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Levofloxacin prophylaxis and parenteral nutrition have a detrimental effect on intestinal microbial networks in pediatric patients undergoing HSCT
Fabbrini, M., D'Amico, F., Leardini, D., Muratore, E., Barone, M., Belotti, T., Forchielli, M. L., Zama, D., Pession, A., Prete, A., et al
Communications biology. 2023;6(1):36
Abstract
The gut microbiome (GM) has shown to influence hematopoietic stem cell transplantation (HSCT) outcome. Evidence on levofloxacin (LVX) prophylaxis usefulness before HSCT in pediatric patients is controversial and its impact on GM is poorly characterized. Post-HSCT parenteral nutrition (PN) is oftentimes the first-line nutritional support in the neutropenic phase, despite the emerging benefits of enteral nutrition (EN). In this exploratory work, we used a global-to-local networking approach to obtain a high-resolution longitudinal characterization of the GM in 30 pediatric HSCT patients receiving PN combined with LVX prophylaxis or PN alone or EN alone. By evaluating the network topology, we found that PN, especially preceded by LVX prophylaxis, resulted in a detrimental effect over the GM, with low modularity, poor cohesion, a shift in keystone species and the emergence of modules comprising several pathobionts, such as Klebsiella spp., [Ruminococcus] gnavus, Flavonifractor plautii and Enterococcus faecium. Our pilot findings on LVX prophylaxis and PN-related disruption of GM networks should be considered in patient management, to possibly facilitate prompt recovery/maintenance of a healthy and well-wired GM. However, the impact of LVX prophylaxis and nutritional support on short- to long-term post-HSCT clinical outcomes has yet to be elucidated.
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2.
Enteral versus Parenteral Nutrition as Nutritional Support after Allogeneic Hematopoietic Stem Cell Transplantation: a Systematic Review and Meta-Analysis
Zama, D., Gori, D., Muratore, E., Leardini, D., Rallo, F., Turroni, S., Prete, A., Brigidi, P., Pession, A., Masetti, R.
Transplantation and cellular therapy. 2021;27(2):180.e1-180.e8
Abstract
Nutritional support for patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been widely debated. Enteral nutrition (EN) is recommended as first-line nutritional support by the main international guidelines. However, these recommendations are based on weak evidence, and there is wide variability in the types of nutritional support among transplantation centers, with the majority providing parenteral nutrition (PN) instead of EN. Here we provide an up-to-date systematic review and meta-analysis of studies comparing EN and PN for nutritional support during the neutropenic period after allo-HSCT. The literature search strategy identified 13 papers, of which 10 compared clinical transplantation outcomes, 2 compared gut microbiota (GM) compositions, and 1 compared systemic metabolic profiles. For the meta-analysis, among the 10 clinical studies, 8 studies in which 2 groups were compared were selected: in 1 group, EN was provided as primary nutritional support in the neutropenic phase after allo-HSCT with or without the addition of PN (EN group), whereas in the other group, only PN was provided as nutritional support. The incidence rates of acute graft-versus-host disease (aGVHD) (relative risk [RR], 0.69; 95% confidence interval [CI], 0.56 to 0.86; P = .0007), aGVHD grade III-IV (RR, 0.44; 95% CI, 0.30 to 0.64; P < .0001), and gut aGVHD (RR, 0.44; 95% CI, 0.30 to 0.66; P < .0001) were lower in the EN group than in the PN group. No differences were found between the 2 groups with regard to the incidence of severe oral mucositis (RR, 0.95; 95% CI, 0.83 to 1.09; P = .46) or overall survival at day +100 (RR, 1.07; 95% CI, 0.95 to 1.21; P = .29). Other variables were too heterogeneous to perform quantitative analyses. The results of the meta-analysis showed that EN reduced the incidence of aGVHD, specifically grade III-IV and gut aGVHD. This result should prompt improved efforts to implement EN as first-line nutritional support in patients undergoing allo-HSCT. Considering the emerging evidence regarding the association between GM dysbiosis and aGVHD onset, we speculate that this protective effect could be attributed to the improved gut eubiosis observed in enterally fed patients. Further studies are warranted to better address the relationship between the GM composition, aGVHD, and the nutritional administration route during HSCT.
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3.
Enteral nutrition protects children undergoing allogeneic hematopoietic stem cell transplantation from blood stream infections
Zama, D., Muratore, E., Biagi, E., Forchielli, M. L., Rondelli, R., Candela, M., Prete, A., Pession, A., Masetti, R.
Nutrition journal. 2020;19(1):29
Abstract
Enteral Nutrition (EN) is recommended as first line nutritional support for patients undergoing Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT), but only few studies exist in the literature which compare EN to Parenteral Nutrition (PN) in the paediatric population.Forty-two consecutive paediatric patients undergoing allo-HSCT at our referral centre between January 2016 and July 2019 were evaluated. Post-transplant and nutritional outcomes of patients receiving EN for more than 7 days (EN group, n = 14) were compared with those of patients receiving EN for fewer than 7 days or receiving only PN (PN group, n = 28). In the EN group, a reduced incidence of Blood Stream Infections (BSI) was observed (p = 0.02) (n = 2 vs. n = 15; 14.3% vs. 53.6%). The type of nutritional support was also the only variable independently associated with BSI in the multivariate analysis (p = 0.03). Platelet engraftment was shorter in the PN group than in the EN group for a threshold of > 20*10(9)/L (p = 0.04) (23.1 vs 35.7 days), but this correlation was not confirmed with a threshold of > 50*10(9)/L. The Body Mass Index (BMI) and the BMI Z-score were no different in the two groups from admission to discharge.Our results highlight that EN is a feasible and nutritionally adequate method of nutritional support for children undergoing allo-HSCT in line with the present literature. Future functional studies are needed to better address the hypothesis that greater intestinal eubyosis maintained with EN may explain the observed reduction in BSI.
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4.
Enteral Nutrition in Pediatric Patients Undergoing Hematopoietic SCT Promotes the Recovery of Gut Microbiome Homeostasis
D'Amico, F., Biagi, E., Rampelli, S., Fiori, J., Zama, D., Soverini, M., Barone, M., Leardini, D., Muratore, E., Prete, A., et al
Nutrients. 2019;11(12)
Abstract
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.