Microbiome-Derived Metabolites in Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

The gut microbiome has emerged as a major character in the context of hematopoietic stem cell transplantation. The biology underpinning this relationship is still to be defined. Recently, mounting evidence has suggested a role for microbiome-derived metabolites in mediating crosstalk between intestinal microbial communities and the host. Some of these metabolites, such as fiber-derived short-chain fatty acids or amino acid-derived compounds, were found to have a role also in the transplant setting. New interesting data have been published on this topic, posing a new intriguing perspective on comprehension and treatment. This review provides an updated comprehensive overview of the available evidence in the field of gut microbiome-derived metabolites and hematopoietic stem cell transplantation.

Gut microbiome in pediatric acute leukemia: from predisposition to cure

“…Butyrate has a pivotal trophic effect on the intestinal epithelial barrier, acting as an energy source for enterocytes and increasing the expression of mucin and tight-junction proteins. Moreover, it possesses anti-inflammatory properties 33,34 . Chemotherapy induces the loss of enterocytes and Paneth cells, which produce antimicrobial peptides, such as alpha defensin and REGIIIγ 35,36 , thus possibly leading to enterococcal overgrowth.…”

“…In particular, there is a reduction in health-promoting taxa, such as Faecalibaterium and Ruminococcus 55 , and a higher presence of genera usually subdominant in the GM, such as Enterococcus, Staphylococcus and Enterobacter 56 . These compositional modifications are also accompanied by functional ones, with a reduction in the levels of numerous microbial-derived molecules, such as short-chain fatty acids 3,33,57,58 . However, it should be noted that most studies on GM modifications during HSCT focus on transplantation for both malignant and non-malignant diseases, and data regarding the differences between these two groups in terms of GM composition remain to be provided.…”

Early stool microbiome and metabolome signatures in pediatric patients undergoing allogeneic hematopoietic cell transplantation

“…Stool metabolites may indicate potential pathways by which the microbiome modulates associations between the microbiome and posttransplant outcomes 51–53 . Metabolites that have been identified as potentially clinically relevant in other cohorts, including short‐chain fatty acids, amino acid‐derived metabolites (tryptophan, tyrosine, choline), riboflavin‐derived metabolites, and bile acids, demonstrated substantial variability between pretransplant samples 41 . We examined previously described adult associations between microbiome diversity and the metabolome.…”

Early microbiome and metabolome signatures in pediatric patients undergoing allogeneic hematopoietic cell transplantation

“…[45][46][47] Metabolites that have been identified as potentially clinically relevant in other cohorts, including short chain fatty acids, amino acid-derived metabolites (tryptophan, tyrosine, choline), riboflavin-derived metabolites and bile acids demonstrated substantial variability between pre-transplant samples. 48 We examined previously described adult associations between microbiome diversity and the metabolome. In adults, stool butyrate and indol levels have been associated with microbial disruption, 34,35 however, we only identified a minimal association between stool indol levels and increased diversity and no association between butyrate levels and diversity.…”

“…This network structure demonstrates important associations between both organisms and metabolites that have been previously identified as inflammatory or immunoregulatory. 48 The heterogeneity of the microbiome and metabolomic layouts early in the transplant course suggests that this may be a potential arena for further exploration within pediatric transplantation.…”