Mycobacterial infection influences bone biomarker levels in patients with Crohn’s disease

2018 ◽  
Vol 96 (7) ◽  
pp. 662-667 ◽  
Author(s):  
Amna Naser ◽  
Ahmad Qasem ◽  
Saleh A. Naser

Patients with Crohn’s disease (CD) have higher risk for osteoporosis following decreased level of osteocalcin. We hypothesize that active inflammation following Mycobacterium avium subsp. paratuberculosis (MAP) infection results in elevation of undercarboxylated osteocalcin (ucOC) and downregulation of active osteocalcin in CD patients and cow-disease model (Johne’s disease). In this study, we measured ucOC, active osteocalcin, and calcium levels in sera from 42 cattle (21 infected with MAP and 21 healthy cattle), 18 CD patients, and 20 controls. The level of ucOC in MAP+ bovine samples was higher than that in MAP− controls (318 ± 57.2 nmol/mL vs. 289 ± 95.8 nmol/mL, P > 0.05). Consequently, mean calcium level in bovine MAP+ was significantly higher than that in bovine-MAP− samples (9.98 ± 0.998 mg/dL vs. 7.65 ± 2.12 mg/dL, P < 0.05). Also, the level of ucOC was higher in CD-MAP+ than in CD-MAP− (561 ± 23.7 nmol/mL vs. 285 ± 19.6 nmol/mL, P < 0.05). Interestingly, the mean osteocalcin level in MAP+ bovine was lower than that in MAP− bovine (797 ± 162 pg/mL vs. 1190 ± 43 pg/mL) and it was lower in CD-MAP+ than in CD-MAP− infection (1.89 ± 0.184 ng/mL vs. 2.19 ± 0.763 ng/mL) (P < 0.05). The correlation between MAP infection and elevation of sera ucOC, reduction of active osteocalcin and increased calcium supports MAP infection role in CD and complications with osteoporosis.

2004 ◽  
Vol 17 (10) ◽  
pp. 1289-1294 ◽  
Author(s):  
Fabien K Baksh ◽  
Sydney D Finkelstein ◽  
Shashi M Ariyanayagam-Baksh ◽  
Patricia A Swalsky ◽  
Edwin C Klein ◽  
...  

2005 ◽  
Vol 71 (4) ◽  
pp. 2130-2139 ◽  
Author(s):  
R. W. Pickup ◽  
G. Rhodes ◽  
S. Arnott ◽  
K. Sidi-Boumedine ◽  
T. J. Bull ◽  
...  

ABSTRACT In South Wales, United Kingdom, a populated coastal region lies beneath hill pastures grazed by livestock in which Mycobacterium avium subsp. paratuberculosis is endemic. The Taff is a spate river running off the hills and through the principal city of Cardiff. We sampled Taff water above Cardiff twice weekly from November 2001 to November 2002. M. avium subsp. paratuberculosis was detected by IS900 PCR and culture. Thirty-one of 96 daily samples (32.3%) were IS900 PCR positive, and 12 grew M. avium subsp. paratuberculosis bovine strains. Amplicon sequences from colonies were identical to the sequence with GenBank accession no. X16293 , whereas 16 of 19 sequences from river water DNA extracts had a single-nucleotide polymorphism at position 214. This is consistent with a different strain of M. avium subsp. paratuberculosis in the river, which is unculturable by the methods we used. Parallel studies showed that M. avium subsp. paratuberculosis remained culturable in lake water microcosms for 632 days and persisted to 841 days. Of four reservoirs controlling the catchment area of the Taff, M. avium subsp. paratuberculosis was present in surface sediments from three and in sediment cores from two, consistent with deposition over at least 50 years. Previous epidemiological research in Cardiff demonstrated a highly significant increase of Crohn's disease in 11 districts. These bordered the river except for a gap on the windward side. A topographical relief map shows that this gap is directly opposite a valley open to the prevailing southwesterly winds. This would influence the distribution of aerosols carrying M. avium subsp. paratuberculosis from the river.


2009 ◽  
Vol 46 (4) ◽  
pp. 717-728 ◽  
Author(s):  
S. Khare ◽  
J. S. Nunes ◽  
J. F. Figueiredo ◽  
S. D. Lawhon ◽  
C. A. Rossetti ◽  
...  

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of chronic enteritis in ruminants (Johne's disease) and a possible etiopathologic agent in human Crohn's disease. The host-pathogen interaction in this chronic disease has largely depended on the randomly collected static lesions studied in subclinically or clinically infected animals. We have established and utilized the neonatal calf ligated ileal loop model to study the early temporal host changes during MAP infection. After inoculation of ligated ileal loop with MAP, samples were analyzed for bacterial invasion, histologic and ultrastructural morphologic changes, and gene expression at several times (0.5–12 hours) postinfection. Our results indicate that MAP invades the intestinal mucosa as early as 0.5 hour postinoculation. Distribution and migration of neutrophils, monocytes/macrophages, and goblet cells were confirmed by histopathology, scanning and transmission electron microscopy. Coincident with the morphologic analysis, we measured by real-time polymerase chain reaction gene expression of various cytokines/chemokines that are involved in the recruitment of mononuclear and polymorphonuclear leukocytes to the site of infection. We also detected expression of several other genes, including intestinal-trefoil factor, profilin, lactoferrin, and enteric β-defensin, which may play significant roles in the early MAP infection. Thus, the calf ligated intestinal loop model may be used as a human disease model to understand the role of MAP in the pathogenesis of Crohn's disease.


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