Work

A Phase I Study of the Prebiotic Fructooligosaccharide in Allogeneic HCT and Evaluation of the Impact of This Compound on the Intestinal Microbiome

Year: 2018

Type: article

Abstract: Decreased intestinal microbiota diversity in patients undergoing hematopoietic stem cell transplant (HCT) is significantly associated with an increased risk of mortality, infection, and graft-versus-host disease. Non-digestible carbohydrates that serve as an energy source for colonic commensal organisms, known as prebiotics, may serve as a therapeutic intervention to support a diverse microbiota and prevent complications from HCT. We conducted a single-arm phase I trial in 15 patients undergoing reduced-intensity allogeneic HCT in order to find the maximum tolerated dose of the prebiotic fructo-oligosaccharide (Figure 1). Stool and blood samples were collected at 7 time points before during and after transplant (Figure 1). We found that 4 of 5 patients tolerated the lowest 5 g/day dose of FOS, and 6 of 10 tolerated the higher dose of 10 g/day of FOS, with tolerability being defined as taking 70% or more of the total number of daily doses. Given our Bayesian optimal interval trial design, we were unable to test the highest 15 g/day dose of FOS. While no severe adverse events were attributed to the prebiotic, those who did not achieve 70% tolerability reported inhibitory flatulence and abdominal discomfort, or could not tolerate oral intake due to severe mucositis. We used shotgun metagenomic sequencing of longitudinal stool samples collected from participants (n = 15) and matched controls (n = 8) to investigate microbiome differences between groups, and here report the findings of these analyses.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2017.12.464