The gut microbiota: a major player in the toxicity of environmental pollutants?

Exposure to environmental chemicals has been linked to various health disorders, including obesity, type 2 diabetes, cancer and dysregulation of the immune and reproductive systems, whereas the gastrointestinal microbiota critically contributes to a variety of host metabolic and immune functions. We aimed to evaluate the bidirectional relationship between gut bacteria and environmental pollutants and to assess the toxicological relevance of the bacteria–xenobiotic interplay for the host. We examined studies using isolated bacteria, faecal or caecal suspensions—germ-free or antibiotic-treated animals—as well as animals reassociated with a microbiota exposed to environmental chemicals. The literature indicates that gut microbes have an extensive capacity to metabolise environmental chemicals that can be classified in five core enzymatic families (azoreductases, nitroreductases, β-glucuronidases, sulfatases and β-lyases) unequivocally involved in the metabolism of >30 environmental contaminants. There is clear evidence that bacteria-dependent metabolism of pollutants modulates the toxicity for the host. Conversely, environmental contaminants from various chemical families have been shown to alter the composition and/or the metabolic activity of the gastrointestinal bacteria, which may be an important factor contributing to shape an individual’s microbiotype. The physiological consequences of these alterations have not been studied in details but pollutant-induced alterations of the gut bacteria are likely to contribute to their toxicity. In conclusion, there is a body of evidence suggesting that gut microbiota are a major, yet underestimated element that must be considered to fully evaluate the toxicity of environmental contaminants

Valorisation of Biowastes for the Production of Green Materials Using Chemical Methods

With crude oil reserves dwindling, the hunt for a sustainable alternative feedstock for fuels and materials for our society continues to expand. The biorefinery concept has enjoyed both a surge in popularity and also vocal opposition to the idea of diverting food-grade land and crops for this purpose. The idea of using the inevitable wastes arising from biomass processing, particularly farming and food production, is, therefore, gaining more attention as the feedstock for the biorefinery. For the three main components of biomass—carbohydrates, lipids, and proteins—there are long-established processes for using some of these by-products. However, the recent advances in chemical technologies are expanding both the feedstocks available for processing and the products that be obtained. Herein, this review presents some of the more recent developments in processing these molecules for green materials, as well as case studies that bring these technologies and materials together into final products for applied usage

Metabolic syndrome is associated with impaired long-term renal allograft function; not all component criteria contribute equally.

Chronic renal transplant dysfunction (CRTD) remains a leading cause of renal allograft loss. Evidence suggests that immunological and ischemic insults are mainly associated with CRTD occurring within the first year after transplantation, whereas nonimmunological insults are predominantly associated with CRTD beyond the first year. Several cardiovascular risk factors, such as obesity, dyslipidemia, hypertension, and diabetes mellitus have been identified as important nonimmunological risk factors for CRTD. These risk factors constitute the metabolic syndrome (MS). As renal allograft function is a surrogate marker of renal allograft loss, we investigated the association of MS with impairment of renal allograft function beyond the first year after transplantation in a cross-sectional study of 606 renal transplant outpatients. Metabolic syndrome was defined using the definition of the National Cholesterol Education Program. Renal allograft function was assessed as the 24-h urinary creatinine clearance. A total of 383 out of 606 patients (63%) suffered from MS at a median time of 6 years (2.6-11.4) post-transplant. Presence of MS was associated with impaired renal allograft function beyond 1 year post-transplant [-4.1 mL/min, 95%CI (-7.1, -1.1)]. The impact of MS did not change appreciably after adjustment for established risk factors for CRTD [-3.1 mL/min, 95%CI (-6.0, -0.2)]. However, not all component criteria of MS contributed equally. Only systolic blood pressure and hypertriglyceridemia were independently associated with impaired renal allograft function beyond 1 year post-transplant in multivariate analyses

Validation of insulin resistance indexes in a stable renal transplant population.

OBJECTIVE: The purpose of this study was to investigate the validity of established insulin resistance indexes, based on fasting blood parameters, in a stable renal transplant population. RESEARCH DESIGN AND METHODS: Fasting insulin, homeostasis model assessment (HOMA), the quantitative insulin sensitivity check index (QUICKI), and McAuley's index were assessed for correlation and agreement with whole-body glucose uptake (M value) divided by prevailing serum insulin concentrations (I value) assessed during a hyperinsulinemic-euglycemic clamp in 51 stable renal transplant recipients, who were at a median of 7.5 years after transplant. Multivariate linear regression analyses were used to determine independent risk factors for insulin resistance. RESULTS: The M/I value correlated with fasting insulin concentration (r = -0.56), HOMA (r = -0.53), QUICKI (r = 0.52), and McAuley's index (r = 0.61) (all P < 0.01). Linear regression showed agreement between all indexes and insulin resistance. However, McAuley's index showed the strongest agreement irrespective of age, sex, renal allograft function, and obesity. In multivariate analysis, fasting insulin concentration (beta = -0.59, P = 0.002), fasting triglyceride concentration (beta = -0.33, P = 0.04), and BMI (beta = -1.22, P = 0.05) were independently associated with the M/I value. CONCLUSIONS: All investigated insulin resistance indexes were valid estimates of insulin resistance in the long-term stable renal transplant population. However, correlation and agreement were strongest for McAuley's index. In addition to fasting insulin and triglyceride concentrations, of which McAuley's index is composed, only BMI seemed to be independently associated with insulin resistance in this population

The predictive value of renal vascular resistance for late renal allograft loss.

The renal artery resistance index (RI), assessed by Doppler ultrasonography, was recently identified as a new risk marker for late renal allograft loss. This finding requires confirmation since RI in that study was not measured at predetermined time points and ultrasonography is operator-dependent. We investigated the predictive value of renal vascular resistance (RVR), a less operator-dependent method as assessed by mean arterial pressure divided by renal blood flow, for the prediction of recipient mortality and death-censored graft loss. RVR was compared to commonly used risk markers such as creatinine clearance (CrCl), serum creatinine (SCreat) and proteinuria (UProt) in 793 first-time cadaveric renal transplant recipients at predetermined time points after transplantation using receiver operating characteristics (ROC) and Cox survival analyses. The present study showed that RVR is a prominent risk marker for recipient mortality and death-censored graft loss. However, the predictive value of RVR for recipient mortality owed mainly to the impact of mean arterial blood pressure. In contrast, RVR constituted more than the sum of its components for death-censored graft loss, but showed less predictive value than SCreat in univariate analysis. As the assessment of RVR is expensive and time-consuming, we believe that RVR holds no clinical merit for the follow-up of renal transplant recipients

Determinants of insulin resistance in renal transplant recipients.

BACKGROUND: Insulin resistance is considered to play an important role in the development of cardiovascular disease, which limits long-term renal transplant survival. Renal transplant recipients are more insulin-resistant compared with healthy controls. It is not known to date which factors relate to this excess insulin resistance. Therefore, we investigated which factors are related to insulin resistance long-term after renal transplantation. METHODS: All renal transplant recipients at our outpatient clinic with a functioning graft for more than one year were invited to participate. We excluded diabetic recipients. Recipient, donor, and transplant characteristics were collected as putative determinants. We used fasting insulin, homeostasis model assessment index, and McAuley's index as valid estimates of insulin resistance. Linear regression models were created to investigate independent determinants of all indexes. RESULTS: A total of 483 recipients (57% male, 50+/-12 years) were analyzed at a median (interquartile range) time of 6.0 (2.6-11.6) years posttransplant. The most consistent determinants across all three indices were body mass index (P<0.001), waist-to-hip ratio (P<0.001), and prednisolone dose (P<0.05). Independent associations were present for total cholesterol (P<0.001), high-density lipoprotein cholesterol (P<0.001), creatinine clearance (P<0.05), recipient age (P<0.001), and gender (P< or =0.002). No independent associations were present for transplant-related factors such as acute rejection treatment or cytomegalovirus seropositivity. CONCLUSIONS: Our results indicate that obesity, distribution of obesity, and prednisolone treatment are the predominant determinants of insulin resistance long term after transplantation. Insulin resistance after renal transplantation could be managed favorably by weight and prednisolone dose reduction, which may reduce cardiovascular disease

Elevated levels of C-reactive protein independently predict accelerated deterioration of graft function in renal transplant recipients.

BACKGROUND: Chronic transplant dysfunction is characterized by a gradual decline in renal function with slowly rising serum creatinine. The underlying mechanism is thought to include inflammation and atherosclerosis. C-reactive protein (CRP) is a well-established marker of both inflammation and atherosclerosis. In this prospective study, we investigated whether CRP could be of use as a clinical marker for early identification of renal transplant recipients at increased risk of deterioration of graft function. METHODS: In this prospective study, all participating patients (n = 606) visited the out-patient clinic at least once a year, and serum creatinine was assessed at every visit. Subjects with a follow-up of 3.0 mg/l (P 1 year post-transplantation. Further prospective studies are required to investigate whether early intervention can prevent deterioration of graft function in subjects with elevated levels of CRP