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

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Author

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. / Gastrointestinal toxicity during induction treatment for childhood acute lymphoblastic leukemia : The impact of the gut microbiota. I: International Journal of Cancer. 2020 ; Bind 147, Nr. 7. s. 1953-1962.

Bibtex

@article{539cb1529680444499a221c909df2e70,
title = "Gastrointestinal toxicity during induction treatment for childhood acute lymphoblastic leukemia: The impact of the gut microbiota",
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 < 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.",
author = "{De Pietri}, Silvia and Ingham, {Anna C} and Frandsen, {Thomas L} and Mathias Rathe and Lukasz Krych and Castro-Mej{\'i}a, {Josue L} and Nielsen, {Dennis S} and Jacob Nersting and Wehner, {Peder S} and Kjeld Schmiegelow and Henrik Hasle and Pamp, {S{\"u}nje J} and Klaus M{\"u}ller",
note = "{\textcopyright} 2020 UICC.",
year = "2020",
month = oct,
day = "1",
doi = "10.1002/ijc.32942",
language = "English",
volume = "147",
pages = "1953--1962",
journal = "International Journal of Cancer",
issn = "0020-7136",
publisher = "JohnWiley & Sons, Inc",
number = "7",

}

RIS

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

N1 - © 2020 UICC.

PY - 2020/10/1

Y1 - 2020/10/1

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.

U2 - 10.1002/ijc.32942

DO - 10.1002/ijc.32942

M3 - Journal article

C2 - 32115690

VL - 147

SP - 1953

EP - 1962

JO - International Journal of Cancer

JF - International Journal of Cancer

SN - 0020-7136

IS - 7

ER -

ID: 61865737