A number of theories regarding the aetiology of Crohn’s disease have been proposed. Diet, infections, other unidentified environmental factors and immune disregulation, all working under the influence of a genetic predisposition, have been viewed with suspicion. Many now believe that Crohn’s disease is a syndrome caused by several aetiologies. The two leading theories are the infectious and autoimmune theories. The leading infectious candidate is Mycobacterium avium subspecies paratuberculosis (Mycobacterium paratuberculosis), the causative agent of Johne’s disease, an inflammatory bowel disease in a variety of mammals including cattle, sheep, deer, bison, monkeys and chimpanzees. The evidence to support M. paratuberculosis infection as a cause of Crohn’s disease is mounting rapidly. Technical advances have allowed the identification and/or isolation of M. paratuberculosis from a significantly higher proportion of Crohn’s disease tissues than from controls. These methodologies include: (i) improved culture techniques; (ii) development of M. paratuberculosis‐specific polymerase chain reaction assays; (iii) development of a novel in situ hybridization method; (iv) efficacy of macrolide and anti‐mycobacterial drug therapies; and (v) discovery of Crohn’s disease‐specific seroreactivity against two specific M. paratuberculosis recombinant antigens. The causal role for M. paratuberculosis in Crohn’s disease and correlation of infection with specific stratification(s) of the disorder need to be investigated. The data implicating Crohn’s as an autoimmune disorder may be viewed in a manner that supports the mycobacterial theory. The mycobacterial theory and the autoimmune theory are complementary; the first deals with the aetiology of the disorder, the second deals with its pathogenesis. Combined therapies directed against a mycobacterial aetiology and inflammation may be the optimal treatment of the disease.

Since Crohn's disease is a transmural disease, we hypothesized that examination of deep submucosal tissues directly involved in the inflammatory disease process may provide unique insights into bacterial populations transgressing intestinal barriers and bacterial populations more representative of the causes and agents of the disease. We performed deep 16s microbiota sequencing on isolated ilea mucosal and submucosal tissues on 20 patients with Crohn's disease and 15 non-inflammatory bowel disease controls with a depth of coverage averaging 81,500 sequences in each of the 70 DNA samples yielding an overall resolution down to 0.0001% of the bacterial population. Of the 4,802,328 total sequences generated, 98.9% or 4,749,183 sequences aligned with the Kingdom Bacteria that clustered into 8545 unique sequences with <3% divergence or operational taxonomic units enabling the identification of 401 genera and 698 tentative bacterial species. There were significant differences in all taxonomic levels between the submucosal microbiota in Crohn's disease compared to controls, including organisms of the Order Desulfovibrionales that were present within the submucosal tissues of most Crohn's disease patients but absent in the control group. A variety of organisms of the Phylum Firmicutes were increased in the subjacent submucosa as compared to the parallel mucosal tissue including Ruminococcus spp., Oscillospira spp., Pseudobutyrivibrio spp., and Tumebacillus spp. In addition, Propionibacterium spp. and Cloacibacterium spp. were increased as well as large increases in Proteobacteria including Parasutterella spp. and Methylobacterium spp. This is the first study to examine the microbial populations within submucosal tissues of patients with Crohn's disease and to compare microbial communities found deep within the submucosal tissues with those present on mucosal surfaces. Our data demonstrate the existence of a distinct submucosal microbiome and ecosystem that is not well reflected in the mucosa and/or downstream fecal material.

It has been more than 25 years since Mycobacterium paratuberculosis was first proposed as an etiologic agent in Crohn's disease based on the isolation of this organism from several patients. Since that time, a great deal of information has been accumulated that clearly establishes an association between M. paratuberculosis and Crohn's disease. However, data are conflicting and difficult to interpret and the field has become divided into committed advocates and confirmed skeptics. This review is an attempt to provide a thorough and objective summary of current knowledge from both basic and clinical research from the views and interpretations of both the antagonists and proponents. The reader is left to draw his or her own conclusions related to the validity of the issues and claims made by the opposing views and data interpretations. Whether M. paratuberculosis is a causative agent in some cases or simply represents an incidental association remains a controversial topic, but current evidence suggests that the notion should not be so readily dismissed. Remaining questions that need to be addressed in defining the role of M. paratuberculosis in Crohn's disease and future implications are discussed.

Because MAP was present in 86% of resected tissue compared to 20% of biopsy specimens from CD patients, we speculate that MAP resides in the submucosal layer closer to the active part of the ulcer rather than on the surface of the mucosal cells. Thus, surgically resected tissue cultured in MGIT medium is a favorable protocol for rapid cultivation of MAP and for investigating its role in CD pathogenesis. The data support the mycobacterial role in CD pathogenesis.

We assessed the safety and efficacy of Fluosol-DA as a red-cell substitute in acute anemia. Twenty-three surgical patients with blood loss and religious objections to receiving blood transfusions were evaluated. Fifteen moderately anemic patients with a mean hemoglobin level (+/- SE) of 7.2 +/- 0.5 g per deciliter had no evidence of a physiologic need for increased arterial oxygen content and did not receive Fluosol-DA. Eight severely anemic patients with a mean hemoglobin level of 3.0 +/- 0.4 g per deciliter met the criteria of need and received the drug until the physiologic need disappeared or a maximal dose of 40 ml per kilogram of body weight was reached. We observed no adverse reactions to Fluosol-DA. The average peak increment in arterial oxygen content with the drug was only 0.7 +/- 0.1 ml per deciliter. There were no appreciable beneficial effects of Fluosol-DA, perhaps because of the small increase in arterial oxygen content, the brief half-life of the drug (24.3 +/- 4.3 hours), and the limited total dose. Six of the eight patients receiving Fluosol-DA died. One of the survivors received red-cell transfusions against his wishes, under a court order, after his total Fluosol-DA dose. Fourteen of the 15 moderately anemic patients survived. The data in this select group of patients refusing blood products suggest that, after blood loss, Fluosol-DA is unnecessary in moderate anemia and ineffective in severe anemia.

On March 24 and 25, 2017 researchers and clinicians from around the world met at Temple University in Philadelphia to discuss the current knowledge of Mycobacterium avium ssp. paratuberculosis (MAP) and its relationship to human disease. The conference was held because of shared concern that MAP is a zoonotic bacterium that poses a threat not only to animal health but also human health. In order to further study this problem, the conferees discussed ways to improve MAP diagnostic tests and discussed potential future anti-MAP clinical trials. The conference proceedings may be viewed on the website. A summary of the salient work in this field is followed by recommendations from a majority of the conferees.

No abstract

Pseudomonas aeruginosa colonization and infection was studied over a 6-mo period in a 36-bed mixed general medical-oncology unit. We used selective media for serial surveillance cultures on 283 patients, the environment, and personnel. Twelve percent of patients were colonized on admission and 10% acquired P. aeruginosa. Using serotyping and multilocus enzyme electrophoresis, we identified 63 genetically distinctive strains; four prevalent strains accounted for 21% of isolates. Only 5 of 33 nosocomial acquisitions were due to horizontal transmission. Nine acquisitions were linked to environmental sources (e.g., sink surfaces), which often harbored antibiotic-resistant strains but posed a risk only to oncology patients. Although significant Pseudomonas infections occurred in only 11% of colonized patients, 63% of colonized severely neutropenic patients--predominantly those who had acquired the prevalent, often environmentally linked strains--developed infections. Thus, P. aeruginosa was a significant pathogen in oncology patients; typing by multilocus enzyme electrophoresis allowed the detection of important environmental sources.