Chronic Interpersonal Stress and the Gut Microbiome
How do stress and depression affect your gut microbiome? Acute and chronic stressors affect the gut microbiota in mice, but human studies addressing stress are a relative rarity. This project addresses the role of an important interpersonal stressor on the gut microbiome, marital stress. Troubled marriages provide fertile soil for stress and depression. Marital discord’s correlates include a 10-fold increased risk for depressive symptomatology.
We have three primary objectives: Aim 1: To characterize the effects of marital stress and depression on the diversity and content of the gut microbiota in healthy adults. Aim 2: To evaluate the impact of changes in mood on changes in the microbiome, as well as the extent to which changes in the microbiome predict mood-related alterations. Aim 3: To evaluate the similarity of the microbiome within couples and its relationship to marital distress.
We will collect data and examine the impact of diet, early childhood adversity (abuse and neglect), gender, age, medications, weight/BMI, and exercise. Important colleagues collaborating on this project include Mike Bailey, PhD (behavioral immunologist, microbiome), Martha Belury, PhD who holds the Carol S. Kennedy Endowed Professorship in Human Nutrition, and Rebecca Andridge, PhD, biostatistician.
Why This Project?
The brain and the gut have a vigorous, ongoing dialogue. Animal studies have clearly demonstrated that stress produces biologically significant alterations in the gut microbiota. For example, among mice exposed to an aggressive mouse, the relative amounts of bacteria in the genus Bacteroides decreased, in contrast to relative increases in bacteria in the genus Clostridium; this was an important study from our collaborator on this project, Michael Bailey. Importantly, the stressor also increased inflammation, and these inflammatory changes were significantly correlated with stress- induced changes in several bacterial genera.
Similarly, bacterial translocation may be inhibited by many members of the genus Lactobacillus. Studies with nonhuman primates showed that stress lowered the shedding of lactobacilli. Decreases in lactobacilli facilitate growth of other members of the microbiota like the clostridia, which in turn promote bacteria translocation from the intestinal lumen into circulation, provoking inflammatory responses.
Inflammation is a risk factor for cancer, cardiovascular disease, and many other diseases of aging. This novel study addresses the ways that marital discord and depression impact the gut microbiome; it will also, in turn, provide evidence about the ways that gut microbes impact emotional responses. It will illuminate the pathways through which marriage can produce both substantial health risks as well as health benefits.
In our prior marital studies we have shown that marital discord promotes inflammation. Our research has shown that chronically abrasive marital relationships heighten production of epinephrine and norepinephrine, stress hormones that stimulate the growth of many enteric bacteria, and heighten inflammation. Recently we found that men and women whose marital discussions were more hostile and who also had a mood disorder history had lower resting energy expenditure, higher insulin, and higher peak triglyceride responses than other participants following high-fat meals. We have also shown that marital distress is associated with heightened proinflammatory cytokine production. These data are clearly in accord with the evidence that depression promotes intestinal permeability, i.e., greater inflammation-inducing endotoxin translocation, described as a “leaky gut,” one obvious pathway to the enhanced inflammation in distressed marriages.
My interest in the microbiome has been fueled by our recent metabolic data. In studies addressing how stress and depression alter metabolic responses to high-fat meals, we showed that depression and stress substantially augment triglyceride responses, raise insulin, and lower fat oxidation following high fat meals. These are examples of a long series of innovative interdisciplinary studies from my lab.
About the Researcher
Janice Kiecolt-Glaser, PhD, the Director of the Ohio State Institute for Behavioral Medicine Research, also holds the title of Distinguished University Professor as well as the S. Robert Davis Chair in the Ohio State College of Medicine. A clinical psychologist who works in the area of psychoneuroimmunology, she has authored more than 250 articles, chapters, and books, most in collaboration with Dr. Ronald Glaser. Their studies have demonstrated important health consequences of stress, including slower wound healing and impaired vaccine responses; they have also shown that chronic stress substantially accelerates inflammation which has been linked with many age-related diseases. In addition, their programmatic work has focused on how personal relationships influence immune and endocrine function, and health. A newer segment of her research focuses on the intersection of nutritional neuroscience and psychoneuroimmunology; her recent work has shown that stress and depression can dysregulate energy metabolism following high-fat meals. Most notable among her honors is her elected membership in the Institute of Medicine (now called the National Academy of Medicine). A Fellow in the American Association for the Advancement of Science, as well as the American Psychological Association, she received the Award for Outstanding Contributions to Health Psychology twice. She is listed in the Institute for Scientific Information’s ISIHighlyCited.com (among the world's most highly cited authors, a group comprising less than one half of one percent of all publishing researchers). She has served on the editorial boards of 11 journals. Her research has been supported by a series of NIH grants, including a MERIT award.