Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities. DESIGN: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts. RESULTS: We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy. CONCLUSION: GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention.

Effect of Telemedicine Dietary Intervention for Endothelial Function in Patients with Type 2 Diabetes Mellitus on Mediterranean Diet.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have a high rate of cardiovascular disease (CVD). The Mediterranean diet is preferred for CVD prevention. Endothelial dysfunction is demonstrated early in T2DM. OBJECTIVES: To study the effects of dietary intervention of T2DM patients without known CVD on endothelial function and vascular inflammation. METHODS: A prospective study enrolled 22 patients with T2DM. Patients were divided randomly into two groups: an intervention group with 12 patients (55 ± 7 years old, 6 women) and a control group with 10 patients (59 ± 10 years old, 5 women). Clinical evaluation included body mass index (BMI) and endothelial function measured by the flow mediated percent change (FMD%). Fasting blood was drawn on entry to the study and 3 months later, measuring C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), total cholesterol, triglycerides, and glycosylated hemoglobin (HbA1C%). The intervention was based on weekly telephone calls by a clinical dietitian for 3 months. RESULTS: In the intervention group CRP and ICAM-1 were reduced (from 4.2 ± 3.3 mg/dl to 0.4 ± 0.5 mg/dl, P = 0.01 and from 258.6 ± 98.3 ng/ml to 171.6 ± 47.7 ng/ml, P = 0.004). Endothelial function (FMD%) was improved (from 0.5 ± 8.0% to 9.5 ± 11.5%, P = 0.014). No change was observed in BMI, HbA1C%, total cholesterol, and triglycerides levels in either group. CONCLUSIONS: Patients with T2DM on the Mediterranean diet who received a weekly telephone call for 3 months improved their endothelial function with reduction of markers of inflammation.

Vascular Reactivity of Adult-Onset Systemic Lupus Erythematosus Patients.

BACKGROUND: Cardiovascular disease (CVD) is more frequent in patients with systemic lupus erythematosus (SLE) compared with age- and sex-matched healthy subjects. SLE is an autoimmune disease that is more prevalent in women (9:1). Women tend to develop CVD in post-menopausal years; however, women with SLE may develop endothelial dysfunction and CVD at a younger age in the pre-menopausal years. OBJECTIVES: To study the endothelial function of adult-onset SLE patients from the north of Israel (the Galilee region) and to determine whether modern management (including biological treatments) changes the risk of developing CVD. METHODS: Thirteen females with adult-onset SLE without renal involvement were recruited to this prospective study. Clinical parameters (age, height, body mass index [BMI]), laboratory parameters (C-reactive protein [CRP] and hemoglobin level), and vascular responsiveness (flow mediated diameter percent change [FMD%]) were evaluated and compared to 11 age-matched healthy females. Student's t-test was used to find differences between the two groups. RESULTS: No difference was observed in adult-onset SLE female patients and their age- and sex-matched controls with regard to age (42.1 ± 11.8 years vs. 36.6 ± 10.8 years, P = NS), BMI (25 ± 1.8 kg/m2 vs. 25 ± 2.5 kg/m2, P = NS), and hemoglobin level (11.9 ± 0.9 gr% vs. 12.7 ± 1.2 gr%, P = NS). However, a significant difference was found in CRP (2.57 ± 2.2 mg vs. 0.60 ± 0.37 mg, P = 0.001), vascular responsiveness (0.94 ± 6.6 FMD% vs. 9.2 ± 8.1 FMD%, P = 0.012), and height (165.7 ± 4.5 cm vs. 171.6 ± 5.8 cm, P = 0.009). CONCLUSIONS: Adult-onset SLE females had impaired endothelial function even though they were treated by modern protocols.

Postnatal administration of leptin antagonist mitigates susceptibility to obesity under high-fat diet in male αMUPA mice.

Perturbations in postnatal leptin signaling have been associated with altered susceptibility to diet-induced obesity (DIO) under high-fat-diet (HFD), albeit with contradicting evidence. Previous studies have shown that alpha murine urokinase-type plasminogen activator (αMUPA) mice have a higher and longer postnatal leptin surge compared with their wild types (WTs) as well as lower body weight and food intake under regular diet (RD). Here we explored αMUPA's propensity for DIO and the effect of attenuating postnatal leptin signaling with leptin antagonist (LA) on energy homeostasis under both RD and HFD. Four-day-old αMUPA pups were treated on alternate days until postnatal day 18 with either vehicle or LA (10 or 20 mg·day-1·kg-1) and weaned into RD or HFD. Compared with RD-fed αMUPA males, HFD-fed αMUPA males showed higher energy intake, even when corrected for body weight difference, and became hyperinsulinemic and obese. Additionally, HFD-fed αMUPA males gained body weight at a higher rate than their WTs mainly because of strain differences in energy expenditure. LA administration did not affect strain differences under RD but attenuated αMUPA's hyperinsulinemia and DIO under HFD, most likely by mediating energy expenditure. Together with our previous findings, these results suggest that αMUPA's leptin surge underlies its higher susceptibility to obesity under HFD, highlighting the role of leptin-related developmental processes in inducing obesity in a postweaning obesogenic environment, at least in αMUPA males. This study therefore supports the use of αMUPA mice for elucidating developmental mechanisms of obesity and the efficacy of early-life manipulations via leptin surge axis in attenuating DIO.

Erectile Dysfunction, Sleep Disorders, and Endothelial Function.

BACKGROUND: Erectile dysfunction (ED) is a syndrome associated with endothelial dysfunction, which may predict cardiovascular events in men presenting with this syndrome. It has been shown to be associated with a higher rate of acute myocardial infarction and cardiovascular mortality, vascular inflammation, and impaired endothelial function. In this review we present the literature findings and describe the mechanistic pathways that are known to be involved in this syndrome and its related clinical consequences.

5,6-δ-DHTL, a stable metabolite of arachidonic acid, is a potential substrate for paraoxonase 1.

Paraoxonase 1 (PON1) is an antiatherogenic high density lipoprotein-associated lactonase. Recent findings revealed that PON1 knockout mice have low blood pressure, which is negatively correlated with the level of 5,6-epoxyeicosatrienoic acid (5,6-EET), a cytochrome P450 -derived arachidonic acid metabolite. 5,6-EET is an endothelium-derived hyperpolarizing factor that causes arterial dilation. Under physiological conditions, 5,6-EET is unstable, transforming to its δ-lactone (5,6-δ-DHTL) that evades the degradation by soluble epoxide hydrolase (sEH), arguing for the existence of yet another enzyme that is responsible specifically for its hydrolysis. We therefore hypothesized that PON1 degrades the 5,6-δ-DHTL, and this specific PON1 lactonase activity thus decreases endothelial vasodilatation. The aim of the present study was to investigate the PON1-5,6-δ-DHTL relationship. A liquid chromatography mass spectrometry based method for 5,6-EET derivatives identification was developed. Tracking the lactonization of 5,6-EET in a physiological solution revealed that 5,6-EET was fully converted into 5,6-δ-DHTL. Incubation of 5,6-δ-DHTL with rePON1 resulted in 85.1±3.4% degradation of the substrate to 5,6 dihydroxytrienoic acid (5,6-DHET), while only 12.0±8.7% hydrolysis was detected in the absence of PON1. Accordingly, the levels of 5,6-DHTL were found to be significantly higher in the PON1KO mice than in the wild type mice. Kinetic analysis revealed values of Vmax=0.021±0.01µM/s and Km=150.99±62.1µM. Calculation of the docking energy suggested possible interaction of the 5,6-δ-DHTL in the catalytic region of PON1 with free energy of-5.57 Kcal/mol, preferentially for the (S) enantiomer. These findings demonstrate that 5,6-δ-DHTL is a PON1 substrate and imply that the 5,6-EET vasodilation effect may be impaired by PON1.

Microbiota Metabolite Profiles and Dietary Intake in Older Individuals with Insomnia of Short vs. Normal Sleep Duration.

Recent evidence suggests that the gut microbiota plays a role in insomnia pathogenesis. This study compared the dietary habits and microbiota metabolites of older adults with insomnia of short vs. normal sleep duration (ISSD and INSD, respectively). Data collection included sleep assessment through actigraphy, dietary analysis using the Food Frequency Questionnaire, and metabolomic profiling of stool samples. The results show that ISSD individuals had higher body mass index and a greater prevalence of hypertension. Significant dietary differences were observed, with the normal sleep group consuming more kilocalories per day and specific aromatic amino acids (AAAs) phenylalanine and tyrosine and branch-chain amino acid (BCAA) valine per protein content than the short sleep group. Moreover, metabolomic analysis identified elevated levels of the eight microbiota metabolites, benzophenone, pyrogallol, 5-aminopental, butyl acrylate, kojic acid, deoxycholic acid (DCA), trans-anethole, and 5-carboxyvanillic acid, in the short compared to the normal sleep group. The study contributes to the understanding of the potential role of dietary and microbial factors in insomnia, particularly in the context of sleep duration, and opens avenues for targeted dietary interventions and gut microbiota modulation as potential therapeutic approaches for treating insomnia.

A personalized diet intervention improves depression symptoms and changes microbiota and metabolite profiles among community-dwelling older adults.

Introduction: The impact of diet on mental well-being and gut microorganisms in humans is well recognized. However, research on the connections between food nutrients, gut microbiota, and mental health remains limited. To address this, the present study aimed to assess the effects of a personalized diet, based on individual needs and aligned with the Mediterranean diet principles, on depression symptoms, quality of life, nutritional intake, and gut microbiota changes among older adults living in the community. Methods: The intervention involved regular visits from a registered dietitian, who provided tailored dietary recommendations. During the 6-month study, participants completed questionnaires to evaluate their depression levels, quality of life, and dietary habits. Additionally, they provided stool samples for analysis of gut microbiota and metabolites. Results: The results demonstrated that the personalized dietary intervention reduced depression symptoms and improved the quality of life among older adults. Furthermore, significant changes in the intake of certain nutrients, such as folate, lutein, zeaxanthin, EPA, and DHA, were observed following the intervention. Moreover, the intervention was associated with increased diversity in the gut microbiome and reduced total short-chain fatty acids, the main metabolites produced by gut microorganisms. The study also revealed correlations between food nutrients, gut microbiota, and mental health parameters. Discussion: In conclusion, this research highlights the potential advantages of personalized dietary interventions in managing depression and enhancing overall well-being among older populations. It also sheds light on the role of gut microbiota and its metabolites in these effects. The findings offer valuable insights into the significance of nutrition and gut health for mental well-being in older adults.

Human atherosclerotic plaque lipid extract impairs the antioxidant defense capacity of monocytes.

UNLABELLED: Oxidative stress, induced by reactive oxygen species (ROS), is implicated in the pathogenesis of plaque formation and instability. During this ongoing oxidative process, cells in the vasculature are exposed to the atherogenicity of the plaque; previous studies have suggested that the arterial plaque, apart from being a consequence of the development of atherosclerosis, is also a cause of its progression. OBJECTIVE: In this study, we challenged this idea by investigating the effect of carotid plaque lipid extract on the human monocyte antioxidant system. METHODS AND RESULTS: Exposure of monocytes to carotid plaque lipid extract (LE) for up to 72 h resulted in a significant increase in the ROS level (170%), with a simultaneous rise of 177% in glutathione oxidation. Experiments revealed a significant decrease, in the intracellular antioxidant enzyme activity of CAT, GPx and TRxR, (by 17, 33 and 43%, respectively). Although the activity of these enzymes subsequently returned to those of the controls, the levels of ROS did not decrease but rather continued increasing with extended LE exposure. Intriguingly, intracellular SOD activity rose significantly and remained high (176%), implying that endogenously produced H(2)O(2), and not O(2)·¯ < is the factor that promotes the oxidative stress resulting from the presence of LE. CONCLUSION: Lipids from the atherosclerotic plaque may contribute to the progression of atherogenic conditions in adjacent regions by weakening the cellular antioxidant system and promoting oxidative stress, mainly through H(2)O(2) production.

Isothiocyanates inhibit psoriasis-related proinflammatory factors in human skin.

OBJECTIVE: 4-Methylthiobutylisothiocyanate (MTBI), the main rocket (Eruca sativa) seed isothiocyanate (ITC), and its oxidized form, sulforaphane (SFN), were assessed for their potential effects on psoriasis-related factors. METHODS: MTBI and SFN were evaluated for their effect on mRNA expression and cytokine secretion in vitro in human monocytes and macrophage-like cells and ex vivo in topically treated inflamed human skin. In addition, they were assayed in vivo for morphological changes in topically treated psoriasiform human skin in severe-combined immunodeficient (SCID) mice. RESULTS: MTBI and SFN contributed to the prevention of inflammation development and reduced ongoing inflammation by downregulating lipopolysaccharide (LPS)-induced mRNA expression of the psoriasis-related cytokines, interleukin (IL)-12/23p40 (25-58 %), tumor necrosis factor (TNF)-α (15-37 %) and IL-6 (25-71 %), in human macrophage-like cells. In monocytes, they tended to act additively on cytokine mRNA and reduced IL-12/23p40 (51 %) secretion. In an ex-vivo inflamed human skin organ culture, MTBI (1 µg/ml) reduced the secretion of IL-1 (39 %) and IL-6 (32 %). Moreover, 2/8 and 3/8 of the MTBI- and SFN-treated psoriasiform SCID mice, respectively, recovered partially or entirely from the psoriasiform process. CONCLUSIONS: Results from these models indicate the potential of rocket seed ITCs as biological agents in the therapy of psoriasis and inflammation-related skin diseases.

Variation in Gut Microbiota Composition is Associated with Sleep Quality and Cognitive Performance in Older Adults with Insomnia.

Purpose: Insomnia, a chronic condition affecting 50% of older adults, is often accompanied by cognitive decline. The mechanism underlying this comorbidity is not fully understood. A growing literature suggests the importance of gut microbiota for brain function. We tested associations between sleep quality and cognitive performance with gut microbiota in older adults with insomnia. Patients and Methods: Seventy-two older adults with insomnia (age 73.2 ± 5.73 years, 56 females) provided stool samples for gut microbial sequencing. Microbiota profile was determined using the DADA2 bioinformatics pipeline. Cognition was assessed with the Cambridge Neuropsychological Test Automated Battery. Objective sleep quality was monitored by a two-week actigraphic recording, and participants completed the Insomnia Severity Index (ISI). We used partial canonical correspondence analysis (pCCA) to examine the relative contribution of insomnia, based on actigraphic sleep efficiency (SE) and ISI, and of cognitive status, based on the Multitasking test of Median Reaction Latency (MTTLMD) and the Spatial Working Memory Between Errors (SWMBE), to variance in microbiota composition. We used Pearson correlations to correlate insomnia and cognitive status parameters with microbiota amplicon sequence variants, genera, and families. Results: The pCCA revealed that sleep quality and cognitive performance explained a variation of 7.5-7.9% in gut microbiota composition in older adults with insomnia. Correlation analysis demonstrated that Lachnoclostridium (genus) correlates positively with SE (r=0.42; P=0.05) and negatively with MTTLMD (r=-0.29; P=0.03), whereas Blautia (genus) correlates negatively with MTTLMD (r=-0.31; P=0.01). Conclusion: Findings demonstrate the associations of sleep quality and cognitive performance with variance in gut microbiota composition and with specific genus abundance in older adults with insomnia. Further studies should validate the findings, determine causal relationships, and evaluate potential interventions for the comorbidity of insomnia and cognitive impairment in older adults with insomnia.

Increased physical activity improves gut microbiota composition and reduces short-chain fatty acid concentrations in older adults with insomnia.

Physical activity (PA) can improve functional abilities, well-being, and independence in older adults with insomnia. Studies have shown that PA may be linked to changes in the gut microbiota composition and its metabolites' concentrations. This association among older adults with insomnia, however, is yet to be determined. We explored the relationships between physical activity (PA) levels, gut microbiota composition, and short-chain fatty acid (SCFA) levels in this population. Forty-nine community-dwelling adults with insomnia symptoms, aged 65 and older, participated in this study. Their average daily step-count and sleep continuity measures over a two-week period were calculated based on Actigraphic recordings. Each participant provided fecal samples for the microbiome and SCFA analyses, anthropometric measures, and information via questionnaires on medical history and food consumption. The gut microbiota composition and SCFA concentrations were determined by next-generation sequencing and Gas chromatography-mass spectrometry, respectively. Participants were divided into two groups (more and less active) according to their median step/day count. We compared the microbiota abundance and SCFA concentrations between groups and performed correlation analysis between gut microbiota abundances and study variables. Different microbiota taxa in each PA group and increased SCFAs in feces of less active individuals were found. Changes in step counts were positively or negatively associated with the relative abundance of 19 ASVs, 3 microorganisms at the family level, and 11 microorganisms at the genus level. Furthermore, significant associations were discovered among physical activity, gut microbiota, SCFAs, and sleep parameters. Our findings provide new insights on the relationship between PA, gut microbiota composition, and primary metabolites in older adults with insomnia.

Glabridin, a phytoestrogen from licorice root, up-regulates manganese superoxide dismutase, catalase and paraoxonase 2 under glucose stress.

The risk of death from cardiovascular diseases (CVDs), which are exacerbated by oxidative stress, is higher in diabetic women. This phenomenon has been attributed to the loss of estradiol-vascular protection. Such knowledge led us to examine the potential of glabridin, a phytoestrogen, to substitute estradiol up-regulation of antioxidant enzymes under high glucose conditions. Chronic glucose stress was found to down-regulate catalase (CAT) and paraoxonase 2 (PON2) mRNA expression by 20% and 17%, respectively, and to decrease PON2 activity by 83% in macrophages. Inflammatory conditions had an additive effect on PON2 expression in a time-dependent manner. Treatment with glabridin, under high glucose stress, increased PON2 activity by 60% and up-regulated its mRNA expression by 3.5 fold. Furthermore, glabridin up-regulated the expression of manganese superoxide dismutase (Mn-SOD) and CAT in monocytes. In conclusion, glabridin has the potential of strengthening the antioxidant defense mechanism and may serve as an antiatherogenic agent in diabetes.

Mice held at an environmental photic cycle oscillating at their tau-like period length do not show the high-fat diet-induced obesity that develops under the 24-hour photic cycle.

Circadian disruptions precede high-fat diet (HFD)-induced obesity (DIO). Deviation of the endogenous circadian rhythm period length (tau) from 24 hours correlates with mice inter-strain DIO under the 24-hour light-dark cycle (T-cycle). Additionally, entrainment to a tau-resembling T-cycle attenuates DIO, to some extent, in muted mice. These phenomena suggest that entrainment to a 24-hour T-cycle promotes DIO beyond that expected from the HFD-induced metabolic disruptions. However, the hypothesis that entrainment to a tau-resembling T-cycle attenuates DIO has not been tested in wild-type mice. Therefore, we examined, in newborn female FVB/N mice, whether DIO found under their 'regular' 24-hour T-cycle is attenuated under a T-cycle oscillating at their tau-resembling period of 23.7 h, which is diverted from 24 hours by only 0.3 h. Compared to mice fed a low-fat diet, those fed an HFD under the 24-hour T-cycle showed a disrupted pattern of circadian locomotor activity prior to DIO onset. Both these phenomena were absent under the tau-like T-cycle. DIO developed under the 24-hour T-cycle despite similar caloric intake, and was associated with the lower locomotor activity of HFD-fed mice compared to the other mouse groups. These results demonstrated that DIO is secondary to HFD-induced circadian disruptions that are not harmonized by the strongest Zeitgeber (light-dark cycle) when oscillating at a period that diverts by as little as ca. 0.3-h from tau. More importantly, imposing a light-dark cycle oscillating at a tau-like period length, which enhances entrainment and presumably reinforces endogenous circadian rhythms, prevented HFD-induced circadian disruptions and enabled tighter control of energy homeostasis, as manifested by the absence of DIO, even under ad-lib HFD feeding. These results support the identification of tau-related biomarkers, which may be considered as risk-factors for DIO. Moreover, these findings may promote the development of clock-related pharmaceutical interventions that will reduce the gap between tau and 24 hours, and increase the robustness of the endogenous and entrained circadian rhythms. This will enable reducing DIO, even without caloric restriction or time-restricted feeding.

The effect of probiotic supplementation on performance, inflammatory markers and gastro-intestinal symptoms in elite road cyclists.

BACKGROUND: Elite athletes may suffer from impaired immune function and gastro-intestinal (GI) symptoms, which may affect their health and may impede their performance. These symptoms may be reduced by multi-strain probiotic supplementation. Therefore, the aim of the current study is to examine the effects of probiotic supplementation on aerobic fitness characteristics, inflammatory markers and incidence and severity of GI symptoms in elite cyclists. METHODS: Twenty-seven male cyclists, ranked elite or category 1 level competitions, were randomly assigned to a multi-strain probiotic-supplemented group (E, n = 11) or placebo group (C, n = 16). All participants visited the laboratory at the beginning of the study and following 90 d of supplementation/placebo. Prior to testing, all participants completed a GI symptoms questionnaire and underwent physical and medical examination, and anthropometric measurements. Venous blood was drawn for inflammatory markers analysis. The cyclists then underwent maximal oxygen consumption (VO2max) test and time-to-fatigue (TTF) test at 85 % of maximal power, 3 h following the VO2max test. All testing procedures were repeated after 90 d of probiotic / placebo treatment (double blind design). RESULTS: Lower incidence of nausea, belching, and vomiting (P < 0.05) at rest, and decreased incidence of GI symptoms during training were found in E group vs. C Group, respectively (∆GI -0.27 ± 0.47 % vs. 0.08 ± 0.29 %, P = 0.03), no significant changes were observed in the incidence of total overall GI symptoms (∆GI -5.6 ± 14.7 % vs. 2.6 ± 11.6 %, P = 0.602) Mean rate of perceived exertion (RPE) values during the TTF were lower in E group (∆RPE: -0.3 ± 0.9 vs. 0.8 ± 1.5, P = 0.04). No significant changes were measured between and within groups in VO2max and TTF values, mean levels of C-reactive protein (CRP), IL-6-and tumor necrosis factor alpha (TNFα) values following treatment. CONCLUSIONS: Probiotics supplementation may have beneficial effects on GI symptoms in elite cyclists. Future studies, using higher doses and during different training seasons, might help understanding the effects of probiotic supplementation on elite athletes' health and performance. TRIAL REGISTRATION: NIH clinicaltrial.gov #NCT02756221 Registered 25 April 2016.

Associations between fecal short-chain fatty acids and sleep continuity in older adults with insomnia symptoms.

Insomnia is a disorder characterized by difficulty falling asleep and poor sleep continuity and is associated with increased risks for physical and cognitive decline. Insomnia with short sleep duration is considered the most biologically severe phenotype of the disorder. Evidence suggests that short-chain fatty acids (SCFAs), the main byproducts of fiber fermentation in the gut, may affect sleep via gut-brain communications. This study explores associations between SCFAs and sleep continuity and compares SCFA concentrations in short vs. normal sleep insomnia phenotypes in older adults. Fifty-nine participants with insomnia symptoms (≥ 65 years), completed 2 weeks of objective sleep monitoring (actigraphy), and were divided into short and normal sleep duration phenotypes via cluster analysis. Sleep measures included total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), and wake after sleep onset (WASO). Stool samples were collected and fecal SCFA concentrations were determined by gas-chromatography-mass-spectrometry (GCMS). Higher concentrations of acetate, butyrate, and propionate, and total SCFAs, were associated with lower SE and longer SOL after controlling for Body Mass Index (BMI). Concentrations were higher in the short sleep duration phenotype. Age, BMI, TST, and SOL explained 40.7% of the variance in total SCFAs. Findings contribute to understanding pathways along the gut-brain axis and may lead to the use of SCFAs as biomarkers of insomnia phenotypes.

Unique Trans-fatty Acid Profile in Children With Attention Deficit Hyperactivity Disorder.

Background: Attention deficit hyperactivity disorder (ADHD) is the most common developmental disorder in children. Studies suggest an association between fatty acids composition and ADHD pathogenesis. We aimed to investigate whether children diagnosed with ADHD present unique fatty acid profiles in red blood cells (RBC), as compared to children without ADHD. Method: We examined 60 children aged 6-14 years, out of which 32 were diagnosed with ADHD, and 28 were not. Blood was collected from all children to quantify an array of 26 fatty acids from RBC membranes. Fatty acid methyl esters were generated by acid transesterification and analyzed by gas chromatography. Results: We found that children with ADHD presented unique fatty acid profiles on RBC membranes with significantly higher levels of most of the trans-fatty acids (Total trans-fatty acids 0.64 ± 0.21 vs. 0.49 ± 0.18 p = 0.003) and lower levels of docosahexaenoic acid (DHA), as compared to controls (4.06 ± 0.79 vs. 4.68 ± 1.37 p = 0.040). Additionally, total trans-fatty acids were higher in children with extremely severe clinical ADHD condition score, as compared to milder ADHD scores and to control children (0.72 ± 0.18, 0.64 ± 0.20, 0.61 ± 0.22, 0.49 ± 0.18, p = 0.010, accordingly). Conclusion: Children with ADHD have higher levels of trans-fatty acids in RBCs, compared to children without ADHD. This study points to a possible link between trans-fatty acids and ADHD. Understanding these findings and the clinical meaning will potentially contribute to a more targeted dietary intervention.

Loneliness, Malnutrition and Change in Subjective Age among Older Adults during COVID-19 Pandemic.

Objectives: We examined the effect of loneliness and the role of two mediating factors, depressive symptoms and malnutrition on subjective age among older adults during the 2020 COVID-19 pandemic, and explored how the pandemic is affecting subjective age. Design: A convenience sample of 201 older adults aged 65 and over was interviewed. Using bootstrapping, we tested the strength and significance of the indirect effect of depressive symptoms and malnutrition (mediators) on the relationship between feelings of loneliness and subjective age. Results: The relationship between feelings of loneliness and subjective age during the COVID-19 pandemic was mediated by malnutrition, but not by depressive symptoms. In addition, the participants felt older during the COVID-19 pandemic compared with the preceding period. Conclusions: An association was found among feelings of loneliness, malnutrition, and subjective age. To overcome these feelings in times of crisis like the pandemic, it is essential to develop new communication methods (technologies for managing and addressing the needs of the older population; technologies to encourage social engagement, and technologies for managing and providing remote medical services) for and with older adults that are effective in reducing loneliness, and to promote good nutrition. Possible practical solutions include new social network technologies for reducing loneliness combined with continued reliance on phone communication as an intervention of psychological support to promote a healthy lifestyle and prevent malnutrition.

Microbial signature in IgE-mediated food allergies.

BACKGROUND: Multiple studies suggest a key role for gut microbiota in IgE-mediated food allergy (FA) development, but to date, none has studied it in the persistent state. METHODS: To characterize the gut microbiota composition and short-chain fatty acid (SCFAs) profiles associated with major food allergy groups, we recruited 233 patients with FA including milk (N = 66), sesame (N = 38), peanut (N = 71), and tree nuts (N = 58), and non-allergic controls (N = 58). DNA was isolated from fecal samples, and 16S rRNA gene sequences were analyzed. SCFAs in stool were analyzed from patients with a single allergy (N = 84) and controls (N = 31). RESULTS: The gut microbiota composition of allergic patients was significantly different compared to age-matched controls both in α-diversity and ß-diversity. Distinct microbial signatures were noted for FA to different foods. Prevotella copri (P. copri) was the most overrepresented species in non-allergic controls. SCFAs levels were significantly higher in the non-allergic compared to the FA groups, whereas P. copri significantly correlated with all three SCFAs. We used these microbial differences to distinguish between FA patients and non-allergic healthy controls with an area under the curve of 0.90, and for the classification of FA patients according to their FA types using a supervised learning algorithm. Bacteroides and P. copri were identified as taxa potentially contributing to KEGG acetate-related pathways enriched in non-allergic compared to FA. In addition, overall pathway dissimilarities were found among different FAs. CONCLUSIONS: Our results demonstrate a link between IgE-mediated FA and the composition and metabolic activity of the gut microbiota.

Potential skin antiinflammatory effects of 4-methylthiobutylisothiocyanate (MTBI) isolated from rocket (Eruca sativa) seeds.

Isothiocyanates (ITCs), which are organosulfur compounds present in cruciferous vegetables, have anticarcinogenic, antiinflammatory, and antiproliferative activities. These biological activities, and the knowledge that rocket seed (Eruca sativa) extract is used in skin disorders in traditional Middle Eastern medicine, led to the isolation and assessment of 4-methylthiobutylisothiocyanate (MTBI), the major ITC in rocket seeds, for its potential in the prevention of inflammatory skin diseases, such as psoriasis. MTBI was found to depress the growth of activated keratinocytes and to arrest the activated THP-1 monocytes in the G2 stage. Both MTBI and its oxidized derivative sulforaphane (SFN), which was found in the rocket seed at a low concentration, downregulated the expression of the proinflammatory genes, tumor necrosis factor (TNF)-alpha and interleukin (IL)-12/23 p40, as well as that of intercellular adhesion molecule-1, in activated THP-1 cells. These results demonstrate that MTBI may deter the inflammation process, as has been reported for SFN. Furthermore, pretreatment with MTBI hindered the induction of the inflammatory state in the THP-1 cells, as shown by the inhibition of cytokine mRNA expression of IL-1beta, IL-12/23 p40, and TNF-alpha. Overall, our results imply that MTBI may represent a new family of natural compounds possessing significant skin inflammation-preventive activities.