Intestinal permeability in patients undergoing stem cell transplantation correlates with systemic acute phase responses and dysbiosis.
Blood Adv
; 7(17): 5137-5151, 2023 09 12.
Article
em En
| MEDLINE
| ID: mdl-37083597
ABSTRACT
Intestinal permeability may correlate with adverse outcomes during hematopoietic stem cell transplantation (HSCT), but longitudinal quantification with traditional oral mannitol and lactulose is not feasible in HSCT recipients because of mucositis and diarrhea. A modified lactuloserhamnose (LR) assay is validated in children with environmental enteritis. Our study objective was to quantify peri-HSCT intestinal permeability changes using the modified LR assay. The LR assay was administered before transplant, at day +7 and +30 to 80 pediatric and young adult patients who received allogeneic HSCT. Lactulose and rhamnose were detected using urine mass spectrometry and expressed as an LR ratio. Metagenomic shotgun sequencing of stool for microbiome analyses and enzyme-linked immunosorbent assay analyses of plasma lipopolysaccharide binding protein (LBP), ST2, REG3α, claudin1, occludin, and intestinal alkaline phosphatase were performed at the same timepoints. LR ratios were increased at day +7 but returned to baseline at day +30 in most patients (P = .014). Conditioning regimen intensity did not affect the trajectory of LR (P = .39). Baseline LR ratios did not vary with diagnosis. LR correlated with LBP levels (r2 = 0.208; P = .0014). High LR ratios were associated with lower microbiome diversity (P = .035), loss of anaerobic organisms (P = .020), and higher plasma LBP (P = .0014). No adverse gastrointestinal effects occurred because of LR. Intestinal permeability as measured through LR ratios after allogeneic HSCT correlates with intestinal dysbiosis and elevated plasma LBP. The LR assay is well-tolerated and may identify transplant recipients who are more likely to experience adverse outcomes.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Transplante de Células-Tronco Hematopoéticas
/
Lactulose
Limite:
Adult
/
Child
/
Humans
Idioma:
En
Revista:
Blood Adv
Ano de publicação:
2023
Tipo de documento:
Article