Prevalence of Mycobacterium avium subsp. paratuberculosis and Escherichia coli in blood samples from patients with inflammatory bowel disease

Abstract

Mycobacterium avium subsp. paratuberculosis (MAP) and adherent-invasive Escherichia coli (AIEC) have been implicated as primary triggers in Crohn's disease (CD). In this study, we evaluated the prevalence of MAP and E. coli (EC) DNA in peripheral blood from 202 inflammatory bowel disease (IBD) patients at various disease periods and compared against 24 cirrhotic patients with ascites (CIR) (non-IBD controls) and 29 healthy controls (HC). MAP DNA was detected by IS900-specific nested PCR, EC DNA by malB-specific nested PCR and AIEC identity, in selected samples, by sequencing of fimH gene. CD patients with active disease showed the highest MAP DNA prevalence among IBD patients (68 %). Infliximab treatment resulted in decreased MAP detection. CIR patients had high individual and coinfection rates (75 % MAP, 88 % EC and 67 % MAP and EC), whilst HC controls had lower MAP prevalence (38 %) and EC was undetectable in this control group. EC DNA prevalence in IBD patients was highly associated with CD, and 80 % of EC from the selected samples of CD patients analyzed carried the fimH30 allele, with a mutation strongly associated with AIEC. Our results show that coinfection with MAP and AIEC is common and persistent in CD, although the high MAP and EC detection in CIR patients suggested that colonization is, at least, partially dependent on increased gut permeability. Nevertheless, facilitative mechanisms between a susceptible host and these two potential human pathogens may allow their implication in CD pathogenesis.

Protective effects induced by alcoholic Phlomis fruticosa and Phlomis herba‐venti extracts in isolated rat colon: Focus on antioxidant, anti‐inflammatory, and antimicrobial activities in vitro

“…In IBDs, there is a significant reduction in beneficial bacteria, including Firmicutes, Bacteroidetes, Actinobacteria, and Verrucomicrobia, with a concomitant increase in anaerobic bacteria of the family Enterobacteriaceae, playing a pathogenic role in the inflamed colon (Zuo & Ng, ). Despite there still being no identification of causative microorganism in IBDs, multiple studies suggested the involvement of pathogens such as Mycobacterium avium paratuberculosis , Clostridium difficile , and Helicobacter and altered commensals such as adherent‐invasive E. coli (Issa et al, ; Thomson et al, ; Nazareth et al, ; Palmela et al, ), whereas case report studies indicated the inflamed colon as a favorable environment for infection of different opportunistic pathogens, including P. aeruginosa and S. aureus (Bettenworth et al, ; Iguidbashian et al, ). A great deal of interest also emerged as regards the involvement of fungi in colon inflammation.…”

“…Finally, considering the potential of P. fruticosa as a source of antimicrobial agents (Ristic et al, 2000), we performed a parallel set of experiments in order to evaluate the effects of P. fruticosa and P. herba-venti on Gram-positive and Gram-negative bacterial strains and fungal species involved in IBDs (Guo et al, 2015;Iguidbashian et al, 2018;Trojanowska et al, 2010;Wang et al, 2018). Microbiome dysbiosis is an increase in the number of bacteria associated with colon mucosa, alongside a reduction in biodiversity (Kaur, Chen, Luther, & Kao, 2011 Helicobacter and altered commensals such as adherent-invasive E. coli (Issa et al, 2007;Thomson et al, 2011;Nazareth et al, 2015;Palmela et al, 2018), whereas case report studies indicated the inflamed colon as a favorable environment for infection of different opportunistic pathogens, including P. aeruginosa and S. aureus (Bettenworth et al, 2013;Iguidbashian et al, 2018). A great deal of interest also emerged as regards the involvement of fungi in colon…”

Intestinal microbiota, fecal microbiota transplantation, and inflammatory bowel disease

“…In one study, peripheral blood from patients with active Crohn's disease had MAP DNA prevalence of 68%, while those with Crohn's in any stage had E. coli 80% of the time. 52 In subjects whose sera tested positive for antigens against MAP, early uncontrolled trials suggested antibiotics against MAP could induce symptomatic improvement. [53][54][55] A large randomized controlled in trial from Australia found an early clinical benefit of antibiotics for MAP in addition to steroids compared to placebo (week 16, 66% v. 50%, p D 0.02).…”

Nanotechnology Based Therapeutics, Drug Delivery Mechanisms and Vaccination approaches for Countering Mycobacterium avium subspecies paratuberculosis (MAP) Associated Diseases

“…Greenstein et al (2007) showed that the accepted use of methotrexate and 6-mercaptopurine (6-MP) for therapy of IBD may be due to the inhibitory action of the drugs on MAP, instead of the generally prevailing idea that the primary mechanism of action is the drug's ability to decrease the production of pro-inflammatory cytokines. Nazareth et al (2015) investigated the growth of MAP in macrophages of CD patients under the influences of Infliximab treatment. A lower MAP CFU count was reported in macrophage cultures.…”