Ketogenic diets may modulate mood disorders, but epidemiological evidence for the dietary ketogenic ratio (DKR)-a ketogenic adherence biomarker-remains limited. We investigated the association between DKR and depressive symptoms,while exploring potential mechanisms involving inflammation and body composition.

Using NHANES 2007-2018 data (30,133 U.S. adults), depressive symptoms were defined by a Patient Health Questionnaire-9 (PHQ-9) score of ≥10. DKR was calculated using the formula: (0.9 × fat +0.46 × protein) / (0.1 × fat +0.58 × protein + carbohydrates). Multivariable logistic regression adjusted for 19 confounders (demographics, comorbidities, lifestyle), restricted cubic splines, and mediation analyses. Robustness was assessed via propensity score matching.

A higher DKR showed a linear dose-response reduction in depressive symptoms risk (OR = 0.13 per unit increase, 95 % CI:0.03-0.48, p = 0.003; Q4 vs. Q1 OR = 0.59, p = 0.012).. Mediation analyses revealed opposing effects: traditional obesity metrics (BMI, waist circumference, BRI) mediated adverse associations (-14.69 % to -11.43 %), while the body shape index (ABSI) displayed protective mediation (11.03 %, p < 0.001). None of the 12 inflammatory markers showed significant mediation, as indicated by p-values >0.05 or mediation proportions <5 %.

DKR inversely associates with depressive symptoms risk, potentially through body composition remodeling rather than anti-inflammatory pathways. ABSI served as a positive mediator in the inverse association between DKR and depressive symptoms. Longitudinal studies are required to confirm causality and clinical utility of DKR.

About one-third of epilepsies are resistant to antiepileptic drugs; thus, uncovering new pathways in the pathophysiology of epilepsy can reduce the global disease burden. Probiotics are live, non-pathogenic microorganisms that benefit the host by regulating the gut microbiome. This review aims to study the effect of probiotics and ketogenic diets on gut microbiota and their potential as a therapy for epilepsy. We conducted a systematic search of the databases PubMed, Scopus, Embase, and the Web of Science for pertinent studies that have been published. Our search methodology was meticulously structured to be exhaustive, integrating targeted keywords and Boolean operators to guarantee the acquisition of all potentially pertinent articles. Probiotics interact with the gut microbiome, balance its composition, and influence the gut-brain axis. Moreover, they reduce neuroinflammation and oxidative stress. The ketogenic diet (KD) affects gut bacteria, influencing neurotransmitter levels and short-chain fatty acids (SCFAs), which play a role in the gut-brain axis. Studies have shown the positive effects of various probiotics in animal models of epilepsy. They demonstrate improvements in seizure activity, anxiety, and neuroinflammation. In human studies, probiotics reduced seizure frequency and enhanced quality of life in patients with drug-resistant epilepsy. We believe using probiotics or dietary interventions like KD could be a promising therapeutic strategy for managing epilepsy. This could reduce seizure frequency and make life better for patients with epilepsy.

Febrile seizures (FS) is the most common type of convulsion in infants and preschool children. This study aimed to investigate the associations between gut microbiota abundance, plasma metabolites, circulating cytokines, and FS. Summary statistics of 211 gut microbiota traits, 1,400 plasma metabolite traits, 91 circulating cytokine traits, and FS were obtained from publicly available genome-wide association studies. Two-sample Mendelian randomization (MR) analysis and causality was inferred using Inverse variance-weighted (IVW), Weighted median, MR-Egger, simple mode-based estimate and weighted mode-based estimate 5 methods. Several sensitivity analyses were also used to ensure the robustness of the results. Furthermore, mediation analysis was used to determine the pathway from gut microbiota to FS mediated by plasma metabolites and circulating cytokines. MR revealed the associations of 1 gut microbiota (phylum Verrucomicrobia), 4 circulating cytokines and 50 plasma metabolites on FS. Based on the known pathogenic metabolites, we observed that the tryptophan, androgen, and sphingolipids pathways are associated with FS. Mediation analysis revealed 1 strongly documented plasma metabolite (Ascorbic acid 2-sulfate) as a mediator linking "gut microbiota to plasma metabolite to FS". Sensitivity analysis was represented no heterogeneity or pleiotropy in this study.Our study provides some causal evidence concerning the effects of the gut microbiota, circulating cytokines, and plasma metabolites on FS, which needs to be verified in randomized controlled trials. These biomarkers provide new insights into the underlying mechanisms of FS and contribute to its prevention, diagnosis, and treatment.

Helicobacter pylori (H. pylori) causes chronic infection in more than half of the population worldwide. Accumulating body of evidence indicates the possible role of H. Pylori infection in extra-intestinal health problems, including epilepsy. This study aims to investigate the efficacy of treating H. pylori infection on seizure frequency among children with drug-resistant idiopathic generalized epilepsy (IGE).

A parallel, two-arm, open-label, randomized controlled trial was conducted on 126 children with drug-resistant IGE and positive H. pylori stool antigen test who were randomly assigned to study and comparison groups in 1.2:1 ratio. Only the study group received H. pylori eradication therapy (esomeprazole, amoxicillin, and clarithromycin) for two weeks. The primary outcome was seizure improvement (≥ 50% seizure frequency reduction compared with baseline) after 2.5 months. Secondary outcomes were occurrence of status epilepticus, escalation of antiseizure medication (ASMs), and adverse effects. Outcomes between the two groups were compared using Chi-square/Fisher exact tests on an intention-to-treat principle. Logistic regression analysis was performed to investigate possible effects of baseline variables on primary outcome.

Seizure improvement occurred in 23 (33%) children in the study group compared with seven (12%) children in the comparison group (Risk ratio [RR] 2.7, 95% confidence interval [CI]: 1.3-5.9; p 0.006). The study group had lower occurrence of status epilepticus (2.9% vs. 14%; RR 0.21, 95%CI: 0.05-0.93; p 0.042) and lesser need for ASMs escalation (4.4% vs. 19.3%; RR 0.23, 95%CI: 0.07-0.77; p 0.010). Adverse effects were more frequent among subjects in the study group, including nausea (15.9% vs. 10.5%) vomiting (8.7% vs. 3.5%), diarrhea (11.6% vs. 5.3%), and skin rash (4.4% vs. 1.8%), but the differences were not statistically significant (p > 0.05). None of baseline participants' variables was significantly associated with the primary outcome.

Treating H. pylori infection may improve seizure control in children with drug-resistant IGE, but further studies are warranted to confirm our findings and explore mechanisms behind seizure improvement following H. pylori eradication therapy.

Registered on www.

gov (identifier: NCT05297695) on 17 March 2022. https://clinicaltrials.gov/study/NCT05297695 .

The gut-brain axis plays an integral role in maintaining overall health, with growing evidence suggesting its impact on the development of various neuropsychiatric disorders, including depression. This review explores the complex relationship between gut microbiota and glutamate (Glu) regulation, highlighting its effect on brain health, particularly in the context of depression following certain neurological insults. We discuss how microbial populations can either facilitate or limit Glu uptake, influencing its bioavailability and predisposing to neuroinflammation and neurotoxicity. Additionally, we examine the role of gut metabolites and their influence on the blood-brain barrier and neurotransmitter systems involved in mood regulation. The therapeutic potential of microbiome-targeted interventions, such as fecal microbiota transplantation, is also highlighted. While much research has explored the role of Glu in major depressive disorders and other neurological diseases, the contribution of gut microbiota in post-neurological depression remains underexplored. Future research should focus on explaining the mechanisms linking the gut microbiota to neuropsychiatric outcomes, particularly in conditions such as post-stroke depression, post-traumatic brain-injury depression, and epilepsy-associated depression. Systematic reviews and human clinical studies are needed to establish causal relationships and assess the efficacy of microbiome-targeted therapies in improving the neuropsychiatric sequalae after neurological insults.

Epilepsy is a common neurological condition characterized by abnormal neuronal activity, often leading to cellular damage and death. There is evidence to suggest that lipid imbalances resulting in cellular death play a key role in the development of epilepsy, including changes in triglycerides, cholesterol, sphingolipids, phospholipids, lipid droplets, and bile acids (BAs). Disrupted lipid metabolism acts as a crucial pathological mechanism in epilepsy, potentially linked to processes such as cellular ferroptosis, lipophagy, and immune modulation of gut microbiota (thus influencing the gut-brain axis). Understanding these mechanisms could open up new avenues for epilepsy treatment. This study investigates the association between disturbances in lipid metabolism and the onset of epilepsy.

Human milk (HM) is recognized as an ideal source of nutrition for newborns; as a result, its multiple bioactive molecules can support the growth of healthy newborns and reduce the risk of mortality and diseases such as asthma, respiratory infections, diabetes (type 1 and 2), and gastrointestinal disorders such as ulcerative colitis and Crohn's disease. Furthermore, it can reduce the severity of necrotizing enterocolitis (NEC) in preterm infants. Moreover, human milk oligosaccharides (HMOs) present in breast milk show an immunomodulatory, prebiotic, and neurodevelopmental effect that supports the microbiota-gut-brain axis.

This study examined the state-of-the-art research, using keywords such as "breastfeeding", "human milk oligosaccharides", "microbiota-gut-brain axis", "infants", and "malnutrition". The literature review was conducted by selecting articles between 2013 and 2024, as the most recent ones. The databases used were Web Science, PubMed, and Scopus.

We found multiple studies examining the composition of HM and infant formula (IF). However, further longitudinal studies and randomized control trials (RCTs) are needed to better understand the clinical outcomes that bioactive components exert on healthy and hospitalized children and how, in conditions of malnutrition, it is necessary to support the growth of the newborn.

In this review, we affirm the importance of human milk and, through it, the modulation of the microbiota and the neuroprotective role in newborns, determining the health of the following years of life.

The microbiota-gut-brain axis (MGBA) is a central nexus that integrates higher cognitive and emotional centers of the central nervous system (CNS) within the intricate functioning of the intestine. Accumulating evidence suggests that dysbiosis in the taxonomic diversity of gut flora plays a salient role in the progression of epilepsy and comorbid secondary complications.

In the current study, we investigated the impact of long-term oral bacteriotherapy (probiotics; 10 mL/kg; 109 colony-forming unit/ml) as an adjunctive treatment intervention with brivaracetam (BRV; 10 mg/kg) over 21 days on pentylenetetrazole (PTZ) induced augmented epileptic response and associated electrographical and behavioral perturbations in mice. Moreover, we also unveiled antioxidant capacity and histopathologic changes in treated versus non-treated animals.

Results revealed combination increases seizure threshold and prevented high ictal spiking. Additionally, it alleviated PTZ-induced neuropsychiatric disturbances such as anxiety and depressive-like phenotype along with cognitive deficits. Furthermore, dual therapy prompted physiological oxidant/antioxidant balance as evidenced by increased activity of antioxidant enzymes (SOD and catalase) and reduced levels of oxidative stressor (MDA). This therapeutic intervention with commensal species suppressed network-driven neuroinflammation and preserved normal cytoarchitecture with intact morphology in the pyramidal layers of cornu ammonis (CA1 and CA3).

Our study provides supporting evidence for the use of probiotics as adjunctive therapy with anti-seizure medications to modulate epileptogenic processes and related multimorbidities, particularly in individuals with drug-resistant seizures.

Emerging research into the human microbiome, an intricate ecosystem of microorganisms residing in and on our bodies, reveals that it plays a pivotal role in maintaining our health, highlighting the potential for microbiome-based interventions to prevent, diagnose, treat, and manage a myriad of diseases. The objective of this review is to highlight the importance of microbiome studies in enhancing our understanding of rare genetic epilepsy and related neurological disorders. Studies suggest that the gut microbiome, acting through the gut-brain axis, impacts the development and severity of epileptic conditions in children. Disruptions in microbial composition can affect neurotransmitter systems, inflammatory responses, and immune regulation, which are all critical factors in the pathogenesis of epilepsy. This growing body of evidence points to the potential of microbiome-targeted therapies, such as probiotics or dietary modifications, as innovative approaches to managing epilepsy. By harnessing the power of the microbiome, we stand to develop more effective and personalized treatment strategies for children affected by this disease and other rare neurological diseases.

The increasing prevalence of neurological disorders such as Alzheimer's, Parkinson's, and multiple sclerosis presents a significant global health challenge. Despite extensive research, the precise mechanisms underlying these conditions remain elusive, with current treatments primarily addressing symptoms rather than root causes. Emerging evidence suggests that gut permeability and the kynurenine pathway are involved in the pathogenesis of these neurological conditions, offering promising targets for novel therapeutic and preventive strategies. Gut permeability refers to the intestinal lining's ability to selectively allow essential nutrients into the bloodstream while blocking harmful substances. Various factors, including poor diet, stress, infections, and genetic predispositions, can compromise gut integrity, leading to increased permeability. This condition facilitates the translocation of toxins and bacteria into systemic circulation, triggering widespread inflammation that impacts neurological health via the gut-brain axis. The gut-brain axis (GBA) is a complex communication network between the gut and the central nervous system. Dysbiosis, an imbalance in the gut microbiota, can increase gut permeability and systemic inflammation, exacerbating neuroinflammation-a key factor in neurological disorders. The kynurenine pathway, the primary route for tryptophan metabolism, is significantly implicated in this process. Dysregulation of the kynurenine pathway in the context of inflammation leads to the production of neurotoxic metabolites, such as quinolinic acid, which contribute to neuronal damage and the progression of neurological disorders. This narrative review highlights the potential and progress in understanding these mechanisms. Interventions targeting the kynurenine pathway and maintaining a balanced gut microbiota through diet, probiotics, and lifestyle modifications show promise in reducing neuroinflammation and supporting brain health. In addition, pharmacological approaches aimed at modulating the kynurenine pathway directly, such as inhibitors of indoleamine 2,3-dioxygenase, offer potential avenues for new treatments. Understanding and targeting these interconnected pathways are crucial for developing effective strategies to prevent and manage neurological disorders.

Functional gastrointestinal disorders (FGIDs) and inflammatory bowel disease (IBD) are common clinical disorders characterized by recurrent diarrhea and abdominal pain. Although their pathogenesis has not been fully clarified, disruptions in intestinal motility and immune function are widely accepted as contributing factors to both conditions, and the brain-gut axis plays a key role in these processes. Traditional Chinese Medicine (TCM) employs a holistic approach to treatment, considers spleen and stomach impairments and liver abnormality the main pathogenesis of these two diseases, and offers a unique therapeutic strategy that targets these interconnected pathways. Clinical evidence shows the great potential of TCM in treating FGIDs and IBD. This study presents a systematic description of the pathological mechanisms of FGIDs and IBD in the context of the brain-gut axis, discusses clinical and preclinical studies on TCM and acupuncture for the treatment of these diseases, and summarizes TCM targets and pathways for the treatment of FGIDs and IBD, integrating ancient wisdom with contemporary biomedical insights. The alleviating effects of TCM on FGID and IBD symptoms are mainly mediated through the modulation of intestinal immunity and inflammation, sensory transmission, neuroendocrine-immune network, and microbiota and their metabolism through brain-gut axis mechanisms. TCM may be a promising treatment option in controlling FGIDs and IBD; however, further high-quality research is required. This review provides a reference for an in-depth exploration of the interventional effects and mechanisms of TCM in FGIDs and IBD, underscoring TCM's potential to recalibrate the dysregulated brain-gut axis in FGIDs and IBD.

The gut-brain axis (GBA) is a crucial communication network linking the gastrointestinal (GI) tract and the central nervous system (CNS). The gut microbiota significantly influences metabolic, immune, and neural functions by generating a diverse array of bioactive compounds that modulate brain function and maintain homeostasis. A pivotal mechanism in this communication is the kynurenine pathway, which metabolises tryptophan into various derivatives, including neuroactive and neurotoxic compounds. Alterations in gut microbiota composition can increase gut permeability, triggering inflammation and neuroinflammation, and contributing to neuropsychiatric disorders. This review elucidates the mechanisms by which changes in gut permeability may lead to systemic inflammation and neuroinflammation, with a focus on the kynurenine pathway. We explore how probiotics can modulate the kynurenine pathway and reduce neuroinflammation, highlighting their potential as therapeutic interventions for neuropsychiatric disorders. The review integrates experimental data, discusses the balance between neurotoxic and neuroprotective kynurenine metabolites, and examines the role of probiotics in regulating inflammation, cognitive development, and gut-brain axis functions. The insights provided aim to guide future research and therapeutic strategies for mitigating GI complaints and their neurological consequences.

In this review, we aim to summarize recent information about the association of B vitamins with immune-metabolic aspects of depression and their connection with the gut-brain axis.

B vitamins may alter depressive symptoms by many various mechanisms such as reducing oxidative stress, inflammation, gut permeability, controlling epigenetics, modifying the microbiome, and stimulating it to produce many beneficial substances such as short-chain fatty acids or neurotransmitters: norepinephrine, dopamine, serotonin, gamma-aminobutyric acid, and acetylcholine.

Specifically, vitamins B1 (thiamine), B6 (pyridoxine), B9 (folate), and B12 (cyanocobalamin), B2 (riboflavin) have been observed to affect depression. Given probiotic's capability to produce vitamins from the B group, and modify intestinal function, inflammation, or metabolic dysfunction, their supplementation might be a possible treatment method for the immunometabolic form of depression. Thus, the intake of certain probiotic bacterial strains simultaneously with controlling the required daily intake of B vitamins may positively affect the course of depression. Circulating B vitamins metabolite levels, especially B9, B12, and B6 may also be biomarkers of depression. Further investigation is needed to find stronger evidence on this topic.

The interplay between inflammation, immune dysregulation, and the onset of neurological disorders, including epilepsy, has become increasingly recognized. Interleukin (IL)-6, a pro-inflammatory cytokine, is suspected to not only mediate traditional inflammatory pathways but also contribute to neuroinflammatory responses that could underpin neuropsychiatric symptoms and broader psychiatric disorders in epilepsy patients. The role of IL-6 receptor (IL6R) blockade presents an intriguing target for therapeutic intervention due to its potential to attenuate these processes.

To explore the potential of IL6R blockade in reducing the risk of epilepsy and investigate whether this pathway might also influence associated psychiatric and neuropsychiatric conditions due to neuroinflammation.

Mendelian randomization (MR) analysis employing single nucleotide polymorphisms (SNPs) in the vicinity of the IL6R gene (total individuals = 408225) was used to evaluate the putative causal relationship between IL6R blockade and epilepsy (total cases/controls = 12891/312803), focal epilepsy (cases/controls = 7526/399290), and generalized epilepsy (cases/controls = 1413/399287). SNP weights were determined by their effect on C-reactive protein (CRP) levels and integrated using inverse variance-weighted meta-analysis as surrogates for IL6R effects. To address potential outlier and pleiotropic influences, sensitivity analyses were conducted employing a variety of MR methods under different modeling assumptions.

The genetic simulation targeting IL6R blockade revealed a modest but significant reduction in overall epilepsy risk [inverse variance weighting: Odds ratio (OR): 0.827; 95% confidence interval (CI): 0.685-1.000; P = 0.05]. Subtype analysis showed variability, with no significant effect observed in generalized, focal, or specific childhood and juvenile epilepsy forms. Beyond the primary inflammatory marker CRP, the findings also suggested potential non-inflammatory pathways mediated by IL-6 signaling contributing to the neurobiological landscape of epilepsy, hinting at possible links to neuroinflammation, psychiatric symptoms, and associated mental disorders.

The investigation underscored a tentative causal relationship between IL6R blockade and decreased epilepsy incidence, likely mediated via complex neuroinflammatory pathways. These results encouraged further in-depth studies involving larger cohorts and multifaceted psychiatric assessments to corroborate these findings and more thoroughly delineate the neuro-psychiatric implications of IL-6 signaling in epilepsy. The exploration of IL6R blockade could herald a novel therapeutic avenue not just for seizure management but also for addressing the broader psychiatric and cognitive disturbances often associated with epilepsy.

In the era of a steadily increasing lifespan, neurodegenerative diseases among the elderly present a significant therapeutic and socio-economic challenge. A properly balanced diet and microbiome diversity have been receiving increasing attention as targets for therapeutic interventions in neurodegeneration. Microbiota may affect cognitive function, neuronal survival and death, and gut dysbiosis was identified in Parkinson's disease (PD). Tryptophan (Trp), an essential amino acid, is degraded by microbiota and hosts numerous compounds with immune- and neuromodulating properties. This broad narrative review presents data supporting the concept that microbiota, the Trp-kynurenine (KYN) pathway and aryl hydrocarbon receptors (AhRs) form a triad involved in PD. A disturbed gut-brain axis allows the bidirectional spread of pro-inflammatory molecules and α-synuclein, which may contribute to the development/progression of the disease. We suggest that the peripheral levels of kynurenines and AhR ligands are strongly linked to the Trp metabolism in the gut and should be studied together with the composition of the microbiota. Such an approach can clearly delineate the sub-populations of PD patients manifesting with a disturbed microbiota-Trp-KYN-brain triad, who would benefit from modifications in the Trp metabolism. Analyses of the microbiome, Trp-KYN pathway metabolites and AhR signaling may shed light on the mechanisms of intestinal distress and identify new targets for the diagnosis and treatment in early-stage PD. Therapeutic interventions based on the combination of a well-defined food regimen, Trp and probiotics seem of potential benefit and require further experimental and clinical research.