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BACKGROUND: We present a digital therapeutic (DTx) using continuous glucose monitoring (CGM) and an advanced artificial intelligence (AI) algorithm to digitally personalize lifestyle interventions for people with type 2 diabetes (T2D). METHOD: A study of 118 participants with non-insulin-treated T2D (HbA1c ≥ 6.5%) who were already receiving standard care and had a mean baseline (BL) HbA1c of 7.46% (0.93) used the DTx for three months to evaluate clinical endpoints, such as HbA1c, body weight, quality of life and app usage, for a pre-post comparison. The study also included an assessment of initial long-term data from a second use of the DTx. RESULTS: After three months of using the DTx, there was an improvement of 0.67% HbA1c in the complete cohort and -1.08% HbA1c in patients with poorly controlled diabetes (BL-HbA1c ≥ 7.0%) compared with standard of care (P < .001). The number of patients within the therapeutic target range (< 7.0%) increased from 38% to 60%, and 33% were on the way to remission (< 6.5%). Patients who used the DTx a second time experienced a reduction of -0.76% in their HbA1c levels and a mean weight loss of -6.84 kg after six months (P < .001) compared with BL. CONCLUSIONS: These results indicate that the DTx has clinically relevant effects on glycemic control and weight reduction for patients with both well and poorly controlled diabetes, whether through single or repeated usage. It is a noteworthy improvement in T2D management, offering a non-pharmacological, fully digital solution that integrates biofeedback through CGM and an advanced AI algorithm.
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OBJECTIVE: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer with limited therapeutic options. KRAS mutations are among the most abundant genetic alterations in iCCA associated with poor clinical outcome and treatment response. Recent findings indicate that Poly(ADP-ribose)polymerase1 (PARP-1) is implicated in KRAS-driven cancers, but its exact role in cholangiocarcinogenesis remains undefined. DESIGN: PARP-1 inhibition was performed in patient-derived and established iCCA cells using RNAi, CRISPR/Cas9 and pharmacological inhibition in KRAS-mutant, non-mutant cells. In addition, Parp-1 knockout mice were combined with iCCA induction by hydrodynamic tail vein injection to evaluate an impact on phenotypic and molecular features of Kras-driven and Kras-wildtype iCCA. Clinical implications were confirmed in authentic human iCCA. RESULTS: PARP-1 was significantly enhanced in KRAS-mutant human iCCA. PARP-1-based interventions preferentially impaired cell viability and tumourigenicity in human KRAS-mutant cell lines. Consistently, loss of Parp-1 provoked distinct phenotype in Kras/Tp53-induced versus Akt/Nicd-induced iCCA and abolished Kras-dependent cholangiocarcinogenesis. Transcriptome analyses confirmed preferential impairment of DNA damage response pathways and replicative stress response mediated by CHK1. Consistently, inhibition of CHK1 effectively reversed PARP-1 mediated effects. Finally, Parp-1 depletion induced molecular switch of KRAS-mutant iCCA recapitulating good prognostic human iCCA patients. CONCLUSION: Our findings identify the novel prognostic and therapeutic role of PARP-1 in iCCA patients with activation of oncogenic KRAS signalling.
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Intoduction: Identification of specific metabolome and lipidome profile of patients with primary sclerosing cholangitis (PSC) is crucial for diagnosis, targeted personalized therapy, and more accurate risk stratification. Methods: Nuclear magnetic resonance (NMR) spectroscopy revealed an altered metabolome and lipidome of 33 patients with PSC [24 patients with inflammatory bowel disease (IBD) and 9 patients without IBD] compared with 40 age-, sex-, and body mass index (BMI)-matched healthy controls (HC) as well as 64 patients with IBD and other extraintestinal manifestations (EIM) but without PSC. Results: In particular, higher concentrations of pyruvic acid and several lipoprotein subfractions were measured in PSC in comparison to HC. Of clinical relevance, a specific amino acid and lipid profile was determined in PSC compared with IBD and other EIM. Discussion: These results have the potential to improve diagnosis by differentiating PSC patients from HC and those with IBD and EIM.
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Paneth cells (PCs), a subset of intestinal epithelial cells (IECs) found at the base of small intestinal crypts, play an essential role in maintaining intestinal homeostasis. Altered PCs function is associated with diverse intestinal pathologies, including ileal Crohn's disease (CD). CD patients with ileal involvement have been previously demonstrated to display impairment in PCs and decreased levels of anti-microbial peptides. Although the immunosuppressive drug Azathioprine (AZA) is widely used in CD therapy, the impact of AZA on IEC differentiation remains largely elusive. In the present study, we hypothesized that the orally administered drug AZA also exerts its effect through modulation of the intestinal epithelium and specifically via modulation of PC function. AZA-treated CD patients exhibited an ileal upregulation of AMPs on both mRNA and protein levels compared to non-AZA treated patients. Upon in vitro AZA stimulation, intestinal epithelial cell line MODE-K exhibited heightened expression levels of PC marker in concert with diminished cell proliferation but boosted mitochondrial OXPHOS activity. Moreover, differentiation of IECs, including PCs differentiation, was boosted in AZA-treated murine small intestinal organoids and was associated with decreased D-glucose consumption and decreased growth rates. Of note, AZA treatment strongly decreased Lgr5 mRNA expression as well as Ki67 positive cells. Further, AZA restored dysregulated PCs associated with mitochondrial dysfunction. AZA-dependent inhibition of IEC proliferation is accompanied by boosted mitochondria function and IEC differentiation into PC.
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Azatioprina , Diferenciación Celular , Enfermedad de Crohn , Mucosa Intestinal , Células de Paneth , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/patología , Enfermedad de Crohn/metabolismo , Azatioprina/farmacología , Células de Paneth/metabolismo , Células de Paneth/efectos de los fármacos , Células de Paneth/patología , Humanos , Diferenciación Celular/efectos de los fármacos , Animales , Ratones , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Femenino , Masculino , Íleon/efectos de los fármacos , Íleon/metabolismo , Íleon/patología , Adulto , Organoides/efectos de los fármacos , Organoides/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Células Epiteliales/patología , Proliferación Celular/efectos de los fármacos , Persona de Mediana Edad , Línea Celular , Índice de Severidad de la EnfermedadRESUMEN
Purpose: The dietary practices (DPs) of university students are influenced by many external factors. Therefore, we investigate how the DPs of students in Germany changed during the SARS-CoV-2 pandemic, what the main motivations were for those changes, and what effect the closure of university catering had on the DPs of students. Methods: A total of 560 students from two universities in Lübeck (Germany) were surveyed online during a pilot phase. The final online questionnaire was subsequently administered at 10 other German universities (399 respondents). The questionnaire surveyed sociodemographic factors, dietary habits, food consumption frequencies, and the relevance of university catering before and during the SARS-CoV-2 pandemic. Results: Regarding changes in DPs, similarities to previous studies were found, especially positive eating behaviors and an increasing interest in health- and nutrition-related sustainability. Students prepared meals freshly more often during the pandemic; consumed legumes, plant-based meats and dairy alternatives more often; and reduced their consumption of meat and milk compared to before the pandemic. The consumption frequency of sweets also decreased. It was observed that students consider eating communal in the university canteen to be highly relevant for their social interactions, which was only possible to a limited extent during the pandemic. Conclusion: In Germany, the DPs of university students as well as criteria regarding health and sustainability changed during the first 2 years of the SARS-CoV-2 pandemic. The social aspect of DPs became evident due to closed university catering. Still, changes in dietary patterns and eating habits were positively related to health and revealed some differences in the cross section of the population.
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BACKGROUND: Accurate biomarkers for disease activity and progression in patients with inflammatory bowel disease (IBD) are a prerequisite for individual disease characterization and personalized therapy. We show that metabolic profiling of serum from IBD patients is a promising approach to establish biomarkers. The aim of this work was to characterize metabolomic and lipidomic serum profiles of IBD patients in order to identify metabolic fingerprints unique to the disease. METHODS: Serum samples were obtained from 55 patients with Crohn's disease (CD), 34 patients with ulcerative colitis (UC), and 40 healthy control (HC) individuals and analyzed using proton nuclear magnetic resonance spectroscopy. Classification of patients and HC individuals was achieved by orthogonal partial least squares discriminant analysis and univariate analysis approaches. Disease activity was assessed using the Gastrointestinal Symptom Rating Scale. RESULTS: Serum metabolome significantly differed between CD patients, UC patients, and HC individuals. The metabolomic differences of UC and CD patients compared with HC individuals were more pronounced than the differences between UC and CD patients. Differences in serum levels of pyruvic acid, histidine, and the branched-chain amino acids leucine and valine were detected. The size of low-density lipoprotein particles shifted from large to small dense particles in patients with CD. Of note, apolipoprotein A1 and A2 serum levels were decreased in CD and UC patients with higher fecal calprotectin levels. The Gastrointestinal Symptom Rating Scale is negatively associated with the concentration of apolipoprotein A2. CONCLUSIONS: Metabolomic assessment of serum samples facilitated the differentiation of IBD patients and HC individuals. These differences were constituted by changes in amino acid and lipoprotein levels. Furthermore, disease activity in IBD patients was associated with decreased levels of the atheroprotective apolipoproteins A1 and A2.
The metabolic and lipidomic serum profile of patients with inflammatory bowel disease was analyzed using proton nuclear magnetic resonance spectroscopy. A significantly altered profile in comparison with healthy control individuals was identified, characterized by more atherogenic properties.
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Lipedema is a chronic condition characterized by disproportionate and symmetrical enlargement of adipose tissue, predominantly affecting the lower limbs of women. This study investigated the use of metabolomics in lipedema research, with the objective of identifying complex metabolic disturbances and potential biomarkers for early detection, prognosis, and treatment strategies. The study group (n = 25) comprised women diagnosed with lipedema. The controls were 25 lean women and 25 obese females, both matched for age. In the patients with lipedema, there were notable changes in the metabolite parameters. Specifically, lower levels of histidine and phenylalanine were observed, whereas pyruvic acid was elevated compared with the weight controls. The receiver operating characteristic (ROC) curves for the diagnostic accuracy of histidine, phenylalanine, and pyruvic acid concentrations in distinguishing between patients with lipedema and those with obesity but without lipedema revealed good diagnostic ability for all parameters, with pyruvic acid being the most promising (area under the curve (AUC): 0.9992). Subgroup analysis within matched body mass index (BMI) ranges (30.0 to 39.9 kg/m2) further revealed that differences in pyruvic acid, phenylalanine, and histidine levels are likely linked to lipedema pathology rather than BMI variations. Changes in low-density lipoprotein (LDL)-6 TG levels and significant reductions in various LDL-2-carried lipids of patients with lipedema, compared with the lean controls, were observed. However, these lipids were similar between the lipedema patients and the obese controls, suggesting that these alterations are related to adiposity. Metabolomics is a valuable tool for investigating lipedema, offering a comprehensive view of metabolic changes and insights into lipedema's underlying mechanisms.
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Lipedema , Humanos , Femenino , Lipedema/metabolismo , Histidina , Ácido Pirúvico , Obesidad , Lípidos , FenilalaninaRESUMEN
INTRODUCTION: Imprecise nutritional recommendations due to a lack of diagnostic test accuracy are a frequent problem for individuals with adverse reactions to foods but no precise diagnosis. Consequently, patients follow very broad and strict elimination diets to avoid uncontrolled symptoms such as diarrhoea and abdominal pain. Dietary limitations and the uncertainty of developing gastrointestinal symptoms after the inadvertent ingestion of food have been demonstrated to reduce the quality of life (QoL) of affected individuals and subsequently might increase the risk of malnutrition and intestinal dysbiosis. This trial aims to investigate the effects of a tailored diet based on the confocal laser endoscopy (CLE) examination result to limit the side effects of unspecific and broad elimination diets and to increase the patient's QoL. METHODS AND ANALYSIS: The study is designed as a prospective, double-blind, monocentric, randomised and controlled trial conducted at the University Hospital of Schleswig-Holstein, Campus Lübeck, Germany. One hundred seventy-two patients with non-IgE-related food allergies and positive CLE results will be randomised to either a tailored diet or a standard fivefold elimination diet. The primary endpoints are the difference between the end and the start of the intervention in health-related QoL and the sum score of the severity of symptoms after 12 weeks. Key secondary endpoints are changes in the severity of symptoms, further QoL measurements, self-assessed state of health and number of days with a pathologically altered stool. Microbiome diversity and metabolome of stool, urine and blood will also be investigated. Safety endpoints are body composition, body mass index and adverse events. ETHICS AND DISSEMINATION: The study protocol was accepted by the ethical committee of the University of Lübeck (AZ: 22-111) on 4 May2022. Results of the study will be published in peer-reviewed journals and presented at scientific meetings. TRIAL REGISTRATION NUMBER: German Clinical Trials Register (DRKS00029323).
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Aplicaciones Móviles , Calidad de Vida , Humanos , Intolerancia Alimentaria , Dieta de Eliminación , Estudios Prospectivos , Método Doble Ciego , Endoscopía , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Dermatitis herpetiformis (DH) is a rare gluten-induced skin disorder characterized predominantly by IgA autoantibodies against endomysium, tissue transglutaminase (TG2/tTG), epidermal transglutaminase (TG3/eTG) and deamidated gliadin. To date, circulating autoantibody reactivity has not been systematically described. OBJECTIVES: Characterization of serum reactivities in DH. METHODS: This multicentre international study analysed sera from 242 patients with DH taken at the time of initial diagnosis. DH-specific IgA and IgG serum autoantibodies were analysed by indirect immunofluorescence (IF) on monkey oesophagus, and by enzyme-linked immunosorbent assay (ELISA) based on recombinant TG2/tTG, TG3/eTG and deamidated gliadin (GAF3X). RESULTS: IgA indirect IF microscopy on monkey oesophagus revealed the highest reactivity (84.3%; specificity 100%) followed by IgA TG2/tTG ELISA (78.5%, specificity 99.0%), IgA TG3/eTG ELISA (72.7%, specificity 95.0%) and IgA GAF3X ELISA (69.0%, specificity 98.5%). CONCLUSIONS: Serum IgA and IgG autoantibodies against endomysium, TG2/tTG, TG3/eTG and deamidated gliadin are highly prevalent in DH. Indirect IF microscopy on monkey oesophagus (IgA) provides the highest diagnostic accuracy that can be further enhanced by 4.5% when combined with IgA TG2/tTG ELISA.
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Dermatitis Herpetiforme , Humanos , Animales , Dermatitis Herpetiforme/diagnóstico , Gliadina , Inmunoglobulina A , Autoanticuerpos , Transglutaminasas , Ensayo de Inmunoadsorción Enzimática , Inmunoglobulina G , HaplorrinosRESUMEN
Type 2 Diabetes Mellitus has reached epidemic levels globally, and several studies have confirmed a link between gut microbial dysbiosis and aberrant glucose homeostasis among people with diabetes. While the assumption is that abnormal metabolomic signatures would often accompany microbial dysbiosis, the connection remains largely unknown. In this study, we investigated how diet changed the gut bacteriome, mycobiome and metabolome in people with and without type 2 Diabetes.1 Differential abundance testing determined that the metabolites Propionate, U8, and 2-Hydroxybutyrate were significantly lower, and 3-Hydroxyphenyl acetate was higher in the high fiber diet compared to low fiber diet in the healthy control group. Next, using multi-omics factor analysis (MOFA2), we attempted to uncover sources of variability that drive each of the different groups (bacterial, fungal, and metabolite) on all samples combined (control and DM II). Performing variance decomposition, ten latent factors were identified, and then each latent factor was tested for significant correlations with age, BMI, diet, and gender. Latent Factor1 was the most significantly correlated. Remarkably, the model revealed that the mycobiome explained most of the variance in the DM II group (12.5%) whereas bacteria explained most of the variance in the control group (64.2% vs. 10.4% in the DM II group). The latent Factor1 was significantly correlated with dietary intake (q < 0.01). Further analyses of the impact of bacterial and fungal genera on Factor1 determined that the nine bacterial genera (Phocaeicola, Ligilactobacillus, Mesosutterella, Acidaminococcus, Dorea A, CAG-317, Caecibacter, Prevotella and Gemmiger) and one fungal genus (Malassezia furfur) were found to have high factor weights (absolute weight > 0.6). Alternatively, a linear regression model was fitted per disease group for each genus to visualize the relationship between the factor values and feature abundances, showing Xylose with positive weights and Propionate, U8, and 2-Hydroxybutyrate with negative weights. This data provides new information on the microbially derived changes that influence metabolic phenotypes in response to different diets and disease conditions in humans.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Microbioma Gastrointestinal/genética , Disbiosis/microbiología , Propionatos , Multiómica , Metabolómica , Bacterias/genética , Ingestión de Alimentos , HidroxibutiratosRESUMEN
Sleep is an important research area in nutritional medicine that plays a crucial role in human physical and mental health restoration. It can influence diet, metabolism, and hormone regulation, which can affect overall health and well-being. As an essential tool in the sleep study, the sleep stage classification provides a parsing of sleep architecture and a comprehensive understanding of sleep patterns to identify sleep disorders and facilitate the formulation of targeted sleep interventions. However, the class imbalance issue is typically salient in sleep datasets, which severely affects classification performances. To address this issue and to extract optimal multimodal features of EEG, EOG, and EMG that can improve the accuracy of sleep stage classification, a Borderline Synthetic Minority Oversampling Technique (B-SMOTE)-Based Supervised Convolutional Contrastive Learning (BST-SCCL) is proposed, which can avoid the risk of data mismatch between various sleep knowledge domains (varying health conditions and annotation rules) and strengthening learning characteristics of the N1 stage from the pair-wise segments comparison strategy. The lightweight residual network architecture with a novel truncated cross-entropy loss function is designed to accommodate multimodal time series and boost the training speed and performance stability. The proposed model has been validated on four well-known public sleep datasets (Sleep-EDF-20, Sleep-EDF-78, ISRUC-1, and ISRUC-3) and its superior performance (overall accuracy of 91.31-92.34%, MF1 of 88.21-90.08%, and Cohen's Kappa coefficient k of 0.87-0.89) has further demonstrated its effectiveness. It shows the great potential of contrastive learning for cross-domain knowledge interaction in precision medicine.
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Research on gut microbiota has generally focused on fecal samples, representing luminal content of the large intestine. However, nutrient uptake is restricted to the small intestine. Abundant immune cell populations at this anatomical site combined with diminished mucus secretion and looser junctions (partly to allow for more efficient fluid and nutrient absorption) also results in intimate host-microbe interactions despite more rapid transit. It is thus crucial to dissect key differences in both ecology and physiology between small and large intestine to better leverage the immense potential of human gut microbiota imprinting, including probiotic engraftment at biological sensible niches. Here, we provide a detailed review unfolding how the physiological and anatomical differences between the small and large intestine affect gut microbiota composition, function, and plasticity. This information is key to understanding how gut microbiota manipulation, including probiotic administration, may strain-dependently transform host-microbe interactions at defined locations.
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Colon , Probióticos , Humanos , Intestino Delgado , Transporte Biológico , HecesRESUMEN
Nuclear Magnetic Resonance (NMR) spectra of human serum and plasma show, besides metabolites and lipoproteins, two characteristic signals termed GlycA and B arising from the acetyl groups of glycoprotein glycans from acute phase proteins, which constitute good markers for inflammatory processes. Here, we report a comprehensive assignment of glycoprotein glycan NMR signals observed in human serum, showing that GlycA and GlycB signals originate from Neu5Ac and GlcNAc moieties from N-glycans, respectively. Diffusion-edited NMR experiments demonstrate that signal components can be associated with specific acute phase proteins. Conventionally determined concentrations of acute phase glycoproteins correlate well with distinct features in NMR spectra (R2 up to 0.9422, p-value <0.001), allowing the simultaneous quantification of several acute phase inflammation proteins. Overall, a proteo-metabolomics NMR signature of significant diagnostic potential is obtained within 10-20â min acquisition time. This is exemplified in serum samples from COVID-19 and cardiogenic shock patients showing significant changes in several acute phase proteins compared to healthy controls.
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Proteínas de Fase Aguda , COVID-19 , Humanos , Proteínas de Fase Aguda/metabolismo , Biomarcadores/metabolismo , Inflamación/metabolismo , Espectroscopía de Resonancia Magnética , Glicoproteínas/metabolismo , Polisacáridos/químicaRESUMEN
(1) Background: Spermidine is a biogenic polyamine that plays a crucial role in mammalian metabolism. As spermidine levels decline with age, spermidine supplementation is suggested to prevent or delay age-related diseases. However, valid pharmacokinetic data regarding spermidine remains lacking. Therefore, for the first time, the present study investigated the pharmacokinetics of oral spermidine supplementation. (2) Methods: This study was designed as a randomized, placebo-controlled, triple-blinded, two-armed crossover trial with two 5-day intervention phases separated by a washout phase of 9 days. In 12 healthy volunteers, 15 mg/d of spermidine was administered orally, and blood and saliva samples were taken. Spermidine, spermine, and putrescine were quantified by liquid chromatography-mass spectrometry (LC-MS/MS). The plasma metabolome was investigated using nuclear magnetic resonance (NMR) metabolomics. (3) Results: Compared with a placebo, spermidine supplementation significantly increased spermine levels in the plasma, but it did not affect spermidine or putrescine levels. No effect on salivary polyamine concentrations was observed. (4) Conclusions: This study's results suggest that dietary spermidine is presystemically converted into spermine, which then enters systemic circulation. Presumably, the in vitro and clinical effects of spermidine are at least in part attributable to its metabolite, spermine. It is rather unlikely that spermidine supplements with doses <15 mg/d exert any short-term effects.
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Espermidina , Espermina , Animales , Adulto , Humanos , Espermidina/análisis , Espermina/análisis , Putrescina/metabolismo , Cromatografía Liquida , Saliva/química , Espectrometría de Masas en Tándem , Poliaminas/metabolismo , Plasma/química , Suplementos Dietéticos/análisis , Mamíferos/metabolismoRESUMEN
Growing evidence supports the use of probiotics to prevent or mitigate obesity-related dysmetabolism and non-alcoholic fatty liver disease (NAFLD). However, frequent reports of responders versus non-responders to probiotic treatment warrant a better understanding of key modifiers of host-microbe interactions. The influence of host diet on probiotic efficacy, in particular against metabolic diseases, remains elusive. We fed C57BL6/J mice a low fat reference diet or one of two energy-matched high fat and high sucrose diets for 12 weeks; a classical high fat diet (HFD) and a customized fast food-mimicking diet (FFMD). During the studies, mice fed either obesogenic diet were gavaged daily with one of two probiotic lactic acid bacteria (LAB) strains previously classified as Lactobaccillus, namely Limosilactobacillus reuteri (L. reuteri)or Lacticaseibacillus paracaseisubsp. paracasei (L. paracasei), or vehicle. The tested probiotics exhibited a reproducible efficacy but dichotomous response according to the obesogenic diets used. Indeed, L. paracaseiprevented weight gain, improved insulin sensitivity, and protected against NAFLD development in mice fed HFD, but not FFMD. Conversely, L. reuteri improved glucoregulatory capacity, reduced NAFLD development, and increased distal gut bile acid levels associated with changes in predicted functions of the gut microbiota exclusively in the context of FFMD-feeding. We found that the probiotic efficacy of two LAB strains is highly dependent on experimental obesogenic diets. These findings highlight the need to carefully consider the confounding impact of diet in order to improve both the reproducibility of preclinical probiotic studies and their clinical research translatability.
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Microbioma Gastrointestinal , Enfermedad del Hígado Graso no Alcohólico , Probióticos , Animales , Ratones , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Reproducibilidad de los Resultados , Obesidad/microbiología , Probióticos/uso terapéutico , Dieta Alta en Grasa/efectos adversos , Ratones Endogámicos C57BLRESUMEN
Whereas most concepts of personalized nutrition (PN) in the past, included genotyping, recent years have brought new approaches that include microbiome analysis to optimize recommendations for diet and lifestyle changes. The new approach, offered by companies, that microbiome analysis provides a real benefit to either more concise recommendations or for increased compliance to PN, is largely lacking scientific validation. Although the microbiome field shows enormous proliferation, it has some major flaws that make its use in the public health domain currently critical. Starting with the quality and representative character of the stool samples, its processing and analysis as well as assembly of metagenome data and the interpretation. Moreover, there is still no consensus of what constitutes a "normal/healthy" microbiome, nor what features characterize a dysbiotic microbiome. And, based on hundreds of individual parameters and environmental factors, the intestinal microbiome shows a huge variability and consequently changing one factor-such as food intake-is likely to have a limited impact in achieving optimized health. The present review intends to summarize the state of consolidated knowledge on human gut microbiome in the context of diet and disease, its key features, and its influencing factors as well as its "add-on" quality for PN offers.
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Microbioma Gastrointestinal , Microbiota , Humanos , Estado Nutricional , Dieta , MetagenomaRESUMEN
Introduction: Impaired glucose homeostasis is a significant risk factor for cardiometabolic diseases, whereas the efficacy of available standard therapies is limited, mainly because of poor adherence. This post-marketing study assessed the glucose-lowering potential of a synbiotic-based formulation. Methods: One hundred ninety-two participants were enrolled in a digital nutrition program with continuous glucose monitoring (CGM) and received a study product comprising Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine. Participants underwent a first sensor phase without supplementation, followed by a 14-day supplementation phase without sensor, and completed by a second sensor phase while continuing supplementation. Fasting glucose levels were determined before and after supplementation by CGM. In addition, the postprandial glycemic response to an oral glucose challenge, body weight, HbA1c concentrations, and BMI was analyzed. Subgroup analyses of subjects with elevated glucose and HbA1c levels vs. normoglycemic subjects were performed. Results: Supplementation with the study product resulted in significant improvements in glucose parameters (delta values: fasting glucose -2,13% ± 8.86; iAUC0-120 -4.91% ± 78.87; HbA1c: -1.20% ± 4.72) accompanied by a significant weight reduction (-1.07 kg ± 2.30) in the study population. Subgroup analyses revealed that the improvements were mainly attributed to a prediabetic subgroup with elevated fasting glucose and HbA1c values before supplementation (delta values: fasting glucose -6.10% 4± 7.89; iAUC0-120 -6.28% ± 115.85; HbA1c -3.31% ± 4.36; weight: -1.47 kg ± 2.82). Conclusion: This study indicates that the synbiotic composition is an effective and convenient approach to counteract hyperglycemia. Further placebo-controlled studies are warranted to test its efficacy in the treatment of cardiometabolic diseases.
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The modulation of inflammatory (auto)immune reactions by nutrients and gut bacterial metabolites is of great interest for potential preventive and therapeutic strategies. B cell-derived plasma cells are major players in inflammatory (auto)immune responses and can exhibit pro- or anti-inflammatory effects through (auto)antibody-dependent and -independent functions. Emerging evidence indicates a key role of nutrients and microbial metabolites in regulating the differentiation of plasma cells as well as their differentiation to pro- or anti-inflammatory phenotypes. These effects might be mediated indirectly by influencing other immune cells or directly through B cell-intrinsic mechanisms. Here, we provide an overview of nutrients and metabolites that influence B cell-intrinsic signaling pathways regulating B cell activation, plasma cell differentiation, and effector functions. Furthermore, we outline important inflammatory plasma cell phenotypes whose differentiation could be targeted by nutrients and microbial metabolites. Finally, we discuss possible implications for inflammatory (auto)immune conditions.
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Autoinmunidad , Células Plasmáticas , Diferenciación Celular , Linfocitos B , NutrientesRESUMEN
BACKGROUND: The German government implemented the Digital Healthcare Act in order to bring Digital Therapeutics into standard medical care. This is one of the first regulatory pathways to reimbursement for Digital Therapeutics (DTx). The Digital Therapeutic sinCephalea is intended to act as a prophylactic treatment of migraine by reducing the migraine days. For this, sinCephalea determines personalized nutritional recommendations using continuous glucose monitoring (CGM) data and enables the patients to follow a personalized low-glycemic nutrition. Migraine is a headache disorder with the highest socioeconomic burden. Emerging evidence shows that CGM-based personalized nutritional recommendations are of prophylactic use in episodic migraine. However, prospective data are yet missing to demonstrate clinical effectiveness. This study is designed to fill this gap. METHODS: Patients between 18 and 65 years of age with proven migraine and a minimal disease severity of 3 migraine days per month are included. After a 4-week baseline phase as a pre-study, patients are randomized to the DTx intervention or a waiting-list control. The objective of the study is to show differences between the intervention and control groups regarding the change of migraine symptoms and of effects of migraine on daily life. DISCUSSION: To our knowledge, this is the first systematic clinical trial with a fully digital program to enable patients with migraine to follow a personalized low-glycemic nutrition in order to reduce their number of migraine days and the migraine-induced impact on daily life. Designing a clinical study using a digital intervention includes some obstacles, which are addressed in this study approach. TRIAL REGISTRATION: German Registry of Clinical Studies (Deutsches Register Klinischer Studien) DRKS-ID DRKS00024657. Registered on March 8, 2021.