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

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

Manual versus Automated Carotid Artery Plaque Component Segmentation in High and Lower Quality 3.0 Tesla MRI Scans

<div><p>Purpose</p><p>To study the interscan reproducibility of manual versus automated segmentation of carotid artery plaque components, and the agreement between both methods, in high and lower quality MRI scans.</p><p>Methods</p><p>24 patients with 30–70% carotid artery stenosis were planned for 3T carotid MRI, followed by a rescan within 1 month. A multicontrast protocol (T1w,T2w, PDw and TOF sequences) was used. After co-registration and delineation of the lumen and outer wall, segmentation of plaque components (lipid-rich necrotic cores (LRNC) and calcifications) was performed both manually and automated. Scan quality was assessed using a visual quality scale.</p><p>Results</p><p>Agreement for the detection of LRNC (<i>Cohen’s</i> kappa (<i>k)</i> is 0.04) and calcification (<i>k</i> = 0.41) between both manual and automated segmentation methods was poor. In the high-quality scans (visual quality score ≥ 3), the agreement between manual and automated segmentation increased to <i>k</i> = <i>0</i>.55 and <i>k</i> = 0.58 for, respectively, the detection of LRNC and calcification larger than 1 mm². Both manual and automated analysis showed good interscan reproducibility for the quantification of LRNC (intraclass correlation coefficient (ICC) of 0.94 and 0.80 respectively) and calcified plaque area (ICC of 0.95 and 0.77, respectively).</p><p>Conclusion</p><p>Agreement between manual and automated segmentation of LRNC and calcifications was poor, despite a good interscan reproducibility of both methods. The agreement between both methods increased to moderate in high quality scans. These findings indicate that image quality is a critical determinant of the performance of both manual and automated segmentation of carotid artery plaque components.</p></div

Interscan reproducibility of quantification of plaque components using manual and automated segmentation.

<p>Interscan reproducibility of quantification of plaque components using manual and automated segmentation.</p

Agreement between manual and automated detection of plaque components.

<p>Agreement between the detection of LRNC- and calcification- containing plaques by manual and automated analysis. Cohen’s kappa values for agreement between manual and automated analysis are shown for all plaque components in all scans; plaque components > 1 mm² in all scans; and plaque components > 1 mm² in high quality scans only.</p

Representative images of manual and automated segmentation of LRNC and calcifications.

<p>Representative images of the manual and automated segmentation of a calcified plaque area and a lipid-rich necrotic core (LRNC) using a multicontrast MRI protocol of the carotid artery. Shown are all the individual MRI sequences (T1w,PDw,T2w,TOF), as well as the manual and automated analysis. Lumen contours were delineated in red for both methods, and outer wall contours were delineated in green for manual segmentation, and light blue for automated segmentation. Calcified plaque areas were coloured orange in manual segmentation, and delineated white in automated segmentation. LRNCs were delineated yellow in both manual and automated segmentation. In these examples, both methods agree on the identification of a large calcified plaque area (left example) and large LRNC (right example). Please also note the identification of three small LRNC areas using automated segmentation (*), which are not detected by manual segmentation.</p