Inflammatory bowel disease is a group of diseases that includes Crohn's disease (CD) and ulcerative colitis. CD is characterized as a chronic inflammatory disease of the gastrointestinal tract, ranging from the mouth to the anus. Although there are gross pathological and histological similarities between CD and Johne's disease of cattle, the cause of CD remains controversial. It is vital to understand fully the cause of this disease because it affects approximately 500,000 people in North America and Europe. It ranges from 27 to 48 cases per 100,000 people. There are many theories on the cause of CD ranging from possible association with environmental factors including microorganisms to imbalance in the intestinal normal flora of the patients. Regardless of the environmental trigger, there is strong evidence that a genetic disposition is a major key in acquiring CD. Many studies have proven the link between mutations in the ATG16L, NOD2/CARD15, IBD5, CTLA4, TNFSF15 and IL23R genes, and CD. The purpose of this review is to examine all genetic aspects and theories of CD, including up to date multiple population studies performed worldwide.

Aim:We evaluated the cellular response of polymorphonuclear leukocytes (PMN) and peripheral blood mononuclear cells (PBMC) against viable Mycobacterium avium subspecies paratuberculosis (MAP) for possible understanding of the role of MAP in the pathogenesis of Crohn's disease (CD) patients. Methods:In vitro phagocytosis and cell proliferation with the aid of Confocal Scanning Laser Microscopy (CSLM) were used to evaluate the immunogenicity of PMN and PBMC freshly obtained from 19 CD patients and 11 healthy controls against viable human-strain MAP, MAP antigens, and Phytohematoagglutonin (PHA), a suspect in CD pathogenesis.Results: MAP DNA was detected in tissue from 15/17(88%) CD subjects, 1/2(50%) UC patients and not in blood samples from 11 healthy controls. PMN phagocytosis was suppressed in 13/19 CD subjects (68%) compared to none in controls (p< 0.001); suppression ranged from 6 to 97%. PBMC phagocytosis was suppressed only in 5/19 (26%) of CD subjects; suppression ranged between 1 to 70%. PMN-specific plasma inhibitors were detected in 9/19 (47%) CD subjects compared to none in controls (P<0.05). Plasma inhibitors specific to PBMC phagocytosis were mildly present in CD patients (3/19 (16%) CD subjects) compared to none in controls. All 13 (68%) CD subjects that have suppressed PMN phagocytosis were also positive for MAP DNA detection in tissue. PBMC from 8/19 (42%) CD subjects showed dysfunctional proliferative response against PHA (ranged between 1 to 82%) compared to 1 healthy control, suggesting possible T-cell anergy. Out of PBMC from the 11 CD subject's that reacted normally to PHA, 7 reacted strongly to MAP PPD; suggesting pre-exposure to Mycobacteria.. Of 11 healthy control subjects, 10 (91%) reacted normally to PHA. Conclusions:It is possible that MAP may directly or indirectly exacerbate a pre-existing defect in phagocyte function -or it may cause the dysfunction employing similar molecular mechanisms used by other pathogenic mycobacteria like M. leprae and M. tuberculosis. Collectively the data supports a mycobacterial role in some CD patients.

The data clearly illustrates that clinical and in vitro-selected MAP mutants with rpoB mutations result in resistance to RIF and RFB, and that a single amino acid change in the beta subunit may have a significant impact on RIF resistance. Unconventional drug susceptibility testing such as our molecular approach will be beneficial for evaluation of antibiotic effectiveness. This molecular approach may also serve as a model for other drugs used for treatment of MAP infections.

The Janibacter species are Gram positive, coryneform bacteria that belong to the Actinobacteria phylum and have been linked to bacteremia in immunocompromised children. We present the first documented adult case of Janibacter hoylei bacteremia. The patient was a 52-year-old woman with a history of recurrent Clostridioides difficile infection, sinus tachycardia and high-risk AML who had been admitted one month prior to presentation for matched unrelated donor hematopoietic stem cell transplant with reduced intensity fludarabine-melphalan. Thirty days post-transplant, the infectious disease team was consulted because blood cultures grew Janibacter hoylei , from one of two blood cultures It took nine days to identify the species. She was treated with linezolid and imipenem. Janibacter are rarely implicated in human pathology, and therein, usually identified in the context of malignancy and relative immunosuppression. J. hoylei was only previously reported from the bloodstream of a previously healthy 8-week-old infant without underlying medical conditions. Antimicrobial susceptibility testing is challenging as only in vitro susceptibility testing of Janibacter terrae has been reported. Given these challenges, it is our hope to illustrate the clinical approach to diagnosis as well as subsequent recommendations for treatment in a particularly challenging case of bacteremia in an AML patient.