The gut microbiome plays a critical role in maintaining children's health and in preventing and treating children's disease. Current application of the gut microbiome in childhood cancer is still lacking. This study aimed to systematically review the following: (1) alternations in the gut microbiome throughout cancer treatment trajectories in children, (2) the associations between the gut microbiome and gastrointestinal (GI) symptoms and psychoneurological symptoms (PNS), and (3) the efficacy of therapeutic interventions in the gut microbiome in children with cancer.

PubMed, EMBASE, the Cochrane Library, and the American Society of Clinical Oncology abstract were searched. Eligible studies included all study types in which the gut microbiome was primarily reported in children with cancer. The Mixed Methods Assessment Tool was used to evaluate the methodology quality of included studies. Seven studies met our eligibility criteria, including two cohort studies, two case-control studies, and three randomized controlled trails.

The findings showed that the diversity estimates of the gut microbiome in children with cancer were lower than those of healthy controls both pre- and post-treatment. Children with cancer showed a significantly lower relative abundance of healthy gut microbiome (e.g., Clostridium XIVa and Bifidobacterium) during and after cancer treatment. No adequate literature was identified to support the associations between dysbiosis of the gut microbiome and GI symptoms/PNS. The use of prebiotics (fructooligosaccharides) and probiotics (Bifidobacterium or Lactobacilli) appears to improve the microenvironment of the gut around 1 month (4-5 weeks) during chemotherapy rather than at the beginning of treatment. Data also suggest that both prebiotic and probiotic interventions decrease clinical side effects (e.g., infection and morbidity risk) in children with cancer.

This study adds to the evidence that dysbiosis of the gut microbiome can be improved using prebiotic and probiotic supplementations in children with cancer. More well-designed experimental studies are needed to confirm this conclusion. Further studies are needed to examine the associations between the gut microbiome and GI symptoms/PNS in childhood cancer.