This study investigates the impact of Roux-en-Y gastric bypass (RYGB) surgery on gut microbiota and its association with metabolic and inflammatory markers in obese individuals. The research design involved profiling gut microbiota from fecal samples of 13 lean controls and 30 obese individuals (including seven type 2 diabetics) before (M0), 3 months (M3), and 6 months (M6) after RYGB. Key findings include: 1. **Bacteroides/Prevotella Group**: Increased at M3 compared to M0, negatively correlated with body mass index (BMI) but dependent on caloric intake. 2. **Escherichia coli**: Increased at M3, inversely correlated with fat mass and leptin levels, independent of food intake. 3. **Lactic Acid Bacteria**: Decreased at M3, including Lactobacillus/Leuconostoc/Pediococcus group and Bifidobacterium genus. 4. **Faecalibacterium prausnitzii**: Lower in diabetic subjects and associated negatively with inflammatory markers at M0 and throughout follow-up, independent of calorie intake. The study suggests that gut microbiota rapidly adapts to the starvation-like condition induced by RYGB, and F. prausnitzii species is linked to reduced low-grade inflammation in obesity and diabetes, regardless of calorie intake. These findings provide new insights into the gut microbiota changes associated with weight loss and their potential role in metabolic and inflammatory phenotypes.This study investigates the impact of Roux-en-Y gastric bypass (RYGB) surgery on gut microbiota and its association with metabolic and inflammatory markers in obese individuals. The research design involved profiling gut microbiota from fecal samples of 13 lean controls and 30 obese individuals (including seven type 2 diabetics) before (M0), 3 months (M3), and 6 months (M6) after RYGB. Key findings include: 1. **Bacteroides/Prevotella Group**: Increased at M3 compared to M0, negatively correlated with body mass index (BMI) but dependent on caloric intake. 2. **Escherichia coli**: Increased at M3, inversely correlated with fat mass and leptin levels, independent of food intake. 3. **Lactic Acid Bacteria**: Decreased at M3, including Lactobacillus/Leuconostoc/Pediococcus group and Bifidobacterium genus. 4. **Faecalibacterium prausnitzii**: Lower in diabetic subjects and associated negatively with inflammatory markers at M0 and throughout follow-up, independent of calorie intake. The study suggests that gut microbiota rapidly adapts to the starvation-like condition induced by RYGB, and F. prausnitzii species is linked to reduced low-grade inflammation in obesity and diabetes, regardless of calorie intake. These findings provide new insights into the gut microbiota changes associated with weight loss and their potential role in metabolic and inflammatory phenotypes.