Presence of Infection by Mycobacterium avium subsp. paratuberculosis in the Blood of Patients with Crohn’s Disease and Control Subjects Shown by Multiple Laboratory Culture and Antibody Methods

Abstract

Mycobacterium avium subspecies paratuberculosis (MAP) has long been suspected to be involved in the etiology of Crohn’s disease (CD). An obligate intracellular pathogen, MAP persists and influences host macrophages. The primary goals of this study were to test new rapid culture methods for MAP in human subjects and to assess the degree of viable culturable MAP bacteremia in CD patients compared to controls. A secondary goal was to compare the efficacy of three culture methods plus a phage assay and four antibody assays performed in separate laboratories, to detect MAP from the parallel samples. Culture and serological MAP testing was performed blind on whole blood samples obtained from 201 subjects including 61 CD patients (two of the patients with CD had concurrent ulcerative colitis (UC)) and 140 non-CD controls (14 patients in this group had UC only). Viable MAP bacteremia was detected in a significant number of study subjects across all groups. This included Pozzato culture (124/201 or 62% of all subjects, 35/61 or 57% of CD patients), Phage assay (113/201 or 56% of all subjects, 28/61 or 46% of CD patients), TiKa culture (64/201 or 32% of all subjects, 22/61 or 36% of CD patients) and MGIT culture (36/201 or 18% of all subjects, 15/61 or 25% of CD patients). A link between MAP detection and CD was observed with MGIT culture and one of the antibody methods (Hsp65) confirming previous studies. Other detection methods showed no association between any of the groups tested. Nine subjects with a positive Phage assay (4/9) or MAP culture (5/9) were again positive with the Phage assay one year later. This study highlights viable MAP bacteremia is widespread in the study population including CD patients, those with other autoimmune conditions and asymptomatic healthy subjects.

Mycobacterium avium subsp. paratuberculosis and Hashimoto’s thyroiditis: Is MAP the trigger?

“…Ns, Not significance. 2010; Kuenstner et al, 2015;Kuenstner et al, 2020). Although its possible role in the onset of various autoimmune diseases has been discussed, globally limited information on this association with HT disease has been presented.…”

“…MAP is the causative agent of JD in ruminants, whose role has been investigated as one of the initiators of various autoimmune diseases in susceptible human hosts ( Ekundayo and Okoh, 2020 ). Some previous studies described the association of MAP with conditions such as CD, type 1 diabetes, RA, MS, lupus erythematosus, and Blue syndrome ( Naser et al., 2004 ; Masala et al., 2011 ; Naser et al., 2013 ; Kuenstner et al., 2015 ; Niegowska et al., 2015 ; Sechi and Dow, 2015 ; Dow, 2016 ; Kuenstner et al., 2017 ; Zamani et al., 2017 ; Bo et al., 2019 ; Ekundayo and Okoh, 2020 ; Kuenstner et al., 2020 ). The culture and PCR-based detection of MAP from the blood of these autoimmune patients and the supportive role of anti-MAP therapy provide helpful evidence for the zoonotic feature of MAP as Kuenstner et al explained in their study ( Naser et al., 2010 ; Kuenstner et al., 2015 ; Kuenstner et al., 2020 ).…”

“…Some previous studies described the association of MAP with conditions such as CD, type 1 diabetes, RA, MS, lupus erythematosus, and Blue syndrome ( Naser et al., 2004 ; Masala et al., 2011 ; Naser et al., 2013 ; Kuenstner et al., 2015 ; Niegowska et al., 2015 ; Sechi and Dow, 2015 ; Dow, 2016 ; Kuenstner et al., 2017 ; Zamani et al., 2017 ; Bo et al., 2019 ; Ekundayo and Okoh, 2020 ; Kuenstner et al., 2020 ). The culture and PCR-based detection of MAP from the blood of these autoimmune patients and the supportive role of anti-MAP therapy provide helpful evidence for the zoonotic feature of MAP as Kuenstner et al explained in their study ( Naser et al., 2010 ; Kuenstner et al., 2015 ; Kuenstner et al., 2020 ). Although its possible role in the onset of various autoimmune diseases has been discussed, globally limited information on this association with HT disease has been presented.…”

Mycobacterium avium ssp. paratuberculosis in the Food Supply: A Public Health Issue

“…Subsequently, a study of CD patients and non-CD control subjects was conducted and demonstrated the presence of viable MAP in the blood of CD patients with a significantly increased odds ratio, but also demonstrated the viable MAP organism in some of the non-CD controls (14). The study employed four different MAP culture methods and four MAP antibody tests, included 201 subjects (61 CD patients and 140 non-CD controls) and was conducted in five laboratories (14).…”

Vaccination of cattle with a virus-vectored vaccine against a major membrane protein ofMycobacterium a. subsp.paratuberculosiselicits CD8 cytotoxic T cells that kill intracellular bacteria

“…subsp. paratuberculosis ( Map ) is one of multiple lineages of mycobacteria that have evolved over the millennia, that have acquired the ability to infect and cause disease in multiple species, including humans (1) (reviewed in Bachmann et al (2)). It is one of the major mycobacterial pathogens impacting the livestock industry and human health.…”