Nutritional modulation of the gut microbiome in allogeneic hematopoietic stem cell transplantation recipients

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a potentially curative strategy for many oncological and non-oncological diseases, but it is associated with marked morbidity and mortality. The disruption of gut microbiota (GM) eubiosis has been linked to major allo-HSCT complications, including infections and acute graft vs. host disease (aGvHD), and correlates with mortality. This increasing knowledge on the role of the GM in the allo-HSCT procedure has led to fascinating ideas for modulating the intestinal ecosystem in order to improve clinical outcomes. Nutritional strategies, either by changing the route of nutritional supplementation or by administering specific molecules, are increasingly being considered as cost- and risk-effective methods of modulating the GM. Nutritional support has also emerged in the past several years as a key feature in supportive care for allo-HSCT recipients, and deterioration of nutritional status is associated with decreased overall survival and higher complication rates during treatment. Herein we provide a complete overview focused on nutritional modulation of the GM in allo-HSCT recipients. We address how pre transplant diet could affect GM composition and its ability to withstand the upsetting events occurring during transplantation. We also provide a complete overview on the influence of the route of nutritional administration on the intestinal ecosystem, with a particular focus on the comparison between enteral and parenteral nutrition (PN). Moreover, as mounting evidence are showing how specific components of post-transplant diet, such as lactose, could drastically shape the GM, we will also summarize the role of prebiotic supplementation in the modulation of the intestinal flora and in allo-HSCT outcomes.

Role of Nutrition in Pediatric Patients with Cancer

“…The composition of the microbiome seems to influence patients’ survival from HSCT and its related complications (such as GVHD, infections, immune reconstitution, hepatic sinusoidal obstruction syndrome, febrile neutropenia, pulmonary complications, and relapse of the primary disease) [ 81 ]. Many GM-derived metabolites may play a key role in mediating important biological processes during HSCT.…”

“…In particular, SCFAs can protect the intestinal epithelium and stimulate mucosal immunity. Both non-nutritional (such as antibiotics) and nutritional interventions can preserve GM from damage that may occur during HSCT or restore GM homeostasis after it [ 81 ].…”

“…Furthermore, SCFAs—GM-derived metabolites—play a key role in mediating important biological processes during HSCT. They can protect the intestinal epithelium from direct damage during HSCT and modulate mucosal immunity by decreasing alloreactivity (protection from acute and chronic GVHD) [ 81 ].…”

Pharmacomicrobiomics in Pediatric Oncology: The Complex Interplay between Commonly Used Drugs and Gut Microbiome

“…128 patients with sufficient dietary fiber intake showed a significant improvement in progression free survival compared to insufficient fiber intake, with no impact of probiotic administration [ 131 ]. Other microbiome-modifying interventions have been proposed to enhance immune checkpoint inhibitor antitumor activity, such as natural polyphenols [ 132 ] and ketogenic diet [ 133 ], but more evidence is needed to implement those interventions in routine clinical practice [ 22 ]. Similarly, anti-CTLA-4 antibodies are used as checkpoint inhibitors in many malignancies.…”

“…The interaction between these drugs and the GM is one of the key components of the complex interplay between the intestinal ecosystem and the host during anticancer therapies. This bidirectional relationship between GM and cancer presents with distinctive features in pediatric patients, considering the rapidly and continuously evolving GM community, the strong impact of complications in growing subjects and the different subsets of diseases that require specific therapies [ 21 , 22 ]. Therefore, the pediatric setting deserves a specific focus when addressing pharmacomicrobiomics.…”