A study in Nutrition & Metabolism finds that adverse alteration of gut microbiome composition in the middle-aged population is related to higher insulin resistance, longer diabetes duration, and is present in diabetic persons using medications.
]. To investigate difference in β diversity between groups, HOMA-IR was reclassified into two groups based on the median , while diabetes duration was reclassified into three groups .
The associations of α diversity measures with insulin resistance, diabetes duration, and stages of diabetes were assessed by linear regression, adjusting for four sets of covariates sequentially. In model 1, we adjusted for the sequencing run. In model 2, age, sex, race, education level, and field center were added. In model 3, we additionally adjusted for smoking, alcohol use, BMI, physical activity, and diet quality score.
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Inflammation-associated gut microbiome in postacute sequelae of SARS-CoV-2 points towards new therapeutic targetsWe read with interest the recent report by Liu et al 1 describing faecal microbiome differences with postacute sequelae of SARS-CoV-2 (PASC), commonly referred to as ‘Long-COVID’. We have previously reported elevated levels of SARS-CoV-2-specific T cells with PASC compared with resolved COVID-19 (RC; no lingering symptoms at the time of sample collection) that correlated with increased levels of the inflammatory marker IL-6, suggesting that elevated inflammation in PASC may be related to immune response to residual virus.2 Although several studies have reported gut microbiome differences during acute COVID-19,3 PASC has received less attention. We, thus, sought to characterise gut microbiome differences in PASC versus RC using faecal samples from our study2 and to relate these differences to inflammation. The faecal microbiome was evaluated using 16S rRNA gene sequencing. Plasma levels of inflammatory markers IL-6 and C reactive protein (CRP) were measured with ELISA (see online supplemental methods). Cohort information is in table 1. IL-6 and CRP were elevated with PASC (figure 1A). Gut microbiome composition did not significantly differ between the PASC and RC cohorts (PERMANOVA; p=0.087; figure 1B), but did correlate with IL-6 and CRP levels (Adonis; IL-6 p=0.03; CRP p=0.01). IL-6 and CRP also correlated with PC1 from a principal coordinates analysis (figure 1C,D), suggesting a relationship between microbiome composition and inflammation in PASC. Using SELBAL,4 which identifies ratios …
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How are changes in coffee and caffeine intake associated with changes in fat tissue?How are changes in coffee and caffeine intake associated with changes in fat tissue? unav HarvardChanSPH coffee caffeine fat faittissue health
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Gut microbiota-derived ursodeoxycholic acid alleviates low birth weight-induced colonic inflammation by enhancing M2 macrophage polarization - MicrobiomeBackground Low birth weight (LBW) is associated with intestinal inflammation and dysbiosis after birth. However, the underlying mechanism remains largely unknown. Objective In the present study, we aimed to investigate the metabolism, therapeutic potential, and mechanisms of action of bile acids (BAs) in LBW-induced intestinal inflammation in a piglet model. Methods The fecal microbiome and BA profile between LBW and normal birth weight (NBW) neonatal piglets were compared. Fecal microbiota transplantation (FMT) was employed to further confirm the linkage between microbial BA metabolism and intestinal inflammation. The therapeutic potential of ursodeoxycholic acid (UDCA), a highly differentially abundant BA between LBW and NBW piglets, in alleviating colonic inflammation was evaluated in both LBW piglets, an LBW-FMT mice model, and a DSS-induced colitis mouse model. The underlying cellular and molecular mechanisms by which UDCA suppresses intestinal inflammation were also investigated in both DSS-treated mice and a macrophage cell line. Microbiomes were analyzed by using 16S ribosomal RNA sequencing. Fecal and intestinal BA profiles were measured by using targeted BA metabolomics. Levels of farnesoid X receptor (FXR) were knocked down in J774A.1 cells with small interfering RNAs. Results We show a significant difference in both the fecal microbiome and BA profiles between LBW and normal birth weight animals in a piglet model. Transplantation of the microbiota of LBW piglets to antibiotic-treated mice leads to intestinal inflammation. Importantly, oral administration of UDCA, a major BA diminished in the intestinal tract of LBW piglets, markedly alleviates intestinal inflammation in LBW piglets, an LBW-FMT mice model, and a mouse model of colitis by inducing M2 macrophage polarization. Mechanistically, UDCA reduces inflammatory cytokine production by engaging BA receptor FXR while suppressing NF-κB activation in macrophages. Conclusions These findings establish a cau
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Discovery of Targets for Immune–Metabolic Antitumor Drugs Identifies Estrogen-Related Receptor AlphaAbstractDrugs that kill tumors through multiple mechanisms have the potential for broad clinical benefits. Here, we first developed an in silico multiomics approach (BipotentR) to find cancer cell–specific regulators that simultaneously modulate tumor immunity and another oncogenic pathway and then used it to identify 38 candidate immune–metabolic regulators. We show the tumor activities of these regulators stratify patients with melanoma by their response to anti–PD-1 using machine learning and deep neural approaches, which improve the predictive power of current biomarkers. The topmost identified regulator, ESRRA, is activated in immunotherapy-resistant tumors. Its inhibition killed tumors by suppressing energy metabolism and activating two immune mechanisms: (i) cytokine induction, causing proinflammatory macrophage polarization, and (ii) antigen-presentation stimulation, recruiting CD8+ T cells into tumors. We also demonstrate a wide utility of BipotentR by applying it to angiogenesis and growth suppressor evasion pathways. BipotentR (http://bipotentr.dfci.harvard.edu/) provides a resource for evaluating patient response and discovering drug targets that act simultaneously through multiple mechanisms.Significance:. BipotentR presents resources for evaluating patient response and identifying targets for drugs that can kill tumors through multiple mechanisms concurrently. Inhibition of the topmost candidate target killed tumors by suppressing energy metabolism and effects on two immune mechanisms.
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You star Tilly Keeper talks toxic relationships and seducing Penn BadgleyWe got the lowdown on sex scenes, toxic love and internalised misogyny on You.
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