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.