Characteristics and Dysbiosis of the Gut Microbiome in Renal Transplant Recipients

Renal transplantation is life-changing in many aspects. This includes changes to the gut microbiome likely due to exposure to immunosuppressive drugs and antibiotics. As a consequence, renal transplant recipients (RTRs) might suffer from intestinal dysbiosis. We aimed to investigate the gut microbiome of RTRs and compare it with healthy controls and to identify determinants of the gut microbiome of RTRs. Therefore, RTRs and healthy controls participating in the TransplantLines Biobank and Cohort Study (NCT03272841) were included. We analyzed the gut microbiome using 16S rRNA sequencing and compared the composition of the gut microbiome of RTRs to healthy controls using multivariate association with linear models (MaAsLin). Fecal samples of 139 RTRs (50% male, mean age: 58.3 ± 12.8 years) and 105 healthy controls (57% male, mean age: 59.2 ± 10.6 years) were collected. Median time after transplantation of RTRs was 6.0 (1.5-12.5)years. The microbiome composition of RTRs was significantly different from that of healthy controls, and RTRs had a lower diversity of the gut microbiome (p < 0.01). Proton-pump inhibitors, mycophenolate mofetil, and estimated glomerular filtration rate (eGFR) are significant determinants of the gut microbiome of RTRs (p < 0.05). Use of mycophenolate mofetil correlated to a lower diversity (p < 0.01). Moreover, significant alterations were found in multiple bacterial taxa between RTRs and healthy controls. The gut microbiome of RTRs contained more Proteobacteria and less Actinobacteria, and there was a loss of butyrate-producing bacteria in the gut microbiome of RTRs. By comparing the gut microbiome of RTRs to healthy controls we have shown that RTRs suffer from dysbiosis, a disruption in the balance of the gut microbiome

Long-Term Dietary Patterns Are Reflected in the Plasma Inflammatory Proteome of Patients with Inflammatory Bowel Disease

Diet plays an important role in the development and progression of inflammatory bowel disease (IBD, comprising Crohn's disease (CD) and ulcerative colitis (UC)). However, little is known about the extent to which different diets reflect inflammation in IBD beyond measures such as faecal calprotectin or C-reactive protein. In this study, we aimed to unravel associations between dietary patterns and circulating inflammatory proteins in patients with IBD. Plasma concentrations of 73 different inflammation-related proteins were measured in 454 patients with IBD by proximity extension assay (PEA) technology. Food frequency questionnaires (FFQ) were used to assess habitual diet. Principal component analysis (PCA) was performed to extract data-driven dietary patterns. To identify associations between dietary patterns and plasma proteins, we used general linear models adjusting for age, sex, BMI, plasma storage time, smoking, surgical history and medication use. Stratified analyses were performed for IBD type, disease activity and protein intake. A high-sugar diet was strongly inversely associated with fibroblast growth factor-19 (FGF-19) independent of IBD type, disease activity, surgical history and deviance from recommended protein intake (false discovery rate (FDR) &lt; 0.05). Conversely, a Mediterranean-style pattern was associated with higher FGF-19 levels (FDR &lt; 0.05). A pattern characterised by high alcohol and coffee intake was positively associated with CCL11 (eotaxin-1) levels and with lower levels of IL-12B (FDR &lt; 0.05). All results were replicated in CD, whereas only the association with FGF-19 was significant in UC. Our study suggests that dietary habits influence distinct circulating inflammatory proteins implicated in IBD and supports the pro- and anti-inflammatory role of diet. Longitudinal measurements of inflammatory markers, also postprandial, are needed to further elucidate the diet-inflammation relationship

Limitations in representation of physical processes preven successful simulation of PM2.5 during KORUS-AQ

High levels of fine particulate matter (PM2.5) pollution in East Asia often exceed local air quality standards. Observations from the Korea United States-Air Quality (KORUS-AQ) field campaign in May and June 2016 showed that development of extreme pollution (haze) occurred through a combination of long-range transport and favorable meteorological conditions that enhanced local production of PM2.5. Atmospheric models often have difficulty simulating PM2.5 chemical composition during haze, which is of concern for the development of successful control measures. We use observations from KORUS-AQ to examine the ability of the GEOS-Chem chemical transport model to simulate PM2.5 composition throughout the campaign and identify the mechanisms driving the pollution event. In the surface level, the model underestimates campaign average sulfate aerosol by −64 % but overestimates nitrate aerosol by 36 %. The largest underestimate in sulfate occurs during the pollution event in conditions of high relative humidity, where models typically struggle to generate the high concentrations due to missing heterogeneous chemistry in aerosol liquid water in the polluted boundary layer. Hourly surface observations show that the model nitrate bias is driven by an overestimation of the nighttime peak. In the model, nitrate formation is limited by the supply of nitric acid, which is biased by +100 % against aircraft observations. We hypothesize that this is due to a missing sink, which we implement here as a factor of five increase in dry deposition. We show that the resulting increased deposition velocity is consistent with observations of total nitrate as a function of photochemical age. The model does not account for factors such as the urban heat island effect or the heterogeneity of the built-up urban landscape resulting in insufficient model turbulence and surface area over the study area that likely results in insufficient dry deposition. Other species such as NH3 could be similarly affected but were not measured during the campaign. Nighttime production of nitrate is driven by NO2 hydrolysis in the model, while observations show that unexpectedly elevated nighttime ozone (not present in the model) should result in N2O5 hydrolysis as the primary pathway. The model is unable to represent nighttime ozone due to an overly rapid collapse of the afternoon mixed layer and excessive titration by NO. We attribute this to missing nighttime heating driving deeper nocturnal mixing that would be expected to occur in a city like Seoul. This urban heating is not considered in air quality models run at large enough scales to treat both local chemistry and long-range transport. Key model failures in simulating nitrate, mainly overestimated daytime nitric acid, incorrect representation of nighttime chemistry, and an overly shallow and insufficiently turbulent nighttime mixed layer, exacerbate the model’s inability to simulate the buildup of PM2.5 during haze pollution. To address the underestimate in sulfate most evident during the haze event, heterogeneous aerosol uptake of SO2 is added to the model which previously only considered aqueous production of sulfate from SO2 in cloud water. Implementing a simple parameterization of this chemistry improves the model abundance of sulfate but degrades the SO2 simulation implying that emissions are underestimated. We find that improving model simulations of sulfate has direct relevance to determining local vs. transboundary contributions to PM2.5. During the haze pollution event, the inclusion of heterogeneous aerosol uptake of SO2 decreases the fraction of PM2.5 attributable to long-range transport from 66 % to 54 %. Locally-produced sulfate increased from 1 % to 46 % of locally-produced PM2.5, implying that local emissions controls would have a larger effect than previously thought. However, this additional uptake of SO2 is coupled to the model nitrate prediction which affects the aerosol liquid water abundance and chemistry driving sulfate-nitrate-ammonium partitioning. An additional simulation of the haze pollution with heterogeneous uptake of SO2 to aerosol and simple improvements to the model nitrate simulation results in 30 % less sulfate due to 40 % less nitrate and aerosol water, and results in an underestimate of sulfate during the haze event. Future studies need to better consider the impact of model physical processes such as dry deposition and boundary layer mixing on the simulation of nitrate and the effect of improved nitrate simulations on the overall simulation of secondary inorganic aerosol (sulfate+nitrate+ammonium) in East Asia. Foreign emissions are rapidly changing, increasing the need to understand the impact of local emissions on PM2.5 in South Korea to ensure continued air quality improvements

ISSN exercise & sport nutrition review: research & recommendations

Sports nutrition is a constantly evolving field with hundreds of research papers published annually. For this reason, keeping up to date with the literature is often difficult. This paper is a five year update of the sports nutrition review article published as the lead paper to launch the JISSN in 2004 and presents a well-referenced overview of the current state of the science related to how to optimize training and athletic performance through nutrition. More specifically, this paper provides an overview of: 1.) The definitional category of ergogenic aids and dietary supplements; 2.) How dietary supplements are legally regulated; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of the ergogenic value of nutrition and dietary supplementation in regards to weight gain, weight loss, and performance enhancement. Our hope is that ISSN members and individuals interested in sports nutrition find this review useful in their daily practice and consultation with their clients

Effect of High versus Low Dairy Consumption on the Gut Microbiome: Results of a Randomized, Cross-Over Study

The influence of dairy on the gut microbiome has not been studied extensively. We performed a randomized cross‐over study to analyze the effect of high dairy intake on the gut microbiome. Subjects were randomly assigned to a high‐dairy diet (HDD) (5–6 dairy portions per day) and a low‐dairy diet (LDD) (≤1 dairy portion per day) for 6 weeks with a washout period of 4 weeks in between both diets. The gut microbiome was assessed using 16S rRNA gene sequencing. Compositionality and functionality of the gut microbiome was assessed using Quantitative Insights Into Microbial Ecology (QIIME) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). Stool consistency was evaluated using the Bristol stool chart. In total, 46 healthy overweight subjects (BMI range 25–30 kg/m2) completed both intervention periods. During the HDD, there was a significantly higher abundance of the genera Streptococcus, Leuconostoc, and Lactococcus, and the species Streptococcus thermophilus, Erysipelatoclostridium ramosum and Leuconostoc mesenteroides (pFDR < 0.10). Furthermore, during the HDD, there was a significantly lower abundance of the genera Faecalibacterium and Bilophila, and the species Faecalibacterium prausnitzii, Clostridium aldenense, Acetivibrio ethanolgignens, Bilophila wadsworthia and Lactococcus lactis (pFDR < 0.10). There were eight subjects who became constipated during the HDD and these subjects all had a lower abundance of F. prausnitzii. This is the first cross‐over study in which the effect of an HDD compared to an LDD on the gut microbiome has been studied. An HDD led to a significantly different composition of the gut microbiome, with a particularly lower abundance of F. prausnitzii and a higher abundance of S. thermophilus. Constipation was observed in several subjects during the HDD. Predicted metabolic pathways were not significantly altered due to an HDD

Progress on Design and Construction of a MuCool Coupling Solenoid Magnet

The MuCool program undertaken by the US Neutrino Factory and Muon Collider Collaboration is to study the behavior of muon ionization cooling channel components. A single superconducting coupling solenoid magnet is necessary to pursue the research and development work on the performance of high gradient, large size RF cavities immersed in magnetic field, which is one of the main challenges in the practical realization of ionization cooling of muons. The MuCool coupling magnet is to be built using commercial copper based niobium titanium conductors and cooled by two cryo-coolers with each cooling capacity of 1.5 W at 4.2 K. The solenoid magnet will be powered by using a single 300A power supply through a single pair of binary leads that are designed to carry a maximum current of 210A. The magnet is to be passively protected by cold diodes and resistors across sections of the coil and by quench back from the 6061 Al mandrel in order to lower the quench voltage and the hot spot temperature. The magnet is currently under construction. This paper presents the updated design and fabrication progress on the MuCool coupling magnet