Changes in gut microbiota predict neutropenia after induction treatment in childhood acute lymphoblastic leukemia

Maria Ebbesen Sørum; Ulrika Boulund; Silvia De Pietri; Sarah Weischendorff; Christian Enevold; Mathias Rathe; Bodil Als-Nielsen; Henrik Hasle; Sünje Johanna Pamp; Jakob Stokholm; Klaus Müller

doi:10.1182/bloodadvances.2024013986

Changes in gut microbiota predict neutropenia after induction treatment in childhood acute lymphoblastic leukemia

Maria Ebbesen Sørum^*, Ulrika Boulund, Silvia De Pietri, Sarah Weischendorff, Christian Enevold, Mathias Rathe, Bodil Als-Nielsen, Henrik Hasle, Sünje Johanna Pamp, Jakob Stokholm, Klaus Müller

^*Corresponding author for this work

Department of Clinical Medicine - Department of Paediatrics

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

1 Citation (Scopus)

Abstract

Delayed neutrophil recovery during acute lymphoblastic leukemia (ALL) treatment increases the risk of infection and causes delay in chemotherapy. Emerging evidence implicates gut microbiota in neutrophil reconstitution after chemotherapy. We explored the interplay between the gut microbiota and neutrophil dynamics, including neutrophil chemoattractants, in 51 children with newly diagnosed ALL. Daily absolute neutrophil count (ANC), weekly plasma chemokines (CXCL1 and CXCL8), granulocyte colony-stimulating factor (G-CSF), and fecal samples were monitored until day 29 during ALL induction treatment. Fecal sequencing using 16S ribosomal RNA revealed an overall significant reduction in bacterial diversity and Enterococcus overgrowth throughout the induction treatment. Prolonged neutropenia (ANC <0.5 × 10⁹ cells per L at day 36) and elevated chemokine levels were associated with a decreased abundance of genera from the Ruminococcaceae and Lachnospiraceae families, decreased Veillonella genus, and Enterococcus overgrowth from diagnosis and throughout induction treatment. G-CSF was upregulated in response to neutropenia but was unrelated to microbiota changes. Overall, this study revealed that a diminished abundance of specific intestinal commensals and Enterococcus overgrowth is associated with delayed neutrophil reconstitution and increased chemokine signaling, indicating that disruption of the microbiota may contribute to prolonged neutropenia. These findings lay the groundwork for future investigations into the mechanisms underlying these associations and their clinical implications for developing gut-sparring strategies to minimize the impact of gut dysbiosis on immune recovery.

Original language	English
Journal	Blood Advances
Volume	9
Issue	7
Pages (from-to)	1508-1521
Number of pages	14
ISSN	2473-9529
DOIs	https://doi.org/10.1182/bloodadvances.2024013986
Publication status	Published - 8 Apr 2025

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@article{2ee8ecf749364f1ebad3eb798f054762,

title = "Changes in gut microbiota predict neutropenia after induction treatment in childhood acute lymphoblastic leukemia",

abstract = "Delayed neutrophil recovery during acute lymphoblastic leukemia (ALL) treatment increases the risk of infection and causes delay in chemotherapy. Emerging evidence implicates gut microbiota in neutrophil reconstitution after chemotherapy. We explored the interplay between the gut microbiota and neutrophil dynamics, including neutrophil chemoattractants, in 51 children with newly diagnosed ALL. Daily absolute neutrophil count (ANC), weekly plasma chemokines (CXCL1 and CXCL8), granulocyte colony-stimulating factor (G-CSF), and fecal samples were monitored until day 29 during ALL induction treatment. Fecal sequencing using 16S ribosomal RNA revealed an overall significant reduction in bacterial diversity and Enterococcus overgrowth throughout the induction treatment. Prolonged neutropenia (ANC <0.5 × 109 cells per L at day 36) and elevated chemokine levels were associated with a decreased abundance of genera from the Ruminococcaceae and Lachnospiraceae families, decreased Veillonella genus, and Enterococcus overgrowth from diagnosis and throughout induction treatment. G-CSF was upregulated in response to neutropenia but was unrelated to microbiota changes. Overall, this study revealed that a diminished abundance of specific intestinal commensals and Enterococcus overgrowth is associated with delayed neutrophil reconstitution and increased chemokine signaling, indicating that disruption of the microbiota may contribute to prolonged neutropenia. These findings lay the groundwork for future investigations into the mechanisms underlying these associations and their clinical implications for developing gut-sparring strategies to minimize the impact of gut dysbiosis on immune recovery.",

author = "S{\o}rum, {Maria Ebbesen} and Ulrika Boulund and {De Pietri}, Silvia and Sarah Weischendorff and Christian Enevold and Mathias Rathe and Bodil Als-Nielsen and Henrik Hasle and Pamp, {S{\"u}nje Johanna} and Jakob Stokholm and Klaus M{\"u}ller",

year = "2025",

month = apr,

day = "8",

doi = "10.1182/bloodadvances.2024013986",

language = "English",

volume = "9",

pages = "1508--1521",

journal = "Blood Advances",

issn = "2473-9529",

publisher = "American Society of Hematology",

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Changes in gut microbiota predict neutropenia after induction treatment in childhood acute lymphoblastic leukemia. / Sørum, Maria Ebbesen; Boulund, Ulrika; De Pietri, Silvia et al.
In: Blood Advances, Vol. 9, No. 7, 08.04.2025, p. 1508-1521.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Changes in gut microbiota predict neutropenia after induction treatment in childhood acute lymphoblastic leukemia

AU - Sørum, Maria Ebbesen

AU - Boulund, Ulrika

AU - De Pietri, Silvia

AU - Weischendorff, Sarah

AU - Enevold, Christian

AU - Rathe, Mathias

AU - Als-Nielsen, Bodil

AU - Hasle, Henrik

AU - Pamp, Sünje Johanna

AU - Stokholm, Jakob

AU - Müller, Klaus

PY - 2025/4/8

Y1 - 2025/4/8

N2 - Delayed neutrophil recovery during acute lymphoblastic leukemia (ALL) treatment increases the risk of infection and causes delay in chemotherapy. Emerging evidence implicates gut microbiota in neutrophil reconstitution after chemotherapy. We explored the interplay between the gut microbiota and neutrophil dynamics, including neutrophil chemoattractants, in 51 children with newly diagnosed ALL. Daily absolute neutrophil count (ANC), weekly plasma chemokines (CXCL1 and CXCL8), granulocyte colony-stimulating factor (G-CSF), and fecal samples were monitored until day 29 during ALL induction treatment. Fecal sequencing using 16S ribosomal RNA revealed an overall significant reduction in bacterial diversity and Enterococcus overgrowth throughout the induction treatment. Prolonged neutropenia (ANC <0.5 × 109 cells per L at day 36) and elevated chemokine levels were associated with a decreased abundance of genera from the Ruminococcaceae and Lachnospiraceae families, decreased Veillonella genus, and Enterococcus overgrowth from diagnosis and throughout induction treatment. G-CSF was upregulated in response to neutropenia but was unrelated to microbiota changes. Overall, this study revealed that a diminished abundance of specific intestinal commensals and Enterococcus overgrowth is associated with delayed neutrophil reconstitution and increased chemokine signaling, indicating that disruption of the microbiota may contribute to prolonged neutropenia. These findings lay the groundwork for future investigations into the mechanisms underlying these associations and their clinical implications for developing gut-sparring strategies to minimize the impact of gut dysbiosis on immune recovery.

AB - Delayed neutrophil recovery during acute lymphoblastic leukemia (ALL) treatment increases the risk of infection and causes delay in chemotherapy. Emerging evidence implicates gut microbiota in neutrophil reconstitution after chemotherapy. We explored the interplay between the gut microbiota and neutrophil dynamics, including neutrophil chemoattractants, in 51 children with newly diagnosed ALL. Daily absolute neutrophil count (ANC), weekly plasma chemokines (CXCL1 and CXCL8), granulocyte colony-stimulating factor (G-CSF), and fecal samples were monitored until day 29 during ALL induction treatment. Fecal sequencing using 16S ribosomal RNA revealed an overall significant reduction in bacterial diversity and Enterococcus overgrowth throughout the induction treatment. Prolonged neutropenia (ANC <0.5 × 109 cells per L at day 36) and elevated chemokine levels were associated with a decreased abundance of genera from the Ruminococcaceae and Lachnospiraceae families, decreased Veillonella genus, and Enterococcus overgrowth from diagnosis and throughout induction treatment. G-CSF was upregulated in response to neutropenia but was unrelated to microbiota changes. Overall, this study revealed that a diminished abundance of specific intestinal commensals and Enterococcus overgrowth is associated with delayed neutrophil reconstitution and increased chemokine signaling, indicating that disruption of the microbiota may contribute to prolonged neutropenia. These findings lay the groundwork for future investigations into the mechanisms underlying these associations and their clinical implications for developing gut-sparring strategies to minimize the impact of gut dysbiosis on immune recovery.

UR - http://www.scopus.com/inward/record.url?scp=105001876617&partnerID=8YFLogxK

U2 - 10.1182/bloodadvances.2024013986

DO - 10.1182/bloodadvances.2024013986

M3 - Journal article

C2 - 39561377

SN - 2473-9529

VL - 9

SP - 1508

EP - 1521

JO - Blood Advances

JF - Blood Advances

IS - 7

ER -

Changes in gut microbiota predict neutropenia after induction treatment in childhood acute lymphoblastic leukemia

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