Hydroxytyrosol (HT) plays a significant role in cardiovascular disease (CVD) protection, and its metabolites are able to protect from the endothelial dysfunction commonly present in atherosclerosis. This randomized double‐blinded, placebo‐controlled crossover trial determined the effect in healthy volunteers of two gastroresistant capsules containing 15 mg/day of HT, for a 3‐week period (HTT). Evaluation of nutritional status, serum metabolites, oxidative stress biomarkers, and gene expression of 9 genes related to oxidative stress, inflammation, and CVDs was performed. Oxidation biomarkers like thiol group (p = 0.001), total antioxidant status (TAS) (p = 0.001), superoxide dismutase 1 (SOD1) (2^−ΔΔCt = 3.7), and plasma concentration of HT (2.83 μg·mL⁻¹) were significantly increased, while nitrite (p = 0.001), nitrate (p = 0.001), and malondialdehyde (MDA) (p = 0.02) were drastically reduced after HTT. A significant reduction of body fat mass percentage (p = 0.01), suprailiac skinfold (p = 0.01), and weight (p = 0.04; Δ% = −0.46%) was observed after HTT. This study shows that regular intake of 15 mg/day of HT changed body composition parameters and modulated the antioxidant profile and the expression of inflammation and oxidative stress‐related genes. However, it is advisable to personalize HT doses in order to exert its health benefits in CVD prevention and protection of LDL‐C particles from oxidative damage. This trial is registered with ClinicalTrials.gov NCT01890070.

Background: Evidence of probiotics effects on gut function, brain activity and emotional behaviour were provided. Probiotics can have dramatic effects on behaviour through the microbiome–gut–brain axis, through vagus nerve. We investigated whether chronic probiotic intake could modulate psychological state, eating behaviour and body composition of normal weight obese (NWO) and preobese–obese (PreOB/OB) compared to normal weight lean women (NWL). Methods: 60 women were enrolled. At baseline and after a 3-week probiotic oral suspension (POS) intake, all subjects underwent evaluation of body composition by anthropometry and dual X-ray absorptiometry, and psychological profile assessment by self-report questionnaires (i.e. EDI-2, SCL90R and BUT). Statistical analysis was carried out using paired t test or a non-parametric Wilcoxon test to evaluate differences between baseline and after POS intake, one-way ANOVA to compare all three groups and, where applicable, Chi square or t test were used to assess symptoms. Results: Of the 48 women that concluded the study, 24% were NWO, 26% were NWL and 50% were PreOB/OB. Significant differences in body composition were highlighted among groups both at baseline and after a POS (p < 0.05). After POS intake, a significant reduction of BMI, resistance, FM (kg and %) (p < 0.05), and a significant increase of FFM (kg and %) (p < 0.05) were observed in all subjects in NOW and PreOB/OB. After POS intake, reduction of bacterial overgrowth syndrome (p < 0.05) and lower psychopathological scores (p < 0.05) were observed in NWO and PreOB/OB women. At baseline and after POS intake, all subjects tested were negative to SCL90R_GSI scale, but after treatment subjects positive to BUT_GSI scale were significantly reduced (8.33%) (p < 0.05) compared to the baseline (33.30%). In NWO and PreOB/OB groups significant differences (p < 0.05) in response to the subscales of the EDI-2 were observed. Significant improvement of the orocecal transit time was observed (p < 0.05) after POS intake. Furthermore, significant differences were observed for meteorism (p < 0.05) and defecation frequency (p < 0.05). Conclusions: A 3-week intake of selected psychobiotics modulated body composition, bacterial contamination, psychopathological scores of NWO and PreOB/OB women. Further research is needed on a larger population and for a longer period of treatment before definitive conclusions can be made. Trial registration ClinicalTrials.gov Id: NCT01890070

Background. Probiotic oral intake, via modulation of the microbiota-gut-brain axis, can impact brain activity, mood, and behavior; therefore, it may be beneficial against psychological distress and anxiety disorders. Inflammatory cytokines can influence the onset and progression of several neurodegenerative mood disorders, and the IL-1βrs16944 SNP is related to high cytokine levels and potentially affects mood disorders. The aim of this study was to examine the combined effect of IL-1βpolymorphism and probiotic administration in mood disorder phenotypes in the Italian population.Methods. 150 subjects were randomized into two different groups, probiotic oral suspension group (POSG) and placebo control group (PCG), and received the relative treatment for 12 weeks. Psychological profile assessment by Hamilton Anxiety Rating Scale (HAM-A), Body Uneasiness Test (BUT), and Symptom Checklist 90-Revised (SCL90R) was administered to all volunteers. Genotyping was performed on DNA extracted from salivary samples.Results. After 12 weeks of intervention, a significant reduction of HAM-A total score was detected in the POSG (p<0.01), compared to the PCG. Furthermore, IL-1βcarriers have moderate risk to develop anxiety (OR=5.90), and in POSG IL-1βcarriers, we observed a reduction of HAM-A score (p=0.02).Conclusions. Consumption of probiotics mitigates anxiety symptoms, especially in healthy adults with the minor A allele of rs16944 as a risk factor. Our results encourage the use of probiotics in anxiety disorders and suggest genetic association studies for psychobiotic-personalized therapy.

Background: The Mediterranean diet (MeD) plays a key role in the prevention of obesity. Among the genes involved in obesity, the Fat mass and obesity-associated gene (FTO) is one of the most known, but its interaction with MeD remained uncertain so far.Methods: We carried out a study on a sample of 188 Italian subjects, analyzing their FTO rs9939609 alleles, and the difference in body composition between the baseline and a 4-weeks nutritional intervention. The sample was divided into two groups: the control group of 49 subjects, and the MeD group of 139 subjects.Results: We found significant relations between MeD and both variation of total body fat (ΔTBFat) (p = 0.00) and gynoid body fat (p = 0.04). ∆TBFat (kg) demonstrated to have a significant relation with the interaction diet-gene (p = 0.04), whereas FTO was associated with the variation of total body water (p = 0.02).Conclusions: MeD demonstrated to be a good nutritional treatment to reduce the body fat mass, whereas data about FTO remain uncertain. Confirming or rejecting the hypothesis of FTO and its influence on body tissues during nutritional treatments is fundamental to decide whether its effect has to be taken into consideration during both development of dietetic plans and patients monitoring.Trial RegistrationClinicalTrials.gov Id: NCT01890070. Registered 01 July 2013,https://clinicaltrials.gov/ct2/show/NCT01890070

Phytosterols and phytostanols are natural products present in vegetable oils, nuts, and seeds, or added to consumer food products whose intake is inversely associated with incidence and prognosis of several cancers. Randomized cancer prevention trials in humans are unfeasible due to time and cost yet the cellular processes and signaling cascades that underpin anti-cancer effects of these phytochemicals have been explored extensively in vitro and in preclinical in vivo models. Here we have performed an original systematic review, meta-analysis, and qualitative interpretation of literature published up to June 2020. MEDLINE, Scopus, and hand-searching identified 408 unique records that were screened leading to 32 original articles that had investigated the effects of phytosterols or phytostanols on cancer biology in preclinical models. Data was extracted from 22 publications for meta-analysis. Phytosterols were most commonly studied and found to reduce primary and metastatic tumor burden in all cancer sites evaluated. Expression of pAKT, and markers of metastasis (alkaline phosphatase, matrix metalloproteases, epithelial to mesenchymal transcription factors, lung and brain colonization), angiogenesis (vascular endothelial growth factor, CD31), and proliferation (Ki67, proliferating cell nuclear antigen) were consistently reduced by phytosterol treatment in breast and colorectal cancer. Very high dose treatment (equivalent to 0.2–1 g/kg body weight not easily achievable through diet or supplementation in humans) was associated with adverse events including poor gut health and intestinal adenoma development. Phytosterols and phytostanols are already clinically recommended for cardiovascular disease risk reduction, and represent promising anti-cancer agents that could be delivered in clinic and to the general population at low cost, with a well understood safety profile, and now with a robust understanding of mechanism-of-action. Graphical Abstract

Triple negative breast cancer (TNBC) is challenging to treat successfully because targeted therapies do not exist. Instead, systemic therapy is typically restricted to cytotoxic chemotherapy, which fails more often in patients with elevated circulating cholesterol. Liver x receptors are ligand-dependent transcription factors that are homeostatic regulators of cholesterol, and are linked to regulation of broad-affinity xenobiotic transporter activity in non-tumor tissues. We show that LXR ligands confer chemotherapy resistance in TNBC cell lines and xenografts, and that LXRalpha is necessary and sufficient to mediate this resistance. Furthermore, in TNBC patients who had cancer recurrences, LXRalpha and ligands were independent markers of poor prognosis and correlated with P-glycoprotein expression. However, in patients who survived their disease, LXRalpha signaling and P-glycoprotein were decoupled. These data reveal a novel chemotherapy resistance mechanism in this poor prognosis subtype of breast cancer. We conclude that systemic chemotherapy failure in some TNBC patients is caused by co-opting the LXRalpha:P-glycoprotein axis, a pathway highly targetable by therapies that are already used for prevention and treatment of other diseases.