Background Obesity is a growing health concern worldwide, including United Arab Emirates. Bariatric surgery is an effective treatment option, with to date unclear weight loss mechanisms. In this prospective study, we explored post-bariatric surgery changes in energy homeostasis, gut peptides, hormones, and gut microbiota.Method We recruited 19 Emirati adults who were planning to undergo sleeve gastrectomy (SG). We assessed the energy requirements using 24-hour diet recalls, indirect calorimetry for resting energy expenditure (REE), and a questionnaire for appetite. Anthropometrics included body mass index (BMI), waist circumference, waist-to-height ratio, fat mass, fat-free mass, and percentage of body fat. Gut peptides, including peptide YY (PYY), glucagon-like peptide-1/2 (GLP-1/2), ghrelin (GHR), cholecystokinin (CCK), insulin, and leptin, were quantified using ELISA. Gut microbiota composition at phylum and genus levels, including the Firmicutes/Bacteroidetes (F/B) ratio and alpha (alpha) and beta (beta) diversity, was determined by sequencing amplicons of the V3-V4 region of the 16S rRNA at baseline and three months post-surgery. Comparisons used paired sample T-test, Wilcoxon, and McNemar test. QIIME 2 was used to identify taxa and their relative abundance; subsequent analyses were done in R for (alpha) and (beta) diversity (package qiime2R) and Wilcoxon signed-rank test in R for differences in microbiota at phylum and genus levels. We conducted Spearman correlation analyses between genera and energy homeostasis, appetite, anthropometrics, hormones, and gut peptides.Method We recruited 19 Emirati adults who were planning to undergo sleeve gastrectomy (SG). We assessed the energy requirements using 24-hour diet recalls, indirect calorimetry for resting energy expenditure (REE), and a questionnaire for appetite. Anthropometrics included body mass index (BMI), waist circumference, waist-to-height ratio, fat mass, fat-free mass, and percentage of body fat. Gut peptides, including peptide YY (PYY), glucagon-like peptide-1/2 (GLP-1/2), ghrelin (GHR), cholecystokinin (CCK), insulin, and leptin, were quantified using ELISA. Gut microbiota composition at phylum and genus levels, including the Firmicutes/Bacteroidetes (F/B) ratio and alpha (alpha) and beta (beta) diversity, was determined by sequencing amplicons of the V3-V4 region of the 16S rRNA at baseline and three months post-surgery. Comparisons used paired sample T-test, Wilcoxon, and McNemar test. QIIME 2 was used to identify taxa and their relative abundance; subsequent analyses were done in R for (alpha) and (beta) diversity (package qiime2R) and Wilcoxon signed-rank test in R for differences in microbiota at phylum and genus levels. We conducted Spearman correlation analyses between genera and energy homeostasis, appetite, anthropometrics, hormones, and gut peptides.Results At three months post-SG, energy intake, appetite, all anthropometric indices, insulin, leptin, and GLP-1 significantly decreased; PYY and GHR significantly increased, and REE was stable. beta-diversity of the gut microbiota and its composition at phylum and genus levels significantly changed post-surgery, yet F/B remained constant. Energy intake, BMI, and appetite negatively correlated with several taxa that significantly increased post-SG.Conclusion Gut peptides, hormones, and microbiota change partly account for bariatric surgery's weight-loss benefits. Understanding these alterations can inform personalized interventions targeting obesity.