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. 2023 Jun 7;11(6):1520.
doi: 10.3390/microorganisms11061520.

Viable Mycobacterium avium subsp. paratuberculosis Colonizes Peripheral Blood of Inflammatory Bowel Disease Patients

Maria Manuela Estevinho  1   2 , José Cabeda  3   4   5 , Mafalda Santiago  2 , Elisabete Machado  3   6   7 , Ricardo Silva  3   4 , Mary Duro  3   4   8 , Inês Pita  9 , Rui Morais  10 , Guilherme Macedo  10 , Tim J Bull  11 , Fernando Magro  2   10 , Amélia Sarmento  3   7   12
Affiliations

Viable Mycobacterium avium subsp. paratuberculosis Colonizes Peripheral Blood of Inflammatory Bowel Disease Patients

Maria Manuela Estevinho et al. Microorganisms. .

Abstract

Pathobionts, particularly Mycobacterium avium subsp. paratuberculosis (MAP) and Escherichia coli isolates with adherence/invasive ability (AIEC) have been associated with inflammatory bowel disease (IBD), particularly Crohn's disease (CD). This study aimed to evaluate the frequency of viable MAP and AIEC in a cohort of IBD patients. As such, MAP and E. coli cultures were established from faecal and blood samples (with a total n = 62 for each) of patients with CD (n = 18), ulcerative colitis (UC, n = 15), or liver cirrhosis (n = 7), as well as from healthy controls (HC, n = 22). Presumptive positive cultures were tested by polymerase chain reaction (PCR), for a positive confirmation of MAP or E. coli identity. E. coli-confirmed isolates were then tested for AIEC identity using adherence and invasion assays in the epithelial cell line of Caco-2 and survival and replication assays in the macrophage cell line of J774. MAP sub-culture and genome sequencing were also performed. MAP was more frequently cultured from the blood and faecal samples of patients with CD and cirrhosis. E. coli presumptive colonies were isolated from the faecal samples of most individuals, in contrast to what was registered for the blood samples. Additionally, from the confirmed E. coli isolates, only three had an AIEC-like phenotype (i.e., one CD patient and two UC patients). This study confirmed the association between MAP and CD; however, it did not find a strong association between the presence of AIEC and CD. It may be hypothesized that the presence of viable MAP in the bloodstream of CD patients contributes to disease reactivation.

Keywords: Crohn’s disease; Escherichia coli; Mycobacterium avium; pathobionts; ulcerative colitis.

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Conflict of interest statement

Fernando Magro served as speaker and received honoraria from: Abbvie, Biogen, Falk, Ferring, Hospira, Janssen, Laboratórios Vitoria, Lilly, Pfizer, Merck Sharp & Dohme, Sandoz, Takeda, UCB and Vifor. All other authors declare no competing interests.

Figures

Figure 1
Figure 1
Flow chart of sample collection and processing; text boxes in grey refer to procedures not performed, due to a lack of positive colonies. Acid-fast bacilli (AFB), Mycobacterium avium subsp. paratuberculosis (MAP); Escherichia coli (EC).
Figure 2
Figure 2
Processing of real-time PCR (qPCR)-positive samples.
See this image and copyright information in PMC

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