Suchergebnisse

Microbioma gastrointestinal; Ferro; Obesitat ; Microbioma gastrointestinal; Hierro; Obesidad ; Gastrointestinal microbiome; Iron; Obesity ; Background: The gut microbiome and iron status are known to play a role in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), although their complex interaction remains unclear. Results: Here, we applied an integrative systems medicine approach (faecal metagenomics, plasma and urine metabolomics, hepatic transcriptomics) in 2 well-characterised human cohorts of subjects with obesity (discovery n = 49 and validation n = 628) and an independent cohort formed by both individuals with and without obesity (n = 130), combined with in vitro and animal models. Serum ferritin levels, as a markers of liver iron stores, were positively associated with liver fat accumulation in parallel with lower gut microbial gene richness, composition and functionality. Specifically, ferritin had strong negative associations with the Pasteurellaceae, Leuconostocaceae and Micrococcaea families. It also had consistent negative associations with several Veillonella, Bifidobacterium and Lactobacillus species, but positive associations with Bacteroides and Prevotella spp. Notably, the ferritin-associated bacterial families had a strong correlation with iron-related liver genes. In addition, several bacterial functions related to iron metabolism (transport, chelation, heme and siderophore biosynthesis) and NAFLD (fatty acid and glutathione biosynthesis) were also associated with the host serum ferritin levels. This iron-related microbiome signature was linked to a transcriptomic and metabolomic signature associated to the degree of liver fat accumulation through hepatic glucose metabolism. In particular, we found a consistent association among serum ferritin, Pasteurellaceae and Micrococcacea families, bacterial functions involved in histidine transport, the host circulating histidine levels and the liver expression of GYS2 and SEC24B. Serum ferritin was also related to bacterial glycine transporters, the host glycine serum levels and the liver expression of glycine transporters. The transcriptomic findings were replicated in human primary hepatocytes, where iron supplementation also led to triglycerides accumulation and induced the expression of lipid and iron metabolism genes in synergy with palmitic acid. We further explored the direct impact of the microbiome on iron metabolism and liver fact accumulation through transplantation of faecal microbiota into recipient's mice. In line with the results in humans, transplantation from 'high ferritin donors' resulted in alterations in several genes related to iron metabolism and fatty acid accumulation in recipient's mice. Conclusions: Altogether, a significant interplay among the gut microbiome, iron status and liver fat accumulation is revealed, with potential significance for target therapies. ; This work was supported by EU-FP7 FLORINASH (Health-F2-2009-241913) to R.B., M.F., J.M.F.R., E.H. and J.K.N. Infrastructure support was provided by the National Institute for Health Research (NIHR) Imperial Biomedical Research Centre (BRC). L.H. was in receipt of an MRC Intermediate Research Fellowship in Data Science (grant number MR/L01632X/1, UK Med-Bio). This work was also partly supported by funding to M.-E.D. (EU METACARDIS under agreement HEALTH-F4-2012-305312, Neuron II under agreement 291840 and the MRC MR/M501797/1) and by grants from the French National Research Agency (ANR-10-LABX-46 [European Genomics Institute for Diabetes]), from the National Center for Precision Diabetic Medicine – PreciDIAB, which is jointly supported by the French National Agency for Research (ANR-18-IBHU- 0001), by the European Union (FEDER), by the Hauts-de-France Regional Council (Agreement 20001891/NP0025517) and by the European Metropolis of Lille (MEL, Agreement 2019_ESR_11) and by Isite ULNE (R-002-20-TALENTDUMAS), also jointly funded by ANR (ANR-16-IDEX-0004-ULNE) the Hauts-de- France Regional Council (Agreement 20002045) and by the European Metropolis of Lille (MEL). J.M.-P. is funded by the Miguel Servet Program from the Instituto de Salud Carlos III (ISCIII CP18/00009), co-funded by the European Social Fund 'Investing in your future'. María Arnoriaga Rodríguez is funded by a predoctoral Río Hortega contract (CM19/00190, co-funded by European Social Fund 'Investing in your future') from the Instituto de Salud Carlos III, Spain. This work was supported by grants to AM from the Spanish Ministry of Science and Innovation (PID2019-105969GB-I00) and Generalitat Valenciana (project Prometeo/2018/133)

Tejido adiposo marrón; Neonatología; Proteina morfogenética ósea ; Teixit adipós marró; Pes neonatal; Proteïna morfogenètica òssia ; Brown adipose tissue; Birth weight; Bone morphogenetic proteins ; The classical dogma states that brown adipose tissue (BAT) plays a major role in the regulation of temperature in neonates. However, although BAT has been studied in infants for more than a century, the knowledge about its physiological features at this stage of life is rather limited. This has been mainly due to the lack of appropriate investigation methods, ethically suitable for neonates. Here, we have applied non-invasive infrared thermography (IRT) to investigate neonatal BAT activity. Our data show that BAT temperature correlates with body temperature and that mild cold stimulus promotes BAT activation in newborns. Notably, a single short-term cold stimulus during the first day of life improves the body temperature adaption to a subsequent cold event. Finally, we identify that bone morphogenic protein 8B (BMP8B) is associated with the BAT thermogenic response in neonates. Overall, our data uncover key features of the setup of BAT thermogenesis in newborns ; The research leading to these results hasreceived funding from the Xunta de Galicia (R.N.: 2016-PG057; M.L.: 2016-PG068);Ministerio de Economía y Competitividad (MINECO) co-funded by the FEDER Pro-gram of EU (R.N.: RTI2018-099413-B-I00; C.D.: BFU2017-87721-P; F.V.: SAF2017-85722-R; M.L.: RTI2018-101840-B-I00: F.V., J.M.F.-R., and M.L.: BFU2017-90578-REDT/Adipoplast); Instituto de Salud Carlos III (J.M.F.-R.: PI15-01934); AtresmediaCorporación (R.N. and M.L.); Fundación BBVA (R.N.); la Caixa Foundation (ID100010434), under the agreement LCF/PR/HR19/52160022 (M.L.); European Founda-tion for the Study of Diabetes (R.N.) and ERC Synergy Grant-2019-WATCH- 810331(R.N.) and Research Grant SOPEGA 2016 (A.U. and M.L.C.). F.V. is an ICREA Aca-demia researcher (Generalitat de Catalunya). I.G.-G. is the recipient of a fellowship fromthe European Union's Horizon 2020 research and innovation program under the MarieSklodowska-Curie actions. The CiMUS is supported by the Xunta de Galicia (2016-2019,ED431G/05). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative ofISCIII. The funders had no role in study design, data collection, and analysis, decision topublish, or preparation of the paper.

PEPPER (Patient Empowerment through Predictive PERsonalised decision support) is an EU-funded research project to develop a personalised clinical decision support system for Type 1 diabetes self-management. The tool provides insulin bolus dose advice and carbohydrate recommendations, tailored to the needs of individuals. The former is determined by Case-Based Reasoning (CBR), an artificial intelligence technique that adapts to new situations according to past experience. The latter uses a predictive computer model that also promotes safety by providing glucose alarms, low-glucose insulin suspension and fault detection.