Roux-en-Y Gastric Bypass Improved Insulin Resistance via Alteration of the Human Gut Microbiome and Alleviation of Endotoxemia.

BACKGROUND: Obesity is a main contributing factor for the development of glucose intolerance and type 2 diabetes mellitus (T2D). Roux-en-Y gastric bypass (RYGB) is believed to be one of the most effective treatments to reduce body weight and improve glucose metabolism. In this study, we sought to explore the underlying mechanisms of weight reduction and insulin resistance improvement after RYGB. METHODS: This was a prospective observational study using consecutive samples of 14 obese subjects undergoing bariatric surgery. Main assessments were serum indexes (blood metabolites, glucose-lipid regulating hormones, trimethylamine-N-oxide (TMAO), and lipopolysaccharide-binding protein (LBP), fecal short-chain fatty acids (SCFAs), and gut microbiota. Correlation analysis of the factors changed by RYGB was used to indicate the potential mechanism by which surgery improves insulin resistance. RESULTS: The subjects showed significant improvement on indices of obesity and insulin resistance and a correlated change of gut microbiota components at 1 month, 3 months, and 6 months post-RYGB operation. In particular, the abundance of a counterobese strain, Akkemansia muciniphila, had gradually increased with the postoperative time. Moreover, these changes were negatively correlated to serum levels of LBP and positively correlated to serum TMAO and fecal SCFAs. CONCLUSIONS: Our findings uncovered links between intestinal microbiota alterations, circulating endotoxemia, and insulin resistance. This suggests that the underlying mechanism of protection of the intestine by RYGB in obesity may be through changing the gut microbiota.

Prolonged postsurgical recovery period and adverse effects of a leptin application in endotoxemic obese rodents.

AIMS: Increasing evidence suggests that the adipokine leptin plays a role in modulating immune responses and mediating the link between metabolism and immune system. Obese patients are more susceptible to infections than normal weight individuals. To define the pathophysiological role of leptin during endotoxemia, we examined the effects of leptin on energy metabolism, hemodynamics and quality of life in normal weight and diet-induced obese rats by means of radio-telemetry. MAIN METHODS: Telemetric-transmitter and a central venous catheter were implanted in male Lewis rats. All animals performed two experiments. First, an intravenous injection of 500µlkg(-1) leptin or vehicle (isotonic saline) was performed. After an infusion time of 30min an i.v. bolus of 0.2ml saline over 1min was injected. In the second phase, infusion of placebo or 500µlkg(-1) leptin and an i.v. bolus injection of 100µlkg(-1)Escherichia coli endotoxin were performed. Mean arterial blood pressure (MAP), locomotor activity and electromyogram were recorded via radio-telemetry. Food and water consumption were assessed daily. Quality of life tests were performed at specific times. KEY FINDINGS: Obese animals displayed a prolonged postsurgical recovery period. No benefit could be observed by exogenous leptin in endotoxemic lean or obese animals regarding nutrition balance and locomotor activity. However, leptin treatment even destabilized MAP in obese endotoxemic animals. SIGNIFICANCE: These data demonstrate the necessity to differentiate between normal weight and obese individuals when targeting novel therapeutic strategies for endotoxemia and point out the body weight dependent postsurgical recovery period.

[Retroperitoneoscopic surgeries for pyoinflammatory diseases of the kidney with varying severity of endotoxemia].

The medical histories of 98 patients with pyoinflammatory diseases of the kidney, who underwent surgery by retroperitoneoscopic access, and 75 patients, who underwent traditional open surgery were analyzed. The degrees of multiple organ dysfunction and endotoxemia were determined in all patients. The groups were comparable in terms of clinical manifestations and severity of intoxication. The advantages of minimally invasive retroperitoneoscopic interventions are demonstrated; they allow to reduce the surgical morbidity, pain after surgery, the frequency and severity of intraoperative complications, length of in-hospital stay, the period of disability, the cost of treatment, and the need for medications.

[Influence of membrane plasmapheresis on the course of endotoxemia in acute destructive pancreatitis].

The results of complex treatment analysis in 147 patients with acute destructive pancreatitis from 2006 to 2012 was made. In membrane plasmapheresis application the reduction of pain and improvement of general condition observed rapidly. By the end of the second day the activity of amylase decreased by 53% urea and creatinine level--by 62 and 56% compared with baseline. Decreasing of the necrotic suppurative complications rate in the main group--15.4%, in control--32.8%, mortality--accordinty 14.1 and 27.6%.

Reduction in endotoxemia, oxidative and inflammatory stress, and insulin resistance after Roux-en-Y gastric bypass surgery in patients with morbid obesity and type 2 diabetes mellitus.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) results in profound weight loss and resolution of type 2 diabetes mellitus (T2DM). The mechanism of this remarkable transition remains poorly defined. It has been proposed that endotoxin (lipopolysaccharide [LPS]) sets inflammatory tone, triggers weight gain, and initiates T2DM. Because RYGB may diminish LPS from endogenous and exogenous sources, we hypothesized that LPS and the associated cascade of oxidative and inflammatory stress would diminish after RYGB. METHODS: Fifteen adults with morbid obesity and T2DM undergoing RYGB were studied. After an overnight fast, a baseline blood sample was collected the morning of surgery and at 180 days to assess changes in glycemia, insulin resistance, LPS, mononuclear cell nuclear factor (NF)-κB binding and mRNA expression of CD14, TLR-2, TLR-4, and markers of inflammatory stress. RESULTS: At 180 days after RYGB, subjects had a significant decrease in body mass index (52.1 ± 13.0 to 40.4 ± 11.1), plasma glucose (148 ± 8 to 101 ± 4 mg/dL), insulin (18.5 ± 2.2 mµU/mL to 8.6 ± 1.0 mµU/mL) and HOMA-IR (7.1 ± 1.1 to 2.1 ± 0.3). Plasma LPS significantly reduced by 20 ± 5% (0.567 ± 0.033 U/mL to 0.443 ± 0.022 E U/mL). NF-κB DNA binding decreased significantly by 21 ± 8%, whereas TLR-4, TLR-2, and CD-14 expression decreased significantly by 25 ± 9%, 42 ± 8%, and 27 ± 10%, respectively. Inflammatory mediators CRP, MMP-9, and MCP-1 decreased significantly by 47 ± 7% (10.7 ± 1.6 mg/L to 5.8 ± 1.0 mg/L), 15 ± 6% (492 ± 42 ng/mL to 356 ± 26 ng/mL) and 11 ± 4% (522 ± 35 ng/mL to 466 ± 35 ng/mL), respectively. CONCLUSION: LPS, NF-κB DNA binding, TLR-4, TLR-2, and CD14 expression, CRP, MMP-9, and MCP-1 decreased significantly after RYGB. The mechanism underlying resolution of insulin resistance and T2DM after RYGB may be attributable, at least in part, to the reduction of endotoxemia and associated proinflammatory mediators.

[Quality of life of patients with hyperendotoxemia after hemicolectomy].

UNLABELLED: The concept of "health" is defined by the World Health Organization (WHO) as a state of complete physical, mental and social well-being and not merely the absence of disease. Currently, one of the most widely used questionnaires of general type is the SF-36 Health Status Survey, proposed the Boston Institute for Health and created on the basis of other already existing tools for assessing QOL. Translated into Russian and testing methodology was conducted by the Institute of clinical and pharmacological studies (St. Petersburg). Any surgical intervention, in particular the removal of part of the colon can lead to a restriction of all aspects (physical, mental and social) of a normal human life. The goal of treatment of any disease should be considered as improving the quality of life of the patient on a background of positive clinical dynamics, assessing the quality of life indicators, which depend on many external and internal factors. AIM: to study the quality of life of patients after hemicolectomy, depending on the type of colon resection and the level of endotoxemia. RESULTS: Analysis of quality of life of patients after undergoing surgery--hemicolectomy carried out using questionnaire SF-36 indicates a decline in general condition and mental health in patients after left-sided hemicolectomy. The study showed a close pathogenetic relationship between endotoxemia and decreased quality of life of patients after hemicolectomy.

[Predictive value of test with procalcitonin in diagnostics of endogenous intoxication severity in extended purulent peritonitis].

Diagnostic significance of the test with procalcitonin (PCT) for estimation of the patients state severity in extended purulent peritonitis (EPP) and prognostication of hospital lethality were studied up. For the comparison making the state severity was estimated in the patients in accordance to SOFA scale, basing on the clinical and laboratory data analysis, the leukocyte index of intoxication (LII) and hematological index of intoxication (HII) on the second postoperative day. In all the patients the symptoms, corresponding to criteria of endogenous abdominal intoxication, were revealed. The EPP course severity was estimated in accordance with the hospital lethality index. There was established, that specific test with PCT owes high prognostic validity in diagnosis of endogenous intoxication severity, it may be applied as a secure diagnostic marker for the state severity estimation and hospital lethality prognostication in patients, suffering EPP. Otherwise, nonspecific markers of endotoxicosis, including LII and HII, lack informativity, owes low prognostic validity and do not permit to estimate of such a patients state severity.

ATIII attenuates endotoxemia induced healing impairment in the colon.

BACKGROUND: Intra-abdominal infections are considered a contributing factor to the impairment of anastomotic healing in patients undergoing surgical procedures of digestive system. Antithrombin (ATIII) is known to improve the microcirculation in sepsis. We hypothesized that it may also positively influence the healing of the colon anastomoses under endotoxemia. MATERIALS AND METHODS: Ninety Balb/c mice (n = 10 per group on day 2, 4, and 7) were randomly assigned to three groups: Control (N), Sepsis (S) (administration of lipopolysaccharides (LPS) dosed at 2 mg/kg bodyweight, 18 h before colon surgery), and Sepsis with ATIII therapy (SIII) (administration of LPS and ATIII). All the animals underwent colonic anastomoses. Immediately after their completion, microcirculatory parameters were measured, and both macroscopic and histological parameters were assessed on day 2, 4, and 7 postoperation. Additionally, immunohistology studies were performed for CD31, ssDNA, and iNOS, along with an examination for bacterial translocation to the mesenteric lymph nodes. RESULTS: Compared with group S, the functional capillary network was denser in the control group N (P < 0.001) and group SIII (P < 0.01). Mean bursting pressures were significantly lower in group S compared with group N, on day 2, 4, and 7, and with group SIII on day 2 and 7. At the anastomosis, the inflammatory infiltrate in group S was denser compared with groups N (P < 0.001) and SIII (P < 0.01). Furthermore, the apoptotic rate was higher, and the vascular density was lower on day 7 in group S compared with groups SIII and N (P < 0.05). Bacterial translocation decreased over time (P < 0.05) with no significant differences between the groups. CONCLUSION: ATIII improved the anastomotic microcirculatory parameters and anastomotic healing in mice with endotoxemia, though the improvement failed to achieve the levels of the control mice.

[Systemic hemodynamics, oxygenating lung function and oxygen transport in patients with acute intestinal obstruction and an endotoxicosis syndrome]. / Sistemnaia gemodinamika, oksigeniruiushchaia funktsiia legkikh i transport kisloroda u bol'nykh s ostroi neprokhodimost'iu kishechnika i sindromom éndotoksikoza.

Systemic hemodynamics, oxygenating function of the lungs, and oxygen budgeting were studied in 32 patients with acute bowel obstruction (ABO) with severe endotoxicosis. Profound disturbances of systemic hemodynamics and blood oxygenation in the lungs underlie the hemostasis changes in this category of patients before and early after operation. These hemostasis changes lead to inadequate oxygen delivery and metabolic requirement of oxygen and are associated with development of oxygen deficiency in tissues. As a rule, patients with ABO with severe endotoxicosis develop acute respiratory failure presenting as adult respiratory distress syndrome on days 2-3 postoperation. Significant differences in the pattern of hemostasis changes and compensatory shifts in survivors and patients dying after ABO are detected at this period, which determine the prognosis and outcome of disease.