Cette production est également responsable d’une perte d’énergie pour l’animal représentant 6 % à 8 % de l’apport alimentaire. Le méthane, puissant gaz à effet de serre (GES), est produit dans le rumen des bovins par la fermentation microbienne anaérobie des aliments. Autoantibodies against cytokines appear to shape the gut microbiome by positively correlating with a taxonomically consistent group of bacteria. The APS-1 microbiome correlates with several APS-1 symptoms, some of which are alleviated after a three-month L. rhamnosus GG abundance was increased post-intervention and corresponded with decreased abundances of Alistipes onderdonkii and Collinsella aerofaciens, two species positively associated with severity of diarrhea in APS-1 patients. rhamnosus GG, a subset of gastrointestinal symptoms were alleviated. After the three-month intervention with the probiotic L. We observed phylogenetically conserved microbial associations with autoantibodies against cytokines. Four overabundant mOTUs were significantly associated with severity of constipation. Of 581 metagenomic operational taxonomic units (mOTUs) characterized in total, 14 were significantly associated with APS-1 compared to healthy controls, with six mOTUs depleted and eight enriched in APS-1 patients. We additionally administered daily doses of the probiotic Lactobacillus rhamnosus GG for three months. We characterized the fecal microbiomes of 28 APS-1 patients and searched for associations with gastrointestinal symptoms, circulating anti-cytokine autoantibodies and tryptophan-related metabolites. We aimed to understand the role of the gut microbiome in APS-1 symptoms and potentially alleviate common gastrointestinal symptoms by probiotic intervention. Gastrointestinal dysfunction is a frequent and disabling manifestation of autoimmune polyendocrine syndrome type 1 (APS-1), a rare monogenic multi-organ autoimmune disease caused by the loss of central AIRE-controlled immune tolerance. Consequently, 2-hydroxyglutarate-lactone may play a critical role in the modulation of the tumor microenvironment. Furthermore, human macrophages showed not only striking differences in uptake of 2-hydroxyglutarate and its lactone but also in the enantiospecific hydrolysis of the latter. Lactone formation does not depend on mutated isocitrate dehydrogenase, but its formation is most probably linked to transport processes across the cell membrane and favored at low environmental pH. Using 13C5-L-glutamine tracer analysis, we showed that 2-hydroxyglutarate is the endogenous precursor of 2-hydroxyglutarate-lactone and that there is a high exchange between these two metabolites. Here, we report a metabolite in human specimens that is closely related to 2-hydroxyglutarate: the intramolecular ester of 2-hydroxyglutarate, 2-hydroxyglutarate-γ-lactone. In recent years, onco-metabolites like D-2-hydroxyglutarate, which is produced in isocitrate dehydrogenase-mutated tumors, have gained increasing interest. ![]() We will further point out potential research questions for metabolomics studies in the context of kidney diseases and summarize the main results and data availability of important studies already conducted in this field. We will offer an overview of important a priori considerations for metabolomics cohort studies, available analytical as well as statistical/bioinformatics data analysis techniques, and subsequent interpretation of metabolic findings. This review provides a guide for future metabolomics studies in human kidney disease cohorts. ![]() ![]() Conducting a metabolomics study in human kidney disease cohorts, however, requires thorough knowledge about the key workflow steps: study planning, sample collection, metabolomics data acquisition and preprocessing, statistical/bioinformatics data analysis, and results interpretation within a biomedical context. Metabolomics, the quantitative study of small organic compounds, called metabolites, in a biological specimen, is gaining more and more importance in nephrology research. Kidney diseases still pose one of the biggest challenges for global health, and their heterogeneity and often high comorbidity load seriously hinders the unraveling of their underlying pathomechanisms and the delivery of optimal patient care.
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