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The Impact of Gut Microbiota Changes on Methotrexate-Induced Neurotoxicity in Developing Young Rats

Yu-Chieh Chen1,2,3, Chih-Yao Hou4, Mei-Hsin Hsu1

  • 1Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan.

Biomedicines
|April 27, 2024
PubMed

Insights

Methotrexate (MTX) treatment for childhood acute lymphoblastic leukemia (ALL) may cause neurotoxicity. This study links MTX-induced gut dysbiosis to altered gut-brain axis communication and impaired neurogenesis.

Area of Science:

  • Neuroscience
  • Microbiology
  • Pediatric Oncology

Background:

  • Methotrexate (MTX) is crucial for treating childhood acute lymphoblastic leukemia (ALL).
  • Survivors often experience cognitive deficits, with gut microbiota-brain interactions implicated in chemotherapy-induced brain injury.
  • Previous research on MTX's gut microbiota effects focused solely on gastrointestinal toxicity.

Purpose of the Study:

  • To investigate the gut-brain axis communication in response to MTX treatment in a young rat model mimicking pediatric ALL protocols.
  • To explore the association between MTX-induced gut microbiota alterations and neurogenesis/repair processes.

Main Methods:

  • Developed a young rat model to simulate MTX treatment protocols used in pediatric ALL.
  • Analyzed the impact of MTX on gut microbiota composition and neurogenesis/repair markers.

Main Results:

  • MTX treatment led to significant changes in gut microbiota composition (gut dysbiosis).
  • An association was observed between gut microbiota alterations and impaired neurogenesis/repair processes.
  • These findings suggest MTX neurotoxicity may be mediated by altered gut-brain axis communication.

Conclusions:

  • MTX treatment in pediatric ALL is linked to gut dysbiosis.
  • Altered gut-brain axis communication due to MTX-induced gut dysbiosis may contribute to neurotoxicity.
  • Targeting the gut microbiota could be a potential strategy to mitigate MTX-related cognitive deficits.
Keywords:
chemotherapycognitive impairmentgut microbiotamethotrexateneurotoxicity

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