Sex differences in hedonic feeding and characterizing the effects of antibiotic-induced microbiome disruption

Abstract Background Obesity continues to be a public health issue in our country. Additionally, there continues to be a higher incidence of severe obesity for women compared to men. Among the proposed causes of obesity is increased hedonic feeding: food intake driven by pleasure and palatability rather than physiological hunger. While hedonic feeding is not the sole culprit for the obesity epidemic, it is a major contributing factor. Emerging evidence shows that the gut microbiome impacts feeding behavior and studies have shown that individuals with obesity exhibit an altered gut microbiome. Methods Here, we used a novel behavioral economics (BE) approach to evaluate hedonic feeding in male and female Sprague-Dawley rats for a high-fat palatable (HFP) reward pellet, before and after antibiotic administration. This BE approach is a de-escalating fixed ratio operant task designed to evaluate a reward’s value and measure how much effort the subject is willing to expend to earn that reward. Using this approach, we measured demand elasticity (α), the rate at which demand falls when the price or effort required increases, and demand at null cost (Q 0 ), a prediction of consumption at null effort extrapolated from the animals’ consumption at low price. Results We determined a higher demand at null cost (Q 0 ) for the HFP reward pellet for females compared to males, as we have observed previously. Next, we administered an antibiotic cocktail in the drinking water to disrupt the gut microbiome and investigate a role of the gut microbiome in hedonic feeding. Female rats administered antibiotics continued to have a higher demand at null cost compared to male control rats, but no statistically significant differences were determined between male and female rats administered antibiotics. We characterized the fecal microbiome genus-level composition and short chain fatty acid (SCFA) levels before and after antibiotic administration. We also characterized serum SCFA and bile acid levels at the end of the study. Conclusions We did not determine a significant effect of antibiotics on hedonic feeding, despite disruption to the fecal microbiome. Additionally, we did not observe striking baseline sex differences in fecal microbiome diversity and composition. This brings to question whether the gut microbiome contributes to sex differences in hedonic feeding. More research will be necessary for network factors such as microbiome – bile acid effects on feeding that exhibit sex differences.