogenes, Campylobacter jejuni and Yersinia enterocolitica in CD and ITB as well as their associations with host-associated genetic polymorphisms in genes majorly involved in pathways of microbial handling and immune responses
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