R01NR020188

The role of the gut microbiome and short-chain fatty acids in the regulation of inflammation and neuropsychological symptoms in patients with head and neck cancer - Abstract:

The goal of this study is to understand the role of the gut microbiome in the development of neuropsychological symptoms (NPS) among patients with head and neck cancer (HNC) through potential roles of short-chain fatty acids and inflammation among patients with head and neck cancer (HNC) receiving chemoradiotherapy.

Patients with HNC experience significant NPS, such as fatigue, depressive symptoms, cognitive dysfunction, and sleep problems. These symptoms often occur as a cluster, influence treatment responses, predict worse survival among HNC patients, and have a more negative impact on patient outcomes and survival than individual symptoms.

Our earlier work, along with others, have shown a robust link between peripheral inflammation and these NPS. However, the biological factors that contribute to inflammation are still not fully understood and the management of NPS is still challenging.

An emerging appreciation of the gut-brain connection has suggested the involvement of the gut microbiome in NPS. Microbiome dysbiosis has been implicated in complex symptoms including fatigue, depression, cognition, sleep, and pain. Our preliminary data indicate that taxa associated with high inflammation were associated with high NPS.

Moreover, the gut microbiome is believed to play immunomodulatory roles, in part mediated by short-chain fatty acids (SCFAs), the most abundant metabolites of bacterial fermentation of dietary fibers in the gut. SCFAs not only play key anti-inflammatory and immunomodulatory roles within the gut and periphery, but also cross the blood-brain barrier leading to decreases in neuroinflammation and improvement in brain homeostasis.

Our preliminary gut microbiome data suggest lower abundance in SCFA-producing taxa in patients with high NPS. Our pilot data on plasma SCFAs echo this trend by showing that lower circulating butyrate, a main SCFA produced by the gut bacteria, was associated with high NPS.

These new exciting data suggest that a restoration of depleted bacteria or their metabolites has the potential to reverse the dysbiosis-associated phenotypes. Therefore, we propose a longitudinal study of 350 HNC patients receiving active treatment to examine the association between the gut microbiome and NPS before and after treatment.

Patients with HNC also have a high risk of dysbiosis due to severe side effects (i.e., mucositis, dry mouth, and difficulty opening mouth) of cancer treatment. These debilitating and long-lasting side effects reduce patients' capability for food intake and could result in marked changes in gut microbiome and subsequently SCFAs.

Taken together, we hypothesize that cancer treatment-induced alterations in the gut microbiota and resulting reductions in SCFAs contribute to high peripheral inflammation and then NPS. Our results may lead to the development of NPS therapies targeting the gut microbiome and production of SCFAs. This may also contribute to NPS management among other cancer patients, given the high prevalence of NPS in a variety of cancer populations.

Emory University

NURSES UNDERSTAND THAT IMPROVING HEALTH AND WELL-BEING MEANS ADDRESSING PEOPLE'S NEEDS IN MULTIPLE SETTINGS, CONTEXTS, AND OVER THE WHOLE LIFE COURSE. SCIENCE SUPPORTED BY THE NATIONAL INSTITUTE OF NURSING RESEARCH (NINR) USES THIS HOLISTIC PERSPECTIVE TO IMPROVE INDIVIDUAL AND POPULATION HEALTH AND ADVANCE HEALTH EQUITY. NINR-SUPPORTED RESEARCH PROMOTES HEALTH AND WELL-BEING BY ADDRESSING NEEDS AT MULTIPLE LEVELS INDIVIDUAL, FAMILY, COMMUNITY, AND SOCIETAL LEVELS AND DEVELOPING TREATMENT AND PREVENTION STRATEGIES THAT ARE RESPONSIVE TO THE REALITY OF PEOPLE'S LIVES. NURSES KNOW PEOPLE, AND PEOPLE TRUST NURSES. PATIENT AND FAMILIES INTERACT WITH NURSES MORE THAN ANY OTHER CLINICIANS. NURSING SCIENCE USES THIS SPECIAL RELATIONSHIP TO BETTER UNDERSTAND PATIENTS, FAMILIES, AND COMMUNITIES AND THE MANY FACTORS THAT INFLUENCE THEIR HEALTH. NURSING SCIENCE SUPPORTED BY NINR USES THIS KNOWLEDGE TO DEVELOP STRATEGIES FOR IMPROVING HEALTH AND WELLNESS ACROSS POPULATIONS, HEALTH CARE SETTINGS, AND THE LIFESPAN, WITH AN EMPHASIS ON ACHIEVING HEALTH EQUITY. NINR-SUPPORTED SCIENTISTS HAVE DEVELOPED INTERVENTIONS FOR: SUPPORTING PARENTS OF PREMATURE INFANTS, PROMOTING HIV PREVENTION IN UNDERSERVED POPULATIONS, IMPROVING TRANSITIONAL CARE LEADING TO BETTER OUTCOMES AND COST-SAVINGS, AND HELPING INNER-CITY CHILDREN MANAGE ASTHMA. NURSING SCIENCE TRANSCENDS THE BOUNDARIES OF DISEASE AND RESEARCH DISCIPLINES TO BETTER UNDERSTAND THE EXPERIENCES OF INDIVIDUALS AND FAMILIES LIVING WITH ILLNESS AND TO DEVELOP PERSONALIZED APPROACHES THAT MAXIMIZE HEALTH AND WELL-BEING FOR INDIVIDUALS AT ALL STAGES OF LIFE, ACROSS DIVERSE POPULATIONS AND SETTINGS. NINR-SUPPORTED SCIENCE USES NURSING SCIENCE'S UNIQUE, PATIENT AND COMMUNITY-FOCUSED PERSPECTIVE AND WIDE REACH ACROSS CLINICAL AND COMMUNITY SETTINGS TO ADVANCE OUR UNDERSTANDING OF THE SOCIAL DETERMINANTS OF HEALTH: THOSE FACTORS THAT ARE AT THE ROOT OF THE INEQUITIES THAT WE SEE, SUCH AS FOOD INSECURITY AND ACCESS TO HEALTHCARE. NINR RESEARCH EFFORTS IN WELLNESS INVESTIGATE THE KEY BIOLOGICAL, BEHAVIORAL, AND SOCIAL FACTORS THAT PROMOTE LONG-TERM HEALTH AND HEALTHY BEHAVIORS AND PREVENT THE DEVELOPMENT OF ILLNESS ACROSS HEALTH CONDITIONS, SETTINGS, AND THE LIFESPAN. RESEARCH IN WELLNESS IS ALSO FOCUSED ON DEVELOPING AND TESTING CULTURALLY APPROPRIATE INTERVENTIONS TO PROMOTE HEALTH AND PREVENT ILLNESS IN MINORITY AND UNDERSERVED GROUPS. NINR ALSO SUPPORTS SCIENCE TO ASSIST INDIVIDUALS, FAMILIES, AND HEALTH CARE PROFESSIONALS IN MANAGING ADVANCED, SERIOUS ILLNESS, AND PLANNING FOR END-OF-LIFE DECISIONS. IN ADDITION, NINR PROMOTES TECHNOLOGICAL ADVANCEMENTS THAT ADDRESS A RANGE OF HEALTH CARE CHALLENGES AND FACILITATE THE DELIVERY OF REAL-TIME PERSONALIZED INFORMATION TO INDIVIDUALS AND FAMILIES, HEALTH CARE PROVIDERS, AND COMMUNITIES. FINALLY, NINR HAS A LONGSTANDING AND CONTINUING COMMITMENT TO DEVELOPING THE NEXT GENERATION OF NURSE SCIENTISTS: THOSE INDIVIDUALS AND TEAM MEMBERS WHO WILL CARRY THE FIELD OF NURSING SCIENCE INTO THE FUTURE. IN ORDER TO PREPARE AN INNOVATIVE, DIVERSE, AND TALENTED NEXT GENERATION OF NURSE SCIENTISTS, NINR SUPPORTS A VARIETY OF TRAINING OPPORTUNITIES FOR SCIENTISTS AND TRAINEES AT ALL CAREER LEVELS, PARTICULARLY THOSE AT AN EARLY CAREER STAGE WHO ARE SO CRITICAL TO SUSTAINING THE FUTURE OF INNOVATIVE RESEARCH AND HIGH QUALITY HEALTH CARE.

93.361 - Nursing Research

National Institute of Nursing Research (NINR) [HHS - NIH]

Atlanta, Georgia 30322 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 284% from $797,582 to $3,064,029.