Mycobacterium avium subspecies paratuberculosis—An environmental trigger of type 1 diabetes mellitus

Dow, Coad Thomas

doi:10.4236/jdm.2012.21014

Cited by 5 publications

(5 citation statements)

References 82 publications

(79 reference statements)

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“…Inherited susceptibility factors mainly include the HLA genotypes DR and DQ and insulin-dependent diabetes mellitus ( IDDM ) genes [1,7,8]. Though genetic predisposition plays a major role in pathogenesis of T1DM, concordance studies on monozygotic twins, the rising incidence over the last 50 years and migrant studies suggest that exogenous factors also pay an important role [9]. Viruses, such as enterovirus and coxsackie, and more recently bacteria such as Mycobacterium avium subspecies paratuberculosis (MAP) have been proposed as possible triggers for the autoimmune response [10,11].…”

Section: Resultsmentioning

confidence: 99%

“…MAP Hsp65 encodes 541 amino acids and Mtb Hsp65 encodes for 540 amino acids with both expressing an estimated 65KDa protein (http://www.uniprot.org/). We hypothesize that molecular mimicry between MAP Hsp65 and human GAD65 might trigger an autoimmune reaction targeting beta cells in pancreatic islets leading to insulin deficiency and T1DM [9,10,14]. …”

Section: Resultsmentioning

confidence: 99%

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Exploring the role of Mycobacterium avium subspecies paratuberculosis in the pathogenesis of type 1 diabetes mellitus: a pilot study

et al. 2013

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BackgroundAlthough the etiology of Type 1 Diabetes mellitus (T1DM) has not been determined, genetic polymorphism in key genes, including SLC11A1, and association with Mycobacterium avium subspecies paratuberculosis (MAP) have been reported. We hypothesize that molecular mimicry between MAP Heat shock protein 65 K (Hsp65) and human Glutamic Acid Decarboxylase 65 K (GAD65) may be the trigger leading to autoimmune destruction of beta cells in patients exposed to MAP.MethodPeptide sequences of MAP Hsp65 and human GAD65 were investigated for amino acid sequence homology and cross reactivity. A total of 18 blood samples from T1DM and controls were evaluated for the presence of MAP.ResultsPeptide BLAST analysis revealed a 44% overall identity between MAP Hsp65 and GAD65 with 75% positives in a 16 amino acid region. PyMOL 3D-structural analyses identified the same 16 amino acid region as a potential epitope for antibody binding. Preliminary data suggests a cross reactivity between MAP Hsp65, and a healthy rat pancreatic tissue homogenate against plasma from T1DM patients and rabbit polyclonal anti-MAP IgG. Long-term culture of human blood resulted MAP detection in 3/10 T1DM and 4/8 controls whereas MAP IgG was detected in 5/10 T1DM samples and 3/8 non-diabetic controls.ConclusionThe high degree of homology between GAD65 and MAP Hsp65 in an antigenic peptide region supports a possible mycobacterial role in triggering autoimmune destruction of pancreatic cells in T1DM. Reactivity of T1DM patient sera with MAP Hsp65 supports this finding. Culture of MAP from the blood of T1DM patients is intriguing. Overall, the preliminary data are mixed and do not exclude a possible role for MAP in T1DM pathogenesis. A larger study including well-characterized controls is needed to investigate the intriguing question of whether MAP is associated with T1DM or not?

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Exploring the role of Mycobacterium avium subspecies paratuberculosis in the pathogenesis of type 1 diabetes mellitus: a pilot study

et al. 2013

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“…It is worth noting that the role of MAP in human intestinal inflammatory diseases, such as Crohn's disease and ulcerative colitis, remains a subject of debate [5]. There is a possibility that animals afflicted with Johne's disease may serve as a source of MAP infection underlying Crohn's disease in humans [6][7][8]. Moreover, MAP has been implicated in an increasingly long list of granulomatous and autoimmune diseases [9] Hence, there is a pressing need for treatments targeting MAP in the context of Crohn's disease.…”

Section: Introductionmentioning

confidence: 99%

Randomized Clinical Trial Demonstrate the Safety Assessment of <em>Dietzia natronolimnaea</em> C79793-74 for Use as a Probiotic in Humans

García Menéndez,

Soto,

Barreto

et al. 2023

Preprint

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Dietzia natronolimnaea C79793-74 has emerged as a potential probiotic strain with implications for managing Crohn's disease. This study evaluates the safety profile of D. natronolimnaea C79793-74 as a probiotic sup-plement. Genotypic characterization involved a 16S rRNA gene and genomic sequencing and genome an-notation. The safety assessment included interrogation of the assembled genome for antibiotic resistance genes and virulence factors, utilizing the CARD and VFDB databases. Notably, the analysis revealed an ab-sence of antibiotic resistance or virulence factors in Dietzia natronolimnaea C79793-74. The safety and tol-erability of D. natronolimnaea C79793-74 were further investigated in an 8-week double-blind, place-bo-controlled clinical trial involving healthy adult participants. A daily dose of 5 x 109 CFU of the probiotic strain was administered. This clinical trial represents the first assessment of the safety of D. natronolimnaea C79793-74 in human subjects. Results demonstrated that participants in both the Dietzia and Placebo groups maintained clinical and hematologic markers within the normal range throughout the study. More-over, the probiotic strain was well-tolerated, with nearly all participants experiencing no severe or medium adverse events. Collectively, the comprehensive data obtained in this study support the inference that Dietzia natronolimnaea C79793-74 is safe and well-tolerated as a nutritional supplement for human con-sumption

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“…Because of MAP's ability to evade immunological control and to prevail in the environment, it may spread within and among free‐wandering and captive animal populations (Manning, ; Pickup et al ., ). Because MAP has been observed to contaminate commercialized and retail milk, its consumption poses a great threat of infection among children (Dow, ). Moreover, different reports suggest the possibility that MAP infection could be the cause of the development of inflammatory diseases, such as Crohn's disease in humans, combined with the concern that MAP is disseminating in the food chain and environment (Greenstein, ).…”

Section: Introductionmentioning

confidence: 99%

Proteome-wide B and T cell epitope repertoires in outer membrane proteins ofMycobacterium aviumsubsp.paratuberculosishave vaccine and diagnostic relevance: a holistic approach

2015

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Mycobacterium avium subsp. paratuberculosis (MAP) is an etiological agent of chronic inflammation of the intestine among ruminants and humans. Currently, there are no effective vaccines and sensitive diagnostic tests available for its control and detection. For this, it is of paramount importance to identify the MAP antigens, which may be immunologically recognized by the host immune system. To address this challenge, we performed identification of the immunogenic epitopes in the MAP outer membrane proteins (OMPs). We have previously identified 57 MAP proteins as OMPs [Rana A, Rub A, Akhter Y. 2014. Molecular BioSystems, 10:2329-2337] and have evaluated them for the epitope selection and analysis employing a computational approach. Thirty-five MAP OMPs are reported with nine-mer peptides showing high binding affinity to major histocompatibility complex (MHC) class I molecules and 28 MAP OMPs with 15-mer peptides of high binding affinity for MHC class II molecules. The presence of MHC binding epitopes indicates the potential cell-mediated immune response inducing capacity of these MAP OMPs in infected host. To further investigate the humoral response inducing properties of OMPs of MAP, we report potential B cell epitopes based on the sequences of peptide antigens and their molecular structures. We also report 10 proteins having epitopes for both B and T cells representing potential candidates which may invoke both humoral and cellular immune responses in the host. These findings will greatly accelerate and expedite the formulation of effective and cost-efficient vaccines and diagnostic tests against MAP infection.

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Mycobacterium avium subspecies paratuberculosis—An environmental trigger of type 1 diabetes mellitus

Cited by 5 publications

References 82 publications

Exploring the role of Mycobacterium avium subspecies paratuberculosis in the pathogenesis of type 1 diabetes mellitus: a pilot study

Exploring the role of Mycobacterium avium subspecies paratuberculosis in the pathogenesis of type 1 diabetes mellitus: a pilot study

Randomized Clinical Trial Demonstrate the Safety Assessment of <em>Dietzia natronolimnaea</em> C79793-74 for Use as a Probiotic in Humans

Proteome-wide B and T cell epitope repertoires in outer membrane proteins ofMycobacterium aviumsubsp.paratuberculosishave vaccine and diagnostic relevance: a holistic approach

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