Sex differences in hedonic feeding: the role of the gut microbiome

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Project Summary Obesity is an epidemic in our country and it is becoming a global problem. Obesity affects more women than men; in fact, there are currently at least 100 million more women with obesity than men, globally. There are multiple proposed causes for rising obesity rates, particularly, increased access to calorie-dense, highly palatable foods and decreased energy expenditure. Hedonic feeding, food intake regardless of physiological hunger and driven by pleasure and palatability, is not the sole culprit for the obesity epidemic, but it is certainly a major contributing factor. Furthermore, there are sex differences in hedonic feeding that could support the observed sex differences in obesity. While previous research has determined overlap between hedonic feeding and drug addiction, there is less known about the role of inputs such as sensation and gastrointestinal physiology on hedonic feeding. A major gap in this field is understanding the role of the gut microbiome in hedonic feeding. The objective of this project is to characterize sex differences in the gut microbiome and their impact on hedonic feeding. We hypothesize that increased consumption of high fat, palatable foods by females compared to males occurs because of a conserved network driven by reproductive success for females. We further hypothesize that part of this network includes the gut microbiome. Expected outcome and impact: This project will produce a characterization of fecal microbiome diversity, composition, and short chain fatty acid production in male and female rats, at different time points, and related to hedonic feeding as determined by a single-session behavioral economics technique with a high fat, palatable reward. Our aims are to: 1) Determine how the gut microbiome impacts sex differences in hedonic feeding. a) Does disruption of the gut microbiome during adulthood increase hedonic feeding in female rats more than male rats? b) Does disruption of the gut microbiome in early life influence sex differences in hedonic feeding during adulthood? c) Does transplantation of gut microbiota from a male rat decrease hedonic feeding in female rats? Does transplantation of gut microbiota from a female rat increase hedonic feeding in male rats? 2) Determine how pregnancy and post-pregnancy impacts hedonic feeding. a) Does pregnancy increase hedonic feeding in female rats? b) Does a previous pregnancy increase palatable food seeking in female rats? This proposed work is important because a better understanding of sex differences in obesity could inform personalized interventions. This work specifically informs gut microbiome-based interventions.