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Metabolic surgery positively changes gut microbiota

Updated: Jul 22, 2021

Metabolic surgery results in a positive phenotypic improvement that occurs simultaneously with gut microbiota changes, but these changes do not for the wider beneficial metabolic health impact of Roux-en-Y Gastric Bypass (RYGB), according to the results of a clinical trial. The study authors said that diet, hormonal changes, bile acids metabolism and physical activity should be further investigated to better explain the metabolic improvement of type 2 diabetic patients with mild obesity after RYGB. The outcomes were reported in the paper, ‘Gut microbiota changes after metabolic surgery in adult diabetic patients with mild obesity: a randomised controlled trial’, published in BMC Diabetology & Metabolic Syndrome.

Researchers from France and Portugal (Centro Hospitalar São João (CHSJ) in Porto, Portugal) wanted to evaluate the association between gut microbiota changes and anthropometric, metabolic and inflammatory profiles after metabolic surgery compared with medical therapy, in type 2 diabetic (T2DM) adults with mild obesity (BMI 30–35 kg/m2). The designed an open-label, randomised controlled clinical trial with two arms: (i) surgical, and (ii) medical. The main outcome was gut microbiota changes after: metabolic surgery (Roux-en-Y gastric bypass—RYGB) versus standard medical therapy. Secondary outcomes included anthropometric, metabolic and inflammatory profiles.

In total, 20 patients were included (ten in each arm) in the trial. The average age was 53 vs. 58 years old, BMI was 33.6 vs. 32.0 kg/m2, A1c was 8.7 vs. 8.2%, and women were 50% vs. 30%, for the surgical arm vs. medical arm, respectively. There were no significant differences in BMI, A1c, fasting glucose, insulin, C-peptide levels, or HOMA-IR between the two arms. However, patients who underwent RYGB had significantly higher weight, visceral fat area, body fat mass, and serum hsCRP at baseline.

One month after the beginning of the study, they reported that there was no evidence of differences in BMI between arms, however, %WL was significantly higher in the surgical category (10.5 vs. 3.1%, p<0.001). In addition, there were no were no significant differences observed at this time in fasting glucose, A1c, or C-peptide between arms. However, they found lower insulin levels (6.6 vs. 18.5 mg/dL, p=0.026) and HOMA-IR (2.5 vs. 6.5, p=0.035) in the surgical arm.

Unsurprisingly, at three months of follow-up, differences in %WL were even more pronounced (17.7 vs. 5.5%, p<0.001) and reported significant differences in BMI (27.7 vs. 30.3 kg/m2, p=0.007) and waist circumference (97.9 vs. 103.3 cm, p=0.034), but none were for fasting glucose, A1c, or C-peptide between both arms. Differences between arms increased in insulin levels (6.0 vs. 17.2 mg/dL, p=0.019) and HOMA-IR (1.9 vs. 6.1, p=0.013).

At six months of follow-up, differences in BMI and %WL continued to be even greater (BMI: 25.7 vs. 30.4 kg/m2, p<0.001; %WL: 23.4 vs. 5.2%, p<0.001) and body fat measures were significantly lower in the surgical arm (visceral fat area, p = 0.029; and body fat mass, p=0.003). Measures of insulin resistance were also significantly reduced in the surgical arm (A1c: 6.2 vs. 7.3%, p=0.038; HOMA-IR: 1.6 vs. 7.2, p<0.001), as were triglycerides (91.9 vs. 143.6 mg/dL, p = 0.049), while HDL-C was significantly increased (54.4 vs. 40.7 mg/dL, p=0.014).

At 12 months of follow-up, the average BMI was 24.6 vs. 30.5 kg/m2 (p<0.001), and A1c was 6.2 vs. 7.7% (p < 0.001) in the surgical vs. medical arm, respectively. The %WL was 25.5% in the surgical arm and 4.9% in the medical arm (p<0.001). Waist circumference, visceral fat area and body fat mass were statistically lower in the surgical arm (p<0.001, p=0.007 and p=0.002, respectively). In addition, fasting glucose, insulinemia, C-peptide, and HOMA-IR were significantly lower in the surgical arm (p=0.007, p=0.020, p=0.020 and p=0.027, respectively), and HDL-C was higher (p=0.004).

At the final endpoint, all participants from the medical arm failed to achieve diabetes remission or improvement, however in the surgical arm, five participants (62.5%) experienced remission from their diabetes (p=0.007 for comparison with medical arm, Chi2 test), two participants (25%) improved their phenotypes and only one showed no improvement.

The authors noted that this is the first randomised controlled clinical trial that simultaneously explored clinical and microbiota changes in diabetic patients with class-1 obesity after RYGB versus standard medical therapy. The results confirm previous studies that RYGB increases microbiome richness, not only in patients with morbid obesity, but also for a broader BMI range, including patients with a BMI 30–35kg/m2.

“In conclusion, our research suggests that there is a remarkable phenotypic improvement after metabolic surgery which occurs simultaneously with gut microbiota changes,” the authors concluded. “Nevertheless, gut microbiome changes alone cannot explain the beneficial metabolic health impact of RYGB. Other mechanisms such as diet, hormonal changes, bile acids metabolism, and physical activity need to be further explored in this equation in order to better explain the metabolic improvement of T2D patients with mild obesity after RYGB.”

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