This study evaluated the effects of long-term intake of nutritive sweeteners (NSs) and non-nutritive sweeteners (NNSs) on body weight, food and energy intake, blood pressure, metabolic parameters, and memory retention in rats. Sixty male Sprague–Dawley rats were randomly divided into six groups ( n = 10 per group): control (water),10% sucrose (SUC), aspartame (ASP), sucralose (SCA), stevia (STV), and 5% xylitol (XYL). Pure NSs (SUC and XYL) and NNSs were added to the drinking water for 18 weeks. ASP, SCA, and STV dosage was based on the estimated daily intake limit: 4.1, 2.0, and 3.4 mg/kg/day, respectively. Chronic access to NNSs did not result in any difference in total weight gain of the rats, while it was significantly elevated in the SUC group compared with the control and NNSs groups. Food intake was significantly lower in all NNSs groups compared with SUC and control groups. Sweetened beverage intake volumes were significantly diminished in all NNSs groups compared with intake in SUC and control groups. Total calories consumed were lower for the STV and XYL groups compared with all other groups. Blood pressure and glucose metabolism did not differ significantly between the groups. All sweeteners increased total cholesterol, low-density lipoprotein, and triglyceride levels. Short-term memory was significantly impaired in the ASP group in the novel object recognition task, while long-term memory was impaired in SUC and STV groups. These metabolic and behavioral results suggest that the long-term intake of NSs or NNSs can be associated with peripheral and central effects.

Introduction: The gut microbiota is vital for human health, and its modulation through dietary and pharmaceutical compounds has gained increasing attention. Among gut microbes, Akkermansia muciniphila has been extensively researched due to its role in maintaining intestinal barrier integrity, regulating energy metabolism, and influencing inflammatory responses. Subject: To analyze and synthesize the available scientific evidence on the influence of various bioactive compounds, including prebiotics, polyphenols, antioxidants, and pharmaceutical agents, on the abundance and activity of A. muciniphila, considering underlying mechanisms, microbial context, and its therapeutic potential for improving metabolic and intestinal health. Methods: A systematic literature review was conducted in accordance with the PRISMA 2020 guidelines. Databases such as PubMed, ScienceDirect, Scopus, Web of Science, SciFinder-n, and Google Scholar were searched for publications from 2004 to 2025. Experimental studies in animal models or humans that evaluated the impact of bioactive compounds on the abundance or activity of A. muciniphila were prioritized. The selection process was managed using the Covidence platform. Results: A total of 78 studies were included in the qualitative synthesis. This review compiles and analyzes experimental evidence on the interaction between A. muciniphila and various bioactive compounds, including prebiotics, antioxidants, flavonoids, and selected pharmaceutical agents. Factors such as the chemical structure of the compounds, microbial environment, underlying mechanisms, production of short-chain fatty acids (SCFAs), and mucin interactions were considered. Compounds such as resistant starch type 2, GOS, 2′-fucosyllactose, quercetin, resveratrol, metformin, and dapagliflozin showed beneficial effects on A. muciniphila through direct or indirect pathways. Discussion: Variability across studies reflects the influence of multiple variables, including compound type, dose, intervention duration, experimental models, and analytical methods. These differences emphasize the need for a contextualized approach when designing microbiota-based interventions. Conclusions: A. muciniphila emerges as a promising therapeutic target for managing metabolic and inflammatory diseases. Further mechanistic and clinical studies are necessary to validate its role and to support the development of personalized microbiota-based treatment interventions.

The physicochemical changes induced by seven different dietary fibers (oat, bamboo, pea, inulin, apple, potato, and wheat) during storage and their effects on the survival of homofermentative Lacticaseibacillus casei subsp. casei (L. casei) in fermented milk matrix were analyzed. For this, an experimental study of the effect of storage time on the microorganisms count and physicochemical properties (pH, titratable acidity, syneresis and viscosity) of milk fermented with L. casei was carried out every two weeks during a storage period of 42 days. Throughout the period studied at 4 °C, no significant differences were found in terms of viscosity values, syneresis rates and L. casei counts, despite the substantial decrease in the pH values. Notably, the substantial increase in the concentration of free hydronium ions (active acidity) in the fiber-enriched matrices during the follow-up period was positively correlated with the L.casei survival. The microbial count determined in all samples was higher than 1 × 10⁷ CFU/g, the minimum value recommended by world organizations for nutraceutical fermented foods. Consequently, the studied prebiotic fibers could be considered in the production of new fermented dairy products with functional properties. Graphical abstract

Background: Prenatal stress has been reported to harm the physiological and biochemical functions of the brain of the offspring, potentially resulting in anxiety- and depression-like behaviors later in life. Trans-Resveratrol (RESV) is known for its anti-inflammatory, anxiolytic, and antidepressant properties. However, whether administering RESV during pregnancy can counteract the anxiety- and depression-like behaviors induced by maternal stress is unknown. Objective: This study aimed to assess the protective potential of RESV against molecular and behavioral changes induced by prenatal stress. Methods: During pregnancy, the dams received 50 mg/kg BW/day of RESV orally. They underwent a movement restriction for forty-five minutes, three times a day, in addition to being exposed to artificial light 24 h before delivery. The male offspring were left undisturbed until early adulthood, at which point they underwent behavioral assessments, including the open field test, elevated plus maze, and forced swim test. Subsequently, they were euthanized, and the hippocampus and prefrontal cortex were extracted for RT-qPCR analysis to measure Bdnf mRNA expression. Results: By weaning, results showed that prenatal stress led to reduced weight gain and, in adulthood, increased anxiety- and depression-like behaviors and changes in Bdnf mRNA expression. However, these effects were attenuated by maternal RESV supplementation. Conclusions: The findings suggest that RESV can prevent anxiety- and depression-like behaviors induced by prenatal stress by modulating Bdnf mRNA expression.

The spike (S) protein of SARS-CoV-2 is a molecular target of great interest for developing drug therapies against COVID-19 because S is responsible for the interaction of the virus with the host cell receptor. Currently, there is no outpatient safety treatment for COVID-19 disease. Furthermore, we consider it of worthy importance to evaluate experimentally the possible interaction of drugs (approved by the Food and Drug Administration) and the S, considering some previously in silico and clinical use. Then, the objective of this study was to demonstrate the in vitro interaction of ivermectin with S. The equilibrium dialysis technique with UV–Vis was performed to obtain the affinity and dissociation constants. In addition, the Drug Affinity Responsive Target Stability (DARTS) technique was used to demonstrate the in vitro interaction of S with ivermectin. The results indicate the interaction between ivermectin and the S with an association and dissociation constant of Ka = 1.22 µM⁻¹ and Kd = 0.81 µM, respectively. The interaction was demonstrated in ratios of 1:50 pmol and 1:100 pmol (S: ivermectin) by the DARTS technique. The results obtained with these two different techniques demonstrate an interaction between S and ivermectin previously explored in silico, suggesting its clinical uses to stop the viral spread among susceptible human hosts.

SARS-CoV-2 is the etiological agent responsible for COVID-19. While most research has focused on structural proteins, the accessory protein Open Reading Frame 8 (ORF8) has attracted attention for its role in immune evasion and the induction of a cytokine storm. Although the exact mechanisms underlying viral pathogenicity remain to be elucidated, oxidative stress has been proposed as a key contributing factor. In this study, we evaluated the effect of intranasal administration of ORF8 on arterial blood pressure and the antioxidant system in different organs of male BALB/c mice at 2- or 8 weeks post-administration. A significant increase in blood pressure and renal total antioxidant capacity was observed in the 8-week group, and decreased catalase activity in the prefrontal cortex was observed in the 2-week group. These findings suggest that ORF8 may contribute to long-term renal alterations and potentially to mechanism relevant to cognitive dysfunction associated with COVID-19.