Food & Function

Flavonoids, plant-derived compounds, are broadly categorized into glycoside (sugar-bonded) and aglycone (sugar-removed) forms and are predominantly found as glycosides in nature. Rutin, a glycoside, is a widely recognized flavonoid with significant potential as an anti-obesity agent. However, its low bioavailability in the body presents challenges in obesity treatment. We aimed to enhance the bioavailability and anti-obesity effect of rutin through microbial involvement. Lactiplantibacillus plantarum HAC03, one of the candidates, demonstrated the ability to hydrolyze rutin into isoquercetin and quercetin in vitro. In a diet-induced obesity mouse model, the combination of rutin and the L. plantarum strain resulted in significant weight loss, reduced adipocyte size and lowered obesity-related biomarkers in the blood, decreased fat-synthesis related gene expression, and increased fatty acid {beta}-oxidation related gene expression compared to other test groups. This includes groups treated with rutin or quercetin alone or in combination with a different species from the same Lactobacillus genus, known for its anti-obesity effect but lacking the ability to hydrolyze rutin. This synergistic combination also alleviated insulin resistance and reduced fat in the liver. Gut microbiota analysis revealed localization of L. plantarum in the ileum and beneficial changes in disrupted microbiota in the intestine. These findings provide insights into underlying mechanisms causing the synergistic effect and suggest a novel combination that is as safe as microbial monotherapies with L. plantarum or L. rhamnosus but more effective in anti-obesity treatment.

The postprandial effects of a novel food-grade extracted salmon polar lipids (SPL) supplement against platelet-activating factor (PAF) and thrombin-induced platelet aggregation in a human pilot study was evaluated. This study was double-blinded, crossover, and placebo controlled in design. Five healthy volunteers completed 4 h time-course trials on 5 separate days. Blood was drawn at baseline before subjects consumed a standardized breakfast with one of the following treatments: a low-dose (0.25 g) or a high-dose (0.5 g) of SPL encapsulated within a stomach resistant capsule (LDSR and HDSR respectively) or a non-resistant capsule (LDSNR and HDSNR, respectively), or placebo capsules containing food-grade glycerin (0.5 g; Placebo). Blood was analyzed at 1 h intervals for 4 h. Among the treatments tested, the high-dose non-resistant capsule (HDSNR) produced the clearest postprandial effects, inducing significant increases in EC50 (reduced platelet sensitivity) for PAF at 2-3 h and for thrombin at 3-4 h post-ingestion. Smaller or delayed effects were observed with the high-dose resistant capsule (HDSR), while low-dose formulations produced minimal changes. Postprandial plasma glucose, lipid profile (TC, HDL-C, LDL-C, TG), fibrinogen, prothrombin time, and activated partial thromboplastin time remained unaffected across all trials. This pilot study provides the first in vivo indication that SPL supplementation may modestly attenuate platelet responsiveness to both PAF and thrombin without altering standard haemostatic or metabolic biomarkers. Larger controlled studies are warranted to confirm these preliminary findings and define optimal dosing and formulation strategies.

The increasing popularity of plant-based meat alternatives (PBMAs) has triggered a contentious debate about their impact on gut health in comparison to traditional animal-based meats. This study investigates the digestibility and bioavailability of a beef patty, a commercial PBMA, and a homemade pea protein-based patty by examining their influence on gut microbial metabolism. Fecal samples from five different donors were utilized to replicate colonic fermentation in vitro, with samples collected at various time points (0, 6, 12, 24, 32, and 48 hours). A rapid biochemical profiling, comparing red meat and meat analogs in terms of traditional biomarkers of gut health (ammonia, phenols, indoles, pH, and short-chain fatty acids), was conducted. Additionally, an untargeted metabolomics workflow specially designed for time-series studies, utilizing ultra-high performance liquid chromatography hyphenated to a quadrupole time-of-flight mass spectrometer (UPLC-QTOF MS), was implemented to assess differences in terms of protein-related gut microbial metabolites (GMMs). The findings of this approach revealed notable differences in the production of intestinal inflammation markers, metabolites related to the carnitine pathways, and GMMs with signaling functions in the intestinal tract during the fermentation of animal- and plant-based burgers.

Aged black garlic (ABG) is rich in organosulfur compounds such as Sallylcysteine (SAC) and may influence lipid metabolism, although evidence from controlled trials remains limited. The aim of this study was to evaluate the impact of a low-dose SAC-optimized ABG on blood lipid profiles in Grade I hypertensive individuals. A randomized, triple-blind, placebo-controlled trial was conducted with 75 Grade I hypertensive participants receiving either 250 mg of ABG or a placebo daily for 12 weeks. Plasma lipoproteins and subclass composition were quantified by NMR spectroscopy, and metabolic clusters were explored using kmeans and PLSDA. ABG supplementation led to a significant reduction in the total number of particles and HDL particles. Detailed analysis of XXL-VLDL particles showed a significant decrease in the percentage of both free and esterified cholesterol, alongside an increase in triglyceride percentage. Conversely, large HDL particles exhibited a beneficial remodeling characterized by an increase in phospholipid content and a decrease in triglyceride percentage. Furthermore, cluster analysis demonstrated that participants with a more adverse baseline metabolic profile experienced a significant reduction in total triglycerides and VLDL-lipid content after ABG intake. These results suggest that low-dose ABG supplementation induces specific qualitative improvements in lipoprotein subclasses, particularly enhancing HDL functionality markers and reducing the cholesterol load in large VLDL particles, which may provide cardiovascular benefits in hypertensive individuals with metabolic impairment

Outcomes from the COSMOS trial have reinforced the notion of flavanols as important plant-derived bioactives contributing to cardiovascular health. As discussions continue on whether specific dietary reference values for flavanols are warranted, it is possible that existing dietary guidelines emphasizing fruits and vegetables already yield sufficient flavanol intake levels. If this were the case, developing flavanol specific dietary reference values might be unnecessary. This study therefore aimed at assessing whether adherence to dietary recommendations for fruit and vegetable intake and overall diet quality achieves flavanol intake levels of 500 mg/day, the amount proven to mediate cardiovascular benefits in the COSMOS trial. Flavanol intake was objectively evaluated using two validated and complementary biomarkers, 5-(3{square},4{square}-dihydroxyphenyl)-{gamma}-valerolactone metabolites (gVLMB) and structurally related (-)-epicatechin metabolites (SREMB), in two geographically distinct studies: COSMOS (US; n=6,509) and EPIC-Norfolk (UK; n=24,154). The results showed that higher fruit and vegetable intakes and diet quality (assessed via the alternative healthy eating index-aHEI) were associated with increased flavanol intake in COSMOS. Nevertheless, fewer than 25% of participants meeting dietary guidelines achieved an estimated flavanol intake of [≥]500 mg/day. Similar findings were observed in EPIC-Norfolk as well as through flavanol intake simulations considering fruits and vegetables commonly consumed in the US diet. In conclusion, adherence to existing dietary guidelines does not yield flavanol intake levels comparable to those shown to provide cardiovascular benefits in COSMOS. Thus, specific dietary reference values for flavanols may still be necessary if aiming to increase the intake of these dietary compounds. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/26346949v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@2966f5org.highwire.dtl.DTLVardef@269232org.highwire.dtl.DTLVardef@483edborg.highwire.dtl.DTLVardef@116a957_HPS_FORMAT_FIGEXP M_FIG C_FIG

This study investigated the dynamic responses to an acute glucose challenge following chronic almond versus cracker consumption for 8 weeks (clinicaltrials.gov ID: NCT03084003). Seventy-three young adults (age: 18-19 years, BMI: 18-41 kg/m2) participated in an 8-week randomized, controlled, parallel-arm intervention and were randomly assigned to consume either almonds (2 oz/d, n=38) or an isocaloric control snack of graham crackers (325 kcal/d, n=35) daily for 8 weeks. Twenty participants from each group underwent a 2-hour oral glucose tolerance test (oGTT) at the end of the 8-week intervention. Metabolite abundances in the oGTT serum samples were quantified using untargeted metabolomics, and targeted analyses for free PUFAs, total fatty acids, oxylipins, and endocannabinoids. Multivariate, univariate, and chemical enrichment analyses were conducted to identify significant metabolic shifts. Findings exhibit a biphasic lipid response distinguished by higher levels of unsaturated triglycerides in the earlier periods of the oGTT followed by lower levels in the latter period in the almond versus cracker group (p-value<0.05, chemical enrichment analyses). Almond (vs. cracker) consumption was also associated with higher AUC120 min of aminomalonate, and oxylipins (p-value<0.05), but lower AUC120 min of L-cystine, N-acetylmannosamine, and isoheptadecanoic acid (p-value<0.05). Additionally, the Matsuda Index in the almond group correlated with AUC120 min of CE 22:6 (r=- 0.46; p-value<0.05) and 12,13 DiHOME (r=0.45; p-value<0.05). Almond consumption for 8 weeks leads to dynamic, differential shifts in response to an acute glucose challenge, marked by alterations in lipid and amino acid mediators involved in metabolic and physiological pathways.

Iron deficiency and anemia are significant global health issues, affecting nearly two billion people worldwide. The World Health Organization recommends iron fortification of foods as an effective strategy to reduce anemia rates. Available iron fortificants, however, are limited by low absorption and/or poor sensory performance. Developing new iron compounds that deliver highly bioavailable ferrous iron in foods without compromising sensory quality remains a challenge. In this work, we introduce oat protein nanofibrils (OatNF) carrying ultrasmall iron nanoparticles as promising iron fortificants for foods and beverages. Tailored synthesis of OatNF hybrids can produce iron nanoparticles in either the ferrous or ferric state. When sodium ascorbate (SA) is used as the reducing agent, the OatNF carry stabilized ferrous iron which is remarkably well absorbed in humans. In iron-deficient women, geometric mean absorption is found to be 46.2% (95% CI: 39.1%-54.7%) when given with water and 13.4% (95% CI: 9.8%-18.3%) when given with a polyphenol-rich food, representing 76% and 66% higher absorption, respectively, than the reference compound, FeSO4. When NaOH is used as the reducing agent, the OatNF carry mainly ferric iron, which is well-absorbed and shows superior sensory performance in reactive food matrices. These promising results introduce OatNF hybrids as a possible cost-effective, plant-based and organoleptic-friendly solution to the global challenge of iron deficiency anemia.

Background/ObjectiveIn a subset of participants from the CALERIE Phase 2 study we evaluated the effects of 2y of [~]25% Calorie Restriction (CR) diet on IgG N-glycosylation (GlycAge), plasma and complement C3 N-glycome as markers of aging and inflammaging. MethodsPlasma samples from 26 participants in the CR group who completed the CALERIE2 trial and were deemed adherent to the intervention ([~]>10 % CR at 12 mo) were obtained from the NIA AgingResearchBiobank. Glycomic investigations using UPLC or LC-MS analyses were conducted on samples from baseline (BL), mid-intervention (12 mo) and post-intervention (24 mo), and changes resulting from the 2y CR intervention were examined. In addition, anthropometric, clinical, metabolic, DNA methylation (epigenetic) and skeletal muscle transcriptomic data were analyzed to identify aging-related changes that occurred in tandem with the N-glycome changes. ResultsFollowing the 2y CR intervention, IgG galactosylation was higher at 24mo compared to BL (p = 0.051), digalactosylation and GlycAge (the IgG-based surrogate for biological age) were not different between BL and 12mo or BL and 24mo, but increased between 12mo and 24mo (p = 0.016, 0.027 respectively). GlycAge was also positively associated with TNF- and ICAM-1 (p=0.030, p=0.017 respectively). Plasma highly branched glycans were decreased by the 2y intervention (BL vs 24 mo: p=0.013), but both plasma and IgG bisecting GlcNAcs were increased (BL vs 24mo: p<0.001, p = 0.01 respectively). Furthermore, total complement C3 protein concentrations were reduced (BL vs 24mo: p <0.001), as were Man9 glycoforms (BL vs 24mo: p<0.001), and Man10 (which is glucosylated) C3 glycoforms (BL vs 24mo: p = 0.046). Conclusions24-mos of CR was associated with several favorable, anti-aging, anti- inflammatory changes in the glycome: increased galactosylation, reduced branching glycans, and reduced GlycAge. These promising CR effects were accompanied by an increase in bisecting GlcNAc, a known pro-inflammatory biomarker. These intriguing findings linking CR, clinical, and glycomic changes may be anti-aging and inflammatory, and merit additional investigation.

ScopeAntioxidants, including vitamin E (VE) and grape seed extract, as anti-aging supplementation have been widely used to improve human health. However, the role of gut microbiota in dietary antioxidant supplementation is debatable. This study aimed to assess the longitudinal impact of dietary supplementation with antioxidant compounds on body health and the gut microbiota. Methods and resultsOne hundred and twenty healthy individuals were randomly divided into a placebo group (amylodextrin) and three experimental groups ingesting different supplement (VE, grape seed extract, or mixed berry juice). Blood and fecal samples were collected during three intervention phases. We found that VE and mixed berry juice ameliorated blood cholesterol levels by reducing the levels of low-density lipoprotein cholesterol (LDL-C) in healthy volunteers. After the intervention, there was an increase in the relative abundance of short-chain fatty acid (SCFA)-producing bacteria and bile acid metabolizers. Specifically, the abundances of Lachnospira sp. and Faecalibacterium spp. increased in the VE and berry juice groups. Interestingly, the gut microbiota of poor responders harbored a greater proportion of disease-associated bacterial species. ConclusionJuice and VE could promote health by lowering LDL-C, partly and indirectly by affecting gut bacteria with the ability to produce SCFAs or metabolize bile acids.

BackgroundFasting has been shown to be one of the most cost-effective methods to improve cardiometabolic health. We studied a 5-day hypocaloric ([~]600 kcal/day) and ketogenic, modified fasting program (MFP) for at-home interventions. We hypothesised that this MFP induces metabolic changes comparable to 5 days of prolonged fasting (75-250kcal/day). MethodsWe tested the MFP in a two-arm randomised controlled trial where sixty-four healthy subjects were randomised to MFP or control group. Serum biochemistry analyses and questionnaires allowed for determining effects on cardiometabolic risk factors. Emotional well-being, possible side effects and physical activity were assessed with questionnaires. Biological pathways and metabolic processes were explored with nuclear magnetic resonance blood metabolomics and gut metagenomics analyses. ResultsMFP participants (n=32) experienced weight loss (-3.1 {+/-} 1.1 kg) persisting one month after the intervention. The MFP induced significant, but transient reductions, in systolic (-6.4 {+/-} 11.5 mmHg) and diastolic (-4.4 {+/-} 7.7 mmHg) blood pressure, glucose levels, HbA1c and coagulation factors. The MFP led to greater reductions in BMI (p=0.006), diastolic pressure (p = 0.009), cholesterol (p = 0.02), and LDL (p = 0.02) in individuals at risk of cardiometabolic diseases compared to healthy individuals. Total cholesterol, LDL-C and HDL-C levels continued decreasing during food reintroduction. The MFP also increased emotional and physical well-being. Blood metabolomics revealed a significant decrease in chronic inflammation markers. Shotgun metagenomics of the gut microbiome showed trends in the changes in relative abundance of the majority of bacterial species and their genomic repertoire of carbohydrate-active enzymes (CAZymes). This reflected a decrease in families metabolising dietary fibre substrates and an increase in families metabolising host-derived glycan substrates. Comparing MFP effects with a previous cohorts 5-day prolonged fasting showed similar metabolic changes. ConclusionThis MFP is safe and effectively improves cardiometabolic health and emotional well-being in healthy individuals. It offers comparable metabolic benefits to those observed during 5-day prolonged fasting in a clinic. It is safe to be practised at home, widely accessible and compatible with individuals everyday life.

IntroductionFiber intake is the most common nutritional inadequacy in the Western diet, with most adults consuming less than half of the recommended intake with only 5% of adults meeting the RDI. A novel, short-chain beta-glucan derived from oats (scOat Fiber), with improved solubility, low viscosity and enhanced palatability, compared to conventional oat fibers, was investigated for its benefits as a source of fiber supplementation. MethodsA 14-day pilot study evaluated the gastrointestinal tolerance and functional benefits of scOat Fiber in 63 healthy adults randomized to receive 5, 10 or 20 g daily doses. The primary outcome, gastrointestinal tolerability, was assessed using the Gastrointestinal Symptom Rating Scale (GSRS). Secondary outcome included glycemic response during rice challenges, measured via continuous glucose monitoring (CGM). CGM was also used to explore overall glucose dynamics. Additional exploratory outcomes (mood, energy, appetite and sleep) were assessed via validated questionnaires. ResultsscOat Fiber was exceptionally well tolerated across all doses, with no increase in GSRS scores, which remained in the low to mild range. Significant reductions in total GSRS scores were observed, with benefits evident after just one week at 5 g/day and maintained over time at both 5 and 10 g/day groups. Evaluation of GSRS sub-categories revealed that the 5 g/day and 10 g/day dose groups experienced significant reductions in abdominal pain symptoms. Both dose groups also demonstrated a significant decrease in constipation at the end of the study. Postprandial glucose responses were attenuated following product use, with a significant reduction in peak glucose during rice challenges after 2 weeks in the 20 g/day group. Both 10 and 20 g/day doses were associated with significant improvement in glycemic metrics during the study, including reductions in glucose mean, all glycemic excursions, and an increase in time-in-range. Exploratory analysis suggested that scOat Fiber may improve mental health and concentration in participants with elevated baseline symptoms. ConclusionsDespite the lack of a placebo control and short duration, the dose-dependent nature of the results supports the potential of scOat Fiber as a well-tolerated and functional source of fiber with benefits including glycemic control, digestive health and mental health (NCT06739941)

Metabolic responses to dietary interventions often show high inter-individual variations, but the factors explaining these variations as well as underlying mechanisms and their interrelation remain largely unknown. Knowing which factors are relevant for the individual response to a dietary intervention and to which extent, is essential to provide targeted dietary recommendations. Therefore, in persons at increased cardiometabolic risk, a 6-week RCT comparing the individual effects of three dietary patterns was conducted. We observed highly individualized effects in the cholesterol-lowering ability of the dietary patterns, which seem mainly related to differences in the lipid and metabolic profile of the participants in addition to diet-specific characteristics, while the gut microbiome and the polygenetic risk for hyperlipidemia modulate the effects. Moreover, the individual response to the interventions might be predicted by machine-learning models providing multi-omics signatures that could be applied as biomarkers for stratification of persons to specific dietary interventions for the optimization of personalized dietary approaches.

There remains a disconnect in plant breeding between increasing nutrient levels in crops at time of harvest and increasing bioaccessible levels of those nutrients during digestion. This study aims to develop and compare simulated digestion models for use in plant breeding and examine bioaccessible nutrient levels in common bean samples with differing seed coat coloration and patterning. The highest trait values (starch and protein hydrolysis, total phenolics, and antioxidant power) were observed from more dynamic digestion models, but even simple dynamic models showed higher trait values than a commonly used static digestion model. The use of these models provided insight on nutrient bioaccessibility; e.g., differences were observed during digestion between common bean genotypes for protein hydrolysis and between growing environments for both total phenolics and protein hydrolysis. Together, these results inform potential future pathways for applying simulated digestion models in plant breeding to improve bioaccessible nutrient levels in crops.

Steroidal alkaloids may be responsible for some of the health benefits of a tomato rich diet, but little is known about their metabolic fate after consumption. The objective of this study was to elucidate the pharmacokinetic parameters of plasma steroidal alkaloids and to define their bioavailability and metabolism following a single tomato containing meal. Healthy subjects (n = 11, 6M/5F) consumed 505 g of tomato juice following a two-week tomato washout and blood plasma were collected post-prandially at 11 time points over 12-hours. Plasma steroidal alkaloids were analyzed using UHPLC-MS. The fractional absorption of steroidal alkaloids was 11.8 {+/-} 7% and over 99% of the absorbed dose were present as metabolized products. The maximum concentration of total plasma steroidal alkaloids in subjects was 406.5 {+/-} 377.0 nmol/L occurring at 6 hours after consumption, with an AUC0-12hr of 2529.0 {+/-} 1644.8 nmol*h/L. Liver S9 enzymatic synthesis of steroidal alkaloid metabolites including trihydroxy-tomatidine and sulfonated dihydroxy-tomatidine improved confidence in compound identification. This study reports the first pharmacokinetic data for tomato steroidal alkaloids, demonstrating moderate absorption and extensive metabolism after tomato juice consumption. These data provide context for future studies investigating the potential role that these compounds may play in human health.

BackgroundEvidence suggests that adherence to the Mediterranean diet (MedDiet) affects human metabolism and may contribute to better cognitive performance. However, the underlying mechanisms are not clear. ObjectiveWe generated a metabolite profile for adherence to MedDiet and evaluated its cross-sectional association with aspects of cognitive performance. MethodsA total of 1,250 healthy Greek middle-aged adults from the Epirus Health Study cohort were included in the analysis. Adherence to the MedDiet was assessed using the 14-point Mediterranean Diet Adherence Screener (MEDAS); cognition was measured using the Trail Making Test, the Verbal Fluency test and the Logical Memory test. A targeted metabolite profiling (n = 250 metabolites) approach was applied, using a high-throughput nuclear magnetic resonance platform. We used elastic net regularized regressions, with a 10-fold cross-validation procedure, to identify a metabolite profile for MEDAS. We evaluated the associations of the identified metabolite profile and MEDAS with cognitive tests, using multivariable linear regression models. ResultsWe identified a metabolite profile composed of 42 metabolites, mainly lipoprotein subclasses and fatty acids, significantly correlated with MedDiet adherence (Pearson r = 0.35, P-value = 5.5 x 10-37). After adjusting for known risk factors and accounting for multiple testing, the metabolite profile and MEDAS were not associated with the cognitive tests. ConclusionsA plasma metabolite profile related to better adherence to the MedDiet was not associated with the tested aspects of cognitive performance, in a middle-aged Mediterranean population.

Calorie restriction (CR) has been widely recognized for its effect in reducing body weight and alleviating diabetes in humans, as well as prolonging life span in animal studies. Gut microbiome shifts contribute to part of the effects of CR, but little is known regarding their influences except on metabolism and immunity. Here we monitored gut microbiome using metagenomics and metatranscriptomics in obese individuals undergoing CR, and revealed microbial determinants that could contribute to successful weight loss. Microbiome changes are linked to changes in blood metabolome and hormones, which eventually correlate to brain functional changes as studied using functional magnetic resonance imaging (fMRI). Brain functional shifts indicate response of central neural system (CNS) to CR, and microbiome constitutes the keystone of gut-brain axis. Animal experiment further reaffirms the gut microbiome changes, metabolic and hormonal shifts of CR, while proteomic analysis of brain tissues suggest that epigenetic modifications of key proteins could explain responses of CNS to CR. Our study establishes linkage between CR, gut microbiome, metabolome/ hormones and CNS function, and demonstrates that CR has multi-facet, coordinated effects on the host, of which many could contribute to weight loss and other beneficial effects.

ScopeChronic, low-grade inflammation is a hallmark of many noncommunicable diseases, including obesity. Diets enriched with tomatoes and soy have been associated with better health outcomes in inflammation-related illnesses, with lycopene and isoflavones considered key bioactive components, respectively. On the basis that whole food combinations may exert greater effects than isolated phytochemicals, we examine the anti-inflammatory and metabolic effects of tomato-soy juice compared to a low carotenoid tomato juice control in obesity. Methods and resultsIn a randomized, crossover trial, 12 healthy adults with obesity were provided either tomato-soy juice (54 mg lycopene/d, 189.9 mg isoflavones/d) or a low carotenoid tomato juice (no isoflavones) daily for 4 weeks, then crossed over to the other treatment following a washout period. Plasma carotenoids, cytokines, and the urine metabolome were measured pre- and post-interventions. Plasma lycopene significantly increased by 2.48-fold after tomato-soy intake. IL-5, IL-12p70, and GM-CSF significantly decreased (P < 0.05), and TNF- trended downward (P = 0.052) following tomato-soy. Soy isoflavones and their metabolites primarily distinguished post-tomato-soy urine profiles. Both interventions induced some shared metabolomic changes in the urine, indicating tomato-driven effects independent of lycopene. ConclusionTomato-soy intake reduced some pro-inflammatory cytokines and altered the urine metabolomic profile in adults with obesity, supporting future studies using this functional food product for other inflammation-related conditions.

Time-restricted eating (TRE) is a promising strategy to prevent obesity and type 2 diabetes, but its effects on lipid metabolism remain controversial. The aim of the present research is to assess and compare the impact of isocaloric early (eTRE) vs. late (lTRE) TRE on the plasma lipidomic profile. This randomized crossover study examines 31 women with overweight or obesity who follow a two-week eTRE and a two-week lTRE in an intended isocaloric setting. Blood plasma and subcutaneous adipose tissue biopsies are analyzed using shotgun lipidomics and transcriptomics, respectively. Between interventions and within the lTRE, lipid species and classes, as well as enzyme activity indices, are not substantially changed. Within the eTRE, changes are observed for 103 lipid species, including a reduction of ceramide and phosphatidylcholine classes, and for the desaturation indices D5D, D6D, and D9D, as well as elongation index ELOVL6. Combined analysis of plasma lipidome and adipose tissue reveals alterations in the glycerophospholipid pathway and in the expression of phospholipase enzymes PLB1, PLA2G6, and PLAG4B, dependent on TRE timing. These results suggest that eating timing during TRE might be crucial for remodeling the plasma lipidome and adipose tissue transcriptome and highlight the need of future lipidomic research in TRE.

BackgroundDianthus superbus L. (DS) treats liver diseases, but its ALI mechanism via gut microbiota/metabolites is unclear. PurposeInvestigate DS effects on CCl-induced ALI and mechanisms. MethodsDS components (HPLC-MS/MS) were identified. ALI rats received DS. Liver/colon injury, fibrosis (biochemistry, histology, IHC, IF, WB for -SMA, Collagen I, Occludin, ZO-1), serum metabolomics, fecal 16S rRNA, and tryptophan-targeted metabolomics were assessed. Antibiotics and FMT from DS-treated donors explored microbiota roles. Results37 components, including Kaempferol and Aurantiamide, were identified. DS attenuated ALI, reducing hepatic -SMA/Collagen I while increasing AhR/Cyp1a1, and upregulating colonic Occludin/ZO-1. FMT replicated DS benefits. Untargeted metabolomics linked effects to Linoleic/Tryptophan metabolism. 16S rRNA showed increased beneficial microbiota (HT002, Lactobacillus, Romboutsia); FMT confirmed Lactobacillus enrichment. DS normalized tryptophan metabolites (4-Hydroxybenzoic acid, L-Kynurenine, Indole-3-carboxaldehyde). ConclusionDS ameliorates ALI gut-microbiota-dependently by modulating tryptophan metabolism, enhancing intestinal barrier function, activating AHR signaling, and suppressing fibrosis biomarkers, indicating its potential as a microbiota modulator for ALI. ImportanceAcute liver injury is a serious health threat with limited treatment options. This study explores how a traditional medicinal herb, Dianthus superbus L. (DS), protects the liver through an unexpected route: the gut. We discovered that DS works by rebalancing the community of gut bacteria, which in turn improves the intestinal barrier and fine-tunes the bodys tryptophan metabolism. This cascade of effects ultimately activates a key cellular pathway (AhR) that reduces liver inflammation and fibrosis. Our findings not only clarify how this traditional remedy works but also highlight the critical role of the gut-liver axis, positioning DS as a promising, microbiota-targeting therapeutic candidate for preventing and treating liver disease.

Diets low in diverse fibre-rich plant foods are a major factor in the rise of chronic diseases globally. The BIOME study (NCT06231706) was a 6-week, parallel design randomised controlled trial in 399 healthy adults in the UK, investigating a simple dietary intervention containing 30+ whole-food ingredients high in plant polyphenolic compounds, fibre and micronutrients. Participants were randomised to the primary intervention (prebiotic blend; 30g/d) or control (bread croutons; 28g/d; isocaloric functional equivalent) or a daily probiotic (L. rhamnosus). The primary outcome was change in favourable and unfavourable microbiome species compared to control, secondary outcomes included changes in blood metabolites, gut symptoms, stool output, anthropometric measures, subjective hunger, sleep, energy and mood. A crossover test meal challenge sub-study was conducted in 34 participants, investigating postprandial glucose responses, subjective hunger, satiety and mood. In the 349 male and female participants (mean age 50yrs) included in the analysis (intention-to-treat), self-reported adherence was high (> 98% for all treatments). Following the prebiotic blend, significant improvements were seen in the change and ranking of favourable and unfavourable species as well as beta diversity (weighted-UniFrac measure), but not in the control or probiotic group. There were significantly greater improvements in self reported indigestion, constipation, heartburn, flatulence and energy, following the prebiotic vs control, and hunger following the prebiotic vs probiotic. Addition of the prebiotic to a high carbohydrate test meal challenge resulted in significant improvements in subjective hunger, fullness, and energy (3h incremental area under the curve). No other significant differences between groups were observed. This prebiotic blend is a simple dietary strategy that benefits gut microbiome composition, gut symptoms and self-reported energy and hunger. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/24309816v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@1b26c20org.highwire.dtl.DTLVardef@d8dd09org.highwire.dtl.DTLVardef@1978cc5org.highwire.dtl.DTLVardef@9ae6a3_HPS_FORMAT_FIGEXP M_FIG C_FIG