Impairment of gut microbial biotin metabolism and host biotin status in severe obesity: effect of biotin and prebiotic supplementation on improved metabolism

Objectives Gut microbiota is a key component in obesity and type 2 diabetes, yet mechanisms and metabolites central to this interaction remain unclear. We examined the human gut microbiome\u27s functional composition in healthy metabolic state and the most severe states of obesity and type 2 diabetes within the MetaCardis cohort. We focused on the role of B vitamins and B7/B8 biotin for regulation of host metabolic state, as these vitamins influence both microbial function and host metabolism and inflammation. Design We performed metagenomic analyses in 1545 subjects from the MetaCardis cohorts and different murine experiments, including germ-free and antibiotic treated animals, faecal microbiota transfer, bariatric surgery and supplementation with biotin and prebiotics in mice. Results Severe obesity is associated with an absolute deficiency in bacterial biotin producers and transporters, whose abundances correlate with host metabolic and inflammatory phenotypes. We found suboptimal circulating biotin levels in severe obesity and altered expression of biotin-associated genes in human adipose tissue. In mice, the absence or depletion of gut microbiota by antibiotics confirmed the microbial contribution to host biotin levels. Bariatric surgery, which improves metabolism and inflammation, associates with increased bacterial biotin producers and improved host systemic biotin in humans and mice. Finally, supplementing high-fat diet-fed mice with fructo-oligosaccharides and biotin improves not only the microbiome diversity, but also the potential of bacterial production of biotin and B vitamins, while limiting weight gain and glycaemic deterioration. Conclusion Strategies combining biotin and prebiotic supplementation could help prevent the deterioration of metabolic states in severe obesity

Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism

Personalized therapy for mycophenolate:Consensus report by the international association of therapeutic drug monitoring and clinical toxicology

When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted.</p

An in-flight calibration assembly for the earth observation instrument Sentinel-4 UVN

peer reviewedAn in-orbit calibration assembly is designed and tested to ensure the radiometric accuracy of Sentinel-4/UVN. One of the calibration method consists in measuring the Sun's irradiance through a diffuser. A major challenge was the apparition of so-called spectral features, which come from speckle patterns due to the thin spectral bands of the instrument. A stack of diffuser was built to increase the average optical path difference above coherence length, thus decreasing the speckle contrast. A unique spectral feature test bench has been developed to validate the performance. A second calibration approach consists in illuminating the instrument with a white light source whose drift is characterized and limited. This paper discusses the design of the calibration assembly and the challenge which were encountered in the process. Also, on-ground tests results are presented, including the description of the test setup, in particular the spectral feature test bench. © 2019 SPIE

The Herschel-PACS grating mechanism: mechanical and optical performance

The Photodetector Array Camera and Spectrometer (PACS), on board the Herschel Space Observatory, is designed for imaging and low and medium resolution spectroscopy in the wavelength region between 57 and 210 μm. This paper reports the design and the testing results of the grating cryogenic mechanism of the PACS spectrometer. The PACS diffraction grating is made from an aluminium substrate, mechanically ruled with a periodicity of 8.5 grooves per mm and gold coated for optimum reflectivity at PACS operating wavelengths. The grating mechanism is capable of accurate positioning (4") of the flat diffraction grating within a large angular throw (44°) in cryogenic environment (4.2 K). Technologies of actuators, position sensors, bearings, servo-control and cryogenic test set-up are presented. The grating mechanism was thoroughly tested, alone and when integrated in the PACS Focal Plane Unit (FPU). The tests were performed in cryogenic conditions, in a set-up fully representative of the flight conditions. Actual mechanical and optical performance obtained with the Flight Model (FM) is presented in detail. Quality of the angular positioning of the mechanism, spectral resolution and optical quality of the grating are analysed.status: publishe

The Herschel-PACS grating mechanism: mechanical and optical performance

The Photodetector Array Camera and Spectrometer (PACS), on board the Herschel Space Observatory, is designed for imaging and low and medium resolution spectroscopy in the wavelength region between 57 and 210 μm. This paper reports the design and the testing results of the grating cryogenic mechanism of the PACS spectrometer. The PACS diffraction grating is made from an aluminium substrate, mechanically ruled with a periodicity of 8.5 grooves per mm and gold coated for optimum reflectivity at PACS operating wavelengths. The grating mechanism is capable of accurate positioning (4") of the flat diffraction grating within a large angular throw (44°) in cryogenic environment (4.2 K). Technologies of actuators, position sensors, bearings, servo-control and cryogenic test set-up are presented. The grating mechanism was thoroughly tested, alone and when integrated in the PACS Focal Plane Unit (FPU). The tests were performed in cryogenic conditions, in a set-up fully representative of the flight conditions. Actual mechanical and optical performance obtained with the Flight Model (FM) is presented in detail. Quality of the angular positioning of the mechanism, spectral resolution and optical quality of the grating are analysed