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Changes in gut, microbiome, and cognition after doxorubicin, cyclophosphamide, and paclitaxel chemotherapy treatment

Cronin, Bailey, Kandel, Sangam, McElroy, Taylor, Syed, Sofia, Swinton, Chase, Corley, Christa, Sridharan, Vijayalakshmi, Robeson, Michael S., Allen, Antiño R.·2026·Scientific Reports
DOI 10.1038/s41598-025-33903-w
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  1. Giaquinto, A. N. et al. Breast Cancer Statistics, 2022. CA: A Cancer Journal for Clinicians, 72(6): 524–541. (2022). · DOI · Paper page
  2. Xiong, X. et al. Breast cancer: pathogenesis and treatments. Signal. Transduct. Target. Ther. 10 (1), 49 (2025). · DOI · Paper page
  3. Vuksanovic, D. et al. Unmet needs in breast cancer survivors are common, and multidisciplinary care is underutilised: the survivorship needs assessment project. Breast Cancer. 28 (2), 289–297 (2021). · DOI
  4. Ewertz, M. & Jensen, A. B. Late effects of breast cancer treatment and potentials for rehabilitation. Acta Oncol. 50 (2), 187–193 (2011). · DOI · Paper page
  5. Coughlin, S. S., Ayyala, D. N. & Cortes, J. E. Problems in living among breast cancer survivors. Curr. Cancer Rep. 3 (1), 101–109 (2021). · DOI
  6. Hinz, A. et al. Quality of life domains in breast cancer survivors: the relationship between importance and satisfaction ratings. Front. Psychol. 13, 923537 (2022). · DOI
  7. Argyriou, A. A. et al. Either called chemobrain or chemofog, the long-term chemotherapy-induced cognitive decline in cancer survivors is real. J. Pain Symptom Manage. 41 (1), 126–139 (2011). · DOI · Paper page
  8. Whittaker, A. L., George, R. P. & O’Malley, L. Prevalence of cognitive impairment following chemotherapy treatment for breast cancer: a systematic review and meta-analysis. Sci. Rep. 12 (1), 2135 (2022). · DOI · Paper page
  9. Rao, V. et al. Chemobrain: A review on mechanistic insight, targets and treatments. Adv. Cancer Res. 155, 29–76 (2022). · DOI
  10. Lomeli, N. et al. Cognitive complications of cancer and cancer-related treatments - Novel paradigms. Neurosci. Lett. 749, 135720 (2021). · DOI
  11. Gutenkunst, S. L. et al. Correlates of cognitive impairment in adult cancer survivors who have received chemotherapy and report cognitive problems. Support Care Cancer. 29 (3), 1377–1386 (2021).
  12. Dyk, K. V. et al. Identifying Cancer-Related cognitive impairment using the FACT-Cog perceived cognitive impairment. JNCI Cancer Spectr. 4 (1), pkz099 (2020). · DOI
  13. Costa, D. S. J. et al. The structure of the FACT-Cog v3 in cancer Patients, Students, and older adults. J. Pain Symptom Manage. 55 (4), 1173–1178 (2018). · DOI
  14. Coombes, R. C. et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. The international collaborative cancer group. J. Clin. Oncol. 14 (1), 35–45 (1996). · doi:10.1200/jco.1996.14.1.35
  15. Coombes, R. C. et al. Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. The international collab. J. Clin. Oncol. 14, 35–45 (1996). · doi:10.1200/jco.1996.14.1.35
  16. Singh, R. K. et al. Therapeutic journery of nitrogen mustard as alkylating anticancer agents: historic to future perspectives. Eur. J. Med. Chem. 151, 401–433 (2018). · DOI · Paper page
  17. Patai, R. et al. Transcriptomic profiling of senescence effects on blood-brain barrier-related gene expression in brain capillary endothelial cells in a mouse model of paclitaxel-induced chemobrain. Geroscience 47 (3), 3677–3691 (2025). · DOI
  18. Osen, A. et al. Cyclophosphamide for severe acute forms of central nervous system inflammatory disorders. J. Neurol. Sci. 451, 120693 (2023). · DOI
  19. Ibrahim, K. M. et al. Molecular mechanisms underlying cyclophosphamide-induced cognitive impairment and strategies for neuroprotection in preclinical models. Mol. Cell. Biochem. 479 (8), 1873–1893 (2024). · DOI
  20. Thorn, C. F. et al. Doxorubicin pathways: pharmacodynamics and adverse effects. Pharmacogenet Genomics. 21 (7), 440–446 (2011). · DOI · Paper page
  21. Carvalho, C. et al. Doxorubicin: the good, the bad and the ugly effect. Curr. Med. Chem. 16 (25), 3267–3285 (2009). · DOI · Paper page
  22. Kampan, N. C. et al. Paclitaxel and Its Evolving Role in the Management of Ovarian Cancer. Biomed Res Int, 2015: 413076. (2015). · DOI · Paper page
  23. Henderson, I. C. et al. Improved outcomes from adding sequential Paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J. Clin. Oncol. 21, 976–983 (2003). · DOI · Paper page
  24. Sougiannis, A. T. et al. Understanding chemotherapy-induced intestinal mucositis and strategies to improve gut resilience. Am. J. Physiol. Gastrointest. Liver Physiol. 320 (5), G712–g719 (2021). · DOI · Paper page
  25. Yasuda, M. et al. Potential role of the NADPH oxidase NOX1 in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice. Am. J. Physiol. Gastrointest. Liver Physiol. 302 (10), G1133–G1142 (2012). · DOI
  26. Li, S., Zhu, S. & Yu, J. The role of gut microbiota and metabolites in cancer chemotherapy. J. Adv. Res. 64, 223–235 (2024). · DOI
  27. Grant, C. V. et al. Microglia are implicated in the development of Paclitaxel chemotherapy-associated cognitive impairment in female mice. Brain Behav. Immun. 108, 221–232 (2023). · DOI
  28. Loman, B. R. et al. Chemotherapy-induced neuroinflammation is associated with disrupted colonic and bacterial homeostasis in female mice. Sci. Rep. 9 (1), 16490 (2019). · DOI
  29. Yardim, A. et al. Silymarin alleviates docetaxel-induced central and peripheral neurotoxicity by reducing oxidative stress, inflammation and apoptosis in rats. Gene 769, 145239 (2021). · doi:10.1016/j.gene.2020.145239
  30. Liu, Q. et al. Effects of docetaxel injection and docetaxel micelles on the intestinal barrier and intestinal microbiota. Adv. Sci. (Weinh). 8 (24), e2102952 (2021). · DOI
  31. Peirce, J. M. & Alvina, K. The role of inflammation and the gut Microbiome in depression and anxiety. J. Neurosci. Res. 97 (10), 1223–1241 (2019). · DOI · Paper page
  32. Alharthi, A. et al. The human gut Microbiome as a potential factor in autism spectrum disorder. Int. J. Mol. Sci. 23 (3), 1363 (2022). · DOI
  33. Ozcan, E. & Hsiao, E. Y. Are changes in the gut Microbiome a contributor or consequence of autism-why not both? Cell. Rep. Med. 3 (1), 100505 (2022). · DOI
  34. Cattaneo, A. et al. Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiol. Aging. 49, 60–68 (2017). · DOI · Paper page
  35. Toh, T. S. et al. Gut Microbiome in parkinson’s disease: new insights from meta-analysis. Parkinsonism Relat. Disord. 94, 1–9 (2022). · DOI
  36. Cantoni, C. et al. Alterations of host-gut Microbiome interactions in multiple sclerosis. EBioMedicine 76, 103798 (2022). · DOI
  37. Nagpal, J. & Cryan, J. F. Host genetics, the Microbiome & behaviour-a ‘Holobiont’ perspective. Cell. Res. 31 (8), 832–833 (2021). · DOI
  38. Cryan, J. F. et al. The gut Microbiome in neurological disorders. Lancet Neurol. 19 (2), 179–194 (2020). · DOI · Paper page
  39. Carloni, S. & Rescigno, M. The gut-brain vascular axis in neuroinflammation. Semin Immunol. 69, 101802 (2023). · DOI
  40. Dalile, B. et al. The role of short-chain fatty acids in microbiota-gut-brain communication. Nat. Rev. Gastroenterol. Hepatol. 16 (8), 461–478 (2019). · DOI · Paper page
  41. Ren, X. et al. Plausible biochemical mechanisms of chemotherapy-induced cognitive impairment (chemobrain), a condition that significantly impairs the quality of life of many cancer survivors. Biochim. Biophys. Acta Mol. Basis Dis. 1865 (6), 1088–1097 (2019). · DOI
  42. Patel, C. et al. Doxorubicin causes cognitive impairment and alters gut microbiota in both male and female juvenile rats. Sci. Rep. 15 (1), 27448 (2025). · DOI
  43. Konduri, S. et al. Epidemiology of male breast cancer. Breast 54, 8–14 (2020). · DOI · Paper page
  44. McElroy, T. et al. Assessing the effects of redox modifier MnTnBuOE-2-PyP 5 + on cognition and hippocampal physiology following Doxorubicin, Cyclophosphamide, and Paclitaxel treatment. Int. J. Mol. Sci. 21 (5), 1867 (2020). · DOI
  45. Yang, M., Silverman, J. L. & Crawley, J. N. Automated three-chambered social approach task for mice. Curr. Protoc. Neurosci. Chapter 8: Unit 8.26 (2011). · DOI · Paper page
  46. Corley, C. et al. Physiological and cognitive changes after treatments of cyclophosphamide, methotrexate, and fluorouracil: implications of the gut Microbiome and depressive-like behavior. Front. Neurosci. 17, 1212791 (2023). · DOI
  47. Semple, B. D., Canchola, S. A. & Noble-Haeusslein, L. J. Deficits in social behavior emerge during development after pediatric traumatic brain injury in mice. J. Neurotrauma. 29 (17), 2672–2683 (2012). · DOI
  48. La-Vu, M. et al. To approach or avoid: an introductory overview of the study of anxiety using rodent assays. Front. Behav. Neurosci. 14, 145 (2020). · DOI · Paper page
  49. Krämer, A. et al. Causal analysis approaches in ingenuity pathway analysis. Bioinformatics 30 (4), 523–530 (2014). · DOI · Paper page
  50. Banerjee, S. et al. Loss of C/EBPdelta exacerbates Radiation-Induced cognitive decline in aged mice due to impaired oxidative stress response. Int. J. Mol. Sci. 20 (4), 885 (2019). · DOI
  51. Nesvizhskii, A. I. et al. A statistical model for identifying proteins by tandem mass spectrometry. Anal. Chem. 75 (17), 4646–4658 (2003). · DOI · Paper page
  52. Graw, S. et al. proteiNorm - A User-Friendly tool for normalization and analysis of TMT and Label-Free protein quantification. ACS Omega. 5 (40), 25625–25633 (2020). · DOI · Paper page
  53. Banerjee, S. et al. C/EBPdelta protects from radiation-induced intestinal injury and sepsis by suppression of inflammatory and nitrosative stress. Sci. Rep. 9 (1), 13953 (2019). · DOI
  54. Bolyen, E. et al. Reproducible, interactive, scalable and extensible Microbiome data science using QIIME 2. Nat. Biotechnol. 37 (8), 852–857 (2019). · DOI · Paper page
  55. Callahan, B. J., McMurdie, P. J. & Holmes, S. P. Exact sequence variants should replace operational taxonomic units in marker-gene data analysis. ISME J. 11 (12), 2639–2643 (2017). · DOI · Paper page
  56. Callahan, B. J. et al. DADA2: High-resolution sample inference from illumina amplicon data. Nat. Methods. 13 (7), 581–583 (2016). · DOI · Paper page
  57. Abraham, A. et al. Machine learning for neuroimaging with scikit-learn. Front. Neuroinform. 8, 14 (2014). · DOI · Paper page
  58. Bokulich, N. A. et al. Optimizing taxonomic classification of marker-gene amplicon sequences with QIIME 2’s q2-feature-classifier plugin. Microbiome 6 (1), 90 (2018). · DOI · Paper page
  59. Quast, C. et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res. 41 (Database issue), D590–D596 (2013).
  60. Robeson, M. S. 2 et al. RESCRIPt: reproducible sequence taxonomy reference database management. PLoS Comput. Biol. 17 (11), e1009581 (2021). · doi:10.1371/journal.pcbi.1009581
  61. Camacho, C. et al. BLAST+: architecture and applications. BMC Bioinform. 10, 421 (2009). · DOI · Paper page
  62. Katoh, K. & Standley, D. M. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol. Biol. Evol. 30 (4), 772–780 (2013). · DOI · Paper page
  63. Nguyen, L. T. et al. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol. Biol. Evol. 32 (1), 268–274 (2015). · DOI · Paper page
  64. Kalyaanamoorthy, S. et al. ModelFinder: fast model selection for accurate phylogenetic estimates. Nat. Methods. 14 (6), 587–589 (2017). · DOI · Paper page
  65. Janssen, S. et al. Phylogenetic placement of exact amplicon sequences improves associations with clinical information. mSystems. 3 (3), e00021–18 (2018). · DOI · Paper page
  66. Willis, A. D. Rarefaction, alpha Diversity, and statistics. Front. Microbiol. 10, 2407 (2019). · DOI · Paper page
  67. McMurdie, P. J. & Holmes, S. Waste not, want not: why rarefying Microbiome data is inadmissible. PLoS Comput. Biol. 10 (4), e1003531 (2014). · DOI · Paper page
  68. Lozupone, C. & Knight, R. UniFrac: a new phylogenetic method for comparing microbial communities. Appl. Environ. Microbiol. 71 (12), 8228–8235 (2005). · DOI · Paper page
  69. Martino, C. et al. A novel sparse compositional technique reveals microbial perturbations. mSystems. 4 (1), e00016–19 (2019). · DOI · Paper page
  70. Fedarko, M. W. et al. Visualizing ‘omic feature rankings and log-ratios using Qurro. NAR Genom Bioinform. 2 (2), lqaa023 (2020). · DOI · Paper page
  71. Lin, H. & Peddada, S. D. Analysis of compositions of microbiomes with bias correction. Nat. Commun. 11 (1), 3514 (2020). · DOI · Paper page
  72. Jolliffe, I. T. & Cadima, J. Principal component analysis: a review and recent developments. Philos Trans A Math Phys Eng Sci, 374(2065): 20150202. (2016). · DOI · Paper page
  73. Shouib, R., Eitzen, G. & Steenbergen, R. A guide to basic RNA sequencing data processing and transcriptomic analysis. Bio Protoc. 15 (9), e5295 (2025).
  74. Szklarczyk, D. et al. The STRING database in 2023: protein-protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 51 (D1), D638–d646 (2023). · DOI · Paper page
  75. Brown, J. P. et al. Transient expression of doublecortin during adult neurogenesis. J. Comp. Neurol. 467 (1), 1–10 (2003). · DOI · Paper page
  76. Ceanga, M. et al. Adult neurogenesis and stroke: A Tale of two neurogenic niches. Front. Neurosci. 15, 700297 (2021). · DOI
  77. Sekeres, M. J. et al. Chemotherapy-Induced cognitive impairment and hippocampal neurogenesis: A review of physiological mechanisms and interventions. Int. J. Mol. Sci. 22 (23), 12697 (2021). · DOI
  78. Colombo, E. & Farina, C. Astrocytes: key regulators of neuroinflammation. Trends Immunol. 37 (9), 608–620 (2016). · DOI · Paper page
  79. Tang, M. et al. Paclitaxel induces cognitive impairment via necroptosis, decreased synaptic plasticity and M1 polarisation of microglia. Pharm. Biol. 60 (1), 1556–1565 (2022). · DOI
  80. Jansen, C. et al. Potential mechanisms for chemotherapy-induced impairments in cognitive function. Oncol. Nurs. Forum. 32 (6), 1151–1163 (2005). · DOI
  81. Kitamura, Y. et al. Doxorubicin and cyclophosphamide treatment produces anxiety-like behavior and Spatial cognition impairment in rats: possible involvement of hippocampal neurogenesis via brain-derived neurotrophic factor and Cyclin D1 regulation. Behav. Brain Res. 292, 184–193 (2015). · DOI
  82. Kogan, J. H., Frankland, P. W. & Silva, A. J. Long-term memory underlying hippocampus-dependent social recognition in mice. Hippocampus 10 (1), 47–56 (2000). · doi:10.1002/(sici)1098-1063(2000)10:1<47::aid-hipo5>3.0.co;2-6
  83. Rein, B., Ma, K. & Yan, Z. A standardized social preference protocol for measuring social deficits in mouse models of autism. Nat. Protoc. 15 (10), 3464–3477 (2020). · DOI · Paper page
  84. Ntagwabira, F. et al. Piperlongumine as a Neuro-Protectant in chemotherapy induced cognitive impairment. Int. J. Mol. Sci. 23 (4), 1–21 (2022). · DOI
  85. Shivakumar, A. B. et al. Extrahippocampal contributions to social memory: the role of septal nuclei. Biol. Psychiatry. 96 (11), 835–847 (2024). · DOI
  86. Belau, M. H. et al. Social relationships and their impact on health-related quality of life in a long-term breast cancer survivor cohort. Cancer 130 (18), 3210–3218 (2024). · DOI
  87. Yang, Y. et al. Social relationships and their associations with affective symptoms of women with breast cancer: A scoping review. PLoS One. 17 (8), e0272649 (2022). · DOI
  88. Vassilev, I. et al. The role of social networks in the self-management support for young women recently diagnosed with breast cancer. PLoS One. 18 (4), e0282183 (2023). · DOI
  89. Seibenhener, M. L. & Wooten, M. C. Use of the open field maze to measure locomotor and anxiety-like behavior in mice. J. Visualized Experiments: JoVE. 96, e52434–e52434 (2015). · DOI · Paper page
  90. Seibenhener, M. L. & Wooten, M. C. Use of the open field maze to measure locomotor and anxiety-like behavior in mice. J. Vis. Exp. 96, e52434 (2015). · DOI · Paper page
  91. Choleris, E. et al. A detailed ethological analysis of the mouse open field test: effects of diazepam, chlordiazepoxide and an extremely low frequency pulsed magnetic field. Neurosci. Biobehav Rev. 25 (3), 235–260 (2001). · DOI · Paper page
  92. Fuchs, E. & Flïugge, G. Experimental animal models for the simulation of depression and anxiety. Dialog. Clin. Neurosci. 8 (3), 323–333 (2006). · DOI
  93. Heidary, Z. et al. Quality of life in breast cancer patients: A systematic review of the qualitative studies. Cancer Control. 30, 10732748231168318 (2023). · DOI
  94. Byron, S. A. et al. Translating RNA sequencing into clinical diagnostics: opportunities and challenges. Nat. Rev. Genet. 17 (5), 257–271 (2016). · DOI · Paper page
  95. Catela, C. et al. The Iroquois (Iro/Irx) homeobox genes are conserved Hox targets involved in motor neuron development. bioRxiv, (2024). · doi:10.1101/2024.05.30.596714
  96. Dou, Z., Son, J. E. & Hui, C. C. Irx3 and Irx5 - Novel regulatory factors of postnatal hypothalamic neurogenesis. Front. Neurosci. 15, 763856 (2021). · DOI
  97. Zhang, Q. et al. Temporal requirements for ISL1 in sympathetic neuron proliferation, differentiation, and diversification. Cell. Death Dis. 9 (2), 247 (2018). · DOI
  98. Sherrill, H. E. et al. Pou4f1 defines a subgroup of type I spiral ganglion neurons and is necessary for normal inner hair cell presynaptic Ca(2+) signaling. J. Neurosci. 39 (27), 5284–5298 (2019). · DOI
  99. Zhang, Y. et al. Foxb1 regulates negatively the proliferation of oligodendrocyte progenitors. Front. Neuroanat. 11, 53 (2017). · DOI
  100. Radyushkin, K. et al. Genetic ablation of the mammillary bodies in the Foxb1 mutant mouse leads to selective deficit of Spatial working memory. Eur. J. Neurosci. 21 (1), 219–229 (2005). · DOI
  101. Inazu, M. Functional expression of choline transporters in the Blood-Brain barrier. Nutrients. 11 (10), 2265 (2019). · DOI
  102. Madrid, L. I. et al. Cholinergic regulation of adult hippocampal neurogenesis and hippocampus-dependent functions. Int. J. Biochem. Cell. Biol. 134, 105969 (2021). · DOI
  103. Jung, C. G. et al. Homeotic factor ATBF1 induces the cell cycle arrest associated with neuronal differentiation. Development 132 (23), 5137–5145 (2005). · DOI
  104. Nguyen, L. D. & Ehrlich, B. E. Cellular mechanisms and treatments for chemobrain: insight from aging and neurodegenerative diseases. EMBO Mol. Med. 12 (6), e12075 (2020). · DOI · Paper page
  105. Paylor, R. et al. Learning impairments and motor dysfunctions in adult Lhx5-deficient mice displaying hippocampal disorganization. Physiol. Behav. 73 (5), 781–792 (2001). · DOI
  106. Reijntjes, D. O. J. & Pyott, S. J. The afferent signaling complex: regulation of type I spiral ganglion neuron responses in the auditory periphery. Hear. Res. 336, 1–16 (2016). · DOI
  107. Tönnies, E. & Trushina, E. Oxidative Stress, synaptic Dysfunction, and alzheimer’s disease. J. Alzheimers Dis. 57 (4), 1105–1121 (2017). · DOI · Paper page
  108. Barbosa-Azevedo, M. et al. Chemotherapy-induced cognitive impairment and glia: A new take on chemobrain? Toxicol. Appl. Pharmacol. 492, 117085 (2024). · DOI
  109. Yau, S. Y., Li, A. & So, K. F. Involvement of Adult Hippocampal Neurogenesis in Learning and Forgetting. Neural Plast, 2015: 717958. (2015). · DOI · Paper page
  110. Couillard-Despres, S. et al. Doublecortin expression levels in adult brain reflect neurogenesis. Eur. J. Neurosci. 21 (1), 1–14 (2005). · DOI · Paper page
  111. John, J. et al. Animal models of chemotherapy-induced cognitive decline in preclinical drug development. Psychopharmacol. (Berl). 238 (11), 3025–3053 (2021). · DOI
  112. Vukovic, J. et al. Immature doublecortin-positive hippocampal neurons are important for learning but not for remembering. J. Neurosci. 33 (15), 6603–6613 (2013). · DOI
  113. Christie, L. A. et al. Impaired cognitive function and hippocampal neurogenesis following cancer chemotherapy. Clin. Cancer Res. 18 (7), 1954–1965 (2012). · DOI · Paper page
  114. Lee, B. E. et al. The cancer chemotherapeutic agent Paclitaxel (Taxol) reduces hippocampal neurogenesis via down-regulation of vesicular zinc. Sci. Rep. 7 (1), 11667 (2017). · DOI
  115. Zhang, Y. et al. Progress of Astrocyte-Neuron crosstalk in central nervous system diseases. Neurochem Res. 49 (12), 3187–3207 (2024). · DOI
  116. Ye, Q. et al. Astrocytic Slc4a4 regulates blood-brain barrier integrity in healthy and stroke brains via a CCL2-CCR2 pathway and NO dysregulation. Cell. Rep. 43 (5), 114193 (2024). · DOI
  117. Watkins, S. et al. Disruption of astrocyte-vascular coupling and the blood-brain barrier by invading glioma cells. Nat. Commun. 5, 4196 (2014). · DOI · Paper page
  118. Was, H. et al. Mechanisms of Chemotherapy-Induced neurotoxicity. Front. Pharmacol. 13, 750507 (2022). · DOI · Paper page
  119. Seigers, R. et al. Cognitive impact of cytotoxic agents in mice. Psychopharmacol. (Berl). 232 (1), 17–37 (2015). · DOI
  120. Cardoso, C. V. et al. Chemobrain in rats: Behavioral, morphological, oxidative and inflammatory effects of doxorubicin administration. Behav. Brain Res. 378, 112233 (2020). · DOI
  121. Cabezas, R. et al. Astrocytic modulation of blood brain barrier: perspectives on parkinson’s disease. Front. Cell. Neurosci. 8, 211 (2014). · DOI · Paper page
  122. Stoll, G. & Jander, S. The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol. 58 (3), 233–247 (1999). · DOI · Paper page
  123. Loane, D. J. & Byrnes, K. R. Role of microglia in neurotrauma. Neurotherapeutics 7 (4), 366–377 (2010). · DOI · Paper page
  124. Joo, K. M. et al. Trans-differentiation of neural stem cells: a therapeutic mechanism against the radiation induced brain damage. PLoS One. 7 (2), e25936 (2012). · DOI
  125. Maurer, S. V. & Williams, C. L. The cholinergic system modulates memory and hippocampal plasticity via its interactions with Non-Neuronal cells. Front. Immunol. 8, 1489 (2017). · DOI · Paper page
  126. Murillo, L. C., Sutachan, J. J. & Albarracín, S. L. An update on Neurobiological mechanisms involved in the development of chemotherapy-induced cognitive impairment (CICI). Toxicol. Rep. 10, 544–553 (2023). · DOI
  127. Onzi, G. R. et al. Chemobrain in breast cancer: Mechanisms, clinical Manifestations, and potential interventions. Drug Saf. 45 (6), 601–621 (2022). · DOI
  128. Minatohara, K., Akiyoshi, M. & Okuno, H. Role of Immediate-Early genes in synaptic plasticity and neuronal ensembles underlying the memory trace. Front. Mol. Neurosci. 8, (2016). · DOI · Paper page
  129. Epstein, I. & Finkbeiner, S. The Arc of cognition: signaling cascades regulating Arc and implications for cognitive function and disease. Semin Cell. Dev. Biol. 77, 63–72 (2018). · DOI
  130. Kovács, K. J. Measurement of immediate-early gene activation- c-fos and beyond. J. Neuroendocrinol. 20 (6), 665–672 (2008). · DOI · Paper page
  131. Penke, Z. et al. Zif268/Egr1 gain of function facilitates hippocampal synaptic plasticity and long-term Spatial recognition memory. Philos. Trans. R Soc. Lond. B Biol. Sci. 369 (1633), 20130159 (2014). · DOI
  132. Hoffman, G. E., Smith, M. S. & Verbalis, J. G. c-Fos and related immediate early gene products as markers of activity in neuroendocrine systems. Front. Neuroendocrinol. 14 (3), 173–213 (1993). · DOI · Paper page
  133. Gallo, F. T. et al. Immediate early Genes, memory and psychiatric disorders: focus on c-Fos, Egr1 and Arc. Front. Behav. Neurosci. 12, 79 (2018). · DOI · Paper page
  134. Corley, C. et al. II, Implications of cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy on hippocampal-dependent cognition and gut Microbiome. Front. Microbiomes. 4 , (2025). · DOI
  135. Barker, N., van Oudenaarden, A. & Clevers, H. Identifying the stem cell of the intestinal crypt: strategies and pitfalls. Cell. Stem Cell. 11 (4), 452–460 (2012). · DOI · Paper page
  136. Sankaran-Walters, S., Hart, R. & Dills, C. Guardians Gut: Enteric Defensins Front. Microbiol., 8: 647. (2017).
  137. Villa, A. & Sonis, S. T. Mucositis: pathobiology and management. Curr. Opin. Oncol. 27 (3), 159–164 (2015). · DOI · Paper page
  138. Elting, L. S. et al. The burdens of cancer therapy. Clinical and economic outcomes of chemotherapy-induced mucositis. Cancer 98 (7), 1531–1539 (2003). · DOI · Paper page
  139. Lee, S. I. & Kang, K. S. Function of capric acid in cyclophosphamide-induced intestinal inflammation, oxidative stress, and barrier function in pigs. Sci. Rep. 7 (1), 16530 (2017). · DOI
  140. Carr, J. S., King, S. & Dekaney, C. M. Depletion of enteric bacteria diminishes leukocyte infiltration following doxorubicin-induced small intestinal damage in mice. PLoS One. 12 (3), e0173429 (2017). · DOI
  141. Zang, X. et al. Prevention of paclitaxel-induced neuropathy by formulation approach. J. Control Release. 303, 109–116 (2019). · DOI
  142. Dekaney, C. M. et al. Regeneration of intestinal stem/progenitor cells following doxorubicin treatment of mice. Am. J. Physiol. Gastrointest. Liver Physiol. 297 (3), G461–G470 (2009). · DOI
  143. Levin, G. et al. Novel fluorescence molecular imaging of chemotherapy-induced intestinal apoptosis. J. Biomed. Opt. 14 (5), 054019 (2009). · DOI
  144. van Heel, D. A. Interleukin 15: its role in intestinal inflammation. Gut 55 (4), 444–445 (2006). · doi:10.1136/gut.2005.079335
  145. Waldmann, T. A. Targeting the interleukin-15/interleukin-15 receptor system in inflammatory autoimmune diseases. Arthritis Res. Ther. 6 (4), 174–177 (2004). · doi:10.1186/ar1202
  146. Li, H. et al. Gut microbiota changes in patients with alzheimer’s disease spectrum based on 16S rRNA sequencing: a systematic review and meta-analysis. Front. Aging Neurosci. 16, 1422350 (2024). · DOI
  147. Pisani, A. et al. Dysbiosis in the gut microbiota in patients with inflammatory bowel disease during remission. Microbiol. Spectr. 10 (3), e0061622 (2022). · DOI
  148. Lozupone, C. A. et al. Quantitative and qualitative beta diversity measures lead to different insights into factors that structure microbial communities. Appl. Environ. Microbiol. 73 (5), 1576–1585 (2007). · DOI · Paper page
  149. Palanivelu, L. et al. Interplay of neuroinflammation and gut microbiota dysbiosis in alzheimer’s disease using diffusion kurtosis imaging biomarker in 3 × Tg-AD mouse models. ACS Chem. Neurosci. 16 (8), 1511–1528 (2025). · DOI
  150. Zaplana, T., Miele, S. & Tolonen, A. C. Lachnospiraceae are emerging industrial biocatalysts and biotherapeutics. Front. Bioeng. Biotechnol. 11, 1324396 (2023). · DOI
  151. Vacca, M. et al. The controversial role of human gut lachnospiraceae. Microorganisms. 8 (4), 573 (2020). · DOI · Paper page
  152. Johnson, D. et al. A Microbial-Based approach to mental health: the potential of probiotics in the treatment of depression. Nutrients. 15 (6), 1382 (2023). · DOI
  153. Needham, B. D., Kaddurah-Daouk, R. & Mazmanian, S. K. Gut microbial molecules in behavioural and neurodegenerative conditions. Nat. Rev. Neurosci. 21 (12), 717–731 (2020). · DOI · Paper page
  154. Yang, J. et al. Development of a colorectal cancer diagnostic model and dietary risk assessment through gut Microbiome analysis. Exp. Mol. Med. 51 (10), 1–15 (2019). · DOI
  155. Kandasamy, S. et al. The role of human gut microbe Ruminococcus gnavus in inflammatory diseases. Progress Microbes Mol. Biology. 6 (1), 1–27 (2023). · DOI
  156. Wong, J. M. et al. Colonic health: fermentation and short chain fatty acids. J. Clin. Gastroenterol. 40 (3), 235–243 (2006). · DOI · Paper page
  157. Kim, Y. J., Jung, D. H. & Park, C. S. Important roles of Ruminococcaceae in the human intestine for resistant starch utilization. Food Sci. Biotechnol. 33 (9), 2009–2019 (2024). · DOI
  158. Omenetti, S. & Pizarro, T. T. The Treg/Th17 axis: A dynamic balance regulated by the gut Microbiome. Front. Immunol. 6, 639 (2015). · DOI · Paper page
  159. Loh, J. S. et al. Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases. Signal. Transduct. Target. Ther. 9 (1), 37 (2024). · DOI · Paper page
  160. Martínez-Ruiz, M., Robeson, M. S. & Piccolo, B. D. Fueling the fire: colonocyte metabolism and its effect on the colonic epithelia. Crit. Rev. Food Sci. Nutr. 65 (33), 8737–8756 (2025). · DOI
  161. Teng, Y. et al. Gut bacterial Isoamylamine promotes age-related cognitive dysfunction by promoting microglial cell death. Cell. Host Microbe. 30 (7), 944–960e8 (2022). · DOI
  162. Yang, J. et al. Dysregulation of Ruminococcaceae and Megamonas could be predictive markers for rapid progression of mild cognitive impairment. Microb. Pathog. 183, 106272 (2023). · DOI
  163. Zhai, S. et al. Effect of lactulose intervention on gut microbiota and short chain fatty acid composition of C57BL/6J mice. Microbiologyopen 7 (6), e00612 (2018). · DOI
  164. Chiantera, V. et al. A critical perspective on the supplementation of Akkermansia muciniphila: benefits and harms. Life (Basel). 13 (6), 1247 (2023). · DOI
  165. Qu, S. et al. Excessive consumption of mucin by over-colonized Akkermansia muciniphila promotes intestinal barrier damage during malignant intestinal environment. Front. Microbiol. 14, 1111911 (2023). · DOI
  166. Patel, P. et al. Oat Bran fiber protects against radiation-induced disruption of gut barrier dynamics and mucosal damage. NPJ Biofilms Microbiomes. 11 (1), 128 (2025). · DOI
  167. Ottman, N. et al. Action and function of Akkermansia muciniphila in Microbiome ecology, health and disease. Best Pract. Res. Clin. Gastroenterol. 31 (6), 637–642 (2017). · DOI · Paper page
  168. Ma, X., Liu, Q. & Yang, G. The multifaceted roles of Akkermansia muciniphila in neurological disorders. Trends Neurosci. 48 (6), 403–415 (2025). · DOI
  169. Chen, X. et al. Lactulose: an indirect antioxidant ameliorating inflammatory bowel disease by increasing hydrogen production. Med. Hypotheses. 76 (3), 325–327 (2011). · DOI
  170. Kim, K. A. et al. High fat diet-induced gut microbiota exacerbates inflammation and obesity in mice via the TLR4 signaling pathway. PLoS One. 7 (10), e47713 (2012). · DOI · Paper page
  171. Murga-Garrido, S. M. et al. Gut Microbiome variation modulates the effects of dietary fiber on host metabolism. Microbiome 9 (1), 117 (2021). · DOI · Paper page
  172. Miranda-Ribera, A. et al. The Zonulin-transgenic mouse displays behavioral alterations ameliorated via depletion of the gut microbiota. Tissue Barriers. 10 (3), 2000299 (2022). · DOI
  173. Heravi, F. S., Naseri, K. & Hu, H. Gut Microbiota Composition in Patients with Neurodegenerative Disorders (Parkinson’s and Alzheimer’s) and Healthy Controls: A Systematic Review. Nutrients. 15 (20), 4365 (2023). · DOI
  174. Waldmann, T. A. The biology of interleukin-2 and interleukin-15: implications for cancer therapy and vaccine design. Nat. Rev. Immunol. 6 (8), 595–601 (2006). · DOI · Paper page
  175. Wu, Y., Tian, Z. & Wei, H. Developmental Funct. Control Nat. Killer Cells Cytokines Front. Immunol., 8: 930. (2017).
  176. Chughtai, S. et al. Chemotherapy-induced cognitive impairment: Mechanisms, emerging biomarkers, and therapeutic interventions. Biochem. Biophys. Res. Commun. 779, 152456 (2025). · DOI
  177. Briones, T. L. & Woods, J. Chemotherapy-induced cognitive impairment is associated with decreases in cell proliferation and histone modifications. BMC Neurosci. 12, 124 (2011). · DOI
  178. Shen, C. L. et al. Fecal microbiota transplantation modulates gut Microbiome composition and glial signaling in brain and colon of rats with neuropathic pain: evidence for microbiota-Gut-Brain axis. J. Frailty Aging. 13 (4), 319–330 (2024). · DOI
  179. Park, J. C. & Im, S. H. Of men in mice: the development and application of a humanized gnotobiotic mouse model for Microbiome therapeutics. Exp. Mol. Med. 52 (9), 1383–1396 (2020). · DOI · Paper page
  180. Dutta, S. & Sengupta, P. Men and mice: relating their ages. Life Sci. 152, 244–248 (2016). · DOI · Paper page
  181. Boykoff, N., Moieni, M. & Subramanian, S. K. Confronting chemobrain: an in-depth look at survivors’ reports of impact on work, social networks, and health care response. J. Cancer Surviv. 3 (4), 223–232 (2009). · DOI · Paper page

Metadata

Authors
Cronin, B., Kandel, S., McElroy, T., Syed, S., Swinton, C., Corley, C., Sridharan, V., Robeson, M. S., & Allen, A. R.
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2026-01-10
Volume
16
Issue
1
ISSN
2045-2322
DOI
10.1038/s41598-025-33903-w
Cited by
4
References
13
Language
en
Licence
Funders
NIH (1R01CA258673)

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This page
CoChat. (2026). Citation check: Changes in gut, microbiome, and cognition after doxorubicin, cyclophosphamide, and paclitaxel chemotherapy treatment. https://app.cochat.ai/papers/10.1038/s41598-025-33903-w
The paper
Cronin, B., Kandel, S., McElroy, T., Syed, S., Swinton, C., Corley, C., Sridharan, V., Robeson, M. S., & Allen, A. R. (2026). Changes in gut, microbiome, and cognition after doxorubicin, cyclophosphamide, and paclitaxel chemotherapy treatment. Scientific Reports. https://doi.org/10.1038/s41598-025-33903-w

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.