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BackgroundVagal afferent neurons represent the key neurosensory branch of the gut-brain axis, which describes the bidirectional communication between the gastrointestinal system and the brain. These neurons are important for detecting and relaying sensory information from the periphery to the central nervous system to modulate feeding behavior, metabolism, and inflammation. Confounding variables complicate the process of isolating the role of the vagal afferents in mediating these physiological processes. Therefore, we developed a microfluidic model of the sensory branch of the gut-brain axis. We show that this microfluidic model successfully compartmentalizes the cell body and neurite terminals of the neurons, thereby simulates the anatomical layout of these neurons to more accurately study physiologically-relevant processes.MethodsWe implemented a primary rat vagal afferent neuron culture into a microfluidic platform consisting of two concentric chambers interconnected with radial microchannels. The microfluidic platform separated cell bodies from neurite terminals of vagal afferent neurons. We then introduced physiologically-relevant gastrointestinal effector molecules at the nerve terminals and assessed their retrograde transport along the neurite or capacity to elicit an electrophysiological response using live cell calcium imaging.ResultsThe angle of microchannel outlets dictated the probability of neurites growing into a chamber versus tracking along chamber walls. When the neurite terminals were exposed to fluorescently-labeled cholera toxin subunit B, the proteins were taken up and retrogradely transported along the neurites over the course of 24 h. Additionally, mechanical perturbation (e.g., rinsing) of the neurite terminals significantly increased intracellular calcium concentration in the distal soma. Finally, membrane-displayed receptor for capsaicin was expressed and trafficked along newly projected neurites, as revealed by confocal microscopy.ConclusionsIn this work, we developed a microfluidic device that can recapitulate the anatomical layout of vagal afferent neurons in vitro. We demonstrated two physiologically-relevant applications of the platforms: retrograde transport and electrophysiological response. We expect this tool to enable controlled studies on the role of vagal afferent neurons in the gut-brain axis.

Background and Purpose Experimental Approach Key Results Conclusion and Implications The limited effectiveness of current pharmacological treatments for alcohol use disorder (AUD) highlights the need for novel therapies. These may involve the glucagon‐like peptide‐1 receptor or the amylin receptor, as treatment with agonists targeting either of these receptors lowers alcohol intake. The complexity of the mechanisms underlying AUD indicates that combining agents could enhance treatment efficacy. While a combination of amylin receptor and GLP‐1 receptor agonists reduced food intake and body weight synergistic‐like, its influence on alcohol intake is unknown.Effects of a range of dose‐combinations of GLP‐1 receptor (dulaglutide) and amylin receptor (salmon calcitonin; sCT) agonists on alcohol intake were explored in male and female rats. We used dose combinations that either lowered alcohol intake as monotherapy (0.1 mg·kg−1 + 5 μg·kg−1), or that did not affect alcohol consumption per se (0.075 mg·kg−1 + 2 μg·kg−1).Acute administration of dulaglutide and sCT (0.1 mg·kg−1 + 5 μg·kg−1) reduced alcohol intake in males, but not in females. When higher doses were evaluated in female rats, a decrease in alcohol intake was observed. Furthermore, the low dose combination (0.075 mg·kg−1 + 2 μg·kg−1) decreased, in in a synergistic‐like manner, alcohol intake and prevented abstinence‐induced drinking without affecting kaolin intake in males. However, tolerance developed during sub‐chronic treatment.Collectively, these findings show that the combination of dulaglutide and sCT decreased, in in a synergistic‐like manner, alcohol consumption in male rats. Contrarily, higher doses are required for females. [ABSTRACT FROM AUTHOR]

Alzheimer's disease, a progressive neurodegenerative disorder marked by cognitive decline, affects millions worldwide. The presence of amyloid plaques and neurofibrillary tangles in the brain is the key pathological feature, leading to neuronal dysfunction and cell death. Current treatment options include pharmacological approaches such as cholinesterase inhibitors, as well as non-pharmacological strategies like cognitive training and lifestyle modifications. Recently, the potential role of probiotics, particularly strains, such as Lactobacillus and Bifidobacterium, in managing neurodegenerative diseases through the gut–brain axis has garnered significant attention. Probiotics can modulate inflammation, produce neurotransmitters, and support neuronal health, potentially slowing disease progression and alleviating symptoms, such as stress and anxiety. Optimizing the pharmacotherapeutic effects of probiotics is critical and involves advanced formulation techniques, such as microencapsulation and nanoencapsulation. Microencapsulation employs natural or synthetic polymers to protect probiotic cells, enhancing their viability and stability against environmental stressors. Methods like extrusion, emulsion, and spray-drying are used to create microcapsules suited for various applications. Nanoencapsulation, on the other hand, operates at the nanoscale, utilizing polymeric or lipid-based nanoparticles to improve the bioavailability and shelf life of probiotics. Techniques, such as nanoprecipitation and emulsification, are employed to ensure stable nanocapsule formation, thereby augmenting the therapeutic potential of probiotics as nutraceutical agents. This study delves into the essential formulation aspects of microencapsulation and nanoencapsulation for beneficial probiotic strains, aimed at managing Alzheimer's disease by optimizing the gut–brain axis. The insights gained from these advanced techniques promise to enhance probiotic delivery efficacy, potentially leading to improved health outcomes for patients suffering from neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The objectives of this study were to determine if weaning would induce behavioral and physiological indicators of a negative affective state, and if supplementation of inactivated Lactobacillus helveticus (ILH) to dairy calves would reduce those indicators of negative affect during weaning. Male Holstein calves (n = 23) were enrolled in the study on d 1 of life. The calves were housed in individual pens in 1 of 4 rooms for the 42-d study. Calves began a step-down weaning from 9 L/d of milk replacer (MR), at 150 g of MR powder/L, on d 35 and received 6 L/d on d 35 to 36, 3 L/d on d 37 to 38, and 0.4 L/d on d 39 to 42. The MR was divided between 3 meals/d until the last 0.4 L/d phase, which was divided between 2 meals/d. Calves had ad libitum water access throughout the study and calf starter from d 28 onward. Within room, calves were assigned to 1 of 2 treatments: (1) control (CON; n = 11) and (2) 5 g of ILH/d split over and mixed into the 0800 h and 2000 h milk feedings from d 3 to 42 (ILH; n = 12). Lying behavior was recorded using HOBO data loggers from d 21 to 41. On d 33, 37, and 41, infrared eye images were taken to determine maximum eye temperature (MET), saliva samples were collected to determine cortisol concentration, and play assessments were conducted to quantify play behavior. On d 34, 38, and 42, blood samples were collected to determine blood serotonin concentration, whereas on d 38 and 39, calves were tested with a cognitive task. A subset of calves (n = 5/treatment) were euthanized to collect gut and brain tissue samples for serotonin concentration on d 43. Weaning resulted in fewer (d 37–41; tendency: d 36), but longer (d 38–41; tendency: d 37), lying bouts and reduced play (d 41), although no changes in lying time, MET, saliva cortisol, nor blood serotonin were detected with initiation of weaning. Supplementation of ILH was associated with less lying time throughout the study, and reduced play duration and higher salivary cortisol during weaning. No differences in lying bouts, play count, blood and tissue (colon, ileum, prefrontal cortex and brain stem) serotonin concentration, and time to complete the cognitive task were detected between the treatments. Overall, weaning induced behavioral changes indicative of negative affective state, and some behavioral differences were observed with ILH supplementation both before and during weaning, with some physiological changes observed during weaning. [ABSTRACT FROM AUTHOR]

This study employed structural and functional magnetic resonance imaging (MRI) to investigate changes in the function and structure of the cerebellum associated with gut-brain axis (GBA) regulation in patients diagnosed with Crohn's disease (CD). The study comprised 20 CD patients, including 12 with active disease (CD-A) and 8 in remission (CD-R), as well as 21 healthy controls. Voxel-based morphometry (VBM) was utilized for structural analysis of cerebellar gray matter volume, while independent component analysis (ICA) was applied for functional analysis of cerebellar functional connectivity (FC). The results showed significant GMV reduction in the left posterior cerebellar lobe across all CD patients compared to HCs, with more pronounced differences in the CD-A subgroup. Additionally, an increase in mean FC of the cerebellar network was observed in all CD patients, particularly in the CD-A subgroup, which demonstrated elevated FC in the vermis and bilateral posterior cerebellum. Correlation analysis revealed a positive relationship between cerebellar FC and the Crohn's Disease Activity Index (CDAI) and a trend toward a negative association with the reciprocal of the Self-rating Depression Scale (SDS) score in CD patients. The study's findings suggest that the cerebellum may play a role in the abnormal regulation of the GBA in CD patients, contributing to a better understanding of the neural mechanisms underlying CD and highlighting the cerebellum's potential role in modulating gut-brain interactions. [ABSTRACT FROM AUTHOR]

Rationale: Stressors play a critical role in the progression of irritable bowel syndrome (IBS). Heterogenous stress causes alterations in our bowel movements which can further cause anxiety and depression-like symptoms, decreasing the ability of individuals worldwide to function in social, academic, and employment settings. Objectives: This study was aimed to investigate the effect of orally administered Nigella sativa (0.2 mL/kg b.wt.) seed oil (NSSO) on stress-induced IBS, anxiety, and depression-like symptoms in Wistar rats. Methods: In the present study, modelling IBS induced anxiety and depression-like symptoms in rodents have been employed to correlate the pathophysiological mechanisms behind this disorder. Moreover, evaluation of ameliorative potential of traditionally used NSSO in IBS was also carried out. Results: Present investigation indicated that acute stress of 1.5 h daily for 20 days induced hyper cortisol, gastrointestinal (GI) hypermotility, diarrhoea, altered levels of short chain fatty acids (SCFAs), and inflammation which are common symptoms of IBS. Furthermore, depression and anxiety-like symptoms were validated in test groups by various behavioral tests and decreased levels of 5-HT-Transporter mRNA gene expression, which are clear indicators of cognitive impairment. Conclusions: It is possible that these IBS-like symptoms may have contributed to the pathogenesis of cognitive deficits and depression. However, the anti-oxidative, anti-inflammatory, anti-spasmodic, and possibly the anti-anxiolytic properties of NSSO helped in the mitigation of altered gut-brain axis. Because the concurrent treatment of NSSO alleviated the symptoms of modified GI function and consequently, the anxious & depressive behavior of the animals. Overall, this research explored the protective efficacy of NSSO against stress-induced IBS and depression-like symptoms, shedding light on the potential of this natural compound as a therapeutic option in the field of gastroenterology and psychiatry. [ABSTRACT FROM AUTHOR]

Rationale: Neurological conditions like Stroke and Alzheimer's disease (AD) often include inflammatory responses in the nervous system. Stroke, linked to high disability and mortality rates, poses challenges related to organ-related complications. Recent focus on understanding the pathophysiology of ischemic stroke includes aspects like cellular excitotoxicity, oxidative stress, cell death mechanisms, and neuroinflammation. Objective: The objective of this paper is to summarize and explore the pathophysiology of ischemic stroke, elucidates the gut-brain axis mechanism, and discusses recent clinical trials, shedding light on novel treatments and future possibilities. Results: Changes in gut architecture and microbiota contribute to dementia by enhancing intestinal permeability, activating the immune system, elevating proinflammatory mediators, altering blood-brain barrier (BBB) permeability, and ultimately leading to neurodegenerative diseases (NDDs). The gut-brain axis's potential role in disease pathophysiology offers new avenues for cell-based regenerative medicine in treating neurological conditions. Conclusion: In conclusion, the gut microbiome significantly impacts stroke prognosis by highlighting the role of the gut-brain axis in ischemic stroke mechanisms. This insight suggests potential therapeutic strategies for improving outcomes. [ABSTRACT FROM AUTHOR]

Purpose of review: The importance of the gut microbiome for human health and well-being is generally accepted, and elucidating the signaling pathways between the gut microbiome and the host offers novel mechanistic insight into the (patho)physiology and multifaceted aspects of healthy aging and human brain functions. Recent findings: The gut microbiome is tightly linked with the nervous system, and gut microbiota are increasingly emerging as important regulators of emotional and cognitive performance. They send and receive signals for the bidirectional communication between gut and brain via immunological, neuroanatomical, and humoral pathways. The composition of the gut microbiota and the spectrum of metabolites and neurotransmitters that they release changes with increasing age, nutrition, hypoxia, and other pathological conditions. Changes in gut microbiota (dysbiosis) are associated with critical illnesses such as cancer, cardiovascular, and chronic kidney disease but also neurological, mental, and pain disorders, as well as chemotherapies and antibiotics affecting brain development and function. Summary: Dysbiosis and a concomitant imbalance of mediators are increasingly emerging both as causes and consequences of diseases affecting the brain. Understanding the microbiota's role in the pathogenesis of these disorders will have major clinical implications and offer new opportunities for therapeutic interventions. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) represents a complex and challenging mental health condition with multifaceted etiology. Recent research exploring the gut-brain axis has shed light on the potential influence of gut microbiota on mental health, offering novel avenues for therapeutic intervention. This paper reviews current evidence on the role of prebiotics and probiotics in the context of MDD treatment. Clinical studies assessing the effects of prebiotic and probiotic interventions have demonstrated promising results, showcasing improvements in depression symptoms and metabolic parameters in certain populations. Notably, prebiotics and probiotics have shown the capacity to modulate inflammatory markers, cortisol levels, and neurotransmitter pathways linked to MDD. However, existing research presents varied outcomes, underscoring the need for further investigation into specific microbial strains, dosage optimization, and long-term effects. Future research should aim at refining personalized interventions, elucidating mechanisms of action, and establishing standardized protocols to integrate these interventions into clinical practice. While prebiotics and probiotics offer potential adjunctive therapies for MDD, continued interdisciplinary efforts are vital to harnessing their full therapeutic potential and reshaping the landscape of depression treatment paradigms. [ABSTRACT FROM AUTHOR]

Background: Epilepsy is a prevalent chronic neurological disorder that is strongly associated with a wide range of psychological, cognitive and social problems. It affects a significant proportion of the global population and has a number of complex etiologies. A growing body of research indicates that there is a strong association between epilepsy and the gut microbiota. Indeed, a substantial body of research has investigated the potential role of epilepsy in relation to the gut microbiota, examining alterations in the abundance, diversity, and relative abundance of the gut microbiota in patients with epilepsy. Methods: This study was conducted in accordance with the PRISMA guidelines and included multiple studies that met specific criteria. A keyword search was conducted in the following databases: PubMed, Embase, and Web of Science. The data extraction and quality assessment were conducted by two independent researchers. A systematic review and meta-analysis of the relationship between patients with epilepsy and gut flora was conducted using the R 4.3.4 software. Results: The results of the analyses indicated that the intestinal flora of patients with epilepsy did not differ significantly in alpha diversity compared to healthy controls. However, the relative abundance of specific flora, such as Verrucomicrobia and Ackermannia was significantly increased in patients, whereas Lactobacillus was significantly decreased. Conclusion: The relationship between epilepsy and gut flora is reciprocal. The present meta-analysis demonstrated that there were no statistically significant alterations in the overall characteristics of the intestinal flora of the patients. However, significant changes were observed in the relative abundance of certain phyla and genera. Consequently, it is hypothesized that epilepsy can cause changes in the relative abundance of specific flora in patients. Furthermore, in conjunction with previous studies, it is believed that changes in intestinal flora can also have an effect on seizures. For example, Lactobacillus may be a beneficial genus that potentially reduces seizures. Conversely, the effect of Akkermansia is two-sided. [ABSTRACT FROM AUTHOR]

Recent advancements in neurophysiology have challenged the long-held paradigm that vagal afferents serve as the primary conduits for physiological signals governing food intake and energy expenditure. An expanding body of evidence now illuminates the critical role of spinal afferent neurons in these processes, necessitating a reevaluation of our understanding of energy homeostasis regulation. This comprehensive review synthesizes cutting-edge research elucidating the multifaceted functions of spinal afferent neurons in maintaining metabolic equilibrium. Once predominantly associated with nociception and pathological states, these neurons are now recognized as integral components in the intricate network regulating feeding behavior, nutrient sensing, and energy balance. We explore the role of spinal afferents in food intake and how these neurons contribute to satiation signaling and meal termination through complex gut-brain axis pathways. The review also delves into the developing evidence that spinal afferents play a crucial role in energy expenditure regulation. We explore the ability of these neuronal fibers to carry signals that can modulate feeding behavior as well as adaptive thermogenesis in adipose tissue influencing basal metabolic rate, and thereby contributing to overall energy balance. This comprehensive analysis not only challenges existing paradigms but also opens new avenues for therapeutic interventions suggesting potential targets for treating metabolic disorders. In conclusion, this review highlights the need for a shift in our understanding of energy homeostasis, positioning spinal afferent neurons as key players in the intricate web of metabolic regulation. [ABSTRACT FROM AUTHOR]

Introduction: Examining the contribution of peripheral systems to cognitive function under healthy circumstances may improve our understanding of the systems that confer risk or resilience in diseased states. Endotoxemia—a pro-inflammatory response to the translocation of bacteria that reside in the gut on other sources (e.g., respiratory tract; infection) into the blood—was hypothesized to relate to worsened cognitive functioning. Gender was explored as a moderator. Methods: A sample of 162 healthy adults (25–65 years old) provided plasma, from which a measure of endotoxemia was determined [i.e., the ratio of lipopolysaccharide binding protein (LBP) to soluble cluster of differentiation 14 receptors (sCD14)]. Participants performed an array of laboratory and ambulatory cognitive tasks at three timepoints, each separated by 9 months. Two sets of multilevel models were used: Prospective models, linking endotoxemia at baseline with changes in cognition across time, and coupling models, which examine correlations of endotoxemia with cognition across time. Results: A prospective model indicated lower levels of endotoxemia at baseline predicted improvements in working memory across the three timepoints; higher levels were associated with no change in cognitive performance. Gender was not found to modulate this finding. Interestingly, a coupling analysis of endotoxemia and gender across time showed that in men, those with higher endotoxemia performed better at the working memory task overall; in women, working memory performance was similar regardless of endotoxemia level. Conclusion: This work provides initial evidence that endotoxemia may be associated with a dampening of improvement in working memory, improvement consistent with practice effects, which should be expected in a sample of healthy, relatively young adults. The findings also provide preliminary evidence that, at least for men, higher degrees of endotoxemia are not inherently negative, and may link with short term positive outcomes for working memory. [ABSTRACT FROM AUTHOR]

The gut–brain axis (GBA) plays a pivotal role in human health and wellness by orchestrating complex bidirectional regulation and influencing numerous critical processes within the body. Over the past decade, research has increasingly focused on the GBA in the context of inflammatory bowel disease (IBD). Beyond its well-documented effects on the GBA–enteric nervous system and vagus nerve dysregulation, and gut microbiota misbalance—IBD also leads to impairments in the metabolic and cellular functions: metabolic dysregulation, mitochondrial dysfunction, cationic transport, and cytoskeleton dysregulation. These systemic effects are currently underexplored in relation to the GBA; however, they are crucial for the nervous system cells' functioning. This review summarizes the studies on the particular mechanisms of metabolic dysregulation, mitochondrial dysfunction, cationic transport, and cytoskeleton impairments in IBD. Understanding the involvement of these processes in the GBA may help find new therapeutic targets and develop systemic approaches to improve the quality of life in IBD patients. [ABSTRACT FROM AUTHOR]

Introduction: Nutraceuticals are food-derived products offering supplementary health benefits. These nutraceuticals have been found effective in the treatment of the Parkinson's disease (PD) as they possess multifaceted effects against neurodegeneration. Nutraceuticals have proven their safety and efficacy in several pre-clinical and clinical trials against PD, however, still there is an urgent need to report the health benefits of nutraceuticals on a broader platform and evaluate their complete molecular mechanism against PD. Area covered: The review emphasizes the role of nutraceuticals in combating pathogenic mechanisms associated with PD. These include, mitochondrial dysfunction, protein ubiquitination, oxidative stress, excitotoxicity, neurotransmitter imbalance, neuroinflammation, inhibition of PPAR-ϒ/PGC-1α/NRF-2, and PON2 signaling pathways. The review also includes pre-clinical and clinical aspects of nutraceuticals in balancing the impaired gut-brain axis in PD. Expert opinion: In recent years there have been many reports on neuroprotective potential of PD. The growing interest showed that various supplements, including polyphenols, vitamins, minerals, and the Mediterranean diet, can aid promising therapeutic properties for relieving PD symptoms. However, at present, there is no specific nutraceutical that has been designed to treat the symptoms of PD. Future studies on nutraceuticals may focus on developing individualized as well as customized therapies using specialized nutraceuticals based on epigenetics and the expression of PD. [ABSTRACT FROM AUTHOR]

Aging-related cognitive impairment, mainly Alzheimer's disease (AD), has been widely studied. However, effective prevention and treatment methods are still lacking. In recent years, researchers have observed beneficial effects of plant-based supplements, such as flavonoids, on cognitive protection. This provides a new clue for the prevention of cognitive dysfunction. Studies have shown that dietary flavonoids have neuroprotective effects, but the mechanism is not clear. In this review, we systematically reviewed the research progress on the effects of dietary flavonoids on gut microbes and their metabolites, and concluded that flavonoids could improve cognitive function through the gut-brain axis. Flavonoids can be absorbed through the intestine, cross the blood-brain barrier, and enter the brain tissue. Flavonoids can inhibit the expression and secretion of inflammatory factors in brain tissue, reduce the damage caused by oxidative stress, clear neural damage proteins and inhibit neuronal apoptosis, thereby ameliorating age-related cognitive disorders. Future work will continue to explore the gut-brain axis and target genes regulated by flavonoids. In addition, clinical research and its mechanisms need to be further explored to provide solutions or advise for patients with cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Chronic ethanol exposure (CEE) is recognized as an important risk factor for depression, and the gut-brain axis has emerged as a key mechanism underlying chronic ethanol exposure-induced anxiety and depression-like behaviors. Short-chain fatty acids (SCFAs), which are the key metabolites generated by gut microbiota from insoluble dietary fiber, exert protective roles on the central nervous system, including the reduction of neuroinflammation. However, the link between gut microbial disturbances caused by chronic ethanol exposure, production of SCFAs, and anxiety and depression-like behaviors remains unclear. Methods: Initially, a 90-day chronic ethanol exposure model was established, followed by fecal microbiota transplantation model, which was supplemented with SCFAs via gavage. Anxiety and depression-like behaviors were determined by open field test, forced swim test, and elevated plus-maze. Serum and intestinal SCFAs levels were quantified using GC-MS. Changes in related indicators, including the intestinal barrier, intestinal inflammation, neuroinflammation, neurotrophy, and nerve damage, were detected using Western blotting, immunofluorescence, and Nissl staining. Results: Chronic ethanol exposure disrupted with gut microbial homeostasis, reduced the production of SCFAs, and led to anxiety and depression-like behaviors. Recipient mice transplanted with fecal microbiota that had been affected by chronic ethanol exposure exhibited impaired intestinal structure and function, low levels of SCFAs, intestinal inflammation, activation of neuroinflammation, a compromised blood-brain barrier, neurotrophic defects, alterations in the GABA system, anxiety and depression-like behaviors. Notably, the negative effects observed in these recipient mice were significantly alleviated through the supplementation of SCFAs. Conclusion: SCFAs not only mitigate damage to intestinal structure and function but also alleviate various lesions in the central nervous system, such as neuroinflammation, and reduce anxiety and depression-like behaviors, which were triggered by transplantation with fecal microbiota that had been affected by chronic ethanol exposure, adding more support that SCFAs serve as a bridge between the gut and the brain. [ABSTRACT FROM AUTHOR]

This paper reviews the effects of gut microbiota in regulating neurodegenerative diseases through controlling gut-brain axis. Specific microbial populations and their metabolites (short-chain fatty acids and tryptophan derivatives) regulate neuroinflammation, neurogenesis and neural barrier integrity. We then discuss ways by which these insights lead to possible interventions - probiotics, prebiotics, dietary modification, and fecal microbiota transplantation (FMT). We also describe what epidemiological and clinical studies have related certain microbiota profiles with the courses of neurodegenerative diseases and how these impact the establishment of microbiome-based diagnostics and individualized treatment options. We aim to guide microbial ecology research on this key link to neurodegenerative disorders and also to highlight collaborative approaches to manage neurological health by targeting microbiome-related factors. [ABSTRACT FROM AUTHOR]

Incretins, such as glucagon‐like peptide‐1 (GLP1) and glucose‐dependent insulinotropic polypeptide (GIP), have advanced the treatment landscape of obesity to a new pinnacle. As opposed to singular incretin effects, oxyntomodulin (OXM) activates glucagon receptors (GCGR) and glucagon‐like peptide‐1 receptors (GLP1R), demonstrating a more dynamic range of effects that are more likely to align with evolving ‘health gains’ goals in obesity care. Here, we will review the molecular insights from their inception to recent developments and challenges. This review will discuss the physiological actions of OXM, primarily appetite regulation, energy expenditure, and glucose homeostasis. Finally, we will shed light on the development of OXM‐based therapies for obesity and associated complications, and outline important considerations for more translational efforts. [ABSTRACT FROM AUTHOR]

Small intestinal bacterial overgrowth (SIBO) is a gastrointestinal condition characterized by abnormal colonization of bacteria in the small intestine, leading to overgrowth and alteration, which is linked to gastrointestinal issues, potentially affecting neurological and mental health. Despite existing research, we still do not understand how SIBO affects tryptophan metabolism and psychiatric diseases. We investigated the literature for connections between SIBO, tryptophan metabolism disruptions, and psychiatric disorders like autism, schizophrenia, Alzheimer's, and Parkinson's diseases. We also explored the interaction between thyroid disorders and their influence on SIBO and psychiatric illnesses. PubMed and Google Scholar databases were searched using keywords and phrases, individual and in combinations, like "SIBO," "gut microbiota," "neurologic disorders," "mental disorders," "tryptophan," "dopamine," and "thyroid disease." We focused on original research and review papers that presented empirical studies conducted on animal models and human subjects published in English between February 1992 to February 2023. The initial 2 634 534 records were preliminary screened based on title and abstract and then subjected to full-text review to exclude publications with insufficient data on SIBO, lack of a psychiatric disorder component, or methodological limitations compromising the integrity of the findings. The analysis highlights the significance of the association between psychiatric disorders and SIBO, emphasizing the role of gut-microbial diversity in mental health. We advocate for more detailed studies, including longitudinal research, to clarify the causal relationships between SIBO, gut dysbiosis, and psychiatric disorders and for an integrated approach while treating complex psychiatric conditions. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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: 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). Conclusion: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

White adipose tissue (WAT) and the gut are involved in the development of neuroinflammation when an organism detects any kind of injury, thereby triggering metainflammation. In fact, the autonomous nervous system innervates both tissues, although the complex role played by the integrated sympathetic, parasympathetic, and enteric nervous system functions have not been fully elucidated. Our aims were to investigate the participation of inflamed WAT and the gut in neuroinflammation. Firstly, we conducted an analysis into how inflamed peripheral WAT plays a key role in the triggering of metainflammation. Indeed, this included the impact of the development of local insulin resistance and its metabolic consequences, a serious hypothalamic dysfunction that promotes neurodegeneration. Then, we analyzed the gut–brain axis dysfunction involved in neuroinflammation by examining cell interactions, soluble factors, the sensing of microbes, and the role of dysbiosis-related mechanisms (intestinal microbiota and mucosal barriers) affecting brain functions. Finally, we targeted the physiological crosstalk between cells of the brain–WAT–gut axis that restores normal tissue homeostasis after injury. We concluded the following: because any injury can result not only in overall insulin resistance and dysbiosis, which in turn can impact upon the brain, but that a high-risk of the development of neuroinflammation-induced neurodegenerative disorder can also be triggered. Thus, it is imperative to avoid early metainflammation by applying appropriate preventive (e.g., lifestyle and diet) or pharmacological treatments to cope with allostasis and thus promote health homeostasis. [ABSTRACT FROM AUTHOR]

Polycystic Ovary Syndrome (PCOS) is a metabolic disorder characterized by hyperandrogenism and related symptoms in women of reproductive age. Emerging evidence suggests that chronic low-grade inflammation plays a significant role in the development of PCOS. The gut microbiota, a complex bacterial ecosystem, has been extensively studied for various diseases, including PCOS, while the underlying mechanisms are not fully understood. This review comprehensively summarizes the changes in gut microbiota and metabolites observed in PCOS and their potential association with the condition. Additionally, we discuss the role of abnormal nuclear factor κB signaling in the pathogenesis of PCOS. These findings offer valuable insights into the mechanisms of PCOS and may pave the way for the development of control and therapeutic strategies for this condition in clinical practice. By bridging the gap between mouse models and clinical patients, this review contributes to a better understanding of the interplay between gut microbiota and inflammation in PCOS, thus paving new ways for future investigations and interventions. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder is a neurodevelopmental disorder characterized by a wide range of behavioral alterations, including impaired social interaction and repetitive behaviors. Numerous pharmacological interventions have been developed for autism spectrum disorder, often proving ineffective and accompanied by a multitude of side effects. The gut microbial alterations observed in individuals with autism spectrum disorder, including elevated levels of Bacteroidetes, Firmicutes, and Proteobacteria, as well as reduced levels of Bifidobacterium, provide a basis for further investigation. Recent preclinical studies have shown favorable outcomes with probiotic therapy, including improvements in oxidative stress, anti-inflammatory effects, regulation of neurotransmitters, and restoration of microbial balance. The aim of this review is to explore the potential of probiotics for the management and treatment of autism spectrum disorder, by investigating insights from recent studies in animals. Autism spectrum disorder is a neurodevelopmental disorder characterized by a wide range of behavioral alterations, including impaired social interaction and repetitive behaviors. Numerous pharmacological interventions have been developed for autism spectrum disorder, often proving ineffective and accompanied by a multitude of side effects. The gut microbiota is the reservoir of bacteria inhabiting our gastrointestinal tract. The gut microbial alterations observed in individuals with autism spectrum disorder, including elevated levels of Bacteroidetes, Firmicutes, and Proteobacteria, as well as reduced levels of Bifidobacterium, provide a basis for further investigation into the role of the gut microbiota in autism spectrum disorder. Recent preclinical studies have shown favorable outcomes with probiotic therapy, including improvements in oxidative stress, anti-inflammatory effects, regulation of neurotransmitters, and restoration of microbial balance. The aim of this review is to explore the potential of probiotics for the management and treatment of autism spectrum disorder, by investigating insights from recent studies in animals. [ABSTRACT FROM AUTHOR]

[Display omitted] • Constipation was associated with an increased risk of Alzheimer's disease (AD) in the South Korean cohort (discovery cohort, HR, 2.04; 95% CI, 2.01–2.07) and the Japan cohort (validation cohort, HR, 2.82; 95% CI, 2.61–3.05). • Loperamide-treated AD mouse model showed increased amyloid-beta and microglia in the brain with slow gut transit. • Loperamide-treated AD mouse model had increased transcription of genes related to norepinephrine secretion and immune responses and decreased transcription of defense against bacteria in colonic tissue. Although the association between Alzheimer's disease (AD) and constipation is controversial, its causality and underlying mechanisms remain unknown. To investigate the potential association between slow gut transit and AD using epidemiological data and a murine model. We conducted a bi-national cohort study in South Korea (discovery cohort, N=3,130,193) and Japan (validation cohort, N=4,379,285) during the pre-observation period to determine the previous diagnostic history (2009–2010) and the follow-up period (2011–2021). To evaluate the causality, we induced slow gut transit using loperamide in 5xFAD transgenic mice. Changes in amyloid-beta (Aβ) and other markers were examined using ELISA, qRT-PCR, RNA-seq, and behavioral tests. Constipation was associated with an increased risk of AD in the discovery cohort (hazard ratio, 2.04; 95% confidence interval [CI], 2.01–2.07) and the validation cohort (hazard ratio; 2.82; 95% CI, 2.61–3.05). We found that loperamide induced slower gut transit in 5xFAD mice, increased Aβ and microglia levels in the brain, increased transcription of genes related to norepinephrine secretion and immune responses, and decreased the transcription of defense against bacteria in the colonic tissue. Impaired gut transit may contribute to AD pathogenesis via the gut-brain axis, thus suggesting a cyclical relationship between intestinal barrier disruption and Aβ accumulation in the brain. We propose that gut transit or motility may be a modifiable lifestyle factor in the prevention of AD, and further clinical investigations are warranted. [ABSTRACT FROM AUTHOR]

Background: The gut–brain axis may mediate mood changes due to strenuous exercise. Therefore, probiotic supplementation may mitigate mood worsening. Purpose: The present study aims to evaluate the effect of probiotic supplementation on mood and immunometabolic parameters after a marathon. Materials and methods: Fourteen marathon runners were selected and divided into placebo and probiotic groups that were supplemented for 30 days. Before and after the marathon, mood (POMS) was assessed, and blood was collected for analysis of immunometabolic parameters. Statistical analysis was performed, and p < 0.05 was considered to determine statistically differences. Results: Tension decreased after the marathon in both groups. Vigor decreased only in the placebo group. Fatigue increased after the marathon in both groups. TMD increased after the marathon in placebo. The IL2/IL-4 ratio decreased in the probiotic group after the marathon compared to before and increased compared to the placebo group. The IL-10 increased after the marathon in placebo. TNF-α increased after the marathon in probiotics. The TNF-α/IL-10 ratio decreased after the marathon in both groups. LPS decreased in the probiotic group after the marathon compared to before and in the placebo group. Conclusions: Thirty days of probiotic supplementation attenuated the impact of marathons on mood worsening. The decrease in LPS in the probiotic group mediated the change in the pro/anti-inflammatory balance, indicating an immunometabolic mechanism by which the gut–brain axis impacts mood after strenuous exercise. [ABSTRACT FROM AUTHOR]

The recovery of neurological deficits after ischemic stroke largely depends on the brain's ability to reorganize its undamaged neuronal circuits and neuronal plasticity phenomena. The consolidated evidence highlights the involvement of the patient's impaired nutritional conditions in post-stroke recovery and unsatisfying rehabilitative outcomes. Standardized nutritional protocols usually applied in hospitalized patients in a rehabilitation setting aim mainly to improve the general health conditions of patients, do not consider the high inter-individual variability in neurorehabilitation outcomes, and are not sufficiently modifiable to provide neuroprotective and restorative dietary patterns that could promote neuronal plasticity and functional recovery during neurorehabilitation. Neuronutrition, an emergent scientific field of neuroscience, represents a valid model of a personalized nutritional approach, assuring, for each patient, nutrients having antioxidant and anti-inflammatory properties, ensuring a balanced microbiota composition, and providing adequate neurotrophic support, essential for improving neuronal plasticity, brain functional recovery, and rehabilitative outcomes. In the present narrative review, we provide an overview of the current knowledge on neuronutrition as an adjuvant strategy of a personalized nutritional approach potentially effective in improving post-stroke neuroplasticity and neurorehabilitation by counteracting or at least limiting post-stroke oxidative/nitrosative stress, neuroinflammation, and gut–brain axis disturbance. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is the most common form of dementia and is a challenge for the modern world due to the due to aging populations. Researchers are trying their best to understand the mechanisms of onset and find effective ways to treat and prevent this disease. The purpose of the following paper is to present the impact of physical activity in the development of Alzheimer's disease. Numerous studies confirm that regular workouts have a positive reflection in the form of slowing the aging of the brain and alleviation of neuropsychiatric symptoms in affected individuals. During muscle work irisin is produced, which plays an important role in the formation of neurons and exhibits an anti-inflammatory effects. This review also looks at the aspect of maintaining proper composition of the gut microbiota, whose imbalance can promote the process of neuronal inflammation and cognitive dysfunction. Attention is also given to issues of training intensity and the effect of of exercise on blood flow in the brain. All of these elements play an important role in preventing and slowing down neurodegeneration. Purpose : The purpose of this scientific paper is to review the current knowledge of the effects of physical activity on the development of Alzheimer's disease. Review methods : We conducted our study as a literature review based on information gathered from PubMed, Embase, Google Scholar using combinations of the following keywords : Alzheimer's disease ; dementia ; physical activity ; cerebral blood flow ; gut-brain axis ; irisin. The state of knowledge : Alzheimer's disease is the most common type of dementia and one of the main neurodegenerative disorders affecting elderly people. Numerous studies confirm that regular exercise has a positive effect on slowing down brain aging and alleviating neuropsychiatric symptoms in patients. According to current knowledge, nerve cell degeneration can be exacerbated by peripheral inflammation that occurs in obesity. An imbalance of bacterial flora in the gastrointestinal tract causes systemic inflammation in the body. This in turn leads to excessive production of pro-inflammatory cytokines and activation of microglia so that the blood-brain barrier becomes leaky. Maintaining the appropriate composition of the gut microbiota plays an important role, as its imbalance can promote neuronal inflammation and cognitive impairment. During physical activity, irisin protein is produced in muscle tissue, which plays an important role in neuronal formation and exhibits anti-inflammatory effects. Currently, there is evidence that irisin can provide a number of beneficial effects, mainly through mechanisms that positively affect the gut microbiome. Attention is also given to issues of training intensity and the effect of exercise on cerebral blood flow. All these factors play an important role in preventing and slowing down neurodegeneration. Conclusion : Based on a review of the available literature, a significant effect of physical activity on the development of Alzheimer's disease can be demonstrated. The accumulated data suggest that physical activity is one of the main protective factors against the development and progression of Alzheimer's disease. Physical activity is associated with a reduction in cardiovascular risk factors and an increase in neuroprotective changes. The neuroprotective effect of physical exercise is dependent on its intensity. In addition, the role of the gut microbiota has been shown to be important for maintaining normal cognitive function. The protein irisin may also have significant neuroprotective potential in relation to the development and progression of cognitive disorders. Physical activity may be one of the strategies to prevent an increase in the incidence of Alzheimer's disease with positive health, economic and social implications in the future. [ABSTRACT FROM AUTHOR]

Temperament is a key predictor of human mental health and cognitive and emotional development. Although human fear behavior is reportedly associated with gut microbiome in infancy, infant gut microbiota changes dramatically during the first 5 years, when the diversity and composition of gut microbiome are established. This period is crucial for the development of the prefrontal cortex, which is involved in emotion regulation. Therefore, this study investigated the relationship between temperament and gut microbiota in 284 preschool children aged 3–4 years. Child temperament was assessed by maternal reports of the Children's Behavior Questionnaire. Gut microbiota (alpha/beta diversity and genera abundance) was evaluated using 16S rRNA sequencing of stool samples. A low abundance of anti‐inflammatory bacteria (e.g., Faecalibacterium) and a high abundance of pro‐inflammatory bacteria (e.g., Eggerthella, Flavonifractor) were associated with higher negative emotionality and stress response (i.e., negative affectivity, β = −0.17, p = 0.004) and lower positive emotionality and reward‐seeking (i.e., surgency/extraversion, β = 0.15, p = 0.013). Additionally, gut microbiota diversity was associated with speed of response initiation (i.e., impulsivity, a specific aspect of surgency/extraversion, β = 0.16, p = 0.008). This study provides insight into the biological mechanisms of temperament and takes important steps toward identifying predictive markers of psychological/emotional risk. [ABSTRACT FROM AUTHOR]

Stroke is a life-threatening condition that impairs the arteries and causes neurological impairment. The incidence of stroke is increasing year by year with the arrival of the aging population. Thus, there is an urgent need for early stroke diagnosis. Short-chain fatty acids (SCFAs) can modulate the central nervous system and directly and indirectly impact behavioral and cognitive functions. This study aimed to investigate the connection between SCFA metabolism and stroke development via bioinformatic analysis. Initially, the Gene Set Enrichment Analysis (GSEA) and immune cell infiltration analysis were performed based on RNA data from stroke patients to comprehend the mechanisms governing stroke pathogenesis. The functional analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Protein-Protein Interaction (PPI), was performed based on the Differentially Expressed Gene (DEG) selected by the limma package. 1220 SCFA metabolism-related genes screened from Genecards databases were intersected with 242 genes in main modules determined by Weighted Gene Co-Expression Network Analysis (WGCNA), and the final 10 SCFA key genes were obtained. GO analysis revealed that these genes were involved in immune response processes. Through lasso regression analyses, we established a stroke early diagnosis model and selected 6 genes with diagnostic value. The genes were validated by the area under curve (AUC) values and had a relatively good diagnostic performance. Finally, 4 potential therapeutic drugs targeting these genes were predicted using the Drug Signatures Database (DSigDB) via Enrichr. In conclusion, this paper analyzes the involvement of SCFAs in the complex gut-brain axis mechanism, which contributes to developing new targets for treating central nervous system diseases and provides new ideas for early ischemic stroke diagnosis. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons, leading to motor and non-motor symptoms. Emerging research has shed light on the role of gut microbiota in the pathogenesis and progression of PD. Nutraceuticals such as curcumin, berberine, phytoestrogens, polyphenols (e.g., resveratrol, EGCG, and fisetin), dietary fibers have been shown to influence gut microbiota composition and function, restoring microbial balance and enhancing the gut-brain axis. The mechanisms underlying these benefits involve microbial metabolite production, restoration of gut barrier integrity, and modulation of neuroinflammatory pathways. Additionally, probiotics and prebiotics have shown potential in promoting gut health, influencing the gut microbiome, and alleviating PD symptoms. They can enhance the gut's antioxidant capacity of the gut, reduce inflammation, and maintain immune homeostasis, contributing to a neuroprotective environment. This paper provides an overview of the current state of knowledge regarding the potential of nutraceuticals and gut microbiota modulation in the prevention and management of Parkinson's disease, emphasizing the need for further research and clinical trials to validate their effectiveness and safety. The findings suggest that a multifaceted approach involving nutraceuticals and gut microbiota may open new avenues for addressing the challenges of PD and improving the quality of life for affected individuals. [ABSTRACT FROM AUTHOR]

The gut microbiota (GM) produces various molecules that regulate the physiological functionality of the brain through the gut-brain axis (GBA). Studies suggest that alteration in GBA may lead to the onset and progression of various neurological dysfunctions. Moreover, aging is one of the prominent causes that contribute to the alteration of GBA. With age, GM undergoes a shift in population size and species of microflora leading to changes in their secreted metabolites. These changes also hamper communications among the HPA (hypothalamic–pituitary–adrenal), ENS (enteric nervous system), and ANS (autonomic nervous system). A therapeutic intervention that has recently gained attention in improving health and maintaining communication between the gut and the brain is calorie restriction (CR), which also plays a critical role in autophagy and neurogenesis processes. However, its strict regime and lifelong commitment pose challenges. The need is to produce similar beneficial effects of CR without having its rigorous compliance. This led to an exploration of calorie restriction mimetics (CRMs) which could mimic CR's functions without limiting diet, providing long-term health benefits. CRMs ensure the efficient functioning of the GBA through gut bacteria and their metabolites i.e., short-chain fatty acids, bile acids, and neurotransmitters. This is particularly beneficial for elderly individuals, as the GM deteriorates with age and the body's ability to digest the toxic accumulates declines. In this review, we have explored the beneficial effect of CRMs in extending lifespan by enhancing the beneficial bacteria and their effects on metabolite production, physiological conditions, and neurological dysfunctions including neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

AbstractContextObjectiveConclusionThe age-induced disruption of gut flora, termed gut dysbiosis, is intimately tied to compromised immune function, augmented oxidative stress and a spectrum of age-linked disorders.This review examines the fundamental mechanisms employed by probiotic strains to modulate gut microbiota composition and metabolic profiles, mitigate cognitive decline via the gut-brain axis (GBA), modulate gene transcription and alleviate inflammatory responses and oxidative stress.We elucidate the capacity of probiotics as a precision intervention to restore gut microbiome homeostasis and alleviate age-related conditions, thereby offering a theoretical framework for probiotics to decelerate ageing, manage age-related diseases, and elevate quality of life. [ABSTRACT FROM AUTHOR]

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Background: In Parkinson's patients, intestinal dysbiosis can occur years before clinical diagnosis, implicating the gut and its microbiota in the disease. Recent evidence suggests the gut microbiota may trigger body-first Parkinson Disease (PD), yet the underlying mechanisms remain unclear. This study aims to elucidate how a dysbiotic microbiome through intestinal immune alterations triggers PD-related neurodegeneration. Methods: To determine the impact of gut dysbiosis on the development and progression of PD pathology, wild-type male C57BL/6 mice were transplanted with fecal material from PD patients and age-matched healthy donors to challenge the gut-immune-brain axis. Results: This study demonstrates that patient-derived intestinal microbiota caused midbrain tyrosine hydroxylase positive (TH +) cell loss and motor dysfunction. Ileum-associated microbiota remodeling correlates with a decrease in Th17 homeostatic cells. This event led to an increase in gut inflammation and intestinal barrier disruption. In this regard, we found a decrease in CD4 + cells and an increase in pro-inflammatory cytokines in the blood of PD transplanted mice that could contribute to an increase in the permeabilization of the blood–brain-barrier, observed by an increase in mesencephalic Ig-G-positive microvascular leaks and by an increase of mesencephalic IL-17 levels, compatible with systemic inflammation. Furthermore, alpha-synuclein aggregates can spread caudo-rostrally, causing fragmentation of neuronal mitochondria. This mitochondrial damage subsequently activates innate immune responses in neurons and triggers microglial activation. Conclusions: We propose that the dysbiotic gut microbiome (dysbiome) in PD can disrupt a healthy microbiome and Th17 homeostatic immunity in the ileum mucosa, leading to a cascade effect that propagates to the brain, ultimately contributing to PD pathophysiology. Our landmark study has successfully identified new peripheral biomarkers that could be used to develop highly effective strategies to prevent the progression of PD into the brain. [ABSTRACT FROM AUTHOR]

Through complex interactions with the host's immune and physiological systems, gut bacteria play a critical role as etiological agents in a variety of human diseases, having an impact that extends beyond their mere presence and affects the onset, progression, and severity of the disease. Gaining a comprehensive understanding of these microbial interactions is crucial to improving our understanding of disease pathogenesis and creating tailored treatment methods. Correcting microbial imbalances may open new avenues for disease prevention and treatment approaches, according to preliminary data. The gut microbiota exerts an integral part in the pathogenesis of numerous health conditions, including metabolic, neurological, renal, cardiovascular, and gastrointestinal problems as well as COVID-19, according to recent studies. The crucial significance of the microbiome in disease pathogenesis is highlighted by this role, which is comparable to that of hereditary variables. This review investigates the etiological contributions of the gut microbiome to human diseases, its interactions with the host, and the development of prospective therapeutic approaches. To fully harness the benefits of gut microbiome dynamics for improving human health, future research should address existing methodological challenges and deepen our knowledge of microbial interactions. [ABSTRACT FROM AUTHOR]

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits. Accumulated evidence has shown a link between alterations in the composition of gut microbiota and both neurobehavioural and gastrointestinal symptoms in children with ASD which are related to the genera Lactobacillus and Bifidobacterium. These genera have been recently categorized as "psychobiotics". Moreover, this study aimed to compare the relative abundance of psychobiotics (L. plantarum, L. reuteri, and B. longum) to the total gut microbiome in typically developing (TD) children and those with ASD in order to correlate the distribution of psychobiotic with the severity and sensory impairments in autism. The ASD children were assessed using the Childhood Autism Rating Scale (CARS), while sensory impairments were evaluated using the Short Sensory Profile (SSP). Furthermore, the gut microbiome was analyzed using the quantitative real-time PCR. The study revealed a statistically significant increase in the relative abundance of L. reuteri and L. plantarum in the TD group in comparison to ASD children. Regarding the SSP total score of ASD children, a statistically significant negative correlation was found between both Lactobacillus and L. plantarum with the under-responsive subscale. For the Autism Treatment Evaluation Checklist (ATEC) score, B. longum and Lactobacillus showed a significant positive correlation with Health/Physical/Behaviour. [ABSTRACT FROM AUTHOR]

The communication between intestinal Glucagon like peptide 1 (GLP-1)-producing cells and the peripheral nervous system has garnered renewed interest considering the availability of anti-obesity and anti-diabetic approaches targeting GLP-1 signaling. While it is well-established that intestinal GLP-1 cells can exert influence through paracrine mechanisms, recent evidence suggests the possible existence of synaptic-like connections between GLP-1 cells and peripheral neurons, including those of the vagus nerve. In this study, using a reporter Phox2b-Cre-Tomato mouse model and super-resolution confocal microscopy, we demonstrated that vagal axons made apparent contacts with less than 0.5% of GLP-1 cells. Moreover, immunohistochemistry combined with super-resolution confocal microscopy revealed abundant post-synaptic density 95 (PSD-95) immunoreactivity within the enteric plexus of the lower intestines of C57/BL6 mice, with virtually none in its mucosa. Lastly, utilizing RNAScope in situ hybridization in the lower intestines of mice, we observed that GLP-1 cells expressed generic markers of secretory cells such as Snap25 and Nefm, but neither synaptic markers such as Syn1 and Nrxn2, nor glutamatergic markers such as Slc17a7. Through theoretical considerations and a critical review of the literature, we concluded that intestinal GLP-1 cells primarily communicate with vagal neurons through paracrine mechanisms, rather than synaptic-like contacts. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The intricate connection between the gut and the brain involves multiple routes. Several viral families begin their infection cycle in the intestinal tract. However, amongst the long list of viral intestinal pathogens, picornaviruses, and astroviruses stand out for their ability to transition from the intestinal epithelia to central or peripheral nervous system cells. In immunocompromised, neonates and young children, these viral infections can manifest as severe diseases, such as encephalitis, meningitis, and acute flaccid paralysis. What confers this remarkable plasticity and makes them efficient in infecting cells of the gut and the brain axes? Here, we review the current understanding of the virus infection along the gut-brain axis for some enteric viruses and discuss the molecular mechanisms of their attenuation. [ABSTRACT FROM AUTHOR]

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by social, behavioral, and cognitive impairments. Several comorbidities, including gastrointestinal (GI) dysregulations, are frequently reported in ASD children. Although studies in animals have shown the crucial role of the microbiota in key aspects of neurodevelopment, there is currently no consensus on how the alteration of microbial composition affects the pathogenesis of ASD. Moreover, disruption of the gut–brain axis (GBA) has been reported in ASD although with limited studies conducted on the Mediterranean population. In our study, we aimed to investigate gut microbiota composition in Lebanese ASD subjects, their unaffected siblings, and a control group from various regions in Lebanon using the 16 S-rRNA sequencing (NGS). Our study revealed a lower abundance of Turicibacter and a significant enrichment on Proteobacteria in the ASD and siblings' groups compared to the controls, indicating that gut microbiota is probably affected by dietary habits, living conditions together with host genetic factors. The study also showed evidence of changes in the gut microbiome of ASD children compared to their siblings and the unrelated control. Bacteroidetes revealed a lower abundance in the ASD group compared to controls and siblings, conversely, Catenibacterium and Tenericutes revealed an increased abundance in the ASD group. Notably, our study identifies alterations in the abundance of Turicibacter and Catenibacterium in ASD children suggesting a possible link between these bacterial taxa and ASD and contributing to the growing body of evidence linking the microbiome to ASD. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease is a progressive neurodegenerative disease characterized by structural changes in the brain, including hippocampal atrophy, cortical thinning, amyloid plaques, and tau tangles. Due to the aging of the global population, the burden of Alzheimer's disease is expected to increase, making the exploration of non-pharmacological interventions, such as physical exercise, an urgent priority. Results: There is emerging evidence that regular physical exercise may mitigate the structural and functional declines associated with Alzheimer's disease. The underlying mechanisms, however, remain poorly understood. Gut–brain axis research is a promising area for further investigation. This system involves bidirectional communication between the gut microbiome and the brain. According to recent studies, the gut microbiome may influence brain health through modulating neuroinflammation, producing neuroactive compounds, and altering metabolic processes. Exercise has been shown to alter the composition of the gut microbiome, potentially impacting brain structure and function. In this review, we aim to synthesize current research on the relationship between physical exercise, structural brain changes in Alzheimer's disease, and the gut–brain axis. Conclusions: In this study, we will investigate whether changes in the gut microbiome induced by physical exercise can mediate its neuroprotective effects, offering new insights into the prevention and treatment of Alzheimer's disease. By integrating findings from neuroimaging studies, clinical trials, and microbiome research, this review will highlight potential mechanisms. It will also identify key gaps in the literature. This will pave the way for future research directions. [ABSTRACT FROM AUTHOR]

Opioid Use Disorder is a chronic condition characterized by compulsive opioid use despite negative consequences, resulting in severe health risks such as overdose and contraction of infectious diseases. High dropout rates in opioid agonist therapy highlight the need for more effective relapse prevention strategies. Animal and clinical studies indicate that opioids influence gut microbiota, which in turn plays a critical role in addiction development and alters behavioral responses to opioids. This study provides a comprehensive review of the literature on the effects of opioids on the gut microbiome and explores the potential of microbiome manipulation as a therapeutic target in opioid addiction. [ABSTRACT FROM AUTHOR]

The gut–brain axis plays a pivotal role in the finely tuned orchestration of food intake, where both homeostatic and hedonic processes collaboratively control our dietary decisions. This interplay involves the transmission of mechanical and chemical signals from the gastrointestinal tract to the appetite centers in the brain, conveying information on meal arrival, quantity, and chemical composition. These signals are processed in the brain eventually leading to the sensation of satiety and the termination of a meal. However, the regulation of food intake and appetite extends beyond the realms of pure physiological need. Hedonic mechanisms, including sensory perception (i.e., through sight, smell, and taste), habitual behaviors, and psychological factors, exert profound influences on food intake. Drawing from studies in animal models and human research, this comprehensive review summarizes the physiological mechanisms that underlie the gut–brain axis and its interplay with the reward network in the regulation of appetite and satiety. The recent advancements in neuroimaging techniques, with a focus on human studies that enable investigation of the neural mechanisms underpinning appetite regulation are discussed. Furthermore, this review explores therapeutic/pharmacological strategies that hold the potential for controlling food intake. [ABSTRACT FROM AUTHOR]

The oral delivery of most atypical antipsychotics is severely challenged by their low oral bioavailability and significant food effects that necessitate patient compliance. Lipid formulations are an attractive delivery system for overcoming the dosing challenges of antipsychotics, but their negative impact on the gut microbiota can interfere with the pharmacodynamic response through disruption of the gut‐brain axis. Here, novel gut microbiota‐targeting microcapsules are engineered to provide a multifunctional approach for improving both the pharmacokinetic and pharmacodynamic properties of the antipsychotic, lurasidone. The microcapsules are comprised of a lipid core that facilitates the solubilization and oral absorption of the lipophilic drug and an outer carbohydrate polymer (inulin) shell that positively modulates the gut microbiota by facilitating microbial fermentation. Fed‐fasted variability in lurasidone solubilization is mitigated through microencapsulation with inulin‐lipid microcapsules (ILM), while microbiota enrichment is coupled with enhanced serotonin levels in the small intestine, faeces, and plasma. The realization of multifunctional ILM confirms the pharmacokinetics and efficacy of mental health therapies, such as antipsychotics, can be optimized through strategic encapsulation within functional formulations that target the gut microbiota for effective modulation of the gut‐brain axis. [ABSTRACT FROM AUTHOR]

The purpose of this study was to explore whether prenatal gut microbiota (GM) and its functions predict the development of offspring temperament. A total of 53 mothers with a 1-year-old child and 41 mothers with a 2-year-old child were included in this study using a mother-infant cohort from central China. Maternal fecal samples collected during the third trimester were analyzed using 16S rRNA V3-V4 gene sequences. Temperament of the child was measured by self-reported data according to the primary caregiver. The effects of GM in mothers on offspring's temperament were evaluated using multiple linear regression models. The results demonstrated that the alpha diversity index Simpson of prenatal GM was positively associated with the activity level of offspring at 1 year (adj. P =.036). Bifidobacterium was positively associated with high-intensity pleasure characteristics of offspring at 1 year (adj. P =.031). Comparatively, the presence of Bifidobacterium found in the prenatal microbiome was associated with low-intensity pleasure characteristics in offspring at 2 years (adj. P =.031). There were many significant associations noted among the functional pathways of prenatal GM and temperament of offspring at 2 years. Our findings support the maternal-fetal GM axis in the setting of fetal-placental development with subsequent postnatal neurocognitive developmental outcomes, and suggest that early childhood temperament is in part associated with specific GM in the prenatal setting. [ABSTRACT FROM AUTHOR]

Active polysaccharides from plants are broadly applied in the food and health industry. The purpose of this study is to identify a new plant active polysaccharide and to investigate its role in modulating spatial memory. Ultrasonics and DEAE-52 chromatography were used to separate and purify the plant active polysaccharide (PAP). Mice were exposed to 100 ppm of lead acetate from birth to 7 weeks old to establish the memory impairment model. PAPs with concentrations of 200 or 400 ppm were fed to the subject mice each day after weaning in a spatiotemporally separated fashion. At the end of the intervention, mice were examined using the Morris water maze test, microbiome sequencing, cytokine profiling and protein analysis. The derived active polysaccharide was constituted by β-anomeric carbon, indicating a new form of PAP. The PAP significantly ameliorates the memory impairment caused by postnatal lead exposure, as evidenced by the preferred coverage of the test mouse in the hidden platform, demonstrating salient neuroregulatory activity. In terms of the gut microbiome in response to PAP treatment, it was found that the 400 ppm PAP reversed the gut dysbiosis, producing a comparable structure to the intact animals, represented by the relative abundance of Firmicutes and Muribaculum, Desulfovibrio, etc. For cytokines, the PAP reversed the plasma levels of IL-6, suggesting an anti-inflammatory trend in the context of proinflammation caused by lead invasion. By injecting an IL-6 antagonist, Tocilizumab, into the deficient mice, the spatial memory was significantly repaired, which demonstrates the central roles of IL-6 in mediating the positive effect of the PAP. Finally, a histone modification mark, H3K27me3, was found to be potent in responding to the signals conveyed by the PAP. The PAP could improve the memory deficits by remodeling the gut–brain axis centered at the microbiota and IL-6, which is regarded as an important cytokine-modulating brain activity. This is an intriguing instance linking neuromodulation with the active polysaccharide, shedding light on the innovative applications of plant polysaccharides due to the scarcity of similar phenotypic connections. [ABSTRACT FROM AUTHOR]

Studies of the composition of the gut microbiome have consistently shown that psychiatric disorders such as schizophrenia are associated with gut dysbiosis. However, research focusing on adolescents with early-onset psychosis remains limited. This study aimed to characterize the microbial communities and their potential metabolic functions in these populations. We identified that genera Desulfovibrionaceae_Incertae_Sedis, Paraprevotella, and several genera from the Oscillospiraceae family were significantly more abundant in patients with schizophrenia compared to non-psychotic individuals, while Dorea showed decreased levels in schizophrenia patients. Furthermore, patients with early-onset psychosis demonstrated a significant reduction in Staphylococcus abundance. Additionally, we observed an increase in Prevotellaceae Leyella and Prevotellaceae Incertae Sedis in patients receiving atypical antipsychotic treatment, along with a rise in the genus Weissella among those treated with sertraline. Conversely, patients on valproate treatment exhibited decreased levels of Desulfovibrionaceae Incertae Sedis, while showing increased levels of Kandleria and Howardella. Functional prediction analysis using PICRUSt2 revealed significant differences in the expression of key enzymes associated with fatty acid metabolism. Gene orthology analysis identified 10 differentially expressed genes in the early-onset psychosis and schizophrenia groups. Our findings underscore the importance of considering dietary factors, pharmacological treatments, and microbial composition in understanding the gut–brain axis in psychiatric disorders. [ABSTRACT FROM AUTHOR]

ABSTRACT: The objectives of this study were to determine if weaning would induce behavioral and physiological indicators of a negative affective state, and if supplementation of inactivated Lactobacillus helveticus (ILH) to dairy calves would reduce those indicators of negative affect during weaning. Male Holstein calves (n = 23) were enrolled in the study on d 1 of life. The calves were housed in individual pens in 1 of 4 rooms for the 42-d study. Calves began a step-down weaning from 9 L/d of milk replacer (MR), at 150 g of MR powder/L, on d 35 and received 6 L/d on d 35 to 36, 3 L/d on d 37 to 38, and 0.4 L/d on d 39 to 42. The MR was divided between 3 meals/d until the last 0.4 L/d phase, which was divided between 2 meals/d. Calves had ad libitum water access throughout the study and calf starter from d 28 onward. Within room, calves were assigned to 1 of 2 treatments: (1) control (CON; n = 11) and (2) 5 g of ILH/d split over and mixed into the 0800 h and 2000 h milk feedings from d 3 to 42 (ILH; n = 12). Lying behavior was recorded using HOBO data loggers from d 21 to 41. On d 33, 37, and 41, infrared eye images were taken to determine maximum eye temperature (MET), saliva samples were collected to determine cortisol concentration, and play assessments were conducted to quantify play behavior. On d 34, 38, and 42, blood samples were collected to determine blood serotonin concentration, whereas on d 38 and 39, calves were tested with a cognitive task. A subset of calves (n = 5/treatment) were euthanized to collect gut and brain tissue samples for serotonin concentration on d 43. Weaning resulted in fewer (d 37–41; tendency: d 36), but longer (d 38–41; tendency: d 37), lying bouts and reduced play (d 41), although no changes in lying time, MET, saliva cortisol, nor blood serotonin were detected with initiation of weaning. Supplementation of ILH was associated with less lying time throughout the study, and reduced play duration and higher salivary cortisol during weaning. No differences in lying bouts, play count, blood and tissue (colon, ileum, prefrontal cortex and brain stem) serotonin concentration, and time to complete the cognitive task were detected between the treatments. Overall, weaning induced behavioral changes indicative of negative affective state, and some behavioral differences were observed with ILH supplementation both before and during weaning, with some physiological changes observed during weaning.