Microbiome Composition in Intestinal Transplantation
Research type
Research Study
Full title
BOWEL MICROBIOME, CLINICAL INFECTION AND REJECTION IN SMALL BOWEL TRANSPLANTATION: A PILOT STUDY.
IRAS ID
213655
Contact name
Effrossyni Gkrania-Klotsas
Contact email
Sponsor organisation
Cambridge University Hospitals NHS Foundation Trust
Duration of Study in the UK
4 years, 9 months, 31 days
Research summary
"Research Summary"
A small bowel transplant is a life-saving procedure for patients who lack sufficient bowel length to absorb nutrients. Because the transplanted bowel comes from another person, the recipient’s immune system recognises that the bowel is different and may try to attack and injure it ("rejection"). Recipients have a high risk of losing the organ or dying from rejection or infection.Up to half of the SBT recipients develop an infection within the first month after transplant and are proactively intensively treated with antibiotics, resulting to colonisation by multidrug - resistant (MDR) bacteria.
Most small bowel rejections happen the first month after the surgery. To allow access to the transplanted organ a surgical window to the bowel is created during the initial transplant procedure and maintained open for one year. The existence of this stoma offers the unparalleled opportunity to follow the changes of composition of bacteria in the bowel that are otherwise inaccessible for direct sampling.
A previous study has shown that the microbiome changes of SBT recipients are temporally associated with risk of infection. Additionally, in other kinds of transplantation, studies have shown that changes in the bowel bacteria ("microbiome") are associated with rejection as well as bloodstream infections. Studies of type of infection that SBT recipients get suggest that the infections are a result of translocation of bacteria from the bowel lumen to the bloodstream, thought to be happening more commonly during times of rejection.
We expect that MDR bacteria will be present in the bowel before bloodstream infections happen. We also expect that the microbiome composition will be different in episodes of rejection and episodes of sepsis.
The ultimate goal is to understand which families of bacteria are associated with protection from infection, colonisation from MDR organisms and rejection and translate this knowledge to appropriate antibiotic and bacterial therapies.
"Summary of results"
Two-thirds of small-bowel transplantation (SBT) recipients develop bacteremia, with the majority of infections occurring within 3 months post-transplant. Sepsis-related mortality occurs in 31% of patients and is commonly caused by bacteria of gut origin, which are thought to translocate across the implanted organ. Serial post-transplant surveillance endoscopies provide an opportunity to study whether the composition of the ileal and colonic microbiota can predict the emergence as well as the pathogen of subsequent clinical infections in the SBT patient population. Five participants serially underwent aspiration of ileal and colonic bowel effluents at transplantation and during follow-up endoscopy either until death or for up to 3 months post-SBT. We performed whole-metagenome sequencing (WMS) of 40 bowel effluent samples and compared the results with clinical infection episodes. Microbiome composition was concordant between participants and timepoint-matched ileal and colonic samples. Four out of five (4/5) participants had clinically significant infections thought to be of gut origin. Bacterial translocation from the gut was observed in 3/5 patients with bacterial infectious etiologies. In all three cases, the pathogens had demonstrably colonized the gut between 1–10 days prior to invasive clinical infection. Recipients with better outcomes received donor grafts with higher alpha diversity. There was an increase in the number of antimicrobial resistance genes associated with longer hospital stay for all participants. This metagenomic study provides preliminary evidence to support the pathogen translocation hypothesis of gut-origin sepsis in the SBT cohort. Ileal and colonic microbiome compositions were concordant; therefore, fecal metagenomic analysis could be a useful surveillance tool for impeding infection with specific gut-residing pathogens.REC name
Wales REC 2
REC reference
18/WA/0105
Date of REC Opinion
17 Jul 2018
REC opinion
Further Information Favourable Opinion