A single strain of bacteria may reduce the severity of graft-versus-host disease

Researchers at the MUSC Hollings Cancer Center have discovered that a single strain of bacteria may reduce the severity of graft-versus-host disease (GVHD), as reported online in February 2021. did. JCI Insight..

Bone marrow transplantation can be a life-saving procedure for patients with blood cancer. However, GVHD is a potentially fatal side effect of transplantation and treatment options are limited. This proof-of-concept study shows that better treatment options are imminent for GVHD patients.

Hanief Sofi, Ph.D., Deputy Director and Lead Author of Basic Sciences at the Hollings Cancer Center. Xue-Zhong Yu, MD, has found that protecting gastrointestinal health is a good goal to reduce severe GVHD.

Patient outcomes are much better if they understand how to keep their intestinal tissue healthy before and after a bone marrow transplant. We know that restoring the diversity of the gut microbiota is an effective solution, but it comes with many challenges. “

Hollings Cancer Center Basic Science Associate Director, Xue-Zhong Yu, MD

Patients with blood cancers such as leukemia should receive radiation therapy and chemotherapy before passing through a new cancer-free immune system Bone marrow transplantation.. The balance between the immune system and the gut flora, the community of microorganisms that inhabit the gut, is especially important for proper gut health.

Unfortunately, radiation therapy and chemotherapy fundamentally upset this balance, reducing microbial flora diversity by a factor of 100 or even a factor of 1,000. This leads to a condition called “leaky gut”.

Clinical studies have shown that patients who recover microbiota diversity faster have better results and lighter GVHD. Decreased microbial flora diversity is associated with more severe GVHD.

Other studies have shown that fecal microbiota transplantation (FMT) may be effective in reducing GVHD, but the challenge is how to get the right donors. Patients’ immunity after bone marrow transplantation is significantly weakened, and the use of FMT in humans increases the risk of exacerbation of infection.

The Yu Institute has used two different strains of mice to establish a GVHD model that closely resembles the biology that occurs in humans after bone marrow transplantation. Mice developed acute GVHD. FMT significantly reduced acute GVHD and reduced donors in this model T cells Organ proliferation, which triggers GVHD.

Next, researchers used gene sequencing to find out which strains differed most between the fecal material of GVHD mice that received FMT and the fecal material of mice that did not receive FMT.

The mouse that showed the best results and the lowest GVHD was B. The level of a bacterium called fragilis was the highest. Mice fed this single bacterial strain were B. It significantly reduced acute and chronic (long-term) GVHD compared to mice that did not receive fragilis. In fact, B. fragilis alone was as good as or better than FMT.

Administration of B. fragilis increased the overall diversity of gut flora, including increasing the amount of other beneficial bacterial strains. Surprisingly, this model reduced GVHD not only by live bacteria, but also by bacteria killed by short-term exposure to high fever.

The observation that B. fragilis is the predominantly effective bacterium in the FMT process was not entirely new. B. Fraziris also reduces autoimmunity in type 1 diabetes and colitis.

The current study by Yu and colleagues has two important findings. First, B. A molecule called polysaccharide A on the surface of fragilis appears to be important for the bacterium’s ability to lower GVHD. If the bacterium is modified to lack the polysaccharide A, then B. GVHD was not reduced compared to mice that did not receive fragilis.

Second, B. Administration of fragilis did not reduce the graft-versus-leukemia or cancer-killing effect of bone marrow transplants, even though it reduced the proliferation of donor T cells in the intestine. This is important because GVHD treatment options that reduce the graft-versus-leukemia effect are not clinically important.

“If this can be reflected in the clinic, it will be a safer, easier and more effective treatment option,” Yu said.

Further research in humans is needed to bring this potential treatment to the clinic. Hematopoietic stem cells, administered via bone marrow transplantation, are a classic immunotherapy for liquid tumors, but there is an urgent need for strategies to make transplantation safer and more beneficial. Researchers at the Hollings Cancer Center continue to look for the most effective treatments to improve patient outcomes and quality of life, he said.