Gut bacteria can be the key to safer stem cell transplantations, study finds

A new study shows that adverse effects in stem cell transplantation are less common when certain microbes are present in the patient’s gut, which opens possibilities to create better conditions synthetically and ensure safer outcomes.

Stem cell transplantations can help cure many haematological conditions – such as leukaemia, myeloma, and lymphoma – in which the bone marrow is damaged and can no longer produce healthy blood cells.

However, there are still considerable risks associated with them, like graft-versus-host disease (GvHD) and transplant-related mortality (TRM). 

GvHD can happen after a stem cell transplantation, when in some cases the donor stem cells, the graft, attack healthy cells in the patient, typically in the skin, the gut or the liver.

It affects up to 30% of patients and can be severe. In some cases, patients respond to steroids, but in many others, they are refractory, reducing the survival outcomes and setting the mortality rate as high as 50%.

Some previous studies have shown that the probability of developing GvHD is related to the recipient’s microbiome, the community of bacteria, fungi, and viruses that reside in patients’ guts.

“There’s been quite a bit of interest in the microbiome because a few landmark studies have shown a correlation between the microbiome and outcomes in stem cell transplantation”, Erik Thiele Orberg from TUM (Technical University of Munich) told Euractiv. 

“We didn’t understand the mechanisms that underlie and confer this effect,” he explained. 

Along with a team of researchers from the TUM and the Universitätsklinikum Regensburg (UKR), Thiele Orberg has tried to fill some of the knowledge gaps in a study.

According to Thiele Orberg, these findings will help identify individuals at risk of developing these adverse reactions during stem cell transplantation. 

In the study, researchers analysed stool samples from a cohort of patients undergoing stem cell transplantation and confirmed that patients with a higher bacterial diversity had better outcomes, including reduced mortality, lower transplant-related mortality, and less relapse. 

They aimed to identify metabolites – substances produced by gut bacteria during metabolism – that could influence immune responses in patients undergoing stem cell transplantation and identify the microbiome contributing to their production. 

Thiele Orberg explained that they were able to find which consortia of protective bacteria,  bacteriophages, and metabolites are highly associated with beneficial outcomes and are useful in identifying their lack in patients, creating a risk of developing GVHD and transplant-related mortality.

New possibilities for future procedures

The researcher’s next step is to figure out how to create this beneficial landscape in the recipient’s guts.

The study’s findings suggest that it may be possible to use synthetic bacteria consortia to produce the protective metabolites identified in the study to improve the transplantations’ outcomes.

All these new data, Thiele Orberg added, could also be used to improve other already established procedures, like faecal microbiota transplantation (FMT), the transplant of faecal matter from a donor into the intestinal tract of a recipient to change their microbiome. 

“It is currently being researched in several advanced clinical trials, but we still have the same burning questions in that field, namely what makes a donor a good donor [for FMT] and why do some patients respond and others don’t,” he explained.

One of the current hypotheses, backed by early pilot experiments, is that the patients who respond to FMT are those able to kick-start their metabolite production after the procedure. 

With these new findings, Thiele Orberg explained that a future standard procedure to ensure better outcomes could go as follows:

A patient undergoing stem cell transplantation would be continuously screened using the immune modulatory metabolite risk index. Once a patient is considered to be at risk, they could be prophylactically treated using metabolite cocktails or precision FMT products from donors that have been previously validated for robust metabolite production. 

All these discoveries open new investigative paths not only for stem cell transplantation but also for new microbiome studies in other cell therapies.

[Edited by Zoran Radosavljevic]

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