Cord colitis syndrome found to have a novel infectious etiology

Image: PD 

1. The genome of a novel bacterium Bradyrhizobium enterica was discovered via gene sequencing in patients with cord colitis. 

2. The association of this bacterium with cord colitis suggests it may be an opportunistic pathogen of humans. 

Study Rundown:  Hematopoietic stem-cell transplantation (HSCT) is a modern procedure used to treat various hematologic and oncologic diseases by repopulating a patient’s immune system by using the cells of a donor.  HSCT requires complete suppression and even destruction of the host’s immune system and therefore may cause many adverse events including graft versus host disease (GVHD) and unusual opportunistic infections.  Colitis is a common adverse effect of HSCT and is thought to stem from various etiologies including bacterial, viral and parasitic infections, as well as GVHD.  Cord colitis is a syndrome specific to patients who have undergone umbilical-cord HSCT and is histopathologically distinct from other forms of colitis.  Additionally, conventional infectious work ups fail to reveal a known infectious pathogen in this disease. 

The authors of this study found that treating cord colitis patients with antibiotics resulted in the resolution of symptoms.  They then performed a sequencing study that identified what appears to be an opportunistic pathogen as the etiology of the disease.  The fact that B. enterica was found in the cord colitis patients and in no controls would suggest it is associated with the syndrome.  However, the overall number of patients with cord colitis who were tested was very small and from a single center.  Additionally, while not a requirement to prove disease causation, the organism was never cultured by the authors.  Demonstrating a change in DNA copy numbers after antibiotic treatment might help fulfill the modern adaptation of Koch’s postulates.  Taken together the results display an impressive demonstration of modern gene sequencing to identify a novel bacterial genome that might be an opportunistic human pathogen.

Click to read the study, published today in NEJM

Background Reading: A reconsideration of Koch’s Postulates

In-Depth [genome sequencing case control study]: The authors of this study selected patients from Brigham and Women’s Hospital who had developed cord colitis after receiving an umbilical cord hematopoietic stem-cell transplant.  Using archived, paraffin-embedded colon biopsy specimens, they performed mass DNA sequencing and subtracted known human and microbial sequences.  The remaining sequences were assembled into a draft genome that was homologous to known bacteria of the bradyrhizobium genus and subsequently dubbed Bradyrhizobium enterica.  They then used polymerase chain reaction (PCR) to identify this genome in 3 additional patients with cord colitis, but found it was not present in patients selected as controls.

By Akira Shishido, MD and Mitalee Patil

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