4. DISCUSSION
This study compared dietary intakes between children with solid tumors
and healthy children and examined associations between dietary intakes
and the gut microbiome in these children. We found that children with
cancer reported significantly higher intakes of macronutrients and
antioxidant nutrients than healthy children, but no differences in major
energy ratios. Additionally, we found significant associations between
macronutrients (e.g., carbohydrates and fiber) and micronutrients (e.g.,
selenium intake and vitamin A) and the gut microbiome alpha-diversity.
In this study, children from the cancer group had higher intake of
macronutrients and micronutrients. Specifically, they showed
significantly higher intakes of daily calories, and a trend of higher
intakes of total protein, fat, carbohydrates, and fiber than the control
group. However, there were no significant differences between the two
study groups if the amount of macronutrients intake is viewed based on
intake percentage. The compromised GI functions and manifestations of
cancer treatment-related GI symptoms affect the absorption of nutrients
among children with cancer, and therefore they need to compensate by
increasing intakes to meet the required energy for daily activities and
cancer recovery. Due to the importance of nutrients in cancer recovery,
the European Society for Clinical Nutrition and Metabolism (ESPEN)
guideline strongly recommends the energy intake of the patients ranging
between 25 and 30 kcal/kg/day to meet the energy expenditure, and the
protein intake above 1g/kg/day and even up to 1.5g/kg/day. Clinically,
this point is also emphasized to the parents, possibly explaining the
reason behind higher nutrition intake in children with cancer. The ESPEN
guideline strongly recommends against any dietary provisions that
restrict energy intake in patients with or at risk of malnutrition38. Therefore, more attention should be paid to
adequate dietary intakes which may be associated with cancer-related
toxicities, such as fatigue and comorbidities such as obesity.
A positive correlation was found between beta-carotene intake and
α-diversity index Faith’s_PD. A high diversity of the gut microbiome
had more healthy effects and a low gut microbiome diversity was
associated with a higher weight gain in the long-term39. When the intake of beta-carotene increases, there
is a higher microbial richness in our sample. Beta-carotene is the most
abundant vitamin A carotenoid precursor in the human diet and can only
be acquired through food or supplements 40. Both
beta-carotene and vitamin A function as antioxidants and participate in
the regulation of host immune responses by activating immune cells such
as macrophages and natural killer cells 41. Studies
have shown that retinoic acid, converted from vitamin A, is a critical
regulator for the intestinal immune response. In mice, a lack of
carotenoids and vitamin A in the diet reduces commensal microbes, and
thus suppresses pro-inflammatory Th17 cell generation in the gut42. Mechanisms of the association between the
beta-carotene intake and microbial richness might be due to the fact
that the supplementation of beta-carotene increases IgA production and
regulates the immune responses in the GI system 41,
which in turn protect the commensal microbes in the gut and help
maintain a high microbial alpha-diversity.
Through the analyses of associations between the gut microbiome and the
diet and nutritional intake levels, positive correlations were reported
between alpha-diversity and carbohydrates and vitamin B6 intakes. These
findings were consistent with previous studies. Vitamin B6 functions as
an essential cofactor for enzymes involved in various metabolic
activities and an increase of vitamin B6 aids in polyunsaturated fatty
acid metabolism, and biosynthesis of arachidonic acid and hepatic
cholesterol 43. An increase of vitamin B6 also reduces
the production of lithocholate 43, a toxic bile acid,
and promotes the homeostasis of microbial communities in the distal gut44, therefore leading to a higher diversity in the gut
microbiome.
Adequate intake of carbohydrates and fiber is positively correlated with
alpha-diversity, probably because children are therefore less likely to
have excessive intake of fat, and the energy density of diet is reduced.
Fiber plays a critical role in the diversity of healthy gut microbiome.
As reported, an increased fiber intake produces more short-chain fatty
acids, which in turn promote intestinal gluconeogenesis and
liponeogenesis 39. Further work suggested that
transitions to the refined diet that lacks soluble fiber is the primary
driver of gut microbiota alterations 45. Therefore,
adequate intake of carbohydrates and fiber promotes GI tract health and
prevents infections and colonization of the gut by pathogenic microbes46. Until now, the exact mechanisms behind the
relationship of carbohydrate intake level and gut microbial diversity
are still not well studied and should be explored in future
investigations.
This study has several limitations. We have a small sample size, and all
children were recruited from Children’s Healthcare of Atlanta, Georgia.
Our findings may not be generalized into other clinical settings. In
addition, we only analyzed the correlations between diet and
alpha-diversity and microbiome abundance. Lastly, these analyses were
conducted without controlling primary confounders, which should be
considered in future work.