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Advances in Intestinal Barrier Preservation and Restoration in the Allogeneic Hematopoietic Cell Transplantation Setting.

ABSTRACT: The intestinal barrier consists of an epithelial lining covered with specialized mucus inhabited by intestinal microbiota. An intact gut barrier ensures a resistance to bacteria and toxins translocation. On the other hand, gut permeability allows the absorption of essential nutrients, fluids and ions. This balance is achieved only by the complex structure and functional characteristics of the intestinal barrier. Allogenic hematopoietic cell transplantation remains the only curative treatment for many hematological diseases, but its application is limited because of possible transplant-related mortality mainly due to graft-versus-host disease and infectious complications. The intestinal barrier has been extensively studied in recent years as the primary site of graft-versus-host disease initiation and propagation. In the present review, we focused on the physiological structure and function of the gut barrier and the evidence of how the disruption of the gut barrier and increased intestinal permeability affects transplant recipients. Finally, therapeutic strategies aiming at intestinal barrier protection with a special focus on microbiome preservation and restoration in the allogenic hematopoietic cell transplantation setting are discussed.

SUBMITTER: Tyszka M

PROVIDER: S-EPMC8201017 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundBacteremia is a frequent complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is unclear whether changes in the intestinal microbiota during allo-HSCT contribute to the development of bacteremia. We examined the microbiota of patients undergoing allo-HSCT, and correlated microbial shifts with the risk of bacteremia.MethodsFecal specimens were collected longitudinally from 94 patients undergoing allo-HSCT, from before transplant until 35 days after transplant. The intestinal microbiota was characterized by 454 pyrosequencing of the V1-V3 region of bacterial 16S ribosomal RNA genes. Microbial diversity was estimated by grouping sequences into operational taxonomic units and calculating the Shannon diversity index. Phylogenetic classification was obtained using the Ribosomal Database Project classifier. Associations of the microbiota with clinical predictors and outcomes were evaluated.ResultsDuring allo-HSCT, patients developed reduced diversity, with marked shifts in bacterial populations inhabiting the gut. Intestinal domination, defined as occupation of at least 30% of the microbiota by a single predominating bacterial taxon, occurred frequently. Commonly encountered dominating organisms included Enterococcus, Streptococcus, and various Proteobacteria. Enterococcal domination was increased 3-fold by metronidazole administration, whereas domination by Proteobacteria was reduced 10-fold by fluoroquinolone administration. As a predictor of outcomes, enterococcal domination increased the risk of Vancomycin-resistant Enterococcus bacteremia 9-fold, and proteobacterial domination increased the risk of gram-negative rod bacteremia 5-fold.ConclusionsDuring allo-HSCT, the diversity and stability of the intestinal flora are disrupted, resulting in domination by bacteria associated with subsequent bacteremia. Assessment of fecal microbiota identifies patients at highest risk for bloodstream infection during allo-HCST.

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Advances in Intestinal Barrier Preservation and Restoration in the Allogeneic Hematopoietic Cell Transplantation Setting.

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