The contribution of gut bacterial metabolites in the human immune signaling pathway of non-communicable diseases.

The interaction disorder between gut microbiota and its host has been documented in different non-communicable diseases (NCDs) such as metabolic syndrome, neurodegenerative disease, and autoimmune disease. The majority of these altered interactions arise through metabolic cross-talk between gut microbiota and host immune system, inducing a low-grade chronic inflammation that characterizes all NCDs. In this review, we discuss the contribution of bacterial metabolites to immune signaling pathways involved in NCDs. We then review recent advances that aid to rationally design microbial therapeutics. A deeper understanding of these intersections between host and gut microbiota metabolism using metabolomics-based system biology platform promises to reveal the fundamental mechanisms that drive metabolic predispositions to disease and suggest new avenues to use microbial therapeutic opportunities for NCDs treatment and prevention. Abbreviations: NCDs: non-communicable disease, IBD: inflammatory bowel disease, IL: interleukin, T2D: type 2 diabetes, SCFAs: short-chain fatty acids, HDAC: histone deacetylases, GPCR: G-protein coupled receptors, 5-HT: 5-hydroxytryptamine receptor signaling, DCs: dendritic cells, IECs: intestinal epithelial cells, T-reg: T regulatory cell, NF-κB: nuclear factor κB, TNF-α: tumor necrosis factor alpha, Th: T helper cell, CNS: central nervous system, ECs: enterochromaffin cells, NSAIDs: non-steroidal anti-inflammatory drugs, AhR: aryl hydrocarbon receptor, IDO: indoleamine 2,3-dioxygenase, QUIN: quinolinic acid, PC: phosphatidylcholine, TMA: trimethylamine, TMAO: trimethylamine N-oxide, CVD: cardiovascular disease, NASH: nonalcoholic steatohepatitis, BAs: bile acids, FXR: farnesoid X receptor, CDCA: chenodeoxycholic acid, DCA: deoxycholic acid, LCA: lithocholic acid, UDCA: ursodeoxycholic acid, CB: cannabinoid receptor, COBRA: constraint-based reconstruction and analysis.

Anticoagulation treatment of cancer patients with deep or superficial leg vein thrombosis - a retrospective observational study of German statutory health insurance claims data (the CERTIFICAT initiative).

Background: Thrombosis is a common complication of cancer with a negative impact on quality of life and overall prognosis. Guidelines recommend low-molecular-weight heparin (LMWH) as initial and prolonged anticoagulation treatment. Little is known about current treatment patterns of these patients in ambulatory care. Patients and methods: The current retrospective observational study interrogates a large German statutory health insurance claims database in order to understand which kind of data can be extracted and analysed. An age- and sex-adjusted sample of about 4.1 million insured people from 2011 to 2016 could be used. Cancer patients with incident deep and superficial leg vein thrombosis were identified. Patients with preexisting cancer were allocated to a normal risk group; those who suffered from simultaneously diagnosed cancer and thrombosis were classified as high-risk group. Results: We identified 322,600 patients with inpatient or outpatient documented cancer diagnosis in at least two different quarters within one year. 87,755 patients were identified with an incident deep or superficial vein thrombosis. 8,201 patients suffered from both cancer and incident thrombosis. 56.9% of the patients received an anticoagulation regimen with predominant LMWH prescription, 24.2% vitamin K antagonists, 17.2% direct oral anticoagulants; in 1.7% of patients, no predominant anticoagulant drug/regime could be identified. On average, patients were prescribed anticoagulants for 4.5 months. An estimate of clinically relevant gastrointestinal bleeding could be derived (1.8% of patients). Conclusions: The dataset allows assigning detailed information of anticoagulant prescriptions in ambulatory care to well-defined groups of cancer patients. A first analysis suggests that in Germany current medical care of patients with cancer-related deep or superficial vein thrombosis does not entirely comply with guideline recommendations regarding type and duration of anticoagulation.

Platelet activation in the presence of neutral protamine Hagedorn insulin: a new feature of antibodies against protamine/heparin complexes.

Essentials Protamine (PRT) is used to stabilize insulin in neutral protamine Hagedorn (NPH) insulin. The interaction between NPH-insulin, anti-PRT/heparin antibodies and platelets was investigated. Anti-PRT/heparin antibodies activate platelets in presence of NPH-insulin dependent on heparin. Cross-reactivity seems to have no major effect on the clinical outcome of medical patients. SUMMARY: Background Protamine (PRT) is used to stabilize insulin in neutral protamine Hagedorn (NPH) insulin, a commonly used therapeutic agent for diabetes mellitus. Immunization against PRT/heparin complexes is common in diabetic patients. Objectives To investigate the impact of NPH-insulin on the interaction between anti-PRT/heparin antibodies and platelets. Methods The interaction between NPH-insulin and anti-PRT/heparin antibodies was tested using in-house enzyme immunoassays. The ability of anti-PRT/heparin antibodies to activate platelets in the presence of NPH-insulin (and heparin) was investigated using flow cytometry. Results Twenty-one out of 80 sera containing anti-PRT/heparin IgG showed binding to NPH-insulin. Anti-PRT/heparin IgG from immunized patients bound to platelets in the presence of NPH-insulin, but not in the presence of native insulin. Anti-PRT/heparin antibodies induced P-selectin expression in the presence of NPH-insulin in a heparin-dependent way (median mean fluorescence intensity in the presence of NPH-insulin: 55, 95% confidence interval [CI] 18.7-100.5 vs. NPH-insulin and heparin: 204, 95% CI 106.5-372.8). The clinical relevance of platelet-activating anti-PRT/heparin antibodies was assessed by investigating a multicenter study cohort of 332 acutely ill medical patients who received heparin. None of the 21 patients with anti-PRT/heparin IgG developed thrombocytopenia or thromboembolic complications. Conclusions Anti-PRT/heparin antibodies activate platelets in the presence of NPH-insulin in a heparin-dependent way. However, results from our preliminary study indicate no major impact of these antibodies on the clinical outcome in medical patients receiving heparin, particularly on thromboembolic complications.