Uso do prebiótico fruto-oligossacarídeo na atenuação da gravidade da mucosite em pacientes com leucemia mielóide aguda sob quimioterapia.

Abstract

Antineoplastic treatment for acute myeloid leukemia causes systemic side effects in patients. Its cytotoxic action also affects healthy tissues, leading to oral and gastrointestinal changes that result in inflammatory manifestations, gastrointestinal mucosal ulceration, and a decrease in functional enterocytes, leading to mucositis. This study aimed to investigate whether the use of prebiotic fructo-oligosaccharides can reduce the severity of mucositis in patients with acute myeloid leukemia undergoing chemotherapy. This was a randomized, triple-blind, longitudinal clinical trial with a quantitative approach conducted at Maranhão's reference cancer hospital. The sample consisted of hospitalized patients with a confirmed diagnosis of acute myeloid leukemia aged between 18 and 69 years. The patients were randomized into two groups (FOS and placebo) and assessed at three time points. Data collection included clinical evaluation using a questionnaire developed by the research team, determination of inflammatory markers, and analysis of the fecal microbiome in relation to diversity and abundance at different taxonomic levels. Analysis of inflammatory cytokine concentrations showed a significant increase in IL-6 in the FOS group at T3 and an increase in IL-10 over time, although without a significant difference. Fecal calprotectin levels in the FOS group decreased from T1 to T3, indicating attenuation of the inflammatory response in the intestine. In the assessment of oral mucositis, patients in the FOS group did not develop mucositis at the end of the study, and its duration was shorter (p < 0.001). On the other hand, patients in the placebo group presented with grade 3 AE, which lasted beyond 21 days of the study. Additionally, three (60%) patients in this group died during the study period. A statistically significant difference was observed in the alpha-diversity analysis using the Shannon index (p = 0.0262), with a reduction in the diversity of “oligotypes” in patients who received FOS supplementation. Comparative analysis of alpha diversity at different time points showed that the FOS group had reduced diversity when comparing T3 vs. T2 (p < 0.01) and T3 vs. T1 (p < 0.001). Analysis of taxonomic profiles at all time points demonstrated the presence of 15 phyla, 14 of which were known and 1 unclassified, with dominance of microorganisms belonging to the phyla Firmicutes, Bacteroidota, Proteobacteria, and Actinobacteria, without significant differences in temporal variation. However, in patients in the FOS group, the genus Enterococcus clearly appeared on the heat map with profiles showing a significant increase in mean relative abundance, with increments at each time point of the study, while the genera Alistipes, Rombutsia, and Ruminococcus showed a significant reduction in differential abundance. In summary, the analysis of the data from the present study suggests that FOS has the potential to be used as an adjunct to conventional therapy to attenuate the severity and duration of mucositis in patients with leukemia undergoing chemotherapy by stimulating beneficial microorganisms in the gut microbiota and inducing modulation of the immune response.