Attention-Deficit Hyperactivity Disorder (ADHD) is a prevalent neurodevelopmental disorder with complex genetic and environmental underpinnings. Emerging evidence suggests a significant role of gut microbiota in ADHD pathophysiology. This study investigates variations in gut microbiota composition and Short-Chain Fatty Acid (SCFA) profiles between children and adolescents with ADHD and healthy controls. The study included 42 ADHD patients and 31 healthy controls, aged 6–18 years. Fecal samples were analyzed for microbial composition using 16S rRNA gene sequencing and for SCFA profiles through gas chromatography-mass spectrometry (GC-MS). The study assessed both α and β diversity of gut microbiota and quantified various SCFAs to compare between the groups. ADHD subjects demonstrated significantly reduced gut microbiota diversity, as indicated by lower α-diversity indices (Shannon index, Observed species, Faith PD index) and a trend towards significance in β-diversity (Weighted UniFrac). Notably, the ADHD group exhibited significantly lower levels of key SCFAs, including acetic, propionic, isobutyric, isovaleric, and valeric acids, highlighting a distinct microbial and metabolic profile in these individuals. This study uncovers significant alterations in gut microbiota and SCFA profiles in children with ADHD, compared to healthy controls. The observed changes in SCFAs, known for their associations with other behavioral and neurologic pathologies, and for their role in neural signaling. These findings offer a metabolite fingerprint that could potentially lead to novel diagnostic and treatment approaches for ADHD, emphasizing the importance of gut microbiota in the disorder’s pathogenesis and management.

Female αMUPA (alpha murine urokinase-like plasminogen activator) transgenic mice show increased lifespan, reduced body weight and food intake, and high-amplitude circadian rhythms with an endogenous period length ( tau ) of 24h, versus their wild types (WT) showing a 23.7-h tau . Our goal was to characterize αMUPA and WT male mice, and their in-strain sexual dimorphism, and to further understand the mechanisms underlying αMUPA’s longevity. Male αMUPA mice showed increased lifespan, reduced body weight and food intake, and aligned endogenous rhythm with a tau of 24.0h versus a tau <24h in WT. However, no differences were found when intake was corrected for metabolic mass in male αMUPA mice. αMUPA’s sexual dimorphism was damped or lacking in all studied traits, while WTs were sexually dimorphic, concluding that αMUPA’s transgene overrides sex-dependent mechanisms involved in lifespan and in energy and circadian homeostasis. As enhanced resonance between tau and external circadian cycle correlates with increased lifespan and reduced body weight in other species, including humans, αMUPA’s 24-h tau could contribute to their longevity. Focusing future research on the mechanistic interconnections between energy homeostasis, circadian homeostasis, sexual dimorphism, and aging, using αMUPA mice, may reveal mechanisms promoting reduced body weight and increased lifespan.

Energy drink (ED) consumption among Israeli-Arab adolescents is widespread. This study aimed to investigate the acute glycemic and insulin effects of EDs in healthy adolescents. Seventy-one Israeli-Arab adolescents (56% girls, average age 16.04 ± 1.03 years) participated in a non-randomized, case-controlled, open-label study. Participants consumed ED (n = 36) or a volume- and carbohydrate-matched non-caffeinated soft drink (SD, n = 35), followed by a 2 h glucose tolerance test. Blood glucose was measured at baseline and 15, 30, 60, and 120 min post-consumption (T0, T15, T30, T60 and T120, respectively). Serum insulin concentration and caffeine relative intensity were determined 45 min post-consumption (T45). Blood glucose levels peaked significantly at T15 and remained significantly higher at T30 in the ED group compared to the SD group (p = 0.005, p = 0.017, respectively). Insulin concentrations were substantially higher at T45 in the ED group (t [64] = 2.794, p = 0.001). This pattern was especially prominent in heavy ED consumers. A positive correlation emerged between the amount of caffeine consumed (mg/kg), blood glucose levels at T15 and T30, and insulin concentration at T45. This study is the first to demonstrate the glycemic and insulin responses to ED consumption in adolescents, suggesting that regulatory measures limiting ED sales to adolescents could improve their health.

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.

Epilepsy is a widespread neurological disorder that remains a critical global public health challenge. While numerous antiepileptic drugs (AEDs) are available, many patients either fail to achieve adequate seizure control or experience significant side effects. One promising alternative is pure cannabidiol (CBD), but using a whole cannabis extract may be equally effective and preferred for some patients. In the current study, we employed the pentylenetetrazole (PTZ)-induced hyperactivity model in zebrafish to compare the effects of CBD with various cannabis extracts. We evaluated three cannabis strains, each subjected to three different extraction methods, and benchmarked the results against the commercially available AED valproic acid (VPA). Our findings revealed that 5.7 µg/mL of CBD and 10 µg/mL of different extracts significantly reduced movement compared to PTZ and VPA. In addition, effective extracts produced effects similar to pure CBD despite containing much lower molecule levels. These results reinforced and expanded previous evidence supporting the clinical potential of both CBD and whole cannabis extracts for seizure control while suggesting a possible entourage effect. Further research is necessary to determine which patients may benefit more from pure CBD versus those who might prefer whole cannabis extracts.

Energy drink (ED) consumption among Israeli-Arab adolescents is widespread. This study aimed to investigate the acute glycemic and insulin effects of EDs in healthy adolescents. Seventy-one Israeli-Arab adolescents (56% girls, average age 16.04±1.03 years) participated in a non-randomized, case-controlled, open-label study. Participants consumed ED (n=36) or a volume- and carbohydrate-matched non-caffeinated soft drink (SD, n=35), followed by a 2 h glucose tolerance test. Blood glucose was measured at baseline and 15, 30, 60, and 120 minutes post-consumption (T0, T15, T30, T60 and T120, respectively). Serum insulin concentration and caffeine relative intensity were determined 45 minutes post-consumption (T45). Blood glucose levels peaked significantly at T15 and remained significantly higher at T30 in the ED group compared to the SD group (p=0.005, p=0.017, respectively). Insulin concentrations were substantially higher at T45 in the ED group (t[64]=2.794, p=0.001). This pattern was especially prominent in heavy ED consumers. A positive correlation emerged between the amount of caffeine consumed (mg/kg), blood glucose levels at T15 and T30, and insulin concentration at T45. This study is the first to demonstrate the glycemic and insulin responses to ED consumption in adolescents, suggesting that regulatory measures limiting ED sales to adolescents could improve their health.