Explore the vast range of titles available.

Background Sarcopenia in liver cirrhosis is associated with low quality of life and high mortality risk. The pathogenesis has yet to be fully understood. We hypothesized that gut microbiome, bile acid (BA) composition and metabolites differ between cirrhotic patients with and without sarcopenia and contribute to pathogenesis. Methods Cirrhotic patients with (n = 78) and without (n = 38) sarcopenia and non‐cirrhotic controls with (n = 39) and without (n = 20) sarcopenia were included in this study. Faecal microbiome composition was studied by 16S rDNA sequencing, serum and faecal BA composition by ultra‐high‐performance liquid chromatography–tandem mass spectrometry, and metabolite composition in serum, faeces and urine by nuclear magnetic resonance. Results Bacteroides fragilis, Blautia marseille, Sutterella spp. and Veillonella parvula were associated with cirrhotic patients with sarcopenia, whereas Bacteroides ovatus was more abundant in cirrhotic patients without sarcopenia. We observed significantly elevated secondary BAs, deoxycholic acid (DCA; P = 0.01) and lithocholic acid (LCA; P = 0.02), and the ratios of deoxycholic acid to cholic acid (DCA:CA; P = 0.04), lithocholic acid to chenodeoxycholic acid (LCA:CDCA; P = 0.03) and 12 alpha‐hydroxylated to non‐12 alpha‐hydroxylated BAs (12‐α‐OH:non‐12‐α‐OH BAs; P = 0.04) in serum of cirrhotic patients with sarcopenia compared with cirrhotic patients without sarcopenia, indicating an enhanced transformation of primary to secondary BAs by the gut microbiome. CA (P = 0.02) and the ratios of CA:CDCA (P = 0.03) and total ursodeoxycholic acid to total secondary BAs (T‐UDCA:total‐sec‐BAs, P = 0.03) were significantly reduced in the stool of cirrhotic patients with sarcopenia compared with cirrhotic patients without sarcopenia. Also, valine and acetate were significantly reduced in the serum of cirrhotic patients with sarcopenia compared with cirrhotic patients without sarcopenia (P = 0.01 and P = 0.03, respectively). Multivariate logistic regression further confirmed the association of B. ovatus (P = 0.01, odds ratio [OR]: 12.8, 95% confidence interval [CI]: 168.1; 2.2), the ratios of 12‐α‐OH:non‐12‐α‐OH BAs (P = 0.03, OR: 2.54, 95% CI: 0.99; 6.55) and T‐UDCA:total‐sec‐BAs (P = 0.04, OR: 0.25, 95% CI: 0.06; 0.98) in serum and stool CA:CDCA (P = 0.04, OR: 0.79, 95% CI: 0.62; 0.99), and serum valine (P = 0.04, OR: 1.00, 95% CI: 1.02; 1.00) with sarcopenia in cirrhosis after correcting for the severity of liver disease and sex. Conclusions Our study suggests a potential functional gut microbiome–host interaction linking sarcopenia with the altered gut microbiomes, BA profiles and amino acids pointing towards a potential mechanistic interplay in understanding sarcopenia pathogenesis.

Lipoproteins are important cardiovascular (CV) risk biomarkers. This study aimed to investigate the associations of lipoprotein subclasses with micro- and macrovascular biomarkers to better understand how these subclasses relate to atherosclerotic CV diseases. One hundred and fifty-eight serum samples from the EXAMIN AGE study, consisting of healthy individuals and CV risk patients, were analysed with nuclear magnetic resonance (NMR) spectroscopy to quantify lipoprotein subclasses. Microvascular health was quantified by measuring retinal arteriolar and venular diameters. Macrovascular health was quantified by measuring carotid-to-femoral pulse wave velocity (PWV). Nineteen lipoprotein subclasses showed statistically significant associations with retinal vessel diameters and nine with PWV. These lipoprotein subclasses together explained up to 26% of variation (R2 = 0.26, F(29,121) = 2.80, p < 0.001) in micro- and 12% (R2 = 0.12, F(29,124) = 1.70, p = 0.025) of variation in macrovascular health. High-density (HDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as triglycerides together explained up to 13% (R2 = 0.13, F(3143) = 8.42, p < 0.001) of micro- and 8% (R2 = 0.08, F(3145) = 5.46, p = 0.001) of macrovascular variation. Lipoprotein subclasses seem to reflect micro- and macrovascular end organ damage more precisely as compared to only measuring HDL-C, LDL-C and triglycerides. Further studies are needed to analyse how the additional quantification of lipoprotein subclasses can improve CV risk stratification and CV disease prediction.

S-adenosyl-L-homocysteine (SAH), the product inhibitor of S-adenosyl-L-methionine-dependent methyltransferases, and its degradation product homocysteine (Hcy) are evolutionarily conserved master regulators of methylation metabolism, which is mediated by more than 200 methyltransferases in humans. Hyperhomocysteinemia (HHcy), characterized by elevated levels of Hcy in the blood, is an independent risk factor for atherosclerosis, a strong predictor of cardiovascular mortality and can cause associated pathology by interfering with methylation-dependent processes. Here, we developed a Drosophila melanogaster fly dietary model of HHcy and a Drosophila melanogaster genetic SAH accumulation model and compared them to corresponding Saccharomyces cerevisiae yeast models to reveal evolutionarily conserved methylation pattern changes responsive to elevation of Hcy levels. Feeding Drosophila an Hcy-containing diet or growing yeast on Hcy-supplemented medium, similarly to genetically blocking SAH degradation, led to SAH accumulation, developmental delay and growth defects. Furthermore, dietary or genetically induced SAH accumulation caused impaired phospholipid and protein methylation in both model organisms. Identification and functional characterization of evolutionarily conserved SAH-dependent methylation targets responsive to elevation of Hcy and/or SAH levels will reveal mechanisms of SAH toxicity in HHcy and help to decipher their role in associated pathologies.

Background Cardiovascular disease represents a significant risk factor for mortality in individuals with type 2 diabetes mellitus (T2DM). High-density lipoprotein (HDL) is believed to play a crucial role in maintaining cardiovascular health through its multifaceted atheroprotective effects and its capacity to enhance glycemic control. The impact of dietary interventions and intermittent fasting (IF) on HDL functionality remains uncertain. The objective of this study was to assess the effects of dietary interventions and IF as a strategy to safely improve glycemic control and reduce body weight on functional parameters of HDL in individuals with T2DM. Methods Before the 12-week intervention, all participants ( n  = 41) of the INTERFAST-2 study were standardized to a uniform basal insulin regimen and randomized to an IF or non-IF group. Additionally, all participants were advised to adhere to dietary recommendations that promoted healthy eating patterns. The IF group ( n  = 19) followed an alternate-day fasting routine, reducing their calorie intake by 75% on fasting days. The participants’ glucose levels were continuously monitored. Other parameters were measured following the intervention: Lipoprotein composition and subclass distribution were measured by nuclear magnetic resonance spectroscopy. HDL cholesterol efflux capacity, paraoxonase 1 (PON1) activity, lecithin cholesterol acyltransferase (LCAT) activity, and cholesterol ester transfer protein (CETP) activity were assessed using cell-based assays and commercially available kits. Apolipoprotein M (apoM) levels were determined by ELISA. Results Following the 12-week intervention, the IF regimen significantly elevated serum apoM levels ( p  = 0.0144), whereas no increase was observed in the non-IF group ( p  = 0.9801). ApoM levels correlated with weight loss and fasting glucose levels in the IF group. Both groups exhibited a robust enhancement in HDL cholesterol efflux capacity ( p  < 0.0001, p  = 0.0006) after 12 weeks. Notably, only the non-IF group exhibited significantly elevated activity of PON1 ( p  = 0.0455) and LCAT ( p  = 0.0117) following the 12-week intervention. In contrast, the changes observed in the IF group did not reach statistical significance. Conclusions A balanced diet combined with meticulous insulin management improves multiple metrics of HDL function. While additional IF increases apoM levels, it does not further enhance other aspects of HDL functionality. Trial registration The study was registered at the German Clinical Trial Register (DRKS) on 3 September 2019 under the number DRKS00018070. Graphical Abstract

Liver cirrhosis is a complex condition characterized by oxidative stress, inflammation, and metabolic dysfunction, contributing to systemic complications and high mortality. High-density lipoprotein (HDL), particularly its small subclasses, is known for its antioxidant, anti-inflammatory, and cholesterol efflux capacities. This study examined changes in HDL subclass distribution and composition in cirrhosis and assessed their prognostic relevance for mortality. We analyzed HDL profiles using nuclear magnetic resonance spectroscopy in patients with compensated (n = 205) and decompensated (n = 158) cirrhosis, compared to healthy controls (n = 16). Across all HDL subclasses in cirrhotic patients, cholesterol content was decreased, and triglyceride levels were elevated. In particular, compensated cirrhosis was associated with a marked reduction in small and extra-small HDL particles, while large HDL levels remained unchanged. This reduction was even more pronounced in decompensated disease. Small HDL particle levels were inversely correlated with oxidative stress markers and liver dysfunction and independently predicted 12-month mortality in patients with compensated cirrhosis, even after adjusting for MELD score. In conclusion, our findings highlight a substantial depletion of small and extra-small HDL particles as a key feature of cirrhosis, linked to oxidative stress and mortality in the compensated stage.

Disruptions in the gut microbiome are linked to various diseases, but their roles in conditions such as age-related muscle loss (sarcopenia) and drug-induced microbial changes remain poorly understood. To address this gap, MyBioScope , a novel in vitro model using the DASbox ® mini bioreactor system and human stool samples, was developed to simulate the anaerobic environment of the gastrointestinal (GI) tract. Bioreactors containing 120–200 mL of cultivation media were inoculated with stool slurry, stabilized over 24 h, and maintained with a customizable feeding protocol for multi-day experiments. Samples were analyzed using 16S rRNA gene sequencing, quantitative PCR, and metabolomics. Four pilot studies were conducted to validate the platform and model specific disease states, including proton pump inhibitor-induced GI tract oralization and microbiome alterations associated with sarcopenia. The workflow incorporated an anaerobic stool collection kit for user-friendly, room-temperature sample transport and storage. Our results demonstrated consistent microbial community structure and metabolic activity within disease-mimicking conditions. MyBioScope enabled reproducible, controlled studies of gut microbial dynamics and provided a scalable tool for investigating disease-specific microbiome changes. This platform may support translational efforts to integrate microbiome insights into clinical research, therapeutic development, and personalized medicine. In conclusion, this novel bioreactor-based in vitro model, MyBioScope, shows strong potential for in-depth exploration of disease-specific microbiomes and can facilitate new ways for integrating the knowledge of the microbiome’s impact on human health and disease into clinical practice. Graphical abstract

Background Aronia melanocarpa is a berry rich in polyphenols known for health benefits. However, the bioavailability of polyphenols has been questioned, and the individual taste acceptance of the fruit with its specific flavor varies. We recently observed substantial differences in the tolerability of aronia juice among healthy females, with half of the individuals tolerating aronia juice without complaints. Given the importance of the gut microbiome in food digestion, we investigated in this secondary analysis of the randomized placebo-controlled parallel intervention study (ClinicalTrials.gov registration: NCT05432362) if aronia juice tolerability was associated with changes in intestinal microbiota and bacterial metabolites, seeking for potential mechanistic insights into the impact on aronia polyphenol tolerance and metabolic outcomes. Results Forty females were enrolled for this 6-week trial, receiving either 100 ml natural aronia juice (verum, V) twice daily or a polyphenol-free placebo (P) with a similar nutritional profile, followed by a 6-week washout. Within V, individuals were categorized into those who tolerated the juice well (Vt) or reported complaints (Vc). The gut microbiome diversity, as analyzed by 16S rRNA gene-based next-generation sequencing, remained unaltered in Vc but changed significantly in Vt. A MICOM-based flux balance analysis revealed pronounced differences in the 40 most predictive metabolites post-intervention. In Vc carbon-dioxide, ammonium and nine O-glycans were predicted due to a shift in microbial composition, while in Vt six bile acids were the most likely microbiota-derived metabolites. NMR metabolomics of plasma confirmed increased lipoprotein subclasses (LDL, VLDL) post-intervention, reverting after wash out. Stool samples maintained a stable metabolic profile. Conclusion In linking aronia polyphenol tolerance to gut microbiota-derived metabolites, our study explores adaptive processes affecting lipoprotein profiles during high polyphenol ingestion in Vt and examines effects on mucosal gut health in response to intolerance to high polyphenol intake in Vc. Our results underpin the importance of individualized hormetic dosing for beneficial polyphenol effects, demonstrate dynamic gut microbiome responses to aronia juice, and emphasize personalized responses in polyphenol interventions. Graphical Abstract DsmAL-oYwbuhyB_vVwEdDj Video Abstract

Considering the relationship between disease severity and the extent of metabolic derangement in heart failure, we hypothesized that the serum levels of metabolites may have prognostic value for 1-year mortality in acute heart failure (AHF). The AHF study was a prospective, observational study enrolling consecutive patients hospitalized due to AHF. Metabolites were measured in serum collected at admission using NMR spectroscopy. Out of 315 AHF patients, 118 (37.5%) died within 1 year after hospitalization for AHF. The serum levels of 8 out of 49 identified metabolites were significantly different between patients who were alive and those who died within 1 year after hospitalization for AHF. Of these, only valine was significantly associated with 1-year mortality (hazard ratio 0.73 per 1 standard deviation increase, 95% confidence interval: 0.59–0.90, p = 0.003) in the multivariable Cox regression analyses. Kaplan–Maier analysis showed significantly higher survival rates in AHF patients with valine levels above the median (>279.2 µmol/L) compared to those with valine levels ≤ 279.2 µmol/L. In a receiver operating characteristics curve analysis, valine was able to discriminate between the two groups with an area under the curve of 0.65 (95% CI 0.59–0.72). We conclude that valine serum levels might be of prognostic value in AHF.

The strong associations between the serum levels of adiponectin and the lipoprotein subclasses observed in healthy subjects are much weaker in patients with metabolic syndrome (MS). However, the impact of sex on these associations remained unexplored. Therefore, in the present study, we examined associations between adiponectin and the lipoprotein subclasses, analyzed by nuclear magnetic resonance spectroscopy, separately in healthy females and males, as well as in females and males with MS. We observed negative correlations between adiponectin and VLDL, IDL, and small-dense LDL in healthy males, but neither in healthy females nor in females or males with MS. Additionally, adiponectin was positively correlated with some HDL subclasses in healthy males and females with MS, but not in healthy females or males with MS. Adjusting for age and either body mass index, waist circumference, C-reactive protein, or interleukin-6 weakened the associations between adiponectin and VLDL and IDL but not small-dense LDL. The adjustment weakened the associations between adiponectin and HDL in healthy males but not in females with MS. Based on our results, we conclude that sex and the presence of MS are strong determinants of the associations between adiponectin and serum lipoproteins and that the complex regulatory network comprising adiponectin and other molecular players involved in the regulation of lipoprotein metabolism is primarily operative in healthy males and females with MS.

Considering the relationship between the extent of metabolic derangement and the disease severity in heart failure, we hypothesized that the lipid content of very-low-density lipoprotein (VLDL) may have prognostic value for 1 year mortality in acute heart failure (AHF). Baseline serum levels of VLDL cholesterol (VLDL-C), VLDL triglycerides (VLDL-TG), VLDL phospholipids (VLDL-PL), and VLDL apolipoprotein B (VLDL-apoB) were measured using NMR spectroscopy. We calculated the ratios of the respective VLDL lipids and VLDL apoB (VLDL-C/VLDL-apoB, VLDL-TG/VLDL-apoB, and VLDL-PL/VLDL-apoB), as estimators of the cholesterol, triglyceride, and phospholipid content of VLDL particles and tested their association with mortality. Out of 315 AHF patients, 118 (37.5%) patients died within 1 year after hospitalization for AHF. Univariable Cox regression analyses revealed a significant inverse association of VLDL-C/VLDL-apoB (hazard ratio (HR) 0.43, 95% confidence interval (CI) 0.29–0.64, p < 0.001), VLDL-TG/VLDL-apoB (HR 0.79, 95% CI 0.71–0.88, p < 0.001), and VLDL-PL/VLDL-apoB (HR 0.37, 95% CI 0.25–0.56, p < 0.001) with 1 year mortality. Of the tested parameters, only VLDL-C/VLDL-apoB remained significant after adjustment for age and sex, as well as other clinical and laboratory parameters that showed a significant association with 1 year mortality in the univariable analyses. We conclude that cholesterol content of circulating VLDL (VLDL-C/VLDL-apoB) might be of prognostic value in AHF.