Bacteria may protect against GVHD-related mortality
GRAPEVINE, TEXAS—Intestinal bacteria can offer protection from death related to graft-vs-host disease (GVHD), according to research presented at the 2014 BMT Tandem Meetings.
Experiments showed that Blautia, commensal bacteria found in the intestinal tract, can protect against GVHD-related mortality in mice and in humans.
So efforts to support Blautia survival—such as restricting the use of antibiotics and promoting better nutrition—may
prevent GVHD-related death, according to researchers.
Robert Jenq, MD, of Memorial Sloan-Kettering Cancer Center in New York, discussed this possibility when presenting this research, which was designated one of the “Best Abstracts” at the meeting (abstract 1*).
Dr Jenq noted that researchers have been trying for decades to determine whether the intestinal flora impact GVHD. Clinical studies have suggested that prophylaxis against anaerobes and gram-positive bacteria can reduce GVHD.
And murine studies have indicated that prophylaxis against gram-negative bacteria can reduce GVHD, that Lactobacillus can reduce GVHD, and that donor microbiota do not impact GVHD.
“If you’re confused, so are we,” Dr Jenq said. “It seems like it’s a mixed picture.”
So he and his colleagues conducted a series of experiments in an attempt to determine if any bacterial subgroups impact the risk of gut GVHD in mice and humans.
Bacteria seem to impact GVHD
The researchers first studied 76 adult transplant patients, analyzing stool samples taken at roughly 10 days after transplant (+/- 4 days). The team performed 16S gene sequencing using the Roche 454 platform.
This revealed the presence of several types of bacteria, including 6 gram-positive Firmicutes, 2 gram-negative Proteobacteria, and 2 gram-negative Bacteroidetes.
The researchers then used a computational assay to determine which of these bacteria might be associated with protection from GVHD. And they identified 2 possibilities—Lactobacillus and Blautia.
Additional analyses revealed that Blautia and Lactobacillus were significantly associated with GVHD-related mortality at 1500 days after transplant (P=0.03 and 0.01, respectively). But there was no significant association with Bacteroides (P=0.6), Enterobacteriales (P=0.2), or Enterococcus (P=0.3).
Blautia appears to affect GVHD-related mortality
To confirm their initial findings, Dr Jenq and his colleagues analyzed a second cohort of 50 adult transplant patients. The team analyzed stool samples for the abundance of bacterial subgroups using a different sequencing platform, Illumina miseq.
This time, they found that Blautia abundance predicted GVHD-related mortality at more than 500 days after transplant, but the abundance of Lactobacillus did not (P=0.01 and 1, respectively).
“Not enough Blautia in your gut seems to lead to an increase in GVHD-related mortality,” Dr Jenq said. “So what does this do to overall survival? In the first cohort, there’s a big difference in overall survival between the ‘haves’ and ‘have nots’ with Blautia [P=0.0008]. And this also holds up in the second cohort [P=0.04].”
Further analyses of data from both cohorts suggested that Blautia abundance was associated with GVHD-related mortality (P=0.004) and relapse-related mortality (P=0.01) but not non-relapse- and non-GVHD-related mortality (P=0.4).
“I don’t have a good explanation for [the relationship between Blautia and relapse-related death],” Dr Jenq said. “This was a surprise finding.”
The researchers also looked at Blautia’s ability to predict GVHD-related mortality. They found that, around day 10 after transplant, Blautia abundance predicts “very strongly” for GVHD-related death.
Another question was whether known GVHD risk factors—such as donor type, race, gender, and performance status—impact Blautia abundance. But an analysis revealed that Blautia is an independent risk factor for GVHD-related mortality.
A possible mechanism
To gain more insight into the association between Blautia and GVHD-related death, Dr Jenq and his colleagues decided to study it in mice.
