Gastrointestinal toxicity during induction treatment for childhood acute lymphoblastic leukemia: The impact of the gut microbiota

Silvia De Pietri*, Anna Cäcilia Ingham, Thomas L. Frandsen, Mathias Rathe, Lukasz Krych, Josue L. Castro‐Mejía, Dennis S. Nielsen, Jacob Nersting, Peder S. Wehner, Kjeld Schmiegelow, Henrik Hasle, Sünje Johanna Pamp, Klaus Müller

*Corresponding author for this work

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Abstract

Intestinal mucositis is a common side effect of chemotherapy leading to diarrhea, abdominal pain and increased risk of infections. The intestinal microbiota has been recognized as a key regulator of mucosal immune responses. Therefore, we hypothesized that intestinal microbial changes would be associated with enterocyte loss and systemic inflammation during induction treatment for childhood acute lymphoblastic leukemia (ALL). We prospectively included 51 children newly‐diagnosed with ALL treated in Denmark in 2015–2018. Plasma C‐reactive protein (CRP), plasma citrulline (marker of functional enterocytes mass) measurements and fecal samplings were performed on treatment Days 1, 8, 15, 22 and 29. Moreover, intestinal mucositis was scored by a trained nurse/physician. Fecal samples in patients and 19 healthy siblings were analyzed by 16S rRNA gene sequencing (V3–V4 region). Bacterial alpha diversity was lower in patients compared to siblings. It decreased from Day 1 to Days 8–22 and increased on Day 29. Shannon alpha diversity index was correlated with CRP on Days 15–29 (rho = −0.33−0.49; p 
Original languageEnglish
JournalInternational Journal of Cancer
Volume147
Issue number7
Pages (from-to)1953-1962
ISSN0020-7136
DOIs
Publication statusPublished - 2020

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