Donor Fecal Microbiota Transplantation Alters Gut Microbiota and Metabolites in Obese Individuals With Steatohepatitis

The intestinal microbiota has been linked to the development and prevalence of steatohepatitis in humans. Interestingly, steatohepatitis is significantly lower in individuals taking a plant-based, low-animal-protein diet, which is thought to be mediated by gut microbiota. However, data on causality between these observations in humans is scarce. In this regard, fecal microbiota transplantation (FMT) using healthy donors is safe and is capable of changing microbial composition in human disease. We therefore performed a double-blind randomized controlled proof-of-principle study in which individuals with hepatic steatosis on ultrasound were randomized to two study arms: lean vegan donor (allogenic n = 10) or own (autologous n = 11) FMT. Both were performed three times at 8-week intervals. A liver biopsy was performed at baseline and after 24 weeks in every subject to determine histopathology (Nonalcoholic Steatohepatitis Clinical Research Network) classification and changes in hepatic gene expression based on RNA sequencing. Secondary outcome parameters were changes in intestinal microbiota composition and fasting plasma metabolomics. We observed a trend toward improved necro-inflammatory histology, and found significant changes in expression of hepatic genes involved in inflammation and lipid metabolism following allogenic FMT. Intestinal microbial community structure changed following allogenic FMT, which was associated with changes in plasma metabolites as well as markers of .Conclusion:Allogenic FMT using lean vegan donors in individuals with hepatic steatosis shows an effect on intestinal microbiota composition, which is associated with beneficial changes in plasma metabolites and markers of steatohepatitis.Peer reviewe

Improvement of Insulin Sensitivity after Lean Donor Feces in Metabolic Syndrome Is Driven by Baseline Intestinal Microbiota Composition

The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own (autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition. We also observed changes in plasma metabolites such as gamma-aminobutyric acid and show that metabolic response upon allogenic FMT (defined as improved insulin sensitivity 6 weeks after FMT) is dependent on decreased fecal microbial diversity at baseline. In conclusion, the beneficial effects of lean donor FMT on glucose metabolism are associated with changes in intestinal microbiota and plasma metabolites and can be predicted based on baseline fecal microbiota composition.Peer reviewe

Evaluation of ultrasmall superparamagnetic iron-oxide (USPIO) enhanced MRI with ferumoxytol to quantify arterial wall inflammation

Background and aims: Inflammation in atherosclerotic plaques is an important determinant of plaque vulnerability, and can be detected non-invasively using ultra-small superparamagnetic iron-oxide (USPIO) enhanced MRI. The aims of the current study were: 1) to determine whether ferumoxytol can be used for USPIO-MRI of atherosclerotic plaques, 2) to establish a protocol for quantitative USPIO-MRI of carotid artery plaques using ferumoxytol, and 3) to study the relation between USPIO uptake and plaque burden and F-18-fluorodeoxyglucose (FDG) uptake (measured by F-18-FDG PET/CT scan) in atherosclerotic plaques. Methods: In 9 patients with carotid artery stenosis >30% and 4 healthy controls, quantitative R2* MRI scans of the carotid arteries were performed before and 72 h after USPIO administration (4 mg/kg ferumoxytol). USPIO uptake was assessed by quantifying the difference in R2* (DR2*) between baseline and post-USPIO scans. In addition to MRI, F-18-FDG PET/CT was performed on both carotid arteries. MR and PET/CT images were co-registered, and F-18-FDG uptake was quantified in all slices containing atherosclerotic plaque. Results: Infusion of ferumoxytol resulted in higher R2* values after 72 h in atherosclerotic plaques (DR2* 24.6 +/- 19.8 s(-1); p = 0.0003), but not in the healthy control vessel wall (DR2* 2.6 +/- 5.6 s(-1), p = 0.23). USPIO uptake in patients was higher in atherosclerotic plaques compared to the patient non-plaque vessel wall (DR2* of 24.6 +/- 19.8 vs. 7.5 +/- 9.3 s(-1), p = 0.004). No correlation was found between USPIO uptake and F-18-FDG uptake in atherosclerotic plaques (R-2 = 0.03, p = 0.55). Conclusions: Ferumoxytol is selectively taken up by atherosclerotic plaques and can thus be used for carotid USPIO-MRI. As USPIO and F-18-FDG uptake in atherosclerotic plaque do not correlate in this cohort, these agents may visualize different pathophysiological aspects of plaque inflammation. (C) 2017 Elsevier B.V. All rights reserve

MR Spectroscopy-derived Proton Density Fat Fraction Is Superior to Controlled Attenuation Parameter for Detecting and Grading Hepatic Steatosis

Purpose: To prospectively compare the diagnostic accuracy of controlled attenuation parameter (CAP) obtained with transient elastography and proton density fat fraction (PDFF) obtained with proton magnetic resonance (MR) spectroscopy with results of liver biopsy in a cohort of adult patients suspected of having nonalcoholic fatty liver disease (NAFLD). Materials and Methods: The institutional review board approved this study. Informed consent was obtained from all patients. The authors evaluated 55 patients suspected of having NAFLD (40 men, 15 women). Patients had a median age of 52.3 years (interquartile range [IQR], 43.7-57.6 years) and a median body mass index of 27.8 kg/m(2) (IQR, 26.0-33.1 kg/m(2)). CAP and PDFF measurements were obtained on the same day, within 27 days of biopsy (IQR, 7-44 days). CAP and PDFF were compared between steatosis grades by using the Jonckheere-Terpstra test. Diagnostic accuracies of CAP and PDFF for grading steatosis were assessed with receiver operating characteristic (ROC) analysis. Within-weeks reproducibility (CAP and PDFF) and within-session repeatability were assessed with linear regression analyses, intraclass correlation coefficients, and coefficients of variation. Results: Steatosis grades at liver biopsy were distributed as follows: S0, five patients; S1, 24 patients; S2, 17 patients; and S3, nine patients. Both PDFF and CAP helped detect histologically proven steatosis (>= S1), but PDFF showed better diagnostic accuracy than CAP in terms of the area under the ROC curve (0.99 vs 0.77, respectively; P=.0334). PDFF, but not CAP, enabled the grading of steatosis (P <.0001). For within-weeks reproducibility, the intraclass correlation coefficient with PDFF was higher than that with CAP (0.95 vs 0.65, respectively; P=.0015); coefficients of variation were similar (19% vs 11%, P=.55). Within-session repeatability of CAP was good, with a coefficient of variation of 4.5%. Conclusion: MR spectroscopy-derived PDFF is superior to CAP in detecting and grading liver steatosis in human NAFL

Colistin resistance in gram-negative bacteria during prophylactic topical colistin use in intensive care units

Topical use of colistin as part of selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) has been associated with improved patient outcome in intensive care units (ICU), yet little is known about the risks of colistin resistance. We quantified effects of selective decontamination on acquisition of colistin-resistant gram-negative bacteria (GNB) using data from a cluster-randomized study and a single-centre cohort. Acquisition of colistin-resistant GNB and conversion from susceptible to resistance in GNB was determined in respiratory samples [from patients receiving SDD (n = 455), SOD (n = 476), or standard care (SC) (n = 315)], and in rectal swabs from 1,840 SDD-patients. Genotyping of converting isolates was performed where possible. The respiratory tract acquisition rates of colistin-resistant GNB were comparable during SDD, SOD, and SC and ranged from 0.7 to 1.1/1,000 patient-days at risk. Rectal acquisition rates during SDD were 0.05). In patients with rectal GNB carriage conversion rates during SDD were 5.4 and 3.2/1,000 days at risk and 15.5 and 12.6/1,000 days at risk when colonized with tobramycin-resistant GNB. Acquisition rates with colistin-resistant GNB in the respiratory tract were low and comparable with and without topical use of colistin. Rates of acquisition of colistin-resistant GNB during SDD were-in ICUs with low endemicity of antibiotic resistance-<2.5/1,000 days at risk, but were fivefold higher during persistent GNB colonization and 15-fold higher during carriage with tobramycin-resistant GNB

A new flexible DBD device for treating infected wounds: in vitro and ex vivo evaluation and comparison with a RF argon plasma jet

Cold plasma has been shown to provide a promising alternative antimicrobial treatment for wound healing. We developed and tested a flexible surface dielectric barrier discharge (DBD) and compared it to an argon gas based plasma jet operated remotely with a distance between plasma plume and sample of 8 mm. Tests were conducted using different models: on cultured cells, on ex vivo human skin and on bacteria (Pseudomonas aeruginosa) (on agar, in suspension, in collagen/elastin matrix or on ex vivo human skin), allowing us to directly compare bactericidal with safety aspects under identical conditions. Both plasma devices were highly efficient when used on bacteria in non-buffered solutions, but DBD was faster in reaching the maximum bacterial reduction. Treatment of bacteria on intact skin with DBD resulted in up to 6 log reductions in 3 min. The jet was far less efficient on intact skin. Even after 8 min treatment no more than 2 log reductions were obtained with the jet. Treatment of bacteria in burn wound models with DBD for 6 min resulted in a 4.5 log reduction. Even when using DBD for 6 min on infected burn wound models with colonizing or biofilm phase bacteria, the log reductions were 3.8 or 3.2 respectively. DBD plasma treatment for 6 min did not affect fibroblast viability, whereas a treatment for 8 min was detrimental. Similarly, treatment with DBD or plasma jet for 6 min did also not affect the metabolic activity of skin biopsies. After treatment for 8 min with DBD or plasma jet, 78% or 60% of activity in skin biopsies remained, respectively. Multiple treatments of in vitro burn wound models with surface DBD for 6 min or with plasma jet for 8 min did not affect re-epithelialization. With the flexible surface DBD plasma strip we were able to quickly inactivate large numbers of bacteria on and in skin. Under the same conditions, viability of skin cells or re-epithelialization was not affected. The DBD source has potential for treating larger wound areas