Josep Maria del Bas

Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by impaired metabolic flexibility, oxidative stress, and disruption of the temporal coordination of hepatic processes. Obesogenic diets contribute to this dysfunction by altering redox homeostasis and autophagy, thereby promoting lipid accumulation and cellular stress. In this study, we investigated whether grape seed proanthocyanidin extract (GSPE), a polyphenol-rich compound with antioxidant properties, can modulate these alterations in a time-dependent manner. Male Fischer 344 rats were fed a standard or cafeteria diet and supplemented with GSPE (25 mg/kg) at the onset of the active phase (ZT12). Liver samples were collected across four Zeitgeber times to evaluate circadian-related proteins, autophagy markers, antioxidant responses, lipid content, and metabolomic profiles. Cafeteria feeding disrupts hepatic homeostasis, reducing BMAL1 protein levels, altering the temporal organization of autophagy markers, and impairing redox regulation. GSPE did not restore core clock protein expression but induced a pronounced, time-specific activation of the NRF2/HO-1 axis, with a marked increase in HO-1 at the onset of the active phase. This effect was associated with a metabolic shift toward amino acid-related pathways linked to redox balance. These findings indicate that GSPE enhances antioxidant defenses in a time-dependent manner, improving redox–metabolic coordination under obesogenic conditions.

Metabolic dysfunction–associated steatotic liver disease (MASLD) is characterized by impaired metabolic flexibility, oxidative stress, and disruption of the temporal coordination of hepatic processes. Obesogenic diets contribute to this dysfunction by altering redox homeostasis and autophagy, thereby promoting lipid accumulation and cellular stress. In this study, we investigated whether grape seed proanthocyanidin extract (GSPE), a polyphenol-rich compound with antioxidant properties, can modulate these alterations in a time-dependent manner. Male Fischer 344 rats were fed a standard or cafeteria diet and supplemented with GSPE (25 mg/kg) at the onset of the active phase (ZT12). Liver samples were collected across four Zeitgeber times to evaluate circadian-related proteins, autophagy markers, antioxidant responses, lipid content, and metabolomic profiles. Cafeteria feeding disrupts hepatic homeostasis, reducing BMAL1 protein levels, altering the temporal organization of autophagy markers, and impairing redox regulation. GSPE did not restore core clock protein expression but induced a pronounced, time-specific activation of the NRF2/HO-1 axis, with a marked increase in HO-1 at the onset of the active phase. This effect was associated with a metabolic shift toward amino acid–related pathways linked to redox balance. These findings indicate that GSPE enhances antioxidant defenses in a time-dependent manner, improving redox–metabolic coordination under obesogenic conditions.

This study explores the development of functional fermented beverages using fibre-rich residues derived from olive pruning, vineyard pruning, chicory root, and red onion, obtained after subcritical water extraction of polyphenols. Two microbial strains, Lactiplantibacillus plantarum and Bacillus subtilis, were evaluated for their fermentation performance across different fibre matrices, with and without sugar supplementation. Key parameters including microbial growth, pH evolution, and reducing sugar content were monitored, and Lactiplantibacillus plantarum showed superior acidification and viability (>9 log CFU/mL), especially in sugar-enriched formulations, while Bacillus subtilis showed a limited performance. Based on fermentation efficiency, three sugar-supplemented formulations were selected to scale-up: olive pruning fibre and vineyard pruning fibre fermented with Lactiplantibacillus plantarum and olive pruning fibre fermented with Bacillus subtilis. Red onion fibre extract was excluded from scale-up experiments due to its high viscosity, which made it impossible to measure reducing sugars, consistent with its high water-holding capacity. Fermentation significantly increased antioxidant capacity, reaching up to 750 µmol Trolox equivalents/L and 18 mg of gallic acid equivalents/L in L. plantarum-fermented samples, confirming microbial release of bound phenolics and formation of bioactive metabolites. The resulting beverages were microbiologically stable (final pH < 4.5), sensorially acceptable, and potentially antioxidant-rich, supporting their role in sustainable food system development and circular bioeconomy.

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.

Background/Objectives: Populations in Mediterranean countries are abandoning the traditional Mediterranean diet (MD) and lifestyle, shifting towards unhealthier habits due to profound cultural and socioeconomic changes. The SWITCHtoHEALTHY project aims to demonstrate the effectiveness of a multi-component nutritional intervention to improve the adherence of families to the MD in three Mediterranean countries, thus prompting a dietary behavior change. Methods: A parallel, randomized, single-blinded, and controlled multicentric nutritional intervention study will be conducted over 3 months in 480 families with children and adolescents aged 3–17 years from Spain, Morocco, and Turkey. The multi-component intervention will combine digital interactive tools, hands-on educational materials, and easy-to-eat healthy snacks developed for this study. Through the developed SWITCHtoHEALTHY app, families will receive personalized weekly meal plans, which also consider what children eat at school. The engagement of all family members will be prompted by using a life simulation game. In addition, a set of activities and educational materials for adolescents based on a learning-through-playing approach will be codesigned. Innovative and sustainable plant-based snacks will be developed and introduced into the children’s dietary plan as healthy alternatives for between meals. By using a full-factorial design, families will be randomized into eight groups (one control and seven interventions) to test the independent and combined effects of each component (application and/or educational materials and/or snacks). The impact of the intervention on diet quality, economy, and the environment, as well as on classical anthropometric parameters and vital signs, will be assessed in three different visits. The COM-B behavioral model will be used to assess essential factors driving the behavior change. The main outcome will be adherence to the MD assessed through MEDAS in adults and KIDMED in children and adolescents. Conclusions: SWITCHtoHEALTHY will provide new insights into the use of sustained models for inducing dietary and lifestyle behavior changes in the family setting. It will facilitate generating, boosting, and maintaining the switch to a healthier MD dietary pattern across the Mediterranean area. Registered Trial, National Institutes of Health, ClinicalTrials.gov (NCT06057324).

Background: Histamine intolerance manifests when there is an imbalance between the production of histamine and the body’s capacity to metabolise it. Within the gastrointestinal tract, diamine oxidase (DAO) plays a pivotal role in breaking down ingested histamine. Insufficient levels of DAO have been linked to various diseases affecting the respiratory, cardiovascular, nervous, muscular, and digestive systems; some of these symptoms are evidenced in fibromyalgia syndrome. This underscores the crucial role of DAO in maintaining the histamine balance and highlights its association with diverse physiological systems and health conditions. The management of fibromyalgia commonly involves the use of psychotropic medications; however, their potential interactions with DAO remain not fully elucidated. Methods: This study delved into the influence of various psychotropic medications on DAO activity through in vitro experiments. Additionally, we explored their impact on the human intestinal cell line Caco-2, examining alterations in DAO expression at both the mRNA and protein levels along with DAO activity. Results: Notably, the examined drugs—sertraline, pregabalin, paroxetine, alprazolam, and lorazepam—did not exhibit inhibitory effects on DAO activity or lead to reductions in DAO levels. In contrast, citalopram demonstrated a decrease in DAO activity in in vitro assays without influencing DAO levels and activity in human enterocytes. Conclusions: These findings imply that a collaborative approach involving psychotropic medications and DAO enzyme supplementation for individuals with fibromyalgia and a DAO deficiency could offer potential benefits for healthcare professionals in their routine clinical practice.

In this study, we examined the metabolic and gut microbiome responses to paraquat (PQ) in male Wistar rats, focusing on oxidative stress effects. Rats received a single intraperitoneal injection of PQ at 15 and 30 mg/kg, and various oxidative stress parameters (i.e., MDA, SOD, ROS, 8-isoprostanes) were assessed after three days. To explore the omic profile, GC-qTOF and UHPLC-qTOF were performed to assess the plasma metabolome; ¹H-NMR was used to assess the urine metabolome; and shotgun metagenomics sequencing was performed to study the gut microbiome. Our results revealed reductions in body weight and tissue changes, particularly in the liver, were observed, suggesting a systemic effect of PQ. Elevated lipid peroxidation and reactive oxygen species levels in the liver and plasma indicated the induction of oxidative stress. Metabolic profiling revealed changes in the tricarboxylic acid cycle, accumulation of ketone body, and altered levels of key metabolites, such as 3-hydroxybutyric acid and serine, suggesting intricate links between energy metabolism and redox reactions. Plasma metabolomic analysis revealed alterations in mitochondrial metabolism, nicotinamide metabolism, and tryptophan degradation. The gut microbiome showed shifts, with higher PQ doses influencing microbial populations (e.g., Escherichia coli and Akkermansia muciniphila) and metagenomic functions (pyruvate metabolism, fermentation, nucleotide and amino acid biosynthesis). Overall, this study provides comprehensive insights into the complex interplay between PQ exposure, metabolic responses, and gut microbiome dynamics. These findings enhance our understanding of the mechanisms behind oxidative stress-induced metabolic alterations and underscore the connections between xenobiotic exposure, gut microbiota, and host metabolism.

Hypertriglyceridemia (HTG) is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD). One of the multiple origins of HTG alteration is impaired lipoprotein lipase (LPL) activity, which is an emerging target for HTG treatment. We hypothesised that early, even mild, alterations in LPL activity might result in an identifiable metabolomic signature. The aim of the present study was to assess whether a metabolic signature of altered LPL activity in a preclinical model can be identified in humans. A preclinical LPL-dependent model of HTG was developed using a single intraperitoneal injection of poloxamer 407 (P407) in male Wistar rats. A rat metabolomics signature was identified, which led to a predictive model developed using machine learning techniques. The predictive model was applied to 140 humans classified according to clinical guidelines as (1) normal, less than 1.7 mmol/L; (2) risk of HTG, above 1.7 mmol/L. Injection of P407 in rats induced HTG by effectively inhibiting plasma LPL activity. Significantly responsive metabolites (i.e. specific triacylglycerols, diacylglycerols, phosphatidylcholines, cholesterol esters and lysophospholipids) were used to generate a predictive model. Healthy human volunteers with the impaired predictive LPL signature had statistically higher levels of TG, TC, LDL and APOB than those without the impaired LPL signature. The application of predictive metabolomic models based on mechanistic preclinical research may be considered as a strategy to stratify subjects with HTG of different origins. This approach may be of interest for precision medicine and nutritional approaches.