Abstract 6731: Gut microbiome associated with the psychoneurological symptom cluster among children with solid tumors receiving chemotherapy
Authors: Bai Jinbing , Martin Melissa , Sutton Kathryn S. , Powell Christie , Olson Thomas , Noh Hye In , Swartz Maria C. , Bruner Deborah Watkins 
Published: April 2023

Background: Children with cancer (CWC) receiving chemotherapy (chemo) report significant suffering from a cluster of psychoneurological symptoms (PNS), including pain, fatigue, anxiety, depression, and cognitive dysfunction. Continuous or severe PNS reduce a child’s quality of life. Chemo can disturb the gut microbiome (GM), which is associated with PNS based on the gut-brain axis. This study aimed to examine associations of GM with PNS and the PNS cluster in CWC undergoing chemo.

Methods: An observational prospective study was conducted in 21 CWC enrolled from Children’s Healthcare of Atlanta. Children with at least 1 cycle of chemo were consented pre-cycle 2 chemo (T1) and followed at the end of chemo (T2). At T1, parents reported children’s demographics; at T1 and T2, PNS (pain, fatigue, anxiety, depression, cognitive dysfunction) were reported by children by the Pediatric PROMIS scales and fecal specimens were collected for GM. T-score of the PROMIS scales was computed; an average of T-scores of the five PNS was computed for the PNS cluster. T-score &gt;50 indicates a significant symptom or symptom cluster. 16S rRNA V4 gene from fecal specimens was sequenced for GM. QIIME 2 was used to examine associations of α- and β-diversity with PNS. Linear discriminant analysis effect size identified microbial taxa associated with each PNS and the PNS cluster.

Results: We analyzed 21 CWC with a mean age of 13 years, 67% male, and 67% white. Children at T2 had higher fatigue (54% vs. 43%), cognitive dysfunction (69% vs. 43%), depressive symptoms (23% vs. 19%), and multiple PNS (62% vs. 48%), but lower pain interference (31% vs. 38%) and anxiety (23% vs. 38%) than those at T1. No association was found for α-diversity at T1; higher α-diversity was associated with lower cognitive dysfunction (Faith’s phylogenetic diversity, p=0.04) and anxiety (Pielou’s_e, p=0.08) at T2; β-diversity (Jaccard distance) showed the GM dissimilarities by levels of pain interference (moderate vs. severe, p=0.02) and levels of anxiety (mild vs. moderate, p=0.07). After controlling for study timepoint, children with low pain interference had an enriched Bacteroides; those with low fatigue had enriched Bacteroides and Turicibacter; those with normal cognitive function had enriched Parasutterella, UBA1819, NK4A214, Sellimonas, and Ruminococcaceae. Children without the PNS cluster had enriched Bacteroides, while those with the PNS cluster had enriched Enterobacteriaceae. Children without multiple PNS had enriched UCG_003.

Conclusions: Children with low PNS showed a higher α-diversity and a higher abundance of taxa involved in nutrition and vitamin metabolism (eg, Bacteroides), reducing inflammation (eg, Turicibacter), and producing short chain fatty acids (eg, Ruminococcaceae). These findings provide potential solutions to treat PNS. Further work is needed to corroborate these associations in CWC.

Citation Format: Jinbing Bai, Melissa Martin, Kathryn S. Sutton, Christie Powell, Thomas Olson, Hye In Noh, Maria C. Swartz, Deborah Watkins Bruner. Gut microbiome associated with the psychoneurological symptom cluster among children with solid tumors receiving chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6731.