Gut Microbiota Diversity Linked to Better Survival After Pediatric HSCT

— Patients with higher diversity also had lower rates of acute graft-versus-host disease

A computer rendering of microbiota in the intestine.

High gut microbiota diversity before allogeneic hematopoietic stem cell transplantation (allo-HSCT) was associated with significantly better survival outcomes in children, according to a multicenter study.

In a cohort of 90 pediatric patients undergoing allo-HSCT, the estimated overall survival rate was 88.9% for those who had higher gut microbiota diversity compared with 62.7% for those with lower diversity at a median follow-up of 52 months (P=0.011), reported Riccardo Masetti, MD, PhD, of the University of Bologna in Italy, and colleagues.

Furthermore, grade II-IV acute graft-versus-host disease (aGvHD) occurred in 20% of the high-diversity group versus 44.4% of those in the low-diversity group (P=0.017), and grade III-IV aGvHD occurred in 2.2% versus 20%, respectively (P=0.007), they wrote in Blood.

"Our study provides the first evidence of a relationship between pre-transplant microbial diversity in the intestinal tract and post-transplant survival in children," Masetti said in a press release. "This finding suggests that interventions to improve microbial diversity before donor transplantation could help more children survive."

There were no statistically significant differences between the high- and low-diversity groups for the cumulative incidence of relapse (13.3% vs 24.4%, P=0.1) and relapse-free survival (80.0% vs 55.4%, P=0.091).

While patients with higher diversity showed a trend towards lower gut aGvHD (11.1% vs 24.4%, P=0.098), the researchers did not perform an analysis of aGvHD-related mortality due to the few deaths from the complication.

There were also no significant differences between the groups in terms of bloodstream infections (23.8% vs 20.9%, P=0.735) and transplant-related mortality (8.9% vs 15.6%, P=0.473).

For this study, Masetti and colleagues analyzed stool samples collected from pediatric patients before and during allo-HSCTs performed from 2013 to 2020 at three hospitals in Italy and one in Poland.

Median patient age at the time of transplant was 9 years, and 59% were boys. Of the included patients, 37% had acute lymphoblastic leukemia, 21% had acute myeloid leukemia, 11% had myelodysplastic syndrome or juvenile myelomonocytic leukemia, and 2% had non-Hodgkin lymphoma, while 29% had non-malignant blood diseases.

Stem cell donors were unrelated in 61% of cases, 20% were HLA-haploidentical relatives, and 19% were identical siblings. The stem cell source was bone marrow in 76% of transplants, peripheral blood stem cell in 23%, and cord blood in 1%.

High gut microbiota diversity was characterized by a relative greater abundance of potentially health-related families, such as Ruminococcaceae and Oscillospiraceae, while lower diversity was characterized by an overabundance of Enterococcaceae and Enterobacteriaceae.

"Network analysis detected short-chain fatty acid producers such as Blautia, Faecalibacterium, Roseburia, and Bacteroides as keystones in the higher-diversity group," Masetti and team wrote. "Enterococcus, Escherichia-Shigella, and Enterobacter were instead the keystones detected in the lower-diversity group."

The authors acknowledged several limitations to their study. For example, they noted that the four different centers in the study resulted in a heterogenous cohort with different disease types, conditioning regimens, and transplant practices. In addition, the number of patients in the study was relatively small and included infants and older children "whose gut microbiota likely follows different ecological rules."

"Large-scale multicenter cohort studies are needed to fully uncover the clinical significance of the age-related gut microbiota configuration in determining patient outcomes," they added.

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    Mike Bassett is a staff writer focusing on oncology and hematology. He is based in Massachusetts.


This work was supported by grants from Fondazione Cassa di Risparmio in Bologna, the Federide ONLUS Association, the Fondazione Regionale per la Ricerca Biomedica, and the Italian Ministry of Health.

The authors reported no conflicts of interest.

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Source Reference: Masetti R, et al "Gut microbiota diversity before allogeneic hematopoietic stem cell transplantation as predictor of mortality in children" Blood 2023; DOI: 10.1182/blood.2023020026.