Cell: Dietary supplementation improves antibiotic-induced graft-versus-host disease after stem cell transplantation

According to a study published in the journal Cell, researchers at the University of Texas MD Anderson Cancer Center have identified a specific gut bacterium associated with advances in antibiotic therapy for allogeneic hematopoietic stem cell transplantation (allogeneic-hsct) for post-graft-host disease (GVHD) and found that nutritional supplementation can prevent antibiotic-induced GVHD
in preclinical models.

The researchers, led by Eiko Hayase, MD, and Robert Jenq, associate professor of genomic medicine, found that certain antibiotics alter the sugar composition of the gut, forcing a normally beneficial bacterium to deplete mucous proteins in the intestinal mucosa, which can lead to complications
such as GVHD.

"Knowing that this family of bacteria likes certain types of sugar, we hypothesized that adding a sugar would somehow disperse its attack on intestinal mucus and reduce those effects, and that's exactly what happened
," Hayase said.
"Through the nutritional changes in these models, we learned that we can alter the function of the microbiome to help avoid adverse events
.
"

Allogeneic hematopoietic stem cell transplantation is a specialized treatment for blood cancers such as leukemia and lymphoma
.
In this therapy, patients obtain healthy hematopoietic stem cells from a donor to replace autohematopoietic stem cells that may be malignant or damaged by other treatments
.
Broad-spectrum antibiotics often used during allogeneic hematopoietic stem cell transplantation have been linked to an increase in the development of GVHD, a disease in which donor immune cells attack recipient tissue, but the underlying cause of this is unknown
.

One option to prevent complications after antibiotic treatment in allogeneic hematopoietic stem cell transplant patients is fecal microbiota transplantation (FMT), a clinical process
that transfers healthy bacteria from screened donors to the recipient's gastrointestinal tract.
However, this approach has not been studied in randomized clinical trials, highlighting that the need for alternative treatment strategies that help prevent complications has not been met
.

In this study, a laboratory model of heterologous hematopoietic stem cell transplantation was treated with meropenem, a commonly used broad-spectrum antibiotic, resulting in thinning of the colonic mucus layer and intestinal GVHD
.
Interestingly, by removing beneficial bacteria and the expansion of specific species by antibiotics, their microbiomes undergo significant changes called Bacteroides polymorphomorphis (BT), in the lining of the intestine
.

Further investigation showed that after treatment with meropenem, the intestinal xylose content decreased
significantly.
Taking note of this, the researchers took oral xylose as a nutritional supplement and found that the intestinal mucus layer thickened again because BT was able to consume sugar preferentially rather than the mucus layer
.

While previous work has investigated the gut microbiota and its relationship to inflammation and GVHD, this study was able to specifically identify bacteria
that cause the mucous membranes to thinn.
In addition, there was no clear understanding of
how antibiotics alter the sugar composition in the gut and how it affects graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Jenq said: "We don't know if anyone has previously tried a sugar supplementation strategy to suppress gut inflammation caused by GVHD, so this provides a compelling, low-risk approach
to helping allogeneic hematopoietic stem cell transplant patients who need to treat infections with broad-spectrum antibiotics.
" "This is a novel approach and we are excited to translate it into human trials
.
" If supplementing with nutrients with specific sugars could do the same in humans, it could simplify our treatment strategies
for similar complications.
”

The authors emphasize that broad-spectrum antibiotics remain beneficial for allogeneic hsct patients and that further research is needed to understand how this approach can
be evaluated in clinical trials.
Currently, researchers are collecting human specimens of Bacteroides in patients undergoing bone marrow transplants to investigate whether they also prioritize the breakdown of mucin
.

Original:

Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease