The Gut Microbiota and Hematopoietic Stem Cell Transplantation: Challenges and Potentials

Fatima, Nosheen; Kaysen, Anne; Wilmes, Paul; Schneider, Jochen G.

doi:10.1159/000492943

Cited by 38 publications

(25 citation statements)

References 49 publications

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“…To this end, the GM structure of twenty pediatric patients undergoing HSCT (ten treated with EN and ten with PN) was analyzed at the baseline, right after the transplant and in the post-HSCT recovery. In parallel, we evaluated the GM functionality as SCFAs production by using GC-MS. As shown in several publications [4][5][6][7]40], right after the transplant we observed the loss of the eubiotic GM layout. However, in EN patients, we assisted in the prompt recovery of a diverse eubiotic GM layout, minimizing the dysbiotic shifts following the HSCT.…”

Section: Discussionsupporting

confidence: 72%

Enteral Nutrition in Pediatric Patients Undergoing Hematopoietic SCT Promotes the Recovery of Gut Microbiome Homeostasis

et al. 2019

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Hematopoietic stem cell transplantation (HSCT) is the first-line immunotherapy to treat several hematologic disorders, although it can be associated with many complications reducing the survival rate, such as acute graft-versus-host disease (aGvHD) and infections. Given the fundamental role of the gut microbiome (GM) for host health, it is not surprising that a suboptimal path of GM recovery following HSCT may compromise immune homeostasis and/or increase the risk of opportunistic infections, with an ultimate impact in terms of aGvHD onset. Traditionally, the first nutritional approach in post-HSCT patients is parenteral nutrition (PN), which is associated with several clinical adverse effects, supporting enteral nutrition (EN) as a preferential alternative. The aim of the study was to evaluate the impact of EN vs. PN on the trajectory of compositional and functional GM recovery in pediatric patients undergoing HSCT. The GM structure and short-chain fatty acid (SCFA) production profiles were analyzed longitudinally in twenty pediatric patients receiving HSCT—of which, ten were fed post-transplant with EN and ten with total PN. According to our findings, we observed the prompt recovery of a structural and functional eubiotic GM layout post-HSCT only in EN subjects, thus possibly reducing the risk of systemic infections and GvHD onset.

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Section: Discussionsupporting

confidence: 72%

Enteral Nutrition in Pediatric Patients Undergoing Hematopoietic SCT Promotes the Recovery of Gut Microbiome Homeostasis

et al. 2019

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“…Whether and how the microbiota contributes to the development of GVHD development and propagation remains an open question. Since the immune system and the microbiota have a robust bidirectional relationship [33][34][35][36][37], it is reasonable to postulate that injury to the gastrointestinal (GI) mucosa secondary to conditioning and antibiotics is essential for GVHD evolution. Increased permeability of the intestine leads to bacterial translocation from the gut lumen, which in turn stimulate the innate immune system via toll-like receptors, priming alloreactive T-cells that drive GVHD [6,36,38].…”

Section: The Microbiome In Hsctmentioning

confidence: 99%

Fecal Microbiota Transplantation for Treatment of Acute Graft-versus-Host Disease

Shouval

Geva

Youngster

2019

CHI

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The growing understanding of the bidirectional relationship between the gastrointestinal (GI) microbiome and the immune system has opened up new avenues for treatment of graft-versus-host disease (GVHD). Fecal microbiota transplantation (FMT) is the transfer of stool from a donor to a recipient who harbors a perturbed GI microbiome resulting in disease. We review the rationale for performing FMT for the treatment of acute GVHD, and summarize data on the safety and efficacy of the procedure among allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Overall, FMT is a promising strategy in treating and preventing HSCT-related complications. However, caution should be exerted as HSCT recipients are highly immunosuppressed and unanticipated infectious adverse events may appear with the increasing application of FMT.

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“…There is growing evidence that antibiotics may alter immune functions that are important for surveillance and control of malignancy through the modification of gut microbiota [28], which have a composition that was shown to be associated with tumorigenesis [29,30]. In the specific setting of HCT, alterations in gut microbiota within the first month following HCT were associated with both incidence and severity of GVHD and hematologic relapse [31,32]. These data may explain the increase of relapse found in the ALLOZITHRO trial where patients received azithromycin before and during engraftment, which is an immunologically vulnerable period for the control of the hematologic malignancy [33,34].…”

Section: Discussionmentioning

confidence: 99%

Azithromycin Use and Increased Cancer Risk among Patients with Bronchiolitis Obliterans after Hematopoietic Cell Transplantation

Cheng

Bondeelle

Gooley

et al. 2020

Biology of Blood and Marrow Transplantation

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Azithromycin exposure during the early phase of allogeneic hematopoietic cell transplantation (HCT) has been associated with an increased incidence of hematologic relapse. We assessed the impact of azithromycin exposure on the occurrence of relapse or new subsequent neoplasm (SN) in patients with bronchiolitis obliterans syndrome (BOS) after HCT who are commonly treated with azithromycin alone or in combination with other agents. In a retrospective study of patients with BOS from 2 large allograft centers, the effect of azithromycin exposure on the risk of relapse or SN was estimated from a Cox model with a time-dependent variable for treatment initiation. The Cox model was adjusted on time-fixed covariates measured at cohort entry, selected for their potential prognostic value. Similar models were used to assess the exposure effect on the cause-specific hazard of relapse, SN, and death free of those events. Sensitivity analyses were performed using propensity score matching. Among 316 patients, 227 (71.8%) were exposed to azithromycin after BOS diagnosis. The corresponding adjusted hazard ratio (HR) in patients exposed to azithromycin versus unexposed was 1.51 (95% confidence interval [CI], 0.90 to 2.55) for relapse or SN, 0.82 (95% CI, 0.37 to 1.83) for relapse, and 2.00 (95% CI, 1.01 to 3.99) for SN. Patients exposed to azithromycin had a significantly lower cause-specific hazard of death free of neoplasm and relapse (adjusted HR, 0.54; 95% CI, 0.34 to 0.89). In conclusion, exposure to azithromycin after BOS after HCT was associated with an increased risk of SN but not relapse.

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The Gut Microbiota and Hematopoietic Stem Cell Transplantation: Challenges and Potentials

Cited by 38 publications

References 49 publications

Enteral Nutrition in Pediatric Patients Undergoing Hematopoietic SCT Promotes the Recovery of Gut Microbiome Homeostasis

Enteral Nutrition in Pediatric Patients Undergoing Hematopoietic SCT Promotes the Recovery of Gut Microbiome Homeostasis

Fecal Microbiota Transplantation for Treatment of Acute Graft-versus-Host Disease

Azithromycin Use and Increased Cancer Risk among Patients with Bronchiolitis Obliterans after Hematopoietic Cell Transplantation

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