Intestinal Energy Harvest as potential mediator for gut microbiota facilitated weight loss in Bariatric Surgery patients

Obesity is a rapidly growing global health concern. Severe obesity is characterized by a body mass index (BMI) > 40 kg/m2, or BMI > 35 kg/m2 with obesity-related health conditions such as chronic inflammation and insulin resistance. Metabolic and bariatric surgery (MBS), including procedures like Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG), has been acknowledged as the most effective treatment in patients with severe obesity. However, a significant subset of patients does not achieve expected weight or suffer weight regain post MBS. Researchers investigated demographic factors that might contribute to sub-optimal weight loss such as race and sex, but these factors do not explain poor outcomes. This discrepancy prompts a deeper exploration into internal biological mechanisms, one of which involves energy harvest and gut microbiota.Energy harvest is a process by which the body extracts energy from ingested food in the gut. Variations in the efficiency of intestinal calorie absorption play a pivotal role in weight loss outcomes. However, factors that affect intestinal energy harvest, and the exact mechanisms through which it impacts weight loss results remain unclear. This dissertation investigated the interrelationships of diet, host intestinal microbiota, intestinal energy harvest and weight loss outcomes following MBS.Intestinal energy harvest was assessed using bomb calorimetry (fecal energy content served as a proxy for calorie absorption), diet was assessed using 24 hour dietary recalls, and microbiota were quantified using fecal metagenomic sequence before and after MBS. Regression and machine learning approaches were used for analysis.We found that bariatric surgery changes the capacity for energy harvest post operatively. A notable difference in relative fecal energy content was observed between patients experiencing optimal and sub-optimal weight loss. Intestinal energy harvest enhanced the predictability of patient weight loss outcomes. However, associations of macronutrient intake to absolute fecal energy density were insignificant. The process of energy harvest appears to be a partial mediator in the relationship between intestinal microbiota and weight loss outcomes in bariatric surgery patients.