Exposure to early life stress (ELS), prenatal or postnatal during childhood and adolescence, can significantly impact mental and physical health. The role of the intestinal microbiome in human health, and particularly mental health, is becoming increasingly evident. This systematic review aims to summarize the clinical data evaluating the effect of ELS on the human intestinal microbiome. The systematic review (CRD42022351092) was performed following PRISMA guidelines, with ELS considered as exposure to psychological stressors prenatally and during early life (childhood and adolescence). Thirteen articles met all inclusion criteria, and all studies reviewed found a link between ELS and the gut microbiome in both prenatal and postnatal periods. However, we failed to find consensus microbiome signatures associated with pre- or postnatal stress, or both. The inconsistency of results is likely attributed to various factors such as different experimental designs, ages examined, questionnaires, timing of sample collection and analysis methods, small population sizes, and the type of stressors. Additional studies using similar stressors and validated stress measures, as well as higher-resolution microbiome analytical approaches, are needed to draw definitive conclusions about the links between stress and the human gut microbiome.

Adverse ventricular remodeling is the heart’s response to damaging stimuli and is linked to heart failure and poor prognosis. Formyl-indolo [3,2-b] carbazole (FICZ) is an endogenous ligand for the aryl hydrocarbon receptor (AhR), through which it exerts pleiotropic effects including protection against inflammation, fibrosis, and oxidative stress. We evaluated the effect of AhR activation by FICZ on the adverse ventricular remodeling that occurs in the early phase of pressure overload in the murine heart induced by transverse aortic constriction (TAC). Cardiac structure and function were evaluated by cardiac magnetic resonance imaging (CMRI) before and 3 days after Sham or TAC surgery in mice treated with FICZ or with vehicle, and cardiac tissue was used for biochemical studies. CMRI analysis revealed that FICZ improved cardiac function and attenuated cardiac hypertrophy. These beneficial effects involved the inhibition of the hypertrophic calcineurin/NFAT pathway, transcriptional reduction in pro-fibrotic genes, and antioxidant effects mediated by the NRF2/NQO1 pathway. Overall, our findings provide new insight into the role of cardiac AhR signaling in the injured heart.

Calcitriol, the bioactive metabolite of vitamin D, interacts with the ubiquitously expressed nuclear vitamin D receptor (VDR) to induce genomic effects, but it can also elicit rapid responses via membrane-associated VDR through mechanisms that are poorly understood. The down-regulation of K⁺ currents is the main origin of electrophysiological remodeling in pathological hypertrophy and heart failure (HF), which can contribute to action potential prolongation and subsequently increase the risk of triggered arrhythmias. Adult mouse ventricular myocytes were isolated and treated with 10 nM calcitriol or vehicle for 15–30 min. In some experiments, cardiomyocytes were pretreated with the Akt inhibitor triciribine. In the adult mouse ventricle, outward K⁺ currents involved in cardiac repolarization are comprised of three components: the fast transient outward current (I_tof), the ultrarapid delayed rectifier K⁺ current (I_kur), and the non-inactivating steady-state outward current (I_ss). K⁺ currents were investigated using the whole-cell or the perforated patch-clamp technique and normalized to cell capacitance to obtain current densities. Calcitriol treatment of cardiomyocytes induced an increase in the density of I_tof and I_kur, which was lost in myocytes isolated from VDR-knockout mice. In addition, calcitriol activated Akt in cardiomyocytes and pretreatment with triciribine prevented the calcitriol-induced increase of outward K⁺ currents. In conclusion, we demonstrate that calcitriol via VDR and Akt increases both I_tof and I_kur densities in mouse ventricular cardiomyocytes. Our findings may provide new mechanistics clues for the cardioprotective role of this hormone in the heart.

Background: Dietary habits are crucial for preventing many diseases, particularly in children and adolescents. Accurate assessment of dietary intake is essential for understanding the relationship between diet and health in these age groups. Objective: This study aimed to evaluate the reproducibility and validity of a Spanish version of the European Prospective Investigation into Cancer and Nutrition (EPIC) Food Frequency Questionnaire (FFQ) in 150 Spanish children and adolescents aged 10 to 17 using the average of 9 days of 24-h dietary recall (24H-DR) as a reference. Methods: Intraclass correlation coefficients (ICCs) were calculated to asses reproducibility and Spearman/Pearson correlation coefficients were calculated to assess validity and reproducibility. Results: The average ICCs were 0.41 for crude nutrients, 0.31 for food groups, 0.31 for energy-adjusted nutrients, and 0.4 for energy-adjusted food groups. Spearman/Pearson correlation coefficients averaged 0.39 and 0.41 for crude and energy-adjusted nutrients, respectively, and 0.51 and 0.47 for corresponding food groups. Regarding validity, the average correlation coefficient for crude, energy-adjusted, and de-attenuated nutrients was 0.32, 0.50, and 0.50, respectively. The highest crude coefficient was 0.50 for vitamin C and fiber, while the highest energy-adjusted coefficient was 0.76 for protein and carbohydrates. The highest de-attenuated coefficient was 0.72 for vitamin B6. Conclusions: Overall, these results suggest that the EPIC FFQ is a valid and reliable instrument for assessing dietary intake in Spanish children and adolescents.

First of all, we would like to express our gratitude for your careful reading of our work and acknowledge the constructive nature of the observations

Background/Objectives: The prevalence of the commensal gut bacterium species, Phascolarctobacterium faecium, has been associated with normal weight in humans. Preclinical evidence suggests that the strain P. faecium DSM 32890 exerts beneficial effects on metabolic and immune function in diet-induced obesity. Herein, we aimed to evaluate the safety and tolerability of this strain in a preclinical study and a pilot interventional trial in humans. Methods: A repeated-dose oral toxicity study of 28 days was performed in Wistar rats (male and female), during which adverse signs and clinical outcomes were assessed, along with histological, hematologic, biochemical, and immune markers. Subsequently, a pilot human intervention trial was conducted, including 20 participants (11 overweight and 9 normal weight) who received P. faecium DSM 32890 daily for 15 days. Body composition, dietary intake, physical activity, clinical data, perceived health, gastrointestinal symptoms, and blood analyses were assessed to determine tolerability and identify potential adverse effects. Results: In rats, the administration of the bacterium did not cause behavioral, physiological, histologic, immune, or biochemical alterations. In humans, there was no evidence of adverse effects on general health, hematological and biochemical profiles, bowel habits, or gastrointestinal symptoms. Overweight participants experienced reductions in flatulence and nausea after the intervention. Conclusions: The consumption of P. faecium DSM 32890 did not raise safety concerns and was well tolerated in rats and humans. The findings represent a step forward in the path toward future, longer-term studies to explore the potential efficacy.