Major Increase in Microbiota-Dependent Proatherogenic Metabolite TMAO One Year After Bariatric Surgery.

BACKGROUND: Trimethylamine-N-oxide (TMAO) is formed in the liver from trimethylamine (TMA), a product exclusively generated by the gut microbiota from dietary phosphatidylcholine and carnitine. An alternative pathway of TMAO formation from carnitine is via the microbiota-dependent intermediate γ-butyrobetaine (γBB). Elevated TMAO levels are associated with cardiovascular disease (CVD), but little is known about TMAO in obesity. Given the proposed contribution of microbiota alterations in obesity and type 2 diabetes (T2D), we investigated the potential impact of obesity, lifestyle-induced weight loss, and bariatric surgery on plasma levels of TMAO, its microbiota-dependent intermediate γBB, and its diet-dependent precursors carnitine and choline. METHODS: TMAO, γBB, carnitine, and choline were measured by high-performance liquid chromatography in 34 obese individuals (17 with and 17 without T2D) undergoing bariatric surgery and 17 controls. RESULTS: TMAO was not elevated in obese patients or reduced by lifestyle interventions but increased approximately twofold after bariatric surgery. Similar to TMAO, plasma levels of γBB were not influenced by lifestyle interventions but increased moderately after bariatric surgery. In contrast, carnitine and choline, which are abundant in nutrients, such as in red meat and eggs, and not microbiota dependent, were reduced after lifestyle interventions and rebounded after bariatric surgery. CONCLUSIONS: The major increase in TMAO after bariatric surgery was unexpected because high TMAO levels have been linked to CVD, whereas bariatric surgery is known to reduce CVD risk. Prospective studies of gut microbiota composition and related metabolites in relation to long-term cardiovascular risk after bariatric surgery are warranted.

Lifestyle changes followed by bariatric surgery lower inflammatory markers and the cardiovascular risk factors C3 and C4.

BACKGROUND: Morbidly obese patients are at risk of developing insulin resistance and cardiovascular disease. Low-grade systemic inflammation is an important factor for this development. We evaluated the effect of bariatric surgery on markers of inflammation, coagulation and glucose metabolism. METHODS: Ninety-seven morbidly obese patients and 17 lean subjects (control group) participated. Anthropometric measurements as well as fasting blood samples were obtained at first admission, prior to surgery, and 1 year after surgery. RESULTS: At admission, the morbidly obese group had significantly elevated levels of the complement components C3 and C4 compared to the lean control group (P<0.0001). Levels of C3 and C4 dropped significantly in the morbidly obese group over time (P<0.0001), and, 1 year after the operation, levels were comparable to those of the control group. The same changes were seen for markers of inflammation (high-sensitivity C-reactive protein, tumor necrosis factor-α, interferon-γ, interleukin-1 receptor antagonist, IL-6, and IL-13), coagulation (fibrinogen and plasminogen activator inhibitor-1), and glucose metabolism (leptin and insulin). There was a positive correlation between changes in C3 and body mass index, weight, coagulation parameters, inflammatory parameters, and leptin, respectively. CONCLUSIONS: Bariatric surgery in morbidly obese patients reduced weight effectively. Even more importantly, the increased levels of several risk factors associated with diabetes and cardiovascular co-morbidity normalized 1 year after surgery.

Bariatric surgery reduces risk factors for development of type 2 diabetes mellitus in morbidly obese, nondiabetic patients.

BACKGROUND: Patients with morbid obesity have a high risk of developing type 2 diabetes mellitus (T2DM). Important risk factors include body mass index (BMI), waist circumference, and insulin resistance. In this prospective study, we investigated if preoperative lifestyle changes followed by bariatric surgery could reduce these risk factors. METHODS: Forty nondiabetic obese patients aged 27-57 years participated. Baseline BMI was 36.1-65.6 kg/m(2). Fasting glucose, C-peptide, and glycated hemoglobin (HbA1c) were measured at baseline and 1 year after surgery. The patients underwent lifestyle changes for a period of 3 months prior to bariatric surgery and were followed for 1 year after surgery. The correlations between risk factors and weight reduction were assessed by a Pearson test. RESULTS: Lifestyle changes resulted in a mean weight reduction of 14.3 kg. One year after bariatric surgery, the patients had a mean reduction in BMI of 17.6. Mean waist circumference was reduced from 136.5 cm to 100.7 cm. At baseline, all 40 patients had a waist circumference >100 cm; 1 year after surgery 18 of 40 patients did. At baseline, 11 out of 40 had insulin resistance (as defined by a homeostasis model score >3.99), whereas 1 year after surgery none of the patients did. There was a statistically significant correlation between change in waist circumference and change in insulin resistance (P<0.02), and between HbA1c and weight loss (P<0.002). CONCLUSIONS: Our study shows that, in morbidly obese individuals, lifestyle changes followed by bariatric surgery led to a significant weight loss and a reduction in risk factors for development of T2DM.