Gastrointestinal toxicity during induction treatment for childhood acute lymphoblastic leukemia: the impact of the gut microbiota
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Gastrointestinal toxicity during induction treatment for childhood acute lymphoblastic leukemia : the impact of the gut microbiota. / De Pietri, Silvia; Ingham, Anna C.; Frandsen, Thomas L.; Rathe, Mathias; Krych, Lukasz; Castro-Mejía, Josue L.; Nielsen, Dennis S.; Nersting, Jacob; Wehner, Peder S.; Schmiegelow, Kjeld; Hasle, Henrik; Pamp, Sünje J.; Müller, Klaus.
In: International Journal of Cancer, Vol. 147, No. 7, 2020, p. 1953-1962.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Gastrointestinal toxicity during induction treatment for childhood acute lymphoblastic leukemia
T2 - the impact of the gut microbiota
AU - De Pietri, Silvia
AU - Ingham, Anna C.
AU - Frandsen, Thomas L.
AU - Rathe, Mathias
AU - Krych, Lukasz
AU - Castro-Mejía, Josue L.
AU - Nielsen, Dennis S.
AU - Nersting, Jacob
AU - Wehner, Peder S.
AU - Schmiegelow, Kjeld
AU - Hasle, Henrik
AU - Pamp, Sünje J.
AU - Müller, Klaus
PY - 2020
Y1 - 2020
N2 - 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 < 0.05) and with citrulline on Days 15 and 29 (although with p values <0.06, rho = 0.32–0.34). The abundance of unclassified Enterococcus species (spp.) was correlated with CRP on Days 22–29 (rho = 0.42–0.49; p < 0.009), while the abundance of unclassified Lachnospiraceae spp. was correlated with citrulline on days 8–15 (rho = 0.48–0.62, p < 0.001). Systemic inflammation, enterocyte loss and relative abundance of unclassified Enterococcus spp. reached a peak around Day 15. In conclusion, specific changes in the microbiota were associated with the severity of enterocyte loss and systemic inflammation during chemotherapy.
AB - 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 < 0.05) and with citrulline on Days 15 and 29 (although with p values <0.06, rho = 0.32–0.34). The abundance of unclassified Enterococcus species (spp.) was correlated with CRP on Days 22–29 (rho = 0.42–0.49; p < 0.009), while the abundance of unclassified Lachnospiraceae spp. was correlated with citrulline on days 8–15 (rho = 0.48–0.62, p < 0.001). Systemic inflammation, enterocyte loss and relative abundance of unclassified Enterococcus spp. reached a peak around Day 15. In conclusion, specific changes in the microbiota were associated with the severity of enterocyte loss and systemic inflammation during chemotherapy.
KW - acute lymphoblastic leukemia
KW - C-reactive protein
KW - citrulline
KW - gastrointestinal toxicity
KW - microbiota
KW - mucositis
U2 - 10.1002/ijc.32942
DO - 10.1002/ijc.32942
M3 - Journal article
C2 - 32115690
AN - SCOPUS:85081719554
VL - 147
SP - 1953
EP - 1962
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 7
ER -
ID: 240143611