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.