Background/Objectives: The ketogenic diet (KD) is a dietary model that can impact metabolic health and microbiota and has been widely discussed in recent years. This study aimed to evaluate the effects of a 6-week KD on biochemical parameters, gut microbiota, and fecal short-chain fatty acids (SCFAs) in women with overweight/obesity. Methods: Overall, 15 women aged 26–46 years were included in this study. Blood samples, fecal samples, and anthropometric measurements were evaluated at the beginning and end of this study. Results: After KD, the mean body mass index decreased from 29.81 ± 4.74 to 27.12 ± 4.23 kg/m², and all decreases in anthropometric measurements were significant (p < 0.05). Fasting glucose, insulin, homeostasis model assessment of insulin resistance, hemoglobin A1C, urea, and creatinine levels decreased, whereas uric acid levels increased (p < 0.05). Furthermore, increased serum zonulin levels were noted (p = 0.001), whereas fecal butyrate, propionate, acetate, and total SCFA levels decreased (p < 0.05). When the changes in microbiota composition were examined, a decrease in beta diversity (p = 0.001) was observed. After the intervention, a statistically significant increase was noted in the Firmicutes/Bacteroidetes ratio (p = 0.001). Although Oscilibacter, Blautia, and Akkermensia relative abundances increased, Prevotella relative abundance and Bifidobacter abundance, which were the dominant genera before the KD, decreased. Moreover, the abundance of some pathogenic genera, including Escherichia, Klebsilella, and Listeria, increased. Conclusions: In healthy individuals, KD may cause significant changes in microbial composition, leading to dysbiosis and long-term adverse outcomes with changes in serum zonulin and fecal SCFA levels.

Background/Objectives: The role of the gut microbiome in the development and progression of many diseases has received increased attention in recent years. Boron, a trace mineral found in dietary sources, has attracted interest due to its unique electron depletion and coordination characteristics in chemistry, as well as its potential role in modulating the gut microbiota. This study investigates the effects of inorganic boron derivatives on the gut microbiota of mice. Methods: For three weeks, boric acid (BA), sodium pentaborate pentahydrate (NaB), and sodium perborate tetrahydrate (SPT) were dissolved (200 mg/kg each) in drinking water and administered to wild-type BALB/c mice. The composition of the gut microbiota was analyzed to determine the impact of these treatments. Results: The administration of BA significantly altered the composition of the gut microbiota, resulting in a rise in advantageous species such as Barnesiella and Alistipes. Additionally, there was a decrease in some taxa associated with inflammation and illness, such as Clostridium XIVb and Bilophila. Notable increases in genera like Treponema and Catellicoccus were observed, suggesting the potential of boron compounds to enrich microbial communities with unique metabolic functions. Conclusions: These findings indicate that boron compounds may have the potential to influence gut microbiota composition positively, offering potential prebiotic effects. Further research with additional analyses is necessary to fully understand the interaction between boron and microbiota and to explore the possibility of their use as prebiotic agents in clinical settings.

Pea3 transcription factor belongs to the PEA3 subfamily within the ETS domain transcription factor superfamily, and has been largely studied in relation to its role in breast cancer metastasis. Nonetheless, Pea3 plays a role not only in breast tumor, but also in other tissues with branching morphogenesis, including kidneys, blood vasculature, bronchi and the developing nervous system. Identification of Pea3 target promoters in these systems are important for a thorough understanding of how Pea3 functions. Present study particularly focuses on the identification of novel neuronal targets of Pea3 in a combinatorial approach, through curation, computational analysis and microarray studies in a neuronal model system, SH-SY5Y neuroblastoma cells. We not only show that quite a number of genes in cancer, immune system and cell cycle pathways, among many others, are either up- or down-regulated by Pea3, but also identify novel targets including ephrins and ephrin receptors, semaphorins, cell adhesion molecules, as well as metalloproteases such as kallikreins, to be among potential target promoters in neuronal systems. Our overall results indicate that rather than early stages of neurite extension and axonal guidance, Pea3 is more involved in target identification and synaptic maturation.

Objective: Drug‐resistant epilepsy (DRE) remains a clinical challenge, as therapies modifying disease trajectory are lacking. Increasing evidence implicates gut microbiota dysbiosis in epilepsy pathophysiology, with short‐chain fatty acids (SCFAs) emerging as key microbial metabolites with neuroprotective and anti‐inflammatory properties. Clinical studies show that people with DRE exhibit gut microbiota alterations that may impair fecal SCFAs production. Here, we investigated whether supplementation of SCFAs confers disease‐modifying effects in a preclinical model of DRE. Methods: Adult male mice were subjected to status epilepticus (SE) and subsequently treated with a balanced mixture of acetate, propionate, and butyrate, or vehicle. Seizure frequency and temporal progression were monitored for 70 days by electroencephalography (EEG). At the study end point, cognitive performance, brain and gut histopathology, and neuroinflammation were assessed, together with metabolomic profiling of feces and blood. Brain SCFA levels and receptor expression were also analyzed in mice and in brain tissue from individuals with DRE. Results: SCFA supplementation reduced the proportion of mice exhibiting a progressive phenotype and decreased the overall progression index (PI) 3‐fold, without significantly altering overall daily seizure frequency. Treatment reduced seizure clustering, improved cognitive deficits, restored hippocampal and intestinal alterations, and partially normalized cerebral SCFAs levels. Metabolomic profiling in epileptic mice and analysis of human epilepsy brain tissue support a mechanistic contribution of gut‐brain axis dysfunction to disease progression. Interpretation: These findings identify SCFAs supplementation as a therapeutic strategy capable of modifying disease trajectory in experimental DRE, with clear translational relevance. ANN NEUROL 2026