About

Monika R. Fleshner is a Professor in the Department of Integrative Physiology at the University of Colorado Boulder. Her research program focuses on understanding the impact of acute and chronic stressor exposure, whether mental or physical, on behavior, neural, hormonal, and immunological functions. She investigates how these systems interact to influence the whole organism and explores the mechanisms by which exercise produces increased stress resistance and stress resilience. Her work is conducted within the Stress Physiology Laboratory, emphasizing the physiological responses to stress and the potential for exercise to modulate stress effects. Dr. Fleshner's academic background includes a B.S. in Psychology from Iowa State University, followed by an M.A. and Ph.D. in Behavioral Neuroscience from the University of Colorado at Boulder. Her professional experience encompasses postdoctoral fellowships and faculty positions at the University of Colorado, where she has advanced from instructor to her current role as a professor. Throughout her career, she has received numerous honors, including the Young Investigator Award from the Psychoneuroimmunology Research Society, the Faculty Appreciation Award, and recognition as a featured scientist on NPR and PBS. She has also served as president of the Psychoneuroimmunology Research Society and the International Society for Exercise Immunology, highlighting her leadership in her field.

Research topics

• Biology
• Physiology
• Medicine
• Bioinformatics
• Immunology
• Microbiology
• Biochemistry
• Internal medicine
• Neuroscience
• Psychiatry
• Endocrinology
• Genetics

Selected publications

• A Prebiotic Diet Containing Galactooligosaccharides and Polydextrose Attenuates Hypergravity-Induced Disruptions to the Microbiome in Female Mice

  Nutrients · 2025-07-24 · 1 citations

  articleOpen accessSenior author

  Background/Objectives: Environmental stressors, including spaceflight and altered gravity, can negatively affect the symbiotic relationship between the gut microbiome and host health. Dietary prebiotics, which alter components of the gut microbiome, show promise as an effective way to mitigate the negative impacts of stressor exposure. It remains unknown, however, if the stress-protective effects of consuming dietary prebiotics will extend to chronic altered-gravity exposure. Methods: Forty female C57BL/6 mice consumed either a control diet or a prebiotic diet containing galactooligosaccharides (GOS) and polydextrose (PDX) for 4 weeks, after which half of the mice were exposed to 3 times the gravitational force of Earth (3g) for an additional 4 weeks. Fecal microbiome samples were collected weekly for 8 weeks, sequenced, and analyzed using 16S rRNA gene sequencing. Terminal physiological endpoints, including immune and red blood cell characteristics, were collected at the end of the study. Results: The results demonstrate that dietary prebiotic consumption altered the gut microbial community structure through changes to β-diversity and multiple genera across time. In addition, consuming dietary prebiotics reduced the neutrophil-to-lymphocyte ratio (NLR) and increased red blood cell distribution width (RDW-CV). Importantly, the prebiotic diet prevented the impacts of altered-gravity on β-diversity and the bloom of problematic genera, such as Clostridium_sensu_stricto_1 and Turicibacter. Furthermore, several prebiotic diet-induced genera-level changes were significantly associated with several host physiological changes induced by 3g exposure. Conclusions: These data demonstrate that the stress-protective potential of consuming dietary prebiotics extends to environmental stressors such as altered gravity, and, potentially, spaceflight.

  PublisherOA PDFDOI

• 0412 Better Objective Sleep in Healthy Adults Is Marked by Increased Bifidobacterium Breve and Saguini

  SLEEP · 2025-05-01

  articleOpen access

  Abstract Introduction Taxa level associations of the human gut microbiota have been reported in relation to sleep health; however, which taxa are associated with good sleep has yet to be determined. Many study methodologies rely on self-reported sleep metrics, 16S rRNA gene-amplicon sequencing or statistical methodologies not designed for gut microbiome assessments, which have limitations. We examined the association between sleep measures assessed by actigraphy followed by one night of in-laboratory polysomnography (PSG) and whole genome sequencing (WGS) gut microbiome taxa. Methods Fifteen healthy participants aged 26±4.0(SD) were instructed to maintain a consistent 8h sleep schedule for fourteen days at home. Wrist actigraphy and time stamped call-ins were assessed for adherence. Following fourteen days of monitoring, participants underwent 8h overnight in-laboratory PSG. Fecal microbiome samples were collected at PSG visit. WGS at the operational genomic unit (OGU) were then referenced against Web of Life 2 for taxonomic assignment. Differential abundance testing (ANCOM-BC) was performed to detect the OGUs associated with individuals with high (≥85%) or low (< 85%) sleep efficiency (SE) assessed via actigraphy. Following, linear regression associations between SE, sleep onset latency (SOL) and wake after sleep onset (WASO) from PSG were tested against these differentially abundant OGUs to determine: 1) whether these associations were maintained with PSG SE and; 2) whether these taxa were associated with SOL or WASO. Results ANCOM-BC determined Bifidobacterium breve and Bifidobacterium saguini species were increased in the high SE wrist actigraphy group (log fold change 2.2, q=0.002 and log fold change 2.0, q=0.006, respectively). Linear regression indicated increased breve and saguini were associated with higher PSG SE (β=0.0003, p=0.03, R²=0.18 and β=0.0013, p=0.02, R²=0.46, respectively). Further investigation into PSG SOL and WASO indicated that the higher SE was due to these strains being associated with decreased WASO, specifically (β=–0.09, p=0.04, R²=0.38 and β=–0.58, p=0.04, R²=0.40, respectively). Conclusion We find that higher SE, specifically by decreased WASO, is associated with higher levels of two Bifidobacterium species, breve and saguini. Bifidobacterium, commonly found in probiotics, may improve subjective sleep quality. Therefore, Bifidobacterium breve and saguini may be specific targets for improving human sleep. Support (if any) ONR N00014-15-1-2809, NIH-T32-HL149646, NIH/NCATS Colorado CTSA-UL1TR002535.

  PublisherOA PDFDOI

• A Prebiotic Diet Containing Galactooligosaccharides and Polydextrose <span aria-describedby="tippy-24">Produces Dynamic and Reproducible Changes in the Gut Microbial Ecosystem in Male Rats

  Preprints.org · 2024-05-10 · 1 citations

  preprintOpen accessSenior author

  Despite substantial evidence supporting the efficacy of prebiotics for promoting host health and stress resilience, few experiments present evidence documenting the dynamic changes in microbial ecology and fecal microbial-modified metabolites across time. Furthermore, the literature reports a lack of reproducible effects of prebiotics on specific bacteria and bacterial-modified metabolites. The current experiments examined whether consumption of diets enriched in prebiotics (galactooligosaccharides, GOS and polydextrose, PDX) compared to control diet, would consistently impact the gut microbiome and microbial-modified bile acids across time and between two research sites. Male Sprague Dawley rats were fed control or prebiotic diets for several weeks, and their gut microbiome and metabolome were examined using 16S rRNA gene sequencing and untargeted LC-MS/MS analysis. Dietary prebiotics altered beta diversity, relative abundances of bacterial genera, and microbially modified bile acids across time. PICRUSt2 analyses identified four inferred functional metabolic pathways modified by prebiotic diet. Correlational network analyses between inferred metabolic pathways and microbial-modified bile acids revealed deoxycholic acid as a potential network hub. All these reported effects were consistent between the two research sites supporting the conclusion that dietary prebiotics robustly changed the gut microbial ecosystem. Consistent with our previous work demonstrating that GOS/PDX reduces the negative impacts of stressor exposure, we propose that ingesting a diet enriched in prebiotics facilitates the development of a health-promoting gut microbial ecosystem.

  PublisherOA PDFDOI

• Exercise does not cause post-exertional malaise in Veterans with Gulf War Illness: A randomized, controlled, dose–response, crossover study

  Brain Behavior and Immunity · 2024-05-20 · 2 citations

  articleOpen access
  PublisherOA PDFDOI

• A Prebiotic Diet Increases Cardiovascular Adaptability Under Hypergravity-Induced Stress

  Physiology · 2024-05-01

  articleSenior author

  Life in space presents significant challenges to mammalian physiology and the longer one is in space, the greater the impact. Three major stressors are present in space: 1) changes in gravitational environment, 2) psychological/physiological stress, and 3) constant low dose radiation. It is critical, therefore, to discover interventions that promote stress resilience. Dietary prebiotics selectively increase the relative abundances of probiotic bacterial species in the gut. We have previously reported that a diet enriched in galactooligosaccharide (GOS) and polydextrose (PDX) compared to control diet robustly elevates parabacteroides distasonis, clostridium leptum, and reduces the negative impact of acute and chronic stress. Interoceptors (e.g., baroreceptors) sense gravity-induced changes in blood pressure and cardiac function/structure. There is evidence that hypergravity disrupts autonomic and cardiovascular homeostasis and function. Cardiovascular homeostasis depends on a sympathetic and parasympathetic balance reflected in heart rate variability (HRV), a measure of cardiovascular stress. The following study was designed to test the hypothesis that GOS+PDX reduces the cardiovascular impacts of living in an altered gravitational environment. Adult female mice were housed in 1G or 3G and were fed GOS+PDX or a matched control diet for 4 weeks on the NASA Ames 1.22-meter radius centrifuge. We recorded electrocardiograms (ECG) in animals from all four groups immediately before, halfway through, and immediately after centrifugation. We analyzed HRV data using a Python-based Jupyter notebook and R. R was used to perform a 1F-LD-1F ANOVA with pair-wise comparisons to quantify changes in HRV longitudinally. Classic time domain based HRV metrics, standard deviation of the successive differences between adjacent R-R intervals and standard deviation of NN intervals, showed little change over time. Instead, frequency domain measures showed results were housing in 3G compared to 1G reliably changed Shannon entropy, Sample entropy, and low to high frequency ratio at each time-point. The changes across time reflected adaptation to hypergravity and a consequent reduction in HRV. Poincare plot analysis and low to high frequency ratio metrics showed divergent compensatory reactions between diets at 3G. Overall, 3G impacted HRV less in mice that were fed the prebiotic diet compared to the control diet. Further longitudinal studies with greater temporal resolution are needed to assess changes in HRV caused by gravitational changes. However, our data suggests the prebiotic diet significantly reduces 3G activation of sympathetic drive and increases parasympathetic drive, potentially reducing cardiovascular stress in animals exposed to high gravity. NASA grant 80NSSC19K1038 funded this project. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

  PublisherDOI

• Exercise immunology and interactions with psychological stress

  2024-09-06

  book-chapterSenior author

  Psychological stress is a potent modulator of immune function. Acute short-term psychological stress leads to transient increases in the number and functions of circulating immune cells, enhancing protection against pathogenic threats. Conversely, exposure to excessive and sustained psychological stressors is associated with impaired immunity and increased risk of infections. A physically active lifestyle contributes to mental and physical wellness. The positive health benefits of regular moderate-intensity exercise training on cardiovascular health, metabolic function, and immunity are irrefutable. Less well-understood, however, is how regular exercise positively impacts the immune system, and how exercise and physical activity modulate the immune response to psychological stress. This chapter will present evidence supporting the concept that regular exercise and physical activity protect immune function from so-called immune-disruptive challenges, such as excessive and chronic stress, by modulating a stress-reactive neural circuitry and relevant immune outcomes associated with improved health.

  PublisherDOI

• Stress biology: Complexity and multifariousness in health and disease

  Figshare · 2024-11-06

  article
  DOI

• SARS-CoV-2 S1 subunit produces a protracted priming of the neuroinflammatory, physiological, and behavioral responses to a remote immune challenge: A role for corticosteroids

  Brain Behavior and Immunity · 2024-07-21 · 11 citations

  article
  PublisherDOI

• Is it the people or the place? The remarkable 30-year period of integrative physiology research in the Carlson Gymnasium at the University of Colorado Boulder

  Journal of Applied Physiology · 2024-06-06 · 1 citations

  article

  Historically, programs of physical education and sport were housed in gymnasium buildings on academic campuses. As physical education evolved to the more scientifically focused successor departments of exercise science and kinesiology, faculty specialization developed in the physiology of exercise. With time, some faculty broadened their research to study the integrative physiology of other biological states and stressors. Through this series of events, a small group of integrative physiologists was formed in the Carlson Gymnasium at the University of Colorado Boulder during the 1990s with the goal of conducting novel biomedical research. The challenges were daunting: no contemporary core laboratory facilities, lack of temperature control, piercing external noise, pests, regular flooding, electrical power outages, and lack of funds for renovation. Despite these obstacles, the group established an innovative program of translational physiological research ranging from high-throughput molecular analyses to cell models to rodent studies to clinical trials in humans. These investigators supported their work with grant awards from the National Institutes of Health (NIH), Department of Defense, National Aeronautics and Space Administration (NASA), American Heart Association, and private research foundations totaling ∼$80 M in direct costs from the late 1980s to 2020. Collectively, the faculty and their laboratory personnel published ∼950 articles in peer-reviewed scientific journals. Over that period, 379 undergraduate students, 340 graduate students, 84 postdoctoral fellows, and dozens of junior research faculty received scientific training in Carlson, supported by >$21 M in extramural funding. What was accomplished by this handful of integrative physiologists speaks to the importance of the qualities of the investigators rather than their research facilities in determining scientific success.

  PublisherDOI

• A Prebiotic Diet Containing Galactooligosaccharides and Polydextrose Produces Dynamic and Reproducible Changes in the Gut Microbial Ecosystem in Male Rats

  Nutrients · 2024-06-06 · 6 citations

  articleOpen accessSenior authorCorresponding

  Despite substantial evidence supporting the efficacy of prebiotics for promoting host health and stress resilience, few experiments present evidence documenting the dynamic changes in microbial ecology and fecal microbially modified metabolites over time. Furthermore, the literature reports a lack of reproducible effects of prebiotics on specific bacteria and bacterial-modified metabolites. The current experiments examined whether consumption of diets enriched in prebiotics (galactooligosaccharides (GOS) and polydextrose (PDX)), compared to a control diet, would consistently impact the gut microbiome and microbially modified bile acids over time and between two research sites. Male Sprague Dawley rats were fed control or prebiotic diets for several weeks, and their gut microbiomes and metabolomes were examined using 16S rRNA gene sequencing and untargeted LC-MS/MS analysis. Dietary prebiotics altered the beta diversity, relative abundance of bacterial genera, and microbially modified bile acids over time. PICRUSt2 analyses identified four inferred functional metabolic pathways modified by the prebiotic diet. Correlational network analyses between inferred metabolic pathways and microbially modified bile acids revealed deoxycholic acid as a potential network hub. All these reported effects were consistent between the two research sites, supporting the conclusion that dietary prebiotics robustly changed the gut microbial ecosystem. Consistent with our previous work demonstrating that GOS/PDX reduces the negative impacts of stressor exposure, we propose that ingesting a diet enriched in prebiotics facilitates the development of a health-promoting gut microbial ecosystem.

  PublisherOA PDFDOI

Recent grants

• NIH Grant R03MH060301

  NIH · $36k · 2000

• Extracellar Hsp72 Is a DAMP Released by Stress

  NSF · $430k · 2010–2013

• NIH Grant R01MH068283

  NIH · $2.9M · 2016

• NIH Grant R01MH06828306A1

  NIH · $337k · 2015

• NIH Grant R01DE021966

  NIH · $2.0M · 2017

Frequent coauthors

• Benjamin N. Greenwood

  University of Colorado Denver

  70 shared

• Steven F. Maier

  University of Colorado Boulder

  64 shared

• Linda R. Watkins

  University of Colorado Boulder

  54 shared

• David M. Diamond

  University of South Florida

  39 shared

• Robert S. Thompson

  University of Colorado Boulder

  35 shared

• Rob Knight

  University of California, San Diego

  26 shared

• Jay Campisi

  Regis University

  24 shared

• Christopher A. Lowry

  University of Colorado Anschutz Medical Campus

  24 shared

Labs

• Stress Physiology LaboratoryPI

Education

• B.S.

  Iowa State University

  1984

• M.A., Behavioral Neuroscience Program

  University of Colorado at Boulder

  1988

• Ph.D., Behavioral Neuroscience Program

  University of Colorado at Boulder

  1990

Awards & honors

• Young Investigator Award, Psychoneuroimmunology Research Soc…
• Motor Board Honor Society, Faculty Appreciation Award (2001)
• National Public Radio- The Infinite Mind, Featured Scientist…
• Independent Investigator Award, National Alliance for Resear…
• Boulder Faculty Assembly Award-Excellence in Research (2009)