Graft versus host disease (GvHD) is a complication in which a person’s donated cells (after a bone marrow transplant, for instance) begin attacking the person’s body. It can be relatively mild, with symptoms such as dry mouth, ulcers and skin rash or life-threatening involving multiple organs and requiring immune-suppression therapies such as prednisone.
Now, researchers at The University of Texas, MD Anderson Cancer Centre, believe they may be able to prevent GvHD by targeting mucus layers in the gut through dietary supplements.
Every 27 minutes, someone in Australia is diagnosed with a blood cancer such as leukaemia, lymphoma or myeloma, with about 16 people succumbing to the disease every day. Over the past ten years, the incidence of blood cancer has grown by 47%.
Treatments for blood cancers often involve radiation or chemotherapy to destroy the cancer-producing cells in the bone marrow. Following this, the patient will often receive a bone marrow transplant (allogeneic haematopoietic stem cell transplantation (allo-HSCT)) from a healthy donor, to replace their destroyed bone marrow and hunt down the last cancerous cells that might be hanging around post-treatment.
To reduce the risk of infection, the patient is frequently prescribed broad-spectrum antibiotics. While an extremely important part of the process, these antibiotics are also associated with an increased risk of developing GvHD – in which the new cells begin to attack the body of the patient – but it has been unclear exactly how this happens.
Now it seems researchers may have finally connected the dots, finding that the antibiotics remove beneficial bacteria, allowing a particular species of bacteria known as Bacteroides thetaiotaomicron (BT) to flourish and expand. This bacteria then consumes mucin (large molecules which make up much of the protein in mucus), thinning the layers of mucus in the colon, which leads to inflammation and GvHD.
In laboratory studies, when HSCT models were treated with a commonly used broad-spectrum antibiotic known as meropenem, not only did the colonic mucus layer become thinner, but researchers noticed a decrease in a type of sugar called xylose in the gut lining.
Xylose is a staple in the diet of BT.
“Knowing that this family of bacteria prefers certain types of sugars, we hypothesized that adding a sugar would, in a way, distract it from attacking the mucin in the gut and reduce these effects, which was the case,” said Dr Eiko Hayase, a postdoctoral fellow at The University of Texas MD Anderson Cancer Centre. By administering oral xylose, the mucus layer once again thickened.
This research marks a number of significant firsts in the field. Although the links between the gut microbiome, inflammation and GvHD has been previously studied, this work is the first to specifically pinpoint BT as the bacteria responsible for thinning the lining of the gut. The research also helps scientists understand more clearly how antibiotics can alter the sugar composition of the gut and how the latter contributes to GvHD after treatment by donor stem cell transplants.
Treatment through oral supplements is an exciting prospect for preventing complications after antibiotic treatments, avoiding the need for faecal microbiota transplantation (FMT) which is still relatively new and not fully studied.
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“We are not aware of anyone previously trying a sugar supplementation strategy for suppressing gut inflammation from graft versus host disease, so this offers a compelling, low-risk approach in helping patients who need to be on broad-spectrum antibiotics in order to treat infections,” said Dr Robert Jenq, an associate professor of Genomic Medicine at The Anderson Cancer Centre.
“This is a novel approach, and we are excited to work on translating this into human trials,” he said. “If nutritional supplementation with specific sugars works the same way in humans, it could simplify the way we approach therapeutic strategies for similar complications.”