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.