Meeting NewsPerspective

Diverse gut microbiota may protect gastrointestinal tract in acute graft-versus-host disease

SALT LAKE CITY — A diverse gut microbiota demonstrated a local protective effect among patients with nongastrointestinal or upper gastrointestinal acute graft-versus-host disease, according to study results presented at the BMT Tandem Meetings.

“Gut microbiota may have utility in future prophylactic or therapeutic interventions in gastrointestinal acute GVHD,” Doris M. Ponce, MD, hematologic oncologist at Memorial Sloan Kettering Cancer Center, said during her presentation.

High diversity of gut microbiota and certain bacterial commensals within Clostridial order are known to be associated with decreased GVHD-related mortality after allogeneic hematopoietic stem cell transplantation. Because the majority of intestinal microbiota biomass resides within the colon, Ponce and colleagues hypothesized that certain features of the microbiota offer local protection of the lower gastrointestinal tract.

Researchers evaluated 286 patients (median age, 52 years) who underwent allogeneic HSCT with either unmodified or CD34-positive selected grafts and who developed acute GVHD by day 100 and had available stool samples between January 2011 and February 2017.

Researchers divided patients into three groups according to the organ involved in acute GVHD: upper gastrointestinal tract only (n = 105), lower gastrointestinal tract with or without upper gastrointestinal involvement (n = 84), and no gastrointestinal tract involvement (n = 97).

Researchers evaluated 1,994 stool samples — for an average of seven per patient — 20 days prior and after GVHD onset. Researchers amplified and sequenced the 16S rRNA gene of the V4-V5 region and measured microbial diversity via the Inverse Simpson Index.

Trends in microbial diversity relative to the day of acute GVHD onset showed distinct dynamics among the three groups.

Before onset, all groups showed similar microbial diversity. However, after day 20, the microbiota of the nongastrointestinal group had the highest diversity, followed by the upper gastrointestinal group. Patients in the lower gastrointestinal group had the lowest microbial diversity.

When researchers grouped samples into preonset (day –19 to 0) and postonset (day 1-20) categories via the Mann-Whitney U test, the microbial diversity in lower gastrointestinal cases (median, 2.05) appeared significantly lower than upper gastrointestinal (median, 2.65) and nongastrointestinal group (median, 3.45) prior to acute GVHD onset (P < .05).

The trend became more prominent after acute GVHD onset — low gastrointestinal cases had a median diversity of 3.14 compared with a median diversity of 5.73 for the upper gastrointestinal group and 7.2 for the nongastrointestinal group (P < .005).

“Of particular interest it is the fact this trend starts before the onset of acute GVHD, indicating eventual possibility of early intervention,” Ponce said. – by Melinda Stevens

Reference:

Ponce DM, et al. Abstract 57. Presented at: BMT Tandem Meetings; Feb. 21-25, 2018; Salt Lake City.

Disclosures: HemOnc Today could not confirm relevant financial disclosures at the time of reporting.

SALT LAKE CITY — A diverse gut microbiota demonstrated a local protective effect among patients with nongastrointestinal or upper gastrointestinal acute graft-versus-host disease, according to study results presented at the BMT Tandem Meetings.

“Gut microbiota may have utility in future prophylactic or therapeutic interventions in gastrointestinal acute GVHD,” Doris M. Ponce, MD, hematologic oncologist at Memorial Sloan Kettering Cancer Center, said during her presentation.

High diversity of gut microbiota and certain bacterial commensals within Clostridial order are known to be associated with decreased GVHD-related mortality after allogeneic hematopoietic stem cell transplantation. Because the majority of intestinal microbiota biomass resides within the colon, Ponce and colleagues hypothesized that certain features of the microbiota offer local protection of the lower gastrointestinal tract.

Researchers evaluated 286 patients (median age, 52 years) who underwent allogeneic HSCT with either unmodified or CD34-positive selected grafts and who developed acute GVHD by day 100 and had available stool samples between January 2011 and February 2017.

Researchers divided patients into three groups according to the organ involved in acute GVHD: upper gastrointestinal tract only (n = 105), lower gastrointestinal tract with or without upper gastrointestinal involvement (n = 84), and no gastrointestinal tract involvement (n = 97).

Researchers evaluated 1,994 stool samples — for an average of seven per patient — 20 days prior and after GVHD onset. Researchers amplified and sequenced the 16S rRNA gene of the V4-V5 region and measured microbial diversity via the Inverse Simpson Index.

Trends in microbial diversity relative to the day of acute GVHD onset showed distinct dynamics among the three groups.

Before onset, all groups showed similar microbial diversity. However, after day 20, the microbiota of the nongastrointestinal group had the highest diversity, followed by the upper gastrointestinal group. Patients in the lower gastrointestinal group had the lowest microbial diversity.

When researchers grouped samples into preonset (day –19 to 0) and postonset (day 1-20) categories via the Mann-Whitney U test, the microbial diversity in lower gastrointestinal cases (median, 2.05) appeared significantly lower than upper gastrointestinal (median, 2.65) and nongastrointestinal group (median, 3.45) prior to acute GVHD onset (P < .05).

The trend became more prominent after acute GVHD onset — low gastrointestinal cases had a median diversity of 3.14 compared with a median diversity of 5.73 for the upper gastrointestinal group and 7.2 for the nongastrointestinal group (P < .005).

“Of particular interest it is the fact this trend starts before the onset of acute GVHD, indicating eventual possibility of early intervention,” Ponce said. – by Melinda Stevens

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Reference:

Ponce DM, et al. Abstract 57. Presented at: BMT Tandem Meetings; Feb. 21-25, 2018; Salt Lake City.

Disclosures: HemOnc Today could not confirm relevant financial disclosures at the time of reporting.

    Perspective
    Marco Mielcarek

    Marco Mielcarek

    Over the last several years, there has been mounting scientific evidence that loss of diversity of bacterial communities in the gastrointestinal (GI) tract is associated with worse outcomes after allogeneic hematopoietic cell transplantation. It has been reported, for example, that high bacterial diversity and relative abundance of certain bacterial commensals within the Clostridialis order are protective against GVHD-associated mortality. A decrease in GI microbial diversity (microbial injury) during transplant has been attributed to the use of certain antibiotics and low caloric intake. These findings suggest that preserving GI microbial diversity during the transplant procedure, or restoring loss of diversity, might lead to better outcomes through reduced GVHD-related morbidity and mortality.

    Ponce and colleagues hypothesized that certain features of the microbiota conferred local protection of the lower GI tract against acute GVHD. In a study that included 286 allograft recipients and by evaluating serial stool samples for changes in microbial diversity over time, they found that patients who had lower gut (colonic) acute GVHD had lower microbial diversity than those with upper gut GVHD (with or without lower gut involvement), and those with no GVHD. If these results can be confirmed, one could envision interventions aimed at preventing the loss of diversity such avoidance of certain types of antibiotics, use of probiotics or controlled oral feeding in patients who would typically only receive parenteral nutrition after transplant. In my opinion, it needs to be demonstrated though that the loss of microbial diversity in patients with lower GI tract GVHD is a cause rather than just the result of GVHD that could have disrupted the mucosal environment certain beneficial bacterial communities depend on.

    • Marco Mielcarek, MD
    • Seattle Cancer Care Alliance

    Disclosures: Mielcarek reports no relevant financial disclosures.

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