The worldwide rapid increase in the prevalence of obesity has been paralleled by a renewed interest in understanding the mechanisms associated with this epidemic. Amongst the many factors that have been implicated as possible causations, changes in our diet (increased processed food consumption) have been pointed as one of the most important players. Since the gut is the most densely colonized and the most diverse microbial community in the human body and since gut microbiome composition and metabolic function are intrinsically associated with diet composition, one has to question what the relationship is between the gut microbiome and obesity. Although some studies have loosely associated obesity with changes in gut microbiome composition, the findings in this field are conflicting.
However, a few crucial studies have demonstrated that in specific circumstances, the introduction of microbiota from an obese donor into gnotobiotic mice was able to “transmit” the obese phenotype. These studies were decisive in understanding that the gut microbiome per se was able to interact with the host in order to change the host’s body composition. Most studies have been performed in germ-free mice. However, some epidemiological studies have shown the association between the use of antibiotics early in life and the predisposition to develop obesity in the first few years of life. Also, the old and widespread practice of adding antibiotics to foods to promote growth in livestock supports the effect of the microbiome on body composition.
Progress in the study of metabolomics has opened a new door to understanding the relationship between the microbiome and host. Metabolites produced by gut bacteria can enter into our bloodstream and in fact, up to one-third of the small molecules in human blood is derived from gut bacteria. Some of those metabolites have been associated with beneficial effects in the human host; but also alterations of those metabolites can lead to harmful outcomes such as increasing inflammation and promoting insulin resistance and obesity.
Current Research Projects
The Ingestive Behavior and Obesity Program (IBOP), Oppenheimer Center for Neurobiology of Stress (CNS)
The UCLA CNS Ingestive Behavior and Obesity Program studies the mechanisms underlying the two-way communication between peripheral signals ( gut microbial metabolites, gut peptides, vagal and adipose tissue signaling) and the brain in controlling body weight and eating behavior in health and in obesity. In recent years a large body of evidence has demonstrated an important link between the gut microbiota and host body weight. Studies in germ-free animals have shown that changes in the gut microbiome can change eating behaviors. The mechanisms underlying these behavioral effects are not well understood but may involve signals from the gut microbiota being transmitted to the brain via the vagus nerve, via gut hormones or via microbial metabolites. Our ongoing research aims to identify the mechanisms underlying these interactions. Specifically, we aim to characterize how gut microbial metabolite profiles interact to control body weight through changes in brain structure/function associated with satiation, hunger and eating behaviors. We will also characterize the impact that sex and race/ethnicity have on gut-microbiome-brain interactions in obesity.
Key People
Dr. Arpana (Annie) Gupta completed a PhD degree in Psychology from the University of Tennessee, Knoxville, followed by an APA accredited clinical internship at Massachusetts General Hospital/Harvard Medical Center. After coming to UCLA she joined the neuroimaging and psychophysiological cores at the Center for Neurobiology of Stress in 2012. She is currently Adjunct Assistant Professor, where she specializes in research that investigates the influence of environmental factors on shaping neurobiological phenotypes associated with stress and pain-based diseases such as obesity and functional gastroenterological disorders (FGIDs) [vuvlodynia, irritable bowel syndrome]. Her programmatic line of research broadly defined focuses on the bidirectional interactions between the brain and peripheral factors (in particular immune factors and gut microbiota-related metabolites) and how these interactions are modified by vulnerability (early adversity, race, adult stress, socioeconomic status [SES], diet) and protective (resilience, exercise) factors in contributing to the underlying pathophysiology of these disorders. She is dedicated to using advanced automated and mathematical analytic techniques, which allows her to integrate information from multiple data sources, while accounting for sex and race differences. Her goal is to develop a comprehensive model that provides a powerful and sensitive biomarker that will increase biological readouts of these stress and pain-based disorders, thus bringing to the forefront those individuals who are at increased risk as a result of disadvantaged backgrounds.
Relevant Recent Publications
- Gupta A, Mayer EA, Sanmiguel CP, Van Horn JD, Woodworth D, Ellingson BM, Fling C, Love A, Tillisch K, Labus JS. Patterns of Brain Structural Connectivity Differentiate Lean from Overweight Subjects. Neuroimage-Clinical, 2015. 13(7): 506-17. doi:10.1016/j.nicl.2015.01.005 [Epub Ahead of Print]. PMCID: PMC4338207.
- Mayer EA, Tillisch K, Gupta A. Gut-Brain Axis and the Microbiota. Journal of Clinical Investigation. 2015; 125(3): 926-38. doi: 10.1172/JCI76304. [Epub ahead of Print]. PMID: 25689247.
- Sanmiguel CP, Gupta A, Mayer EA. Gut Microbiome and Obesity: A Plausible Explanation for Obesity. Current Obesity Reports. 2015. In press.
Active Funding in Microbiome-Related Research
| Funding Agency/Grant Number: | American Psychological Fellowship – Visionary Grant |
| Title: | “Mind Altering Microorganisms: Sex and Race Differences in the Influence of Gut Microbiota on Brain Signatures in Obese Healthy Control Subjects” | Goals: | The goal of the proposed study is to assess sex (males versus females) and race (African Americans versus non-Hispanic White Americans) differences in the influence of gut-microbiota on brain signatures in obese subjects |
Claudia Sanmiguel is the Ingestive Behaviors and Obesity Program (IBOP) director at the Oppenheimer Center for Neurobiology of Stress (CNS) and she is a clinical instructor at the UCLA Digestive Diseases Division. She was born in Bogota, Colombia where she studied Medicine at the Pontificia Universidad Javeriana and specialized in Internal Medicine and Gastroenterology. Then she moved to Alberta, Canada where she did research on gastrointestinal motility and the use of artificial pacemakers and stimulators for the treatment of gastrointestinal disorders. She continued her research career at the Cleveland Clinic in Ohio and at the Cedars Sinai Medical Center in Los Angeles, where she explored the use of pacemakers and electrical stimulators for the treatment of obesity and obesity related diabetes mellitus, as well as, studied gastric electromechanical signals related to eating behavior and satiety. As part of pursuing a research career in United States, she completed her residency in Internal Medicine at Cedars-Sinai Medical Center and trained in Gastroenterology at the University of California Los Angeles. She has continued her pursue on understanding the mechanisms that regulate eating behavior in health and in obesity, and the role of the brain/gut/microbiome axis in interpreting and regulating those behaviors. She has published several papers in well known GI and bioengineering journals and presented her research results in North American and International meetings. She currently has partial NIH funding for a study on the role of brain activity and changes in eating behavior in weight loss after bariatric surgery and how some peripheral signals coming from visceral fat and gut microbiome may play a role in obesity and weight loss. She is also doing research on neuroplasticity in brain areas related to eating hehaviors in response to neuromodulation.
Recent Relevant Publications
- Sanmiguel C, Gupta A, Mayer EA. Gut Microbiome and Obesity: A Plausible Explanation for Obesity. Curr Obes Rep. 2015 Jun;4(2):250-261.
- Sanmiguel CP, Gupta A, Labus LS, Coveleskie K, KaragiannidisI , AlaverdyanM, Ashe-McNalley C, Stains J, and others. Adiposity Is Associated With Alterations Within the Brain Reward System in Adult Subjects. Gastroenterology 2015, Vol. 148, Issue 4, S-674
- Gupta A, Mayer EA, Sanmiguel CP, Van Horn JD, Woodworth D, Ellingson BM, Fling C, Love A, Tillisch K, Labus JS. Patterns of Brain Structural Connectivity Differentiate Lean from Overweight Subjects. Neuroimage-Clinical, 2015; 7: 506–517.
- Sanmiguel CP, Coveleskie K, Gupta A, Kilpatrick L, Labus J, Ashe-McNalley C, Dutson EP, Mayer EA. Association of abdominal fat with resting state low frequency brain activity in human subjects. Neurogastroenterology & Motility. 2013; 25, Suppl 1:14
- Sanmiguel CP, Ito Y, Hagiike M, Conklin JL, Lalezari D, Soffer EE. The effect of eating on Lower Esophageal Sphincter electrical activity. American Journal of Physiology Gastrointest Liver Physiology. 2009 Apr; 296(4): G793-797.
- Sanmiguel CP, Conklin JF, Cunneen SA, Barnett P, Phillips EH, Kipnes M, Pilcher J, Soffer EE. Gastric Electrical Stimulation with the TANTALUS® System in Obese Type 2 Diabetes Patients: Effect on Weight and Glycemic Control. J Diabetes Science and Technology. 2009; 3: 964-970
- Sanmiguel CP, Haddad W, Aviv R, Cunneen SA, Phillips EH, Kapella W, Soffer EE. The TANTALUS TM System for obesity: effect on gastric emptying of solids and ghrelin plasma levels. Obes Surg. 2007; 17: 1503-9.
- Aviv R, Policker S, Brody F, Bitton O, Haddad W, Kliger a, Sanmiguel CP, Soffer EE. Circadian patterns of gastric electrical and mechanical activity in dogs. Neurogastroenterol Motil. 2008; 20:63-8
- Aviv R, Sanmiguel CP, Kliger A, Policker S, Haddad W, Hagiike M, Soffer EE. The use of gastric electrical signals for algorithm for Automatic Eating Detection in dogs. Neurogastroenterol Motil.; 2008, 20:369-76.