Two-thirds of the US population is either overweight or obese. Obesity is one of the major drivers of preventable diseases and health care costs. In the US, current estimates for these costs range from $147 to $210 billion per year. Obesity is a multifactorial disease: genetics, lifestyle...

Background/Objectives: A high-energy-density (HED) diet promotes body weight gain, fat accumulation, and gut dysbiosis, contributing to obesity. The aim of this study was to characterize the initial response to HED diet consumption, as well as identify any sex differences in body composition, systemic inflammation, gut microbiome, and fecal fat excretion in rats. Methods: Male and female Sprague-Dawley rats were fed a low-energy-density (LED) diet for 10 days and were then switched to an HED diet for four weeks. Food intake, body weight, and body composition were measured routinely. Serum samples were collected to measure inflammatory cytokines/chemokines. Fecal samples were collected for microbiome analysis and lipid content. Results: After the HED diet, all rats gained body weight and fat mass, with males exhibiting increased susceptibility to weight gain. Males displayed either a diet-induced obesity phenotype (DIO-P) or a diet-resistant (DR) phenotype, as characterized by their differential body weight gain. Males showed elevated TGF-β levels, while females exhibited increases in Interferon gamma-inducible protein 10 (IP-10), regulated on activation, normal T cell expressed and secreted (RANTES) protein, and basic fibroblast growth factor (FGFb). Changes in gut microbiota composition revealed a reduction in beneficial species, like Bacteroides uniformis and Parabacteroides distasonis, and an increase in species such as Akkermansia muciniphila. Sex differences in fat metabolism were shown in the greater fecal fat excretion observed in males. Conclusions: Our study demonstrates that short-term consumption of a high-energy diet elicits notable sex-specific differences in body weight, body composition, inflammatory markers, gut microbiota, and fat excretion in Sprague-Dawley rats. While we recognize that this study has a small sample size and a short-term intervention, our findings highlight the critical role of sex as a biological variable in diet-induced obesity research.

The microbiome lies at the forefront of scientific research, as researchers work to uncover its mysterious influence on human development and disease. This paper reviews how the microbiome is studied, how researchers can improve its study, and what clinical applications microbiome research might yield. For this review, we analyzed studies concerning the role of the microbiome in disease and early development, the common methodologies by which the microbiome is researched in the lab, and modern clinical treatments for dysbiosis and their possible future applications. We found that the gut microbiome is essential for proper development of various physiological systems and that gut dysbiosis is a clear factor in the etiology of various diseases. Furthermore, we found that germ-free animal models and microbiome manipulation techniques are inadequate, reducing the efficacy of microbiome research. Nonetheless, research continues to show the significance of microbiome manipulation in the clinical treatment of disease, having shown great promise in the prevention and treatment of dysbiosis. Though the clinical applications of microbiome manipulation are currently limited, the significance of dysbiosis in the etiology of a wide array of diseases indicates the significance of this research and highlights the need for more effective research methods concerning the microbiome.

Rats and mice were studied for changes in meal-taking structure in a closed operant food economy, in which the consummatory or unit prices for food were increased. In experiment 1, as food price increased, male rats modestly decreased the number of meals per day and increased mean meal size. Female rats were similar to males but had smaller meal size and, at low costs, took more meals per day. In experiment 2, male and female B6 mice reduced food intake as price increased, accompanied by decreased meal number without change in meal size. They showed grazing-like behavior in the first part of the night. In contrast, we report in experiment 3, a large increase in intake and meal size during the final trimester of pregnancy. In experiment 4, we report that CD1 male mice subjected to a unit price series performed comparably to rats, and not like B6 mice. Other CD1 mice were tested using an interval schedule, and we found that mice were able to adapt eating patterns to greatly increased time demands without compromising total intake. Data are discussed in terms of the intercalation of food acquisition with global patterns of activity. Such interactions of organism and food environment are in particular need of mechanistic investigation.

Microbiota dysbiosis has been associated with chronic diseases ranging from gastrointestinal inflammatory and metabolic conditions to neurological changes affecting the gut-brain neural axis, mental health, and general well-being. However, current animal studies using oral gavage and gnotobiotic animals do not allow for non-invasive long-term access to gut microbiome. The purpose of the present study was to evaluate the feasibility of 3D-printed fistula implants through the body wall and into the cecum of rats to obtain long-term access to gut microbiome. Cecal fistulas were designed and 3D-printed using a high temperature resin (Formlabs; acrylic and methacrylic mixture). Nine male Sprague-Dawley rats underwent the fistula implantation. Food intake, body weight, and body fat were measured to determine the impact of fistula manipulation. Gut microbiome, vagal afferents in the hindbrain, and microglia activation were analyzed to determine if fistula implantation disrupted the gut-brain neural axis. We found that the procedure induced a transient decrease in microbial diversity in the gut that resolved within a few weeks. Fistula implantation had no impact on food intake, body weight, fat mass, or microglia activation. Our study shows that 3D-printed cecal fistula implantation is an effective procedure that allows long-term and minimally invasive access to gut microbiome.