Obesity, characterized by excessive adipose tissue accumulation, has reached epidemic proportions globally, and strongly correlates with various diseases, including cardiovascular disease, diabetes, and cancer. This burden is increasingly affecting adolescents. The Mediterranean diet, known for its health benefits, is being increasingly studied for its potential in preventing metabolic diseases like obesity. This study aims to characterize and quantify the phenolic compounds in typical Mediterranean diet products, such as sourdough bread, chickpeas, pomegranate juice, nuts, and olive oil, which can be part of personalized dietary interventions targeting youth obesity thanks to their nutritional profile and phytochemical content. Using UHPLC-MSn, a total of 93 phenolic compounds across 12 subclasses were identified, with notable differences in both the number and concentration of compounds among food products. The diversity of phenolic compounds suggests potential synergistic effects, which may contribute to the bioactive profile of the Mediterranean diet and its association with health-promoting outcomes. This work provides a comprehensive reference for the phenolic composition of Mediterranean diet foods, supporting their selection in nutritional interventions.

Maternal consumption of a Western diet (WD) during critical developmental periods has been shown to program long-term metabolic dysfunction in offspring. However, it remains unclear whether these early exposures leave a persistent transcriptomic imprint into adulthood and whether this signature can be reshaped by postnatal interventions, limiting insight into underlying mechanisms and opportunities for early intervention. Here, we aimed to identify long-term transcriptomic signatures associated with maternal WD exposure during gestation and lactation using peripheral blood mononuclear cells (PBMCs) from adult male and female offspring. We further evaluated the potential of two early-life interventions - maternal dietary normalization and pup leptin supplementation during lactation - to reverse these alterations. The offspring from dams fed a normal-fat diet during gestation and lactation was used as a control group. Considering all groups, the expression of 90 genes differed between the control and WD offspring. Both interventions normalized the expression of most genes altered by maternal WD exposure (83 and 76 out of 90, respectively), shifting the global transcriptomic profile toward control levels. Multivariate analyses identified the 20 highest-ranked contributors to the PLS-DA model distinguishing offspring of WD-fed dams from controls, with stronger discriminatory capacity in males than in females, suggesting coordinated dysregulation of immunometabolic pathways, primarily involving immune and inflammatory signaling, cell fate regulation, and metabolic homeostasis. In conclusion, interventions during lactation may effectively reverse most transcriptomic alterations associated with adverse maternal conditions, supporting this period as a critical window for postnatal reprogramming. These findings suggest that early nutritional interventions may help mitigate long-term health risks associated with adverse maternal diet and support the use of PBMC transcriptomic signatures as potential minimally invasive biomarkers of developmental programming.

Peripheral blood mononuclear cells (PBMCs) can act as surrogates for metabolic adaptations in different tissues at the gene expression level and distinguish between healthy and disease states. We evaluated whether alterations induced by ovariectomy in rats, a model of postmenopausal estrogen deficiency, were influenced by the age at which the procedure was performed. Using a transcriptomic approach, we investigated whether PBMCs reflected molecular changes associated with menopause, assessing their potential as minimally invasive biomarkers to monitor menopause-related health alterations. Ovariectomized rats recapitulated many alterations observed in postmenopausal women, including changes in the accretion of white adipose tissue depots, insulin resistance, and bone mineral density, being the effects more pronounced in 35-week-old than in 25-week-old rats. PBMCs transcriptome profiling from 35-week-old animals revealed that these cells captured the molecular signatures associated with estrogen deficiency. Most mRNA changes involved genes related to immune function, stress responses, lipid metabolism, and bone homeostasis, providing insights into postmenopausal pathophysiology, such as osteoporosis and immunometabolic disturbances. These findings demonstrate that PBMC molecular profiles reliably reflect systemic postmenopausal alterations, supporting their potential use as a surrogate tissue to monitor and predict the impact of therapeutic interventions on postmenopausal health through a minimally invasive and repeatable sampling method.

Natural menopause marks the end of female reproductive capacity, yet its relationship with biological aging remains unclear. Earlier menopause has been associated with reduced lifespan and increased disease risk, but whether menopause itself accelerates aging or reflects an underlying faster biological aging trajectory remains unresolved. Here, we combined animal models of menopausal transition with epigenetic analyses in postmenopausal women, to investigate this relationship. In rats, neither ovariectomy-induced menopause nor natural reproductive senescence resulted in increased epigenetic age acceleration. In postmenopausal women, accelerated epigenetic aging was observed only in individuals who reached postmenopause earlier than the cohort median, independent of metabolic health status. Exploratory differential DNA methylation analysis suggested an association between age at menopause and pathways involved in longevity, chromatin regulation, and neurodegeneration. Together, these findings support a model in which the timing of reproductive aging reflects systemic biological aging rather than driving it, positioning age at menopause as a potential biomarker of the rate of biological aging.

Perimenopause is a transitional phase leading to female reproductive senescence, which can cause vasomotor symptoms and increase the risk of osteoporosis, obesity, and metabolic-related disturbances in middle-aged and older women. Nevertheless, little is known regarding the underlying mechanisms linked to menopausal transition, which could be of great value in designing new interventions addressed to improve the health of both perimenopausal and postmenopausal women. We used an ovarian-intact middle-aged model of rats resembling the characteristics of human perimenopause and applied liquid and gas chromatography quadrupole time-of-flight mass spectrometry approaches for the determination of polar and lipid-related metabolites to identify characteristic circulating signatures across perimenopause. The gradual loss of regularity in the estrous cycle occurring during the natural transition to reproductive senescence was associated with altered circulating levels of estradiol, progesterone, and luteinizing hormone (LH) and, in rats that were in an acyclic state, with ovary atrophy and with a lack of stromal luteinization and corpus luteum. These results were accompanied by progressively significant changes in the 144 lipid-related metabolites detected in serum as the estrous cycles were losing regularity. Furthermore, we identified 18 lipid-related metabolites—including 9 phosphatidylcholines, 4 lysophosphatidylcholines, 2 phosphatidylethanolamines, cholesterol ester (18:2), 5α-androstane-3,17-diol, and 17,18-dihydroxyarachidonic acid—that already changed with the transition from a regular to an irregular estrous cycle and anticipated the changes in blood progesterone, LH, and cholesterol levels that occurred in acyclic rats. These metabolites could be used as a potential multivariate biomarker of early perimenopause. The translational applicability of these findings deserves further research.

Background/Objectives. Preterm birth (PTB), affecting approximately 11.1% of pregnancies globally, often results from inflammation at the maternal–fetal interface triggered by microbial or immune dysregulation. This study investigates the efficacy of cell-free supernatant derived from Bifidobacterium longum subsp. infantis CECT 7210 and Lacticaseibacillus paracasei CECT 30660 in mitigating inflammation-induced PTB in a murine model. Methods. Lipopolysaccharide (LPS) was administered to induce preterm labor and systemic inflammation, mimicking infection-related PTB. Results. The results demonstrated that combined administration of CECT 7210 and CECT 30660 cell-free supernatants reduced preterm deliveries from 85.6% to 42.8% in mice and significantly attenuated systemic and intrauterine proinflammatory cytokines, including TNF-α and IL-6, in maternal plasma and myometrial tissues. Importantly, this anti-inflammatory effect was independent of maternal progesterone or oxytocin levels, suggesting a direct modulation of immune responses in this animal model. The cell-free supernatant combination also inhibited the growth of pathogenic bacteria, including Streptococcus agalactiae, highlighting its antimicrobial potential. Conclusions. This study underscores the potential of CECT 7210 and CECT 30660 cell-free supernatants as a therapeutic strategy to reduce the risk of PTB by targeting inflammation pathways. The findings pave the way for further preclinical and clinical research to validate the efficacy of these cell-free supernatants in preventing PTB and associated complications, offering a promising alternative to traditional probiotic approaches.

Iron deficiency anaemia is a global health issue affecting millions of people. Though effective, conventional iron sources used for supplementation often cause gastrointestinal side effects. This preclinical study evaluated the efficacy and tolerability of three iron supplements-ferrous bisglycinate, LIPOFER™ microcapsules (Def-LFe1), and a commercially available microencapsulated iron pyrophosphate (Def-Fe2)-in reversing diet-induced iron deficiency in rats compared to FeSO4. The study included three phases: (a) First, animals underwent a 24-day iron depletion period; (b) then, animals were exposed to a 21-day repletion period, receiving treatments at a human-equivalent dose of 80 mg of elemental iron; and (c) finally, to evaluate gastrointestinal tolerability, animals were supplemented with each treatment for 9 weeks. All supplements reversed iron deficiency within 14 days without adverse gastrointestinal effects. However, based on the decrease in TIBC and transferrin levels, coupled with the higher haemoglobin levels, Def-LFe1 demonstrated a higher absorption rate than Def-Fe2. In addition, the group supplemented with LIPOFER™ showed higher feed efficiency, especially compared to the control and FeSO4 groups. FeSO4 increased IL-6 gene expression in the colon, while Def-LFe1 did not. These findings highlight LIPOFER™ as a promising alternative to conventional iron supplementation. Further studies should be conducted to clarify these issues.

Many women have sought alternative therapies to address menopause. Recently, a multi-ingredient supplement (MIS) containing L-histidine, L-carnosine, L-serine, and L-cysteine has been shown to be effective at ameliorating hepatic steatosis (HS) in ovariectomized (OVX) rats, a postmenopausal oestrogen deficiency model. Considering that HS frequently accompanies obesity, which often occurs during menopause, we aimed to investigate the effects of this MIS for 8 weeks in OVX rats. Twenty OVX rats were orally supplemented with either MIS (OVX-MIS) or vehicle (OVX). Ten OVX rats received vehicle orally along with subcutaneous injections of 17β-oestradiol (OVX-E2), whereas 10 rats underwent a sham operation and received oral and injected vehicles (control group). MIS consumption partly counteracted the fat mass accretion observed in OVX animals, leading to decreased total fat mass, adiposity index and retroperitoneal white adipose tissue (RWAT) adipocyte hypertrophy. OVX-MIS rats also displayed increased lean mass and lean/fat ratio, suggesting a healthier body composition, similar to the results reported for OVX-E2 animals. MIS consumption decreased the circulating levels of the proinflammatory marker CRP, the total cholesterol-to-HDL-cholesterol ratio and the leptin-to-adiponectin ratio, a biomarker of diabetes risk and metabolic syndrome. RWAT transcriptomics indicated that MIS favourably regulated genes involved in adipocyte structure and morphology, cell fate determination and differentiation, glucose/insulin homeostasis, inflammation, response to stress and oxidative phosphorylation, which may be mechanisms underlying the beneficial effects described for OVX-MIS rats. Our results pave the way for using this MIS formulation to improve the body composition and immunometabolic health of menopausal women.

Background: Personalized nutrition (PN) has been proposed as a strategy to increase the effectiveness of dietary recommendations and ultimately improve health status. Objectives: We aimed to assess whether including omics-based PN in an e-commerce tool improves dietary behavior and metabolic pro fi le in general population. Methods: A 21-wk parallel, single-blinded, randomized intervention involved 193 adults assigned to a control group following Mediterranean diet recommendations ( n = 57, completers = 36), PN ( n = 70, completers = 45), or personalized plan (PP, n = 68, completers = 53) integrating a behavioral change program with PN recommendations. The intervention used metabolomics, proteomics, and genetic data to assist participants in creating personalized shopping lists in a simulated e-commerce retailer portal. The primary outcome was the Mediterranean diet adherence screener (MEDAS) score; secondary outcomes included biometric and metabolic markers and dietary habits. Results: Volunteers were categorized with a scoring system based on biomarkers of lipid, carbohydrate metabolism, inflammation, oxidative stress, and microbiota, and dietary recommendations delivered accordingly in the PN and PP groups. The intervention signi fi cantly increased MEDAS scores in all volunteers (control - 3 points; 95% confidence interval [CI]: 2.2, 3.8; PN - 2.7 points; 95% CI: 2.0, 3.3; and PP - 2.8 points; 95% CI: 2.1, 3.4; q < 0.001). No signi fi cant differences were observed in dietary habits or health parameters between PN and control groups after adjustment for multiple comparisons. Nevertheless, personalized recommendations significantly (false discovery rate < 0.05) and selectively enhanced the scores calculated with biomarkers of carbohydrate metabolism ( beta :- 0.37; 95% CI:- 0.56,- 0.18), oxidative stress ( beta :- 0.37; 95% CI:- 0.60,- 0.15), microbiota ( beta :- 0.38; 95% CI:- 0.63,- 0.15), and inflammation ( beta :- 0.78; 95% CI:- 1.24,- 0.31) compared with control diet. Conclusions: Integration of personalized strategies within an e-commerce - like tool did not enhance adherence to Mediterranean diet or improved health markers compared with general recommendations. The metabotyping approach showed promising results and more research is guaranteed to further its in PN.

In recent years many women have looked for alternative therapies to address menopause. Hesperidin, phytosterols and curcumin are bioactive compounds that can ameliorate some cardiovascular risk factors associated with menopause, although there are no data concerning the effects of their combined supplementation. We used ovariectomized (OVX) rats, a postmenopausal model with oestrogen deficiency, to evaluate whether supplementation with a multi-ingredient (MI) including hesperidin, phytosterols and curcumin for 57 days would display beneficial effects against fat mass accretion and metabolic disturbances associated with menopause. Twenty OVX rats were orally supplemented with either MI (OVX-MI) or vehicle (OVX). Furthermore, 10 OVX rats orally received the vehicle along with subcutaneous injections of 17 beta-oestradiol biweekly (OVX-E2), whereas 10 rats were sham operated and received oral and injected vehicles (control group; SH). MI supplementation partly counteracted the fat mass accretion observed in OVX animals, which was evidenced by decreased total fat mass, adiposity index, the weight of retroperitoneal, inguinal and mesenteric white adipose tissue (MWAT) depots and MWAT adipocyte hypertrophy. These effects were accompanied by a significant decrease in the circulating levels of leptin and the mRNA levels of the fatty acid uptake-related genes Lpl and Cd36 in MWAT. These results were very similar to those observed in OVX-E2 animals. OVX-MI rats also displayed a higher lean body mass, lean/fat mass ratio, adiponectin-to-leptin ratio and insulin sensitivity than their OVX counterparts. Our findings can pave the way for using this MI formulation as an alternative therapy to manage obesity and to improve the cardiometabolic health of menopausal women. In recent years many women have looked for alternative therapies to address menopause.

BACKGROUND:In a previous study, the 84-day administration of glycosaminoglycans (GAGs), with or without native collagen type II (NC), in an osteoarthritis (OA)-induced rabbit model slowed down OA progression, improved several micro- and macroscopic parameters and magnetic resonance imaging (MRI) biomarkers in cartilage, and increased hyaluronic acid levels in synovial fluid. To elucidate the potential underlying mechanisms, a transcriptomics approach was conducted using medial femoral condyle and trochlea samples. RESULTS:The administration of chondroitin sulfate (CS), glucosamine hydrochloride (GlHCl), and hyaluronic acid (HA), with (CGH-NC) or without (CGH) NC, strongly modulated several genes involved in chondrocyte extracellular matrix (ECM) remodeling and homeostasis when compared to non-treated rabbits (CTR group). Notably, both treatments shared the main mechanism of action, which was related to ECM modulation through the down-regulation of genes encoding proteolytic enzymes, such as ADAM metallopeptidase with thrombospondin type 1 motif, 9 (Adamts9), and the overexpression of genes with a relevant role in the synthesis of ECM components, such as aggrecan (Acan) in both CGH-NC and CGH groups, and fibronectin 1 (Fn1) and collagen type II, alpha 1 (Col2A1) in the CGH group. Furthermore, there was a significant modulation at the gene expression level of the mTOR signaling pathway, which is associated with the regulation of the synthesis of ECM proteolytic enzymes, only in CGH-NC-supplemented rabbits. This modulation could account for the better outcomes concerning the microscopic and macroscopic evaluations reported in these animals. CONCLUSIONS:In conclusion, the expression of key genes involved in chondrocyte ECM remodeling and homeostasis was significantly modulated in rabbits in response to both CGH and CGH-NC treatments, which would partly explain the mechanisms by which these therapies exert beneficial effects against OA.

Background and objectives: Youth obesity is likely to persist into adulthood, so it is important to tackle it from childhood to prevent associated risks in the future [...]

Personalized nutrition (PN) has gained much attention as a tool for empowerment of consumers to promote changes in dietary behavior, optimizing health status and preventing diet related diseases. Generalized implementation of PN faces different obstacles, one of the most relevant being metabolic characterization of the individual. Although omics technologies allow for assessment the dynamics of metabolism with unprecedented detail, its translatability as affordable and simple PN protocols is still difficult due to the complexity of metabolic regulation and to different technical and economical constrains. In this work, we propose a conceptual framework that considers the dysregulation of a few overarching processes, namely Carbohydrate metabolism, lipid metabolism, inflammation, oxidative stress and microbiota-derived metabolites, as the basis of the onset of several non-communicable diseases. These processes can be assessed and characterized by specific sets of proteomic, metabolomic and genetic markers that minimize operational constrains and maximize the information obtained at the individual level. Current machine learning and data analysis methodologies allow the development of algorithms to integrate omics and genetic markers. Reduction of dimensionality of variables facilitates the implementation of omics and genetic information in digital tools. This framework is exemplified by presenting the EU-Funded project PREVENTOMICS as a use case.

The consumption of diets rich in saturated fats is known to be associated with higher mortality. The adoption of healthy habits, for instance adhering to a Mediterranean diet, has proved to exert a preventive effect towards cardiovascular diseases and dyslipidemia. Little is known about how a suboptimal diet can affect brain function, structure, and the mechanisms involved. The aims of this study were to examine how a high-fat diet can alter the brain N-glycan and lipid profile in male Golden Syrian hamsters and to evaluate the potential of a Mediterranean-like diet to reverse this situation. During twelve weeks, hamsters were fed a normal fat diet (CTRL group), a high-fat diet (HFD group), and a high-fat diet followed by a Mediterranean-like diet (MED group). Out of seventy-two identified N-glycans, fourteen were significant (p < 0.05) between HFD and CTRL groups, nine between MED and CTRL groups, and one between MED and HFD groups. Moreover, forty-nine lipids were altered between HFD and CTRL groups, seven between MED and CTRL groups, and five between MED and HFD groups. Our results suggest that brain N-glycan composition in high-fat diet-fed hamsters can produce events comparable to those found in some neurodegenerative diseases, and may promote brain ageing.

Skin photoaging is primarily caused by ultraviolet radiation and can lead to the degradation of skin extracellular matrix components, resulting in hyperpigmentation and skin elasticity loss. In this area, polyphenols have become of great interest because of their antioxidant, anti-inflammatory and antiaging properties. Here, we evaluated the effects of the pomegranate natural extract Pomanox((R)) on skin health-related parameters in normal and UV-induced photoaging conditions in human fibroblast Hs68 cells. Moreover, the inhibitory effects of Pomanox((R)) on tyrosinase activity were assessed. In normal conditions, Pomanox((R)) significantly modulated collagen and hyaluronic acid metabolisms. In UV-exposed cells, both preventive and regenerative treatments with Pomanox((R)) positively modulated hyaluronic acid metabolism and decreased ROS levels. However, only the preventive treatment modulated collagen metabolism. Finally, Pomanox((R)) showed a marked inhibitory capacity of tyrosinase activity (IC50 = 394.7 mu g/mL). The modulation of skin health-related parameters exhibited by Pomanox((R)) open a wide range of potential applications of this product.

The gut microbiota contributes to the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Histidine is a key energy source for the microbiota, scavenging it from the host. Its role in NAFLD is poorly known. Plasma metabolomics, liver transcriptomics, and fecal metagenomics were performed in three human cohorts coupled with hepatocyte, rodent, and Drosophila models. Machine learning analyses identified plasma histidine as being strongly inversely associated with steatosis and linked to a hepatic transcriptomic signature involved in insulin signaling, inflammation, and trace amine-associated receptor 1. Circulating histidine was inversely associated with Proteobacteria and positively with bacteria lacking the histidine utilization (Hut) system. Histidine supplementation improved NAFLD in different animal models (diet-induced NAFLD in mouse and flies, ob/ob mouse, and ovariectomized rats) and reduced de novo lipogenesis. Fecal microbiota transplantation (FMT) from low-histidine donors and mono-colonization of germ-free flies with Enterobacter cloacae increased triglyceride accumulation and reduced histidine content. The interplay among microbiota, histidine catabolism, and NAFLD opens therapeutic opportunities.

PurposeBacillus coagulans GBI-30, 6086 (BC30) was previously shown to improve nutrient digestibility and amino acid absorption from milk protein in vitro. However, the effect of supplementation with this probiotic on lactose digestibility has not yet been evaluated in vivo.MethodsWistar female rats were exposed to an acute high-lactose diet (LD; 35% lactose) meal challenge after 7 days of administration of BC30 (LD-BC; n = 10) or vehicle (LD-C; n = 10). Rats treated with vehicle and exposed to control diet (CD; 35% corn starch) meal were used as controls (CD-C; n = 10). Carbohydrate oxidation (CH_OX) and lipid oxidation (L_OX) were monitored by indirect calorimetry before and after lactose challenge. After the challenge, rats were treated daily with vehicle or probiotic for an additional week and were fed with CD or LD ad libitum to determine the effects of BC30 administration in a lactose-induced diarrhoea and malnutrition model.ResultsLD-C rats showed lower CH_OX levels than CD rats, while LD-BC rats showed similar CH_OX levels compared to CD rats during the lactose challenge, suggesting a better digestion of lactose in the rats supplemented with BC30. BC30 completely reversed the increase in the small intestine length of LD-C animals. LD-BC rats displayed increased intestinal mRNA Muc2 expression. No significant changes were observed due to BC30 administration in other parameters, such as serum calprotectin, intestinal MPO activity, intestinal A1AT and SGLT1 levels or intestinal mRNA levels of Claudin2 and Occludin.ConclusionTreatment with BC30 improved the digestibility of lactose in an acute lactose challenge and ameliorated some of the parameters associated with lactose-induced malnutrition.

The aim of this study was to assess the effects of a mixture of four dietary fibers on obese rats. Four groups of male Wistar rats were fed with either standard chow (STD) or cafeteria diet (CAF) and were orally supplemented with either fibre mixture (2 g kg−1 of body weight) (STD+F or CAF+F groups) or vehicle (STD+VH or CAF+VH groups). We studied a wide number of biometric, biochemical, transcriptomic, metagenomic and metabolomic variables and applied an integrative multivariate approach based on multiple factor analysis and Pearson's correlation analysis. A significant reduction in body weight, adiposity, HbA1c and HDL-cholesterol serum levels, and colon MPO activity was observed, whereas cecal weight and small intestine length:weight ratio were significantly increased in F-treated groups compared to control animals. CAF+F rats displayed a significant enhancement in energy expenditure, fat oxidation and fresh stool weight, and a significant reduction in adiponectin and LPS serum levels, compared to control group. Animals in STD+F group showed reduced serum LDL-cholesterol levels and a significant reduction in total cholesterol levels in the liver compared to STF+VH group. The intervention effect was reflected at the metabolomic (i.e., production of short-chain fatty acids, phenolic acids, and amino acids), metagenomic (i.e., modulation of Ruminococcus and Lactobacillus genus) and transcriptomic (i.e., expression of tight junctions and proteolysis) levels. Altogether, our integrative multi-omics approach highlights the potential of supplementation with a mixture of fibers to ameliorate the impairments triggered by obesity in terms of adiposity, metabolic profile, and intestinal health.

Supplementation with natural bioactive compounds has been proposed to be a complementary tool to the calorie-restricted diets and physical exercise programs used to tackle human overweight, obesity and Metabolic syndrome. Herein, we evaluated the effects of 14 weeks of calorie-restricted cafeteria diet either alone or combined with oral administration of the polyphenol oleuropein in obese adult male rats, compared with a control group fed standard chow and a group fed cafeteria diet. Animals were sacrificed at the age of 26 weeks and several tissues of interest were removed. The results showed that both dietary interventions reduced the adiposity index (p < 0.05 and p < 0.01, respectively), and specifically the abdominal fat depots (mesenteric: p < 0.01 and p < 0.01, respectively; and epididymal: both diets p < 0.001) and restored the decreased soleus skeletal muscle mass. Both interventions decreased leptin mRNA expression in mesenteric white adipose tissue (p < 0.05) and normalized hypothalamic Agrp mRNA expression compared to cafeteria-fed obese rats (p < 0.05). However, only the calorie-restricted cafeteria diet supplemented with oleuropein induced additional lower retroperitoneal adipose accretion (p < 0.05) and increased hypothalamic leptin receptor mRNA levels (p < 0.05). Experiments with female animals, at different doses and longer intervention periods, are needed to better determine the potential benefits of this dietary treatment.