1. INTRODUCTION
Approximately 16 000 children and adolescents are diagnosed with cancer in the United States (U.S.) each year 1. Among children with cancer, about 30% of them are diagnosed with extracranial solid tumors 2. Malnutrition is a common complication in children with cancer 3. Current literature has reported that both malnutrition and undernutrition are highly prevalent from diagnosis until the completion of therapy, particularly among children with solid tumors 4,5.
The gut microbiome, defined as the collection of microbes and their genomes in the gastrointestinal (GI) tract 6, plays a critical role in human health and disease 7. Accumulating evidence has demonstrated that long-term diet is a primary driver of the diversity and composition of the gut microbiome8,9, accounting for 44% of the total variation in average microbiome composition. Previous study showed that there was significant longitudinal pairing of diet with the microbiome for 78% of the subjects 10. Intake of specific dietary components further indicated how certain bacteria respond to specific nutrients11. Nutrients such as protein, fat, digestible and non-digestible carbohydrate, prebiotics, and polyphenols could individually induce shifts in the gut microbiome with secondary effects on host immunologic and metabolic markers 10,11. Thus, it is important to build a healthy gut microbiome through modulating diet 9.
Maintaining a healthy gut microbiome is critical among children with cancer as dysbiosis in the gut microbial composition has been widely reported across the continuum of cancer treatment12-15 and even survivorship 16. Dysbiotic gut microbiome (i.e., loss of keystone taxa, loss of diversity, shifts in metabolic capacity, or blooms of pathogens)17,18 not only interferes with cancer chemotherapeutic metabolism, but also serves as a potential biomarker of GI toxicity in children with cancer, including mucositis, diarrhea, constipation, and infections 19. Based on the microbiome-gut-brain axis20,21, disrupted gut microbiome was associated with psychoneurological toxicities such as inflammatory pain, fatigue, anxiety, depression, and cognitive dysfunction12,21-23. Currently, dysbiotic gut microbiome profiles have been reported in children with cancer receiving treatments (e.g., chemotherapy) as well as cancer survivors 13,24. Specifically, children and adolescents with acute lymphoblastic leukemia (ALL) reported a lower diversity of the gut microbiome than healthy controls 13,25; compared with the day before chemotherapy, the number of bacteria dramatically decreased after chemotherapy started 26. Additionally, Cozen et al. found that cancer survivors of adolescent and young adult Hodgkin lymphoma showed a significantly lower value of unique operational taxonomic units (OTUs) of the gut microbiome than healthy controls16.
There is a lack of research focusing on the gut microbiome in children with solid tumors 12 and relationships between diet and changes in the gut microbiome have yet to be studied8. As children with cancer experience both malnutrition and alterations in the gut microbiome across cancer treatments, understanding associations between diet and the gut microbiome could provide new insights into biological mechanisms of cancer treatment-related symptoms and toxicities. Finding out the relationship between the gut microbiome and diet in children with solid tumors could help clinicians better understand how to use diet to modulate the gut microbiome, therefore relieving treatment-related GI toxicities (e.g., stomatitis, constipation, and diarrhea) and central nervous system (CNS)-related toxicities (e.g., anxiety and cognitive dysfunction). Thus, the purposes of this study were to: 1) compare the intake of macronutrients and antioxidant nutrients between children with solid tumors post-chemotherapy (within 1 year) and those of healthy controls; and 2) examine the association between macronutrients, antioxidant nutrients and the gut microbiome in this population.