Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List

Full text release has been delayed at the author's request until May 05, 2025

ETD Abstract Container

Abstract Header

Cancer and cancer treatments induce immune dysfunction, gut microbiome disruption, and physiological and behavioral symptoms

Otto, Lauren D
http://orcid.org/0000-0001-5793-3395
http://rave.ohiolink.edu/etdc/view?acc_num=osu1713370005659678

Abstract Details

2024, Doctor of Philosophy, Ohio State University, Biomedical Sciences.
Cancer patients experience debilitating physiological (e.g., gastrointestinal) and behavioral (e.g., cognitive decline) symptoms due to the cancer itself and subsequent cancer treatments. These symptoms are related to reduced quality of life and treatment delays and dose reductions, thereby increasing patient mortality. Inflammation and gut microbiome disruptions are both commonly hypothesized to play a role in these symptoms. Here, I investigate the extent to which breast cancer and chemotherapy independently and synergistically cause immune dysfunction, gut microbiome disruption, and physiological and behavioral symptoms. Chapter 2 characterizes a comprehensive breast cancer mouse model in terms of immune, neuroimaging, and behavioral effects. In this model, chemotherapy induced inflammation, neuroimaging alterations, and reduced locomotor activity. In chapter 3, I demonstrate that mammary tumors blunt microglial and behavioral responses to immune challenges in mice. This impairment of immune and behavioral responses is specific to a peripheral route of immune challenge administration, suggesting a non-brain-specific mechanism. Chapter 4 demonstrates that chemotherapy induces gut microbiome disruption, elevates circulating TNF-α, and induces cognitive decline in breast cancer patients. Furthermore, cognitive decline is related to decreases in microbial diversity but not elevated circulating cytokines. Finally, in chapter 5, I show that decreased gut microbial diversity prior to chemotherapy treatment predisposes breast cancer patients to chemotherapy-induced gut microbiome disruption and gastrointestinal symptoms. The findings of this work demonstrate that tumors lead to immune dysfunction and behavioral consequences in a preclinical model of breast cancer. Furthermore, this work delineates the roles of chemotherapy-induced gut microbiome disruption and inflammation in the development of cognitive decline and gastrointestinal symptoms in a population of breast cancer patients.
Leah Pyter (Advisor)
Baldwin Way (Committee Member)
Jonathan Godbout (Committee Member)
Tamar Gur (Committee Member)
282 p.
Biomedical Research
cancer; neuroimmunology; inflammation; chemotherapy; cognition; microbiome

Recommended Citations

Citations

  • Otto, L. D. (2024). Cancer and cancer treatments induce immune dysfunction, gut microbiome disruption, and physiological and behavioral symptoms [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1713370005659678

    APA Style (7th edition)

  • Otto, Lauren. Cancer and cancer treatments induce immune dysfunction, gut microbiome disruption, and physiological and behavioral symptoms. 2024. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1713370005659678.

    MLA Style (8th edition)

  • Otto, Lauren. "Cancer and cancer treatments induce immune dysfunction, gut microbiome disruption, and physiological and behavioral symptoms." Doctoral dissertation, Ohio State University, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=osu1713370005659678

    Chicago Manual of Style (17th edition)

osu1713370005659678
© 2024, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.