Project description:Background Alterations of the gut microbiome have been linked to multiple chronic diseases. However, the drivers of such changes remain largely unknown. The oral cavity acts as a major route of exposure to exogenous factors including pathogens, and processes therein may affect the communities in the subsequent compartments of the gastrointestinal tract. Here, we perform strain-resolved, integrated multi-omic analyses of saliva and stool samples collected from eight families with multiple cases of type 1 diabetes mellitus (T1DM). Results We identified distinct oral microbiota mostly reflecting competition between streptococcal species. More specifically, we found a decreased abundance of the commensal Streptococcus salivarius in the oral cavity of T1DM individuals, which is linked to its apparent competition with the pathobiont Streptococcus mutans. The decrease in S. salivarius in the oral cavity was also associated with its decrease in the gut as well as higher abundances in facultative anaerobes including Enterobacteria. In addition, we found evidence of gut inflammation in T1DM as reflected in the expression profiles of the Enterobacteria as well as in the human gut proteome. Finally, we were able to follow transmitted strain-variants from the oral cavity to the gut at the metagenomic, metatranscriptomic and metaproteomic levels, highlighting not only the transfer, but also the activity of the transmitted taxa along the gastrointestinal tract. Conclusions Alterations of the oral microbiome in the context of T1DM impact the microbial communities in the lower gut, in particular through the reduction of “oral-to-gut” transfer of Streptococcus salivarius. Our results indicate that the observed oral-cavity-driven gut microbiome changes may contribute towards the inflammatory processes involved in T1DM. Through the integration of multi-omic analyses, we resolve strain-variant “mouth-to-gut” transfer in a disease context.
Project description:First version (1.0) of the Eindhoven Diabetes Simulator (EDES) model, describing postprandial glucose and insulin dynamics for a healthy human. Model can also be used to simulate insulin resistance (pre-diabetes, Metabolic Syndrome) and Type 2 Diabetes Mellitus (T2DM). Next to simulating a meal, the model can simulate oral glucose tolerance tests (OGTT's).
Project description:The application of multi-omic evaluations, multi-dimensional analysis methods, and new cheminformatics-based visualization tools to provide an in depth understanding of the molecular changes taking place in preeclampsia (PRE) and gestational diabetes mellitus (GDM) patients. Since PRE and GDM are two prevalent pregnancy complications that result in adverse health effects for both the mother and fetus during pregnancy and later in life, a better understanding of each is essential. The multi-omic evaluations performed here provide new insight into the end-stage molecular profiles of each disease, thereby supplying crucial information for earlier diagnosis and potential treatments. Datasets here represent lipid samples analyzed via Ion Mobility Mass Spectrometry.
Project description:Diabetes mellitus (DM) after transplantation remains a crucial clinical problem in kidney transplantation. To obtain insights into molecular mechanisms underlying the development of post-transplant diabetes mellitus (PTDM) and its early impact on glomerular structures, here we comparatively analyze the proteome of histologically normal appearing glomeruli from patients with PTDM from normoglycemic (NG) transplant recipients, and from recipients with pre-existing type 2 DM (PTDM)
Project description:Type 2 diabetes mellitus represents a major health problem with increasing prevalence worldwide. Limited efficacy of current therapies have prompted a search for novel therapeutic options. Here we show that treatment of pre-diabetic mice with mitochondrially targeted tamoxifen, a potential anti-cancer agent with senolytic activity, improves glucose tolerance and reduces body weight with most pronounced reduction of visceral adipose tissue due to reduced food intake, suppressed adipogenesis and elimination of senescent cells. Glucose-lowering effect of mitochondrially targeted tamoxifen is linked to improvement of type 2 diabetes mellitus-related hormones profile and is accompanied by reduced lipid accumulation in liver. Lower senescent cell burden in various tissues, as well as its inhibitory effect on pre-adipocyte differentiation, results in lower level of circulating inflammatory mediators that typically enhance metabolic dysfunction. Targeting senescence with mitochodrially targeted tamoxifen thus represents an approach to the treatment of type 2 diabetes mellitus and its related comorbidities, promising a complex impact on senescence-related pathologies in aging population of patients with type 2 diabetes mellitus with potential translation into the clinic.
Project description:To evaluate molecular consequences of insulin-deficient diabetes mellitus for lung tissue, we used clinically diabetic pig model of mutant INS gene induced diabetes of youth (MIDY). A multi-omics analysis combining in-depth data-independent acquisition proteomics, and targeted lipidomics revealed multiple dysregulated proteins and lipids and associated biological pathways in the MIDY lung.
Project description:The understanding of protein alterations in the diabetic heart is of vital importance because of increased risk of cardiovascular co-morbidities. The study aims at elucidating metabolic pathways in the diabetic rat heart during development of Type 2 diabetes mellitus using MS based proteomics.
Project description:The understanding of protein alterations in the diabetic heart is of vital importance because of increased risk of cardiovascular co-morbidities. The study aims at elucidating metabolic pathways in the diabetic rat heart during development of Type 2 diabetes mellitus using MS based proteomics.
Project description:The understanding of protein alterations in the diabetic heart is of vital importance because of increased risk of cardiovascular co-morbidities. The study aims at elucidating metabolic pathways in the diabetic rat heart during development of Type 2 diabetes mellitus using MS based proteomics.
