Abstract 720: Comparison of the gut microbiome between children with solid tumor receiving chemotherapy and healthy children
Authors: Bai Jinbing , Kocaman Kumru , Slack Julia , Martin Melissa , Powell Christie , Sutton Kathryn S. , George Bradley , Olson Thomas , Konstantinidis Konstantinos T. , Bruner Deborah W. 
Published: June 2022

Abstract
Background: Chemotherapy is commonly used for children with cancer. Intensive chemotherapy can disturb the gut microbiome, which may be associated with treatment-related toxicities. This study aimed to compare profiles of the gut microbiome in children with solid tumors pre- and post-chemotherapy with those of healthy children.
Methods: A case-control study was conducted in 44 children (21 with solid tumors and 23 healthy). Children aged 7-18 years with solid tumors receiving chemotherapy were recruited from Children’s Healthcare of Atlanta (CHOA); healthy children were recruited by e-news in CHOA. The gut microbiome was measured using stool specimens that were collected pre cycle 2 chemotherapy and post the completion of all chemotherapy for cancers, and only once for healthy controls. Demographics and clinical variables (e.g., race and use of antibiotics) were reported by parents. Bacterial 16S rRNA gene V4 region was amplified and sequenced. Bacterial taxonomies were assigned using the Silva reference via QIIME 2. Permutational multivariate analysis of variance, analysis of composition of microbiomes, and linear discriminant analysis effect size were used to compare the gut microbiome between cancer and healthy children.
Results: Children with solid tumors and healthy controls showed no differences in age, race, and BMI; more boys were enrolled in the solid tumor group than the healthy group (p=0.009). Both groups were dominated by phyla Firmicutes and Bacteroidetes. Compared to healthy children, children with solid tumors had significantly lower α-diversity metrics: Shannon p=0.042 and Chao1 p=0.015; children pre- (Shannon p=0.021; Chao1 p=0.024) and post-chemotherapy (Shannon p=0.011; Chao1 p=0.025) showed lower α-diversity metrics than healthy children; and difference was not significant between children pre- and post-chemotherapy. The β-diversity analysis (Bray-Curtis distance) showed that study group (p=0.008), gender (p=0.017), race (p=0.009), and cancer type (p=0.001) impacted the gut microbiome dissimilarities. Children with solid tumors had a lower abundance of phylum Verrucomicrobiotaand a higher abundance of genus Acidaminoccous than healthy controls; healthy children had a higher abundance of beneficial genera Prevotella and Akkermansia. Children with solid tumors had enriched in pathogenic oropportunistically pathogenic genera Clostridioides and Enterococcus. Children post all chemotherapy had enriched genera Blautia and CAG-352 associated with gut-brain axis.
Conclusions: Children with solid tumors suggested different diversity profiles of the gut microbiome and a higher abundance of pathogenic taxa than healthy children. These different gut microbial profiles may be associated with treatment toxicities. Additional studies are needed to further corroborate these associations in children with cancer and reveal the underlying mechanisms.
Citation Format: Jinbing Bai, Kumru Kocaman, Julia Slack, Melissa Martin, Christie Powell, Kathryn S. Sutton, Bradley George, Thomas Olson, Konstantinos T. Konstantinidis, Deborah W. Bruner. Comparison of the gut microbiome between children with solid tumor receiving chemotherapy and healthy children [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 720.