Aims
The purpose is to find the gut microbial fingerprinting of pediatric patients with type 1 diabetes.
Methods
The microbiome of 31 children with type 1 diabetes at onset and of 25 healthy children was determined using multiple polymorphic region of the 16S rRNA. We performed machine learning analyses and metagenome functional analysis in order to identify significant taxa and their metabolic pathways content.
Results
Compared with healthy controls, patients showed a significantly higher relative abundance of the following most important taxa: B.stercoris, B.fragilis, B.intestinalis, B.bifidum, Gammaproteobacteria and its descendants, Holdemania, Synergistetes and its descendants. On the contrary the relative abundance of B.vulgatus, Deltaproteobacteria and its descendants, Parasutterella and the Lactobacillus, Turicibacter genera was significantly lower in patients with respects to healthy controls. The predicted metabolic pathway more associated with type 1 diabetes patients concerns "Carbon metabolism", sugar and iron metabolisms in particular. Among the clinical variables considered, BMI-SDS, anti insulin autoantibodies, glycemia, HbA1c, Tanner and age at onset emerged as the most significant positively or negatively correlated with specific clusters of taxa.
Conclusions
The relative abundance and the supervised analyses confirmed the importance of B. stercoris in type 1 diabetes patients at onset and showed a relevant role of Synergistetes and its descendants in patients with respect to healthy controls. In general the robustness and the coherence of the showed results underline the relevance of studying the microbioma using multiple polymorphic regions, different types of analysis and different approaches within each analysis.
This study sets up reference values for pediatric population and shows that in normal controls serum hepcidin react differently to puberty in females vs. males. In addition, it suggests that serum hepcidin may discriminate microcytic inflammatory anemia of Juvenile Idiopathic Arthritis from iron deficiency anemia. Overall these findings may represent a helpful tool for future studies tailored to understand the role of hepcidin in management of iron disorders in children.
The elevation of at least one biochemical marker of myocardial necrosis is frequent following successful PCI with routine stent implantation. CK-MB mass is the most practical marker, having optimal kinetic and peaking with the first 12-18 hours post-PCI. Definitive data on the prognostic role and the applicability for the diagnosis of myocardial infarction of minor elevation of CK-MB mass or isolated increase of TnI are lacking.
Recent increasing evidence supports a role for neuronal type signaling in bone. Specifically glutamate receptors have been found in cells responsible for bone remodeling, namely the osteoblasts and the osteoclasts. While most studies have focused on ionotropic glutamate receptors, the relevance of the metabotropic glutamate signaling in bone is poorly understood. Specifically type 1 metabotropic glutamate (mGlu1) receptors are expressed in bone, but the effect of its ablation on skeletal development has never been investigated. Here we report that Grm1 mice, homozygous for an inactivating mutation of the mGlu1 receptor, and mainly characterized by ataxia and renal dysfunction, exhibit decreased body weight, bone length and bone mineral density compared to wild type (WT) animals. Blood analyses of the affected mice demonstrate the absence of changes in circulating factors, such as vitamin D and PTH, suggesting renal damage is not the main culprit of the skeletal phenotype. Cultures of osteoblasts lacking functional mGlu1 receptors exhibit less homogeneous collagen deposition than WT cells, and present increased expression of osteocalcin, a marker of osteoblast maturation. These data suggest that the skeletal damage is directly linked to the absence of the receptor, which in turn leads to osteoblasts dysfunction and earlier maturation. Accordingly, skeletal histomorphology suggests that Grm1 mice exhibit enhanced bone maturation, resulting in premature fusion of the growth plate and shortened long bones, and further slowdown of bone apposition rate compared to the WT animals. In summary, this work reveals novel functions of mGlu1 receptors in the bone and indicates that in osteoblasts mGlu1 receptors are necessary for production of normal bone matrix, longitudinal bone growth, and normal skeletal development.
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