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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: Previous research has shown a significant link between gut microbiota in children with autism spectrum disorder (ASD) and attention‐deficit hyperactivity disorder (ADHD). However, much remains unknown because of the heterogeneity of disorders and the potential confounders such as dietary patterns and control group variations. Methods: Children aged 6–12 years who had been clinically diagnosed with ASD and/or ADHD, their unaffected neurotypical siblings, and non‐related neurotypical volunteers were recruited cross‐sectionally. The ASD diagnosis was confirmed using the Autism Diagnostic Observation Schedule‐2 (ADOS‐2) in all patients, including those with ADHD. Standardized DNA extraction and sequencing methods were used to compare gut microbial alpha‐diversity among the groups. Dietary diversity was calculated from a standardized dietary questionnaire form. We compared the difference in gut microbiome between patients with ASD and/or ADHD with neurotypical siblings and non‐related neurotypical controls. Results: Ninety‐eight subjects were included in the study (18 with ASD, 19 with ADHD, 20 with both ASD and ADHD, 13 neurotypical siblings, and 28 non‐related neurotypical controls). The alpha‐diversity indices, such as Chao 1 and Shannon index, showed a significant difference between the groups in a Linear mixed‐effect model (F(4, 93) = 4.539, p =.02), (F(4, 93) = 3.185, p =.017), respectively. In a post‐hoc pairwise comparison, patients with ASD had lower alpha‐diversity compared with non‐related controls after Bonferroni correction. Dietary diversity shown in Shannon index did not differ among the groups (F(4, 84) = 1.494, p =.211). Conclusions: Our study indicates disorder‐specific microbiome differences in patients with ASD. In future research on gut microbiota in neurodevelopmental disorders, it is necessary to consider the impact of ASD and ADHD co‐occurrence, and strictly control for background information such as diet, to elucidate the gut–microbiota interaction in ASD and ADHD for exploring the potential of therapeutic interventions. [ABSTRACT FROM AUTHOR]

As one of the most urgent social and health problems in the world, neurodegenerative diseases have always been of interest to researchers. However, the pathological mechanisms and therapeutic approaches are not achieved. In addition to the established roles of oxidative stress, inflammation and immune response, changes of gut microbiota are also closely related to the pathogenesis of neurodegenerative diseases. Gut microbiota is the central player of the gut–brain axis, the dynamic bidirectional communication pathway between gut microbiota and central nervous system, and emerging insights have confirmed its indispensability in the development of neurodegenerative diseases. In this review, we discuss the complex relationship between gut microbiota and the central nervous system from the perspective of the gut–brain axis; review the mechanism of microbiota for the modulation different neurodegenerative diseases and discuss how different dietary patterns affect neurodegenerative diseases via gut microbiota; and prospect the employment of gut microbiota in the therapeutic approach to those diseases. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The microbiome-gut-brain axis is altered by environmental stressors such as heat, diet, and pollutants as well as microbes in the air, water, and soil. These stressors might alter the host's microbiome and symbiotic relationship by modifying the microbial composition or location. Compartmentalized mutualistic microbes promote the beneficial interactions in the host leading to circulating metabolites and hormones such as insulin and leptin that affect inter-organ functions. Inflammation and oxidative stress induced by environmental stressors may alter the composition, distribution, and activities of the microbes in the microbiomes such that the resultant metabolite and hormone changes are no longer beneficial. The microbiome-gut-brain axis and immune adverse changes that may accompany environmental stressors are reviewed for effects on innate and adaptive immune cells, which may make host immunity less responsive to pathogens and more reactive to self-antigens. Cardiovascular and fluid exchanges to organs might adversely alter organ functionality. Organs, especially the brain, need a consistent supply of nutrients and clearance of debris; disruption of these exchanges by stressors, and involvement of gut microbiome are discussed regarding neural dysfunctions with Alzheimer's disease, autistic spectrum disorders, viral infections, and autoimmune diseases. The focus of this review includes the manner in which environmental stressors may disrupt gut microbiota leading to adverse immune and hormonal influences on development of neuropathology related to hyperhomocysteinemia, inflammation, and oxidative stress, and how certain therapeutics may be beneficial. Strategies are explored to lessen detrimental effects of environmental stressors on central and peripheral health navigated toward (1) understanding neurological disorders and (2) promoting environmental and public health and well-being. [ABSTRACT FROM AUTHOR]

Context: The proportion of the elderly population is on the rise across the globe, and with it the prevalence of age-related neurodegenerative diseases. The gut microbiota, whose composition is highly regulated by dietary intake, has emerged as an exciting research field in neurology due to its pivotal role in modulating brain functions via the gut-brain axis. Objectives: We aimed at conducting a systematic review of preclinical and clinical studies investigating the effects of dietary interventions on cognitive ageing in conjunction with changes in gut microbiota composition and functionality. Methods: PubMed and Scopus were searched using terms related to ageing, cognition, gut microbiota and dietary interventions. Studies were screened, selected based on previously determined inclusion and exclusion criteria, and evaluated for methodological quality using recommended risk of bias assessment tools. Results: A total of 32 studies (18 preclinical and 14 clinical) were selected for inclusion. We found that most of the animal studies showed significant positive intervention effects on cognitive behavior, while outcomes on cognition, microbiome features, and health parameters in humans were less pronounced. The effectiveness of dietary interventions depended markedly on the age, gender, degree of cognitive decline and baseline microbiome composition of participants. Conclusion: To harness the full potential of microbiome-inspired nutrition for cognitive health, one of the main challenges remains to better understand the interplay between host, his microbiome, dietary exposures, whilst also taking into account environmental influences. Future research should aim toward making use of host-specific microbiome data to guide the development of personalized therapies. [ABSTRACT FROM AUTHOR]

There is growing concern about the role of the microbiota-gut-brain axis in neurological illnesses, and it makes sense to consider microglia as a critical component of this axis in the context of epilepsy. Microglia, which reside in the central nervous system, are dynamic guardians that monitor brain homeostasis. Microglia receive information from the gut microbiota and function as hubs that may be involved in triggering epileptic seizures. Vagus nerve bridges the communication in the axis. Essential axis signaling molecules, such as gamma-aminobutyric acid, 5-hydroxytryptamin, and short-chain fatty acids, are currently under investigation for their participation in drug-resistant epilepsy (DRE). In this review, we explain how vagus nerve connects the gut microbiota to microglia in the brain and discuss the emerging concepts derived from this interaction. Understanding microbiota-gut-brain axis in epilepsy brings hope for DRE therapies. Future treatments can focus on the modulatory effect of the axis and target microglia in solving DRE. [ABSTRACT FROM AUTHOR]

Background and Hypothesis The gut-brain axis plays important roles in both gastrointestinal diseases (GI diseases) and schizophrenia (SCZ). Moreover, both GI diseases and SCZ exhibit notable abnormalities in brain subcortical volumes. However, the genetic mechanisms underlying the comorbidity of these diseases and the shared alterations in brain subcortical volumes remain unclear. Study Design Using the genome-wide association studies data of SCZ, 14 brain subcortical volumes, and 8 GI diseases, the global polygenic overlap and local genetic correlations were identified, as well as the shared genetic variants among those phenotypes. Furthermore, we conducted multi-trait colocalization analyses to bolster our findings. Functional annotations, cell-type enrichment, and protein-protein interaction (PPI) analyses were carried out to reveal the critical etiology and pathology mechanisms. Study Results The global polygenic overlap and local genetic correlations informed the close relationships between SCZ and both GI diseases and brain subcortical volumes. Moreover, 84 unique lead-shared variants were identified. The associated genes were linked to vital biological processes within the immune system. Additionally, significant correlations were observed with key immune cells and the PPI analysis identified several histone-associated hub genes. These findings highlighted the pivotal roles played by the immune system for both SCZ and GI diseases, along with the shared alterations in brain subcortical volumes. Conclusions These findings revealed the shared genetic architecture contributing to SCZ and GI diseases, as well as their shared alterations in brain subcortical volumes. These insights have substantial implications for the concurrent development of intervention and therapy targets for these diseases. [ABSTRACT FROM AUTHOR]

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Although the aetio‐pathogenesis of inflammatory bowel diseases (IBD) is not entirely clear, the interaction between genetic and adverse environmental factors may induce an intestinal dysbiosis, resulting in chronic inflammation having effects on the large‐scale brain network. Here, we hypothesized inflammation‐related changes in brain topology of IBD patients, regardless of the clinical form [ulcerative colitis (UC) or Crohn's disease (CD)]. To test this hypothesis, we analysed source‐reconstructed magnetoencephalography (MEG) signals in 25 IBD patients (15 males, 10 females; mean age ± SD, 42.28 ± 13.15; mean education ± SD, 14.36 ± 3.58) and 28 healthy controls (HC) (16 males, 12 females; mean age ± SD, 45.18 ± 12.26; mean education ± SD, 16.25 ± 2.59), evaluating the brain topology. The betweenness centrality (BC) of the left hippocampus was higher in patients as compared with controls, in the gamma frequency band. It indicates how much a brain region is involved in the flow of information through the brain network. Furthermore, the comparison among UC, CD and HC showed statistically significant differences between UC and HC and between CD and HC, but not between the two clinical forms. Our results demonstrated that these topological changes were not dependent on the specific clinical form, but due to the inflammatory process itself. Broader future studies involving panels of inflammatory factors and metabolomic analyses on biological samples could help to monitor the brain involvement in IBD and to clarify the clinical impact. [ABSTRACT FROM AUTHOR]

The human microbiota is an intricate micro-ecosystem comprising a diverse range of dynamic microbial populations mainly consisting of bacteria, whose interactions with hosts strongly affect several physiological and pathological processes. The gut microbiota is being increasingly recognized as a critical player in maintaining homeostasis, contributing to the main functions of the intestine and distal organs such as the brain. However, gut dysbiosis, characterized by composition and function alterations of microbiota with intestinal barrier dysfunction has been linked to the development and progression of several pathologies, including intestinal inflammatory diseases, systemic autoimmune diseases, such as rheumatic arthritis, and neurodegenerative diseases, such as Alzheimer's disease. Moreover, oral microbiota research has gained significant interest in recent years due to its potential impact on overall health. Emerging evidence on the role of microbiota–host interactions in health and disease has triggered a marked interest on the functional role of bacterial extracellular vesicles (BEVs) as mediators of inter-kingdom communication. Accumulating evidence reveals that BEVs mediate host interactions by transporting and delivering into host cells effector molecules that modulate host signaling pathways and cell processes, influencing health and disease. This review discusses the critical role of BEVs from the gut, lung, skin and oral cavity in the epithelium, immune system, and CNS interactions. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a serious global public health issue, recognized as a chronic and progressive disease that can affect multiple organs, including the gastrointestinal (GI) tract. Research shows that there is a specific link between the GI tract and the central nervous system, termed the gut–brain axis, which consists of bidirectional exchange between these two. Several preclinical and clinical studies have demonstrated intestinal barrier dysfunction, intestinal inflammation and gut dysbiosis in patients with TBI. It is proven that probiotics can modulate the inflammatory process and modify gut microbiota. Numerous animal studies and human clinical trials have proven the effectiveness of selected bacterial strains as an adjuvant treatment in reducing inflammation, infection rates and time spent in intensive care of hospitalized patients suffering from brain injury. Thus, this review summarizes the current evidence regarding the beneficial effects of probiotic administration in patients suffering from TBI-related complications. This review will help identify novel therapeutic strategies in the future as probiotics have an extensive history of apparently safe use. [ABSTRACT FROM AUTHOR]

Summary: The human gut microbiome is well‐recognized as a key player in maintaining health. However, it is a dynamic entity that changes across the lifespan. How the microbial changes that occur in later decades of life shape host health or impact age‐associated inflammatory neurological diseases such as multiple sclerosis (MS) is still unclear. Current understanding of the aging gut microbiome is largely limited to cross‐sectional observational studies. Moreover, studies in humans are limited by confounding host‐intrinsic and extrinsic factors that are not easily disentangled from aging. This review provides a comprehensive summary of existing literature on the aging gut microbiome and its known relationships with neurological diseases, with a specific focus on MS. We will also discuss preclinical animal models and human studies that shed light on the complex microbiota–host interactions that have the potential to influence disease pathology and progression in aging individuals. Lastly, we propose potential avenues of investigation to deconvolute features of an aging microbiota that contribute to disease, or alternatively promote health in advanced age. [ABSTRACT FROM AUTHOR]

Several studies have provided interesting evidence about the role of the bidirectional communication between the gut and brain in the onset and development of several pathologic conditions, including inflammatory bowel diseases (IBDs), neurodegenerative diseases, and related comorbidities. Indeed, patients with IBD can experience neurologic disorders, including depression and cognitive impairment, besides typical intestinal symptoms. In parallel, patients with neurodegenerative disease, such as Parkinson disease and Alzheimer disease, are often characterized by the occurrence of functional gastrointestinal disorders. In this context, enteric glial cells and brain astrocytes are emerging as pivotal players in the initiation/maintenance of neuroinflammatory responses, which appear to contribute to the alterations of intestinal and neurologic functions observed in patients with IBD and neurodegenerative disorders. The present review was conceived to provide a comprehensive and critical overview of the available knowledge on the morphologic, molecular, and functional changes occurring in the enteric glia and brain astroglia in IBDs and neurologic disorders. In addition, our intent is to identify whether such alterations could represent a common denominator involved in the onset of comorbidities associated with the aforementioned disorders. This might help to identify putative targets useful to develop novel pharmacologic approaches for the therapeutic management of such disturbances. [ABSTRACT FROM AUTHOR]

The gut is a digestive organ that absorbs nutrients but also plays a vital role in immune response and defense against external compounds. The complex interaction between the gut microbiota and other organs including the immune system of the host has been known in various contexts, yielding the notion of 'axes' between the gut and other organs. While the presence of various gut-organ axes has been reported, the lack of adequate in vitro model systems for studying this interaction has restricted a deeper insight into these phenomena. Recently developed microphysiological systems (MPS), also known as organ-on-a-chip, allow researchers to study complex interactions between diverse organs, and here we provide a review of how recently developed gut-on-a-chip systems are used for building models of various diseases that were difficult to study. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cross-fostering induced social deficit involved in the vagal gut-to-brain axis in the adulthood of mice. • Gut-innervating sensory neurons connect with PVN oxytocin neurons across multiple synapses. • Sex-specific alteration in gut microbiota and its metabolites may be involved in social impairments and immune imbalances brought by cross-fostering via the gut-brain axis. • Cross-fostering social cognitive impairment may result from a combination of PVN oxytocinergic neurons, gut microbiota, and metabolites. The gut microbiota and neurological development of neonatal mice are susceptible to environmental factors that may lead to altered behavior into adulthood. However, the role that changed gut microbiota and neurodevelopment early in life play in this needs to be clarified. In this study, by modeling early-life environmental changes by cross-fostering BALB/c mice, we revealed the effects of the environment during the critical period of postnatal development on adult social behavior and their relationship with the gut microbiota and the nervous system. The neural projections exist between the ascending colon and oxytocin neurons in the paraventricular nuclei (PVN), peripheral oxytocin levels and PVN neuron numbers decreased after cross-fostering, and sex-specific alteration in gut microbiota and its metabolites may be involved in social impairments and immune imbalances brought by cross-fostering via the gut-brain axis. Our findings also suggest that social cognitive impairment may result from a combination of PVN oxytocinergic neurons, gut microbiota, and metabolites. [ABSTRACT FROM AUTHOR]

• The gut microbiota link to the Research Domains Criteria functional domains. • The associations span across neurodevelopmental and stress-related disorders. • There is a mix of domain-specific and psychiatry-general microbiota associations. • A dimensional approach clarifies the specificity of the gut-brain relationship. • The identified genera suggest involvement of immune-related processes. Changes in microbial composition are observed in various psychiatric disorders, but their specificity to certain symptoms or processes remains unclear. This study explores the associations between the gut microbiota composition and the Research Domain Criteria (RDoC) domains of functioning, representing symptom domains, specifically focusing on stress-related and neurodevelopmental disorders in patients with and without psychiatric comorbidity. The gut microbiota was analyzed in 369 participants, comprising 272 individuals diagnosed with a mood disorder, anxiety disorder, attention deficit/hyperactivity disorder, autism spectrum disorder, and/or substance use disorder, as well as 97 psychiatrically unaffected individuals. The RDoC domains were estimated using principal component analysis (PCA) with oblique rotation on a range of psychiatric, psychological, and personality measures. Associations between the gut microbiota and the functional domains were assessed using multiple linear regression and permanova, adjusted for age, sex, diet, smoking, medication use and comorbidity status. Four functional domains, aligning with RDoC's negative valence, social processes, cognitive systems, and arousal/regulatory systems domains, were identified. Significant associations were found between these domains and eight microbial genera, including associations of negative valence with the abundance of the genera Sellimonas , CHKCI001 , Clostridium sensu stricto 1 , Oscillibacter, and Flavonifractor ; social processes with Sellimonas ; cognitive systems with Sporobacter and Hungatella; and arousal/regulatory systems with Ruminococcus torques (all p FDR < 0.05). Our findings demonstrate associations between the gut microbiota and the domains of functioning across patients and unaffected individuals, potentially mediated by immune-related processes. These results open avenues for microbiota-focused personalized interventions, considering psychiatric comorbidity. However, further research is warranted to establish causality and elucidate mechanistic pathways. [ABSTRACT FROM AUTHOR]

Obesity is a chronic disease caused primarily by the imbalance between the amount of calories supplied to the body and energy expenditure. Not only does it deteriorate the quality of life, but most importantly it increases the risk of cardiovascular diseases and the development of type 2 diabetes mellitus, leading to reduced life expectancy. In this review, we would like to present the molecular pathomechanisms underlying obesity, which constitute the target points for the action of anti-obesity medications. These include the central nervous system, brain–gut–microbiome axis, gastrointestinal motility, and energy expenditure. A significant part of this article is dedicated to incretin-based drugs such as GLP-1 receptor agonists (e.g., liraglutide and semaglutide), as well as the brand new dual GLP-1 and GIP receptor agonist tirzepatide, all of which have become "block-buster" drugs due to their effectiveness in reducing body weight and beneficial effects on the patient's metabolic profile. Finally, this review article highlights newly designed molecules with the potential for future obesity management that are the subject of ongoing clinical trials. [ABSTRACT FROM AUTHOR]

Neuropsychiatric disorders are clinical conditions that affect cognitive function and emotional stability, often resulting from damage or disease in the central nervous system (CNS). These disorders are a worldwide concern, impacting approximately 12.5% of the global population. The gut microbiota has been linked to neurological development and function, implicating its involvement in neuropsychiatric conditions. Due to their interaction with gut microbial communities, probiotics offer a natural alternative to traditional treatments such as therapeutic drugs and interventions for alleviating neuropsychiatric symptoms. Introduced by Metchnikoff in the early 1900s, probiotics are live microorganisms that provide various health benefits, including improved digestion, enhanced sleep quality, and reduced mental problems. However, concerns about their safety, particularly in immunocompromised patients, warrant further investigation; this has led to the concept of "paraprobiotics", inactivated forms of beneficial microorganisms that offer a safer alternative. This review begins by exploring different methods of inactivation, each targeting specific cellular components like DNA or proteins. The choice of inactivation method is crucial, as the health benefits may vary depending on the conditions employed for inactivation. The subsequent sections focus on the potential mechanisms of action and specific applications of probiotics and paraprobiotics in neuropsychiatric therapy. Probiotics and paraprobiotics interact with gut microbes, modulating the gut microbial composition and alleviating gut dysbiosis. The resulting neuropsychiatric benefits primarily stem from the gut-brain axis, a bidirectional communication channel involving various pathways discussed in the review. While further research is needed, probiotics and paraprobiotics are promising therapeutic agents for the management of neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

The gut-brain axis plays an important role in Parkinson's disease (PD) by acting as a route for vagal propagation of aggregated α-synuclein in the gut-first endophenotype and as a mediator of gastrointestinal dyshomeostasis via the nigro-vagal pathway in the brain-first endophenotype of the disease. One important mechanism by which the gut-brain axis may promote PD is by regulating gastrointestinal redox homeostasis as overwhelming evidence suggests that oxidative stress plays a key role in the etiopathogenesis and progression of PD and the gastrointestinal tract maintains redox homeostasis of the organism by acting as a critical barrier to environmental and microbiological electrophilic challenges. The present aim was to utilize the bilateral intrastriatal 6-hydroxydopamine (6-OHDA) brain-first PD model to study the effects of isolated central pathology on redox homeostasis of the gastrointestinal tract. Three-month-old male Wistar rats were either not treated (intact controls; CTR) or treated bilaterally intrastriatally with vehicle (CIS) or 6-OHDA (6-OHDA). Motor deficits were assessed with the rotarod performance test, and the duodenum, ileum, and colon were dissected for biochemical analyses 12 weeks after the treatment. Lipid peroxidation, total antioxidant capacity, low-molecular-weight thiols, and protein sulfhydryls, the activity of total and Mn/Fe superoxide dismutases, and total and azide-insensitive catalase/peroxidase were measured. Both univariate and multivariate models analyzing redox biomarkers indicate that significant disturbances in gastrointestinal redox balance are not present. The findings demonstrate that motor impairment observed in the brain-first 6-OHDA model of PD can occur without concurrent redox imbalances in the gastrointestinal system. [ABSTRACT FROM AUTHOR]

The gut-brain axis (GBA) plays a dominant role in maintaining homeostasis as well as contributes to mental health maintenance. The pathways that underpin the axis expand from macroscopic interactions with the nervous system, to the molecular signals that include microbial metabolites, tight junction protein expression, or cytokines released during inflammation. The dysfunctional GBA has been repeatedly linked to the occurrence of anxiety- and depressive-like behaviors development. The importance of the inflammatory aspects of the altered GBA has recently been highlighted in the literature. Here we summarize current reports on GBA signaling which involves the immune response within the intestinal and blood-brain barrier (BBB). We also emphasize the effect of stress response on altering barriers' permeability, and the therapeutic potential of microbiota restoration by probiotic administration ormicrobiota transplantation, based on the latest animal studies. Most research performed on various stress models showed an association between anxiety- and depressive-like behaviors, dysbiosis of gut microbiota, and disruption of intestinal permeability with simultaneous changes in BBB integrity. It could be postulated that under stress conditions impaired communication across BBB may therefore represent a significant mechanism allowing the gut microbiota to affect brain functions. [ABSTRACT FROM AUTHOR]

The gastrointestinal (GI) tract, home to the largest microbial population in the human body, plays a crucial role in overall health through various mechanisms. Recent advancements in research have revealed the potential implications of gut-brain and vice-versa communication mediated by gut-microbiota and their microbial products in various diseases including type-2 diabetes and Alzheimer's disease (AD). AD is the most common type of dementia where most of cases are sporadic with no clearly identified cause. However, multiple factors are implicated in the progression of sporadic AD which can be classified as non-modifiable (e.g., genetic) and modifiable (e.g. Type-2 diabetes, diet etc.). Present review focusses on key players particularly the modifiable factors such as Type-2 diabetes (T2D) and diet and their implications in microbiota-gut-brain (MGB) and brain-gut (BG) communication and cognitive functions of healthy brain and their dysfunction in Alzheimer's Disease. Special emphasis has been given on elucidation of the mechanistic aspects of the impact of diet on gut-microbiota and the implications of some of the gut-microbial products in T2D and AD pathology. For example, mechanistically, HFD induces gut dysbiosis with driven metabolites that in turn cause loss of integrity of intestinal barrier with concomitant colonic and systemic chronic low-grade inflammation, associated with obesity and T2D. HFD-induced obesity and T2D parallel neuroinflammation, deposition of Amyloid β (Aβ), and ultimately cognitive impairment. The review also provides a new perspective of the impact of diet on brain-gut and microbiota-gut-brain communication in terms of transcription factors as a commonly spoken language that may facilitates the interaction between gut and brain of obese diabetic patients who are at a higher risk of developing cognitive impairment and AD. Other commonality such as tyrosine kinase expression and functions maintaining intestinal integrity on one hand and the phagocytic clarence by migratory microglial functions in brain are also discussed. Lastly, the characterization of the key players future research that might shed lights on novel potential pharmacological target to impede AD progression are also discussed. [ABSTRACT FROM AUTHOR]

Children diagnosed with autism spectrum disorder (ASD) are at an increased risk of experiencing gastrointestinal (GI) discomfort, which has been linked to dysfunctions in the microbiome–gut–brain axis. The bidirectional communication between gut and brain plays a crucial role in the overall health of individuals, and alterations in the gut microbiome can contribute to immune activation and gut–brain dysfunction in ASD. Despite the limited and controversial results of pre-/probiotic applications in ASD, this review comprehensively maps the association between ASD clinical symptoms and specific bacterial taxa and evaluates the efficacy of pre-/probiotics in modulating microbiota composition, reducing inflammatory biomarkers, alleviating difficulties in GI distress, sleep problems, core and other ASD-associated symptoms, as well as relieving parental concerns, separately, in individuals with ASD. Beyond simply targeting core ASD symptoms, this review highlights the potential of pre-/probiotic supplementations as a strategy to modulate gut homeostasis and immune response, and to delineate the potential mechanisms by which its direct or mediating effects can alleviate gut–brain dysfunction and poor nutritional status in ASD management. Further well-designed randomized controlled trials are needed to strengthen the existing evidence and establish optimal protocols for the use of pre-/probiotics in the context of ASD. [ABSTRACT FROM AUTHOR]

Evidence shows that neurodegenerative and neuropsychiatric disorders are influenced by alterations in the gut microbiome. Various diseases have been linked to microbiome dysbiosis, yet there are inconclusive data regarding which microorganisms are associated with each disorder. The aim of our study is to systematically review the recent literature of the past decade to clarify whether the gut microbiome contributes to the understanding of pathogenesis and progression of neurodegenerative disorders. Most included studies showed a strong correlation between the relative abundance of certain microorganisms, mainly species of the phyla Firmicutes and Bacteroidetes, and disorders such as Parkinson's disease (PD) and Alzheimer's disease (AD). It is speculated that the microorganisms and their byproducts have a significant role in brain protein accumulation, neuro-inflammation, and gut permeability. The estimation of microbial populations could potentially improve clinical outcomes and hinder the progression of the disease. However, further research is needed to include more diseases and larger patient samples and identify specific species and subspecies associated with these disorders. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that interactions between the brain and gut microbiota significantly impact brain function and mental health. In the present study, we aimed to investigate whether young, healthy adults without psychiatric diagnoses exhibit differences in metabolic stool and microbiota profiles based on depression/anxiety scores and heart rate variability (HRV) parameters. Untargeted nuclear magnetic resonance-based metabolomics was used to identify fecal metabolic profiles. Results were subjected to multivariate analysis through principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), and the metabolites were identified through VIP score. Metabolites separating asymptomatic and symptomatic groups were acetate, valine, and glutamate, followed by sugar regions, glutamine, acetone, valerate, and acetoacetate. The main metabolites identified in high vagal tone (HVT) and low vagal tone (LVT) groups were acetate, valerate, and glutamate, followed by propionate and butyrate. In addition to the metabolites identified by the PLS-DA test, significant differences in aspartate, sarcosine, malate, and methionine were observed between the groups. Levels of acetoacetate were higher in both symptomatic and LVT groups. Valerate levels were significantly increased in the symptomatic group, while isovalerate, propionate, glutamate, and acetone levels were significantly increased in the LVT group. Furthermore, distinct abundance between groups was only confirmed for the Firmicutes phylum. Differences between participants with high and low vagal tone suggest that certain metabolites are involved in communication between the vagus nerve and the brain. [ABSTRACT FROM AUTHOR]

Stroke, as a serious cerebral vascular disease with high incidence and high rates of disability and mortality, has limited therapeutic options due to the narrow time window. Compelling evidence has highlighted the significance of the gut microbiota and gut–brain axis as critical regulatory factors affecting stroke. Along the microbiota–gut–brain axis, tryptophan metabolism further acquires increasing attention for its intimate association with central nervous system diseases. For the purpose of exploring the potential role of tryptophan metabolism in stroke and providing systematic insights into the intricate connection of the microbiota–gut–brain axis with the pathological procedure of stroke, this review first summarized the practical relationship between microbiota and stroke by compiling the latest case-control research. Then, the microbiota–gut–brain axis, as well as its interaction with stroke, were comprehensively elucidated on the basis of the basic anatomical structure and physiological function. Based on the crosstalk of microbiota–gut–brain, we further focused on the tryptophan metabolism from the three major metabolic pathways, namely, the kynurenine pathway, serotonin pathway, and microbial pathway, within the axis. Moreover, the effects of tryptophan metabolism on stroke were appreciated and elaborated here, which is scarcely found in other reviews. Hopefully, the systematic illustration of the mechanisms and pathways along the microbiota–gut–brain axis will inspire more translational research from metabolic perspectives, along with more attention paid to tryptophan metabolism as a promising pharmaceutical target in order to reduce the risk of stroke, mitigate the stroke progression, and ameliorate the stroke prognosis. [ABSTRACT FROM AUTHOR]

The microbes in the gut are crucial for maintaining the body's immune system and overall gut health. However, it is not fully understood how an unstable gut environment can lead to more severe cases of SARS-CoV-2 infection. The gut microbiota also plays a role in the gut-brain axis and interacts with the central nervous system through metabolic and neuroendocrine pathways. The interaction between the microbiota and the host's body involves hormonal, immune, and neural pathways, and any disruption in the balance of gut bacteria can lead to dysbiosis, which contributes to pathogen growth. In this context, we discuss how dysbiosis could contribute to comorbidities that increase susceptibility to SARS-CoV-2. Probiotics and fecal microbiota transplantation have successfully treated infectious and non-infectious inflammatory-related diseases, the most common comorbidities. These treatments could be adjuvant therapies for COVID-19 infection by restoring gut homeostasis and balancing the gut microbiota. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic inflammatory disease that leads to demyelination and damage to the central nervous system. It is well known, the significance of the involvement and influence of the immune system in the development and course of MS. Nowadays, more and more studies are demonstrating that an important factor that affects the action of the immune system is the gut microbiota. Changes in the composition and interrelationships in the gut microbiota have a significant impact on the course of MS. Dysbiosis affects the disease course mainly by influencing the immune system directly but also by modifying the secreted metabolites and increasing mucosal permeability. The essential metabolites affecting the course of MS are short-chain fatty acids, which alter pro- and anti-inflammatory responses in the immune system but also increase the permeability of the intestinal wall and the blood–brain barrier. Dietary modification alone can have a significant impact on MS. Based on these interactions, new treatments for MS are being developed, including probiotics administration, supplementation of bacterial metabolites, fecal microbiota transplantation, and dietary changes. Further studies may serve to develop new drugs and therapeutic approaches for MS. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) remains a leading cause of death and disability that places a great physical, social, and financial burden on individuals and the health system. In this review, we summarize new research into the metabolic changes described in clinical TBI trials, some of which have already shown promise for informing injury classification and staging. We focus our discussion on derangements in glucose metabolism, cell respiration/mitochondrial function and changes to ketone and lipid metabolism/oxidation to emphasize potentially novel biomarkers for clinical outcome prediction and intervention and offer new insights into possible underlying mechanisms from preclinical research of TBI pathology. Finally, we discuss nutrition supplementation studies that aim to harness the gut/microbiome-brain connection and manipulate systemic/cellular metabolism to improve post-TBI recovery. Taken together, this narrative review summarizes published TBI-associated changes in glucose and lipid metabolism, highlighting potential metabolite biomarkers for clinical use, the cellular processes linking these markers to TBI pathology as well as the limitations and future considerations for TBI "omics" work. [ABSTRACT FROM AUTHOR]

Acute large hemispheric infarction (ALHI) is an overwhelming emergency with a great challenge of gastrointestinal dysfunction clinically. Here, we initially proposed delayed bowel movements as the clinical phenotype of strike to gut-brain axis (GBA) in ALHI patients by epidemiological analysis of 499 acute ischemic stroke (AIS) patients. 1H NMR-based metabolomics revealed that AIS markedly altered plasma global metabolic profiling of patients compared with healthy controls. Risk factors of strike on GBA were the National Institutes of Health Stroke Scale (NIHSS) score ≥ 5 and stroke onset time ≤ 24 h. As a result, first defecating time after admission to the hospital ≥2 days could be considered as a potential risk factor for strike on GBA. Subsequently, the ALHI Bama miniature (BM) pig model with acute symptomatic seizure was successfully established by ligation of the left ascending pharyngeal artery combined with local air injection. Clinical phenotypes of brain necrosis such as hemiplegia were examined with brain diffusion-weighted imaging (DWI) and pathological diagnosis. In addition to global brain injury and inflammation, we also found that ALHI induced marked alterations of intestinal barrier integrity, the gut microbial community, and microbiota-derived metabolites including serotonin and neurotransmitters in both plasma and multiple brain tissues of BM pigs. These findings revealed that microbiota-gut-brain axis highly contributed to the occurrence and development of ALHI. [ABSTRACT FROM AUTHOR]

Recombinant interleukin-22 (rIL-22) has been reported as a protective agent in murine models of diseases driven by epithelial injury. Parasites have a circadian rhythm and their sensitivity to a certain drug may vary during the day. Therefore, this work aimed to investigate the effect of rIL-22 administration at different times of the day on the inflammation, oxidative status, and neurotransmitter release in the gut-brain axis of the Schistosoma mansoni-infected mice. Sixty male BALB/c mice aged six weeks weighing 25–30 g were divided into a control group (injected intraperitoneally with PBS), mice infected with 80 ± 10 cercariae of S. mansoni (infected group) then injected intraperitoneally with PBS, and rIL-22 treated groups. rIL-22 was administrated intraperitoneally (400 ng/kg) either at the onset or offset of the light phase for 14 days. IL-22 administration reduced the levels of IL-1β, tumor necrosis factor-alpha (TNF-α), nuclear factor kappa beta (NF-κβ), and enhanced the production of IL-22 and IL-17. The treatment with IL-22 increased glutathione (GSH) and reduced malondialdehyde (MDA) and nitric oxide (NO) levels both in the ileum and brain. The B-cell lymphoma 2 (BCL2) protein level in the ileum was diminished after IL-22 administration. Brain-derived neurotrophic factor (BDNF) and neurotransmitter release (serotonin, 5HT, norepinephrine, NE, dopamine, DA, Glutamate, Glu, and -amino butyric acid, GABA) were improved by rIL-22. In conclusion, rIL-22 showed promising immunotherapy for inflammation, oxidative damage, and neuropathological signs associated with schistosomiasis. The efficacy of IL-22 increased significantly upon its administration at the time of light offset. [ABSTRACT FROM AUTHOR]

[Display omitted] • Gut microbiota contributes to the pathogenesis of multiple sclerosis. • Probiotic supplementation has a positive impact on immune and inflammatory responses. • The engineered probiotics is being explored as a therapeutic strategy for MS. Multiple sclerosis (MS) is a neurological autoimmune disorder predominantly afflicting young adults. The etiology of MS is intricate, involving a variety of environmental and genetic factors. Current research increasingly focuses on the substantial contribution of gut microbiota in MS pathogenesis. The commensal microbiota resident within the intestinal milieu assumes a central role within the intricate network recognized as the gut-brain axis (GBA), wielding beneficial impact in neurological and psychological facets. As a result, the modulation of gut microbiota is considered a pivotal aspect in the management of neural disorders, including MS. Recent investigations have unveiled the possibility of using probiotic supplements as a promising strategy for exerting a positive impact on the course of MS. This therapeutic approach operates through several mechanisms, including the reinforcement of gut epithelial integrity, augmentation of the host's resistance against pathogenic microorganisms, and facilitation of mucosal immunomodulatory processes. The present study comprehensively explains the gut microbiome's profound influence on the central nervous system (CNS). It underscores the pivotal role played by probiotics in forming the immune system and modulating neurotransmitter function. Furthermore, the investigation elucidates various instances of probiotic utilization in MS patients, shedding light on the potential therapeutic advantages afforded by this intervention. [ABSTRACT FROM AUTHOR]

[Display omitted] The functioning of the brain and its impact on behavior, emotions, and cognition can be affected by both neurological and psychiatric disorders that impose a significant burden on global health. Phytochemicals are helpful in the treatment of several neurological and psychological disorders, including anxiety, depression, Huntington's disease (HD), Parkinson's disease (PD), Alzheimer's disease (AD), and autism spectrum disorder (ASD), because they have symptomatic benefits with few adverse reactions. Changes in gut microbiota have been associated with many neurological and psychiatric conditions. This review focuses on the potential efficacy of phytochemicals such as flavonoids, terpenoids, and polyphenols in regulating gut flora and providing symptomatic relief for a range of neurological and psychological conditions. Evidence-based research has shown the medicinal potentials of these phytochemicals, but additional study is required to determine whether altering gut microbiota might slow the advancement of neurological and psychological problems. [ABSTRACT FROM AUTHOR]

(Poly)phenols are a group of naturally occurring phytochemicals present in high amounts in plant food and beverages with various structures and activities. The impact of (poly)phenols on brain function has gained significant attention due to the growing interest in the potential benefits of these dietary bioactive molecules for cognitive health and neuroprotection. This review will therefore summarise the current knowledge related to the impact of (poly)phenols on brain health presenting evidence from both epidemiological and clinical studies. Cellular and molecular mechanisms in relation to the observed effects will also be described, including their impact on the gut microbiota through the modulation of the gut‐brain axis. Although (poly)phenols have the potential to modulate the gut‐brain axis regulation and influence cognitive function and decline through their interactions with gut microbiota, anti‐inflammatory and antioxidant properties, further research, including randomised controlled trials and mechanistic studies, is needed to better understand the underlying mechanisms and establish causal relationships between (poly)phenol intake and brain health. [ABSTRACT FROM AUTHOR]

Background: The burden on society grows as the number of individuals with cognitive impairment rises. Numerous research have discovered a connection between cognitive impairment and the gut-brain axis, which is useful in examining the pathophysiology of cognitive impairment and potential therapeutic approaches. As a result, this article explores developments and trends in the research concerning the gut-brain axis and cognitive impairment through a bibliometric analysis of the contributions made by various countries/regions, institutions, authors, and journals. Methods: We looked for articles on gut-brain axis and cognitive impairment from 2014 to 2023 in the Web of Science Core Collection. For the descriptive analysis, figures and tables were taken using GraphPad Prism 6 and WPS Office 2024. For the visual analysis of the countries/regions, institutions, authors, and keywords, VOSviewer was utilized. Results: We obtained 458 publications from 1 January 2014 to 9 September 2023. The country with the most publications (175, 38.21%) was China. The country with the greatest total number of citations (3,138, 17.22%) was the United States of America. The highest number of articles (15, 3.26%) was issued by Zhejiang University. The most published first author is Karsas M. In this field, Nutrients have published the most articles (24). The most often occurring keywords include "Alzheimer's disease," "cognitive impairment," "gut microbiota," "inflammation," "diet," etc. "Stroke," "tau," "probiotics," "exercise," "fecal microbiota transplantation," etc. emerged later. Conclusion: An increasing amount of research has focused on the connection between cognitive impairment and the gut-brain axis. In this area, the United States of America and China have both made significant contributions. The author team's collaboration has to be improved. Our study contributes to understanding the field's current state and predicting its future trend. [ABSTRACT FROM AUTHOR]

The role of the gut microbiota in the pathophysiology of depression has been explored in numerous studies, which have confirmed that the baseline gut microbial profiles of patients with depression differ from those of healthy individuals. The gut microbiome affects metabolic activity in the immune and central nervous systems and regulates intestinal ecology through the neuroendocrine system. Additionally, baseline changes in the gut microbiota differed among patients with depression who demonstrated varying treatment response. Currently, probiotics are an emerging treatment for depression; however, the efficacy of modulating the gut microbiota in the treatment of depression remains uncertain. Additionally, the mechanisms by which changes in the gut microbiota affect treatment response in patients with depression remain unclear. In this review, we aimed to summarize the differences in the baseline gut microbiota between the remission and non-remission groups after antidepressant therapy. Additionally, we summarized the possible mechanisms that may contribute to antidepressant resistance through the effects of the gut microbiome on the immune and nervous systems, various enzymes, bioaccumulation, and blood-brain barrier, and provide a basis for treating depression by targeting the gut microbiota. [ABSTRACT FROM AUTHOR]

Background: Given the increasing interest in the role of gut microbiota in glioblastoma multiforme (GBM), our objective was to examine the potential causal relationship between gut microbiota and GBM, as well as the mediating effects of specific metabolites. Methods: A bidirectional two-sample Mendelian randomization (MR) analysis was conducted to investigate the associations between 196 microbial taxa and GBM. A two-step MR technique was used to identify significant mediators in this relationship. Subsequently, a mediation analysis was performed to explore and quantify the mediating effects of specific metabolites on the causal relationship between gut microbiota and GBM. Results: Five taxa showed significant associations with GBM. Among them, family Victivallaceae [odds ratio (OR): 1.95; 95% confidence interval (CI): 1.21, 3.13; p = 0.005] and genus Lactococcus (OR: 1.81; 95% CI: 1.04, 3.15; p = 0.036) were positively correlated with the risk of GBM, while phylum Cyanobacteria had a protective effect against GBM (OR: 0.45; 95% CI: 0.22, 0.89; p = 0.021). The mediation analysis revealed that the connections among family Victivallaceae, genus Lactococcus, phylum Cyanobacteria and GBM were mediated by Methyl-4-hydroxybenzoate sulfate, phosphoethanolamine and dehydroepiandrosterone sulfate. Each of these accounted for 7.27, 7.98, and 8.65%, respectively. Conclusion: Our study provides evidence supporting a potential causal association between certain gut microbiota taxa and GBM. The study highlights the central role of gut microbiota in GBM pathogenesis and their interactions with vital serum metabolites. This paves the way for potential novel therapeutic interventions in GBM management. [ABSTRACT FROM AUTHOR]

Accumulating evidence suggests that gut inflammation is implicated in neuroinflammation in Alzheimer's and Parkinson's diseases. Despite the numerous connections it remains unclear how the gut and the brain communicate and whether gut dysbiosis is the cause or consequence of these pathologies. Importantly, several reports highlight the importance of mitochondria in the gut-brain axis, as well as in mechanisms like gut epithelium self-renewal, differentiation, and homeostasis. Herein we comprehensively address the important role of mitochondria as a cellular hub in infection and inflammation and as a link between inflammation and neurodegeneration in the gut-brain axis. The role of mitochondria in gut homeostasis and as well the crosstalk between mitochondria and gut microbiota is discussed. Significantly, we also review studies highlighting how gut microbiota can ultimately affect the central nervous system. Overall, this review summarizes novel findings regarding this cross-talk where the mitochondria has a main role in the pathophysiology of both Alzheimer's and Parkinson's disease strengthen by cellular, animal and clinical studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Canine behavioral disorders have become one of the most common concerns and challenging issues among dog owners. Therefore, to face this challenge, searching for novel therapeutic methods is highly required. Accumulated data show that mammals' gut microbiome, immune system, and nervous system are in continuous communication and influence animal physiology and behavior. This review aimed to summarize and discuss the most important scientific pieces of evidence on the relationship between mental disorders and gut microbiota in dogs, simultaneously presenting comparable outcomes in humans and rodent models. A comprehensive overview of crucial mechanisms of the gut–brain axis is included. Additionally, the possible effects of the fecal microbiome transplantation procedure as a new tool to manipulate gut microbiota are discussed. Canine behavioral disorders have become one of the most common concerns and challenging issues among dog owners. Thus, there is a great demand for knowledge about various factors affecting dogs' emotions and well-being. Among them, the gut–brain axis seems to be particularly interesting, especially since in many instances the standard treatment or behavioral therapies insufficiently improve animal behavior. Therefore, to face this challenge, the search for novel therapeutic methods is highly required. Existing data show that mammals' gut microbiome, immune system, and nervous system are in continuous communication and influence animal physiology and behavior. This review aimed to summarize and discuss the most important scientific evidence on the relationship between mental disorders and gut microbiota in dogs, simultaneously presenting comparable outcomes in humans and rodent models. A comprehensive overview of crucial mechanisms of the gut–brain axis is included. This refers especially to the neurotransmitters crucial for animal behavior, which are regulated by the gut microbiome, and to the main microbial metabolites—short-chain fatty acids (SCFAs). This review presents summarized data on gut dysbiosis in relation to the inflammation process within the organism, as well as the activation of the hypothalamic–pituitary–adrenal (HPA) axis. All of the above mechanisms are presented in this review in strict correlation with brain and/or behavioral changes in the animal. Additionally, according to human and laboratory animal studies, the gut microbiome appears to be altered in individuals with mental disorders; thus, various strategies to manipulate the gut microbiota are implemented. This refers also to the fecal microbiome transplantation (FMT) method, based on transferring the fecal matter from a donor into the gastrointestinal tract of a recipient in order to modulate the gut microbiota. In this review, the possible effects of the FMT procedure on animal behavioral disorders are discussed. [ABSTRACT FROM AUTHOR]

Opioids are commonly used for the management of severe chronic cancer pain. Their well-known pharmacological effects on the gastrointestinal system, particularly opioid-induced constipation (OIC), are the most common limiting factors in the optimization of analgesia, and have led to the wide use of laxatives and/or peripherally acting mu-opioid receptor antagonists (PAMORAs). A growing interest has been recently recorded in the possible effects of opioid treatment on the gut microbiota. Preclinical and clinical data, as presented in this review, showed that alterations of the gut microbiota play a role in modulating opioid-mediated analgesia and tolerability, including constipation. Moreover, due to the bidirectional crosstalk between gut bacteria and the central nervous system, gut dysbiosis may be crucial in modulating opioid reward and addictive behavior. The microbiota may also modulate pain regulation and tolerance, by activating microglial cells and inducing the release of inflammatory cytokines and chemokines, which sustain neuroinflammation. In the subset of cancer patients, the clinical meaning of opioid-induced gut dysbiosis, particularly its possible interference with the efficacy of chemotherapy and immunotherapy, is still unclear. Gut dysbiosis could be a new target for treatment in cancer patients. Restoring the physiological amount of specific gut bacteria may represent a promising therapeutic option for managing gastrointestinal symptoms and optimizing analgesia for cancer patients using opioids. [ABSTRACT FROM AUTHOR]

Functional gastrointestinal disorders (FGIDs) are characterized by chronic gastrointestinal symptoms in the absence of overt pathology and affect a significant percentage of the worldwide population. They are commonly accompanied by co-morbid psychiatric symptomatology and are associated with significant suffering and great healthcare services utilization. There is growing evidence that dysregulation of the gut–brain axis and disturbances in the processing of afferent interoceptive signals lie at the heart of these disorders. In this context, the aim of the current review was to detect and critically review original articles focusing on the role of interoception in the pathophysiology of FGIDs. Our search yielded 38 relevant studies. FGID patients displayed increased visceral sensitivity, enhanced attention to gastrointestinal interoceptive cues, and greater emotional arousal when coping with gut-derived sensations. Neuroimaging studies have shown significant structural and functional changes in regions of the interoceptive network, while molecular and genetic studies have revealed significant associations between interoceptive signaling and deficits in excitatory neurotransmission, altered endocrine and immune physiological pathways, and aberrant expression of transient receptor potential channel genes. Finally, there were emerging data suggesting that interoception-based interventions may reduce physical symptoms and improve quality of life and should be integrated into FGID clinical management practices. [ABSTRACT FROM AUTHOR]

We conducted a 12-week randomized double-blind placebo-controlled clinical trial to investigate the potential impact of Bifidobacterium bifidum (Bf-688) supplementation on attention-deficit/hyperactivity disorder (ADHD). Children with ADHD who were already receiving a stable dose of methylphenidate (MPH) treatment were enrolled and were randomly assigned to two groups: one receiving add-on Bf-688 (daily bacterial count of 5 × 109 CFUs) (n = 51) and the other receiving a placebo (n = 51). All participants underwent assessments using Conners' Continuous Performance Test (CPT) and Conners' Continuous Auditory Test of Attention (CATA). Additionally, fecal samples were collected at the beginning of the trial (week 0) and at the endpoint (week 12). Remarkably, the group receiving Bf-688 supplementation, but not the placebo group, exhibited significant improvements in omission errors in CPT as well as Hit reaction time in both CPT and CATA. Gut microbiome analysis revealed a significant increase in the Firmicutes to Bacteroidetes ratio (F/B ratio) only in the Bf-688 group. Furthermore, we identified significant negative correlations between N-Glycan biosynthesis and Hit reaction time in both CPT and CATA. Our results demonstrate that the probiotic Bf-688 supplement can enhance neuropsychological performance in children with ADHD, possibly by altering the composition of the gut microbiota, ultimately leading to reduced N-Glycan biosynthesis. [ABSTRACT FROM AUTHOR]

Schizophrenia is a disease with a complex etiology that significantly impairs the functioning of patients. In recent years, there has been increasing focus on the importance of the gut microbiota in the context of the gut–brain axis. In our study, we analyzed data on the gut–brain axis in relation to schizophrenia, as well as the impacts of eating habits, the use of various supplements, and diets on schizophrenia. Additionally, the study investigated the impact of antipsychotics on the development of metabolic disorders, such as diabetes, dyslipidemia, and obesity. There may be significant clinical benefits to be gained from therapies supported by supplements such as omega-3 fatty acids, B vitamins, and probiotics. The results suggest the need for a holistic approach to the treatment of schizophrenia, incorporating both drug therapy and dietary interventions. [ABSTRACT FROM AUTHOR]

Background: The gut microbiota is believed to influence neurodevelopment through the gut–brain axis, but prior studies have shown inconsistent results regarding early childhood antibiotic exposure and subsequent risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). The purpose of this study was to evaluate the hypothesis that exposure to antibacterial agents in the first 2 years of life increases the risk of ASD and/or ADHD. Methods: This was a retrospective cohort study using 2003–2019 data from the National Health Insurance Research Database in Taiwan. Livebirths born between 2004 and 2016 were identified and separated into singleton, full sibling, and exposure-discordant sibling pair cohorts. The exposure group included children who filled at least one prescription for antibacterial agents between 0 and 2 years old in outpatient settings. The outcome, ASD and/or ADHD, was defined by at least one inpatient or outpatient diagnosis. The maximum follow-up age was 15 years in this study. Potential neonatal, maternal and paternal confounders were adjusted for. Cox proportional hazards models were used to estimate the relative event risk. Results: The final sample contained 946,581 children in the singleton cohort, 1,142,693 children in the full sibling cohort, and 352,612 children in the exposure-discordant sibling pair cohort. Antibiotic exposure marginally increased the risk of ASD and/or ADHD in the singleton cohort (adjusted hazard ratio [aHR]: 1.06, 95% confidence interval [CI]: 1.04–1.07) and in the full sibling cohort (aHR: 1.03, 95% CI: 1.01–1.04). A slight decrease in the risk of ASD and/or ADHD was observed in the exposure-discordant sibling pair cohort (aHR: 0.92, 95% CI: 0.90–0.94). Conclusions: The results suggest that early life antibiotic exposure has minimal impact on the risk of ASD and/or ADHD. Given that the estimated effects are marginal and close to null, concerns about ASD and/or ADHD risk increase should not postpone or deter timely and reasonable antibiotic use. [ABSTRACT FROM AUTHOR]

Depression, projected to be the predominant contributor to the global disease burden, is a complex condition with diverse symptoms including mood disturbances and cognitive impairments. Traditional treatments such as medication and psychotherapy often fall short, prompting the pursuit of alternative interventions. Recent research has highlighted the significant role of gut microbiota in mental health, influencing emotional and neural regulation. Fecalmicrobiota transplantation (FMT), the infusion of fecal matter from a healthy donor into the gut of a patient, emerges as a promising strategy to ameliorate depressive symptoms by restoring gut microbial balance. The microbial-gut-brain (MGB) axis represents a critical pathway through which to potentially rectify dysbiosis and modulate neuropsychiatric outcomes. Preclinical studies reveal that FMT can enhance neurochemicals and reduce inflammatory markers, thereby alleviating depressive behaviors. Moreover, FMT has shown promise in clinical settings, improving gastrointestinal symptoms and overall quality of life in patients with depression. The review highlights the role of the gut-brain axis in depression and the need for further research to validate the longterm safety and efficacy of FMT, identify specific therapeutic microbial strains, and develop targeted microbial modulation strategies. Advancing our understanding of FMT could revolutionize depression treatment, shifting the paradigm toward microbiome-targeting therapies. [ABSTRACT FROM AUTHOR]

Microglial inflammatory response is a pathological process frequently found in patients with depression. and in animal models, which is believed to be closely related to depression. The potential mechanisms of inducing microglial inflammatory response hy depression includes the direct or indirect regulation of glucocorticoid level changes after activation of the hypothalamic-pituitary-adrenal (HPA) axis, the effect of intestinal microbial metabolites through immune and neural pathways in the brain-gut axis, and the direct activation of damage associated molecular patterns (DAMPs) in microglia. [ABSTRACT FROM AUTHOR]

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder potentially linked to gut dysbiosis. This comparative cross-sectional study profiled the gut microbiota in 24 treatment-naïve Thai children diagnosed with ADHD and 24 healthy ones matched by age and gender (median age: 7 years). Fecal microbial compositions were genetically analyzed using 16s rRNA gene amplicon sequencing. The study findings indicated no statistically significant differences in microbial diversity between groups, although Firmicutes and Actinobacteria appeared dominant in both groups. Moreover, ADHD patients exhibited enrichment in Alloprevotella, CAG-352, Succinivibrio, and Acidaminococcus genera, while healthy controls had higher levels of Megamonas, Enterobacter, Eubacterium hallii, and Negativibacillus genera. Spearman correlation analysis demonstrated a significant positive association between CAG-352 and inattention and hyperactivity/impulsivity scores, whereas the Eubacterium hallii group and Megamonas exhibited negative correlations with these symptomatology domains. Beta-carotene intake was associated with the Eubacterium hallii group and Succinivibrio: likewise, vitamin B2 intake was associated with Alloprevotella. Additional research should aim to elucidate the underlying mechanisms influencing clinical biomarkers that signify alterations in specific gut microbiome profiles linked to ADHD. [ABSTRACT FROM AUTHOR]

• In line with our prior studies in mice, gut bacteria-derived PGN fragments disseminate and reach the Drosophila brain. • Sensing of circulating PGN fragments triggers immune and stress signaling pathways in the central nervous system. • Gut derived PGN fragments primarily induce an inflammatory response in perineurial glia at the brain-circulation interface. • Continuous activation of immune signaling in perineurial glia correlates with neurological decline and reduced lifespan. Metabolites and compounds derived from gut-associated bacteria can modulate numerous physiological processes in the host, including immunity and behavior. Using a model of oral bacterial infection, we previously demonstrated that gut-derived peptidoglycan (PGN), an essential constituent of the bacterial cell envelope, influences female fruit fly egg-laying behavior by activating the NF-κB cascade in a subset of brain neurons. These findings underscore PGN as a potential mediator of communication between gut bacteria and the brain in Drosophila , prompting further investigation into its impact on all brain cells. Through high-resolution mass spectrometry, we now show that PGN fragments produced by gut bacteria can rapidly reach the central nervous system. In Addition, by employing a combination of whole-genome transcriptome analyses, comprehensive genetic assays, and reporter gene systems, we reveal that gut bacterial infection triggers a PGN dose-dependent NF-κB immune response in perineurial glia, forming the continuous outer cell layer of the blood–brain barrier. Furthermore, we demonstrate that persistent PGN-dependent NF-κB activation in perineurial glial cells correlates with a reduction in lifespan and early neurological decline. Overall, our findings establish gut-derived PGN as a critical mediator of the gut-immune-brain axis in Drosophila. [ABSTRACT FROM AUTHOR]

• Vagotomy mitigates Salmonella-induced systemic infection and anxiety-like behavior. • Vagotomy alleviates the Salmonella-induced gut inflammation and neuroinflammation. • Vagotomy enhanced GABA production and related microbes abundance in the infected mice. • Vagotomy relies on GABA production to alleviate gut inflammation. The vagus nerve, a pivotal link within the gut-brain axis, plays a critical role in maintaining homeostasis and mediating communication between the gastrointestinal tract and the brain. It has been reported that gastrointestinal infection by Salmonella typhimurium (S. typhimurium) triggers gut inflammation and manifests as anxiety-like behaviors, yet the mechanistic involvement of the vagus nerve remains to be elucidated. In this study, we demonstrated that unilateral cervical vagotomy markedly attenuated anxiety-like behaviors induced by S. typhimurium SL1344 infection in C57BL/6 mice, as evidenced by the open field test and marble burying experiment. Furthermore, vagotomy significantly diminished neuronal activation within the nucleus of the solitary tract and amygdala, alongside mitigating aberrant glial cell activation in the hippocampus and amygdala. Additionally, vagotomy notably decreases serum endotoxin levels, counters the increase in splenic Salmonella concentration, and modulates the expression of inflammatory cytokines—including IL-6, IL-1β, and TNF-α—in both the gastrointestinal tract and brain, with a concurrent reduction in IL-22 and CXCL1 expression. This intervention also fostered the enrichment of beneficial gut microbiota, including Alistipes and Lactobacillus species, and augmented the production of gamma-aminobutyric acid (GABA) in the gut. Administration of GABA replicated the vagotomy's beneficial effects on reducing gut inflammation and anxiety-like behavior in infected mice. However, blockade of GABA receptors with picrotoxin abrogated the vagotomy's protective effects against gut inflammation, without influencing its impact on anxiety-like behaviors. Collectively, these findings suggest that vagotomy exerts a protective effect against infection by promoting GABA synthesis in the colon and alleviating anxiety-like behavior. This study underscores the critical role of the vagus nerve in relaying signals of gut infection to the brain and posits that targeting the gut-brain axis may offer a novel and efficacious approach to preventing gastrointestinal infections and associated behavioral abnormalities. [ABSTRACT FROM AUTHOR]

[Display omitted] • MAdCAM-1 MRI signal positively correlates with disease severity in two EAE models. • The number of T CD4+ and B cells decreases in the ileum during disease course. • These two populations are increased concomitantly in the spinal cord. • High MAdCAM-1 signal at early phase is associated with a delayed disease onset. • Low MAdCAM-1 signal at remission increases the risk of secondary progressive EAE. Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. Recent evidence suggests that lymphocyte trafficking in the intestines could play a key role in its etiology. Nevertheless, it is not clear how intestinal tissue is involved in the disease onset nor its evolution. In the present study, we aimed to evaluate intestinal inflammation dynamic throughout the disease course and its potential impact on disease progression. We used tissue immunophenotyping (immunohistofluorescence and flow cytometry) and a recently described molecular magnetic resonance imaging (MRI) method targeting mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to assess intestinal inflammation in vivo in two distinct animal models of MS (Experimental Autoimmune Encephalomyelitis − EAE) at several time points of disease progression. We report a positive correlation between disease severity and MAdCAM-1 MRI signal in two EAE models. Moreover, high MAdCAM-1 MRI signal during the asymptomatic phase is associated with a delayed disease onset in progressive EAE and to a lower risk of conversion to a secondary-progressive form in relapsing-remitting EAE. During disease evolution, in line with a bi-directional immune communication between the gut and the central nervous system, we observed a decrease in T-CD4+ and B lymphocytes in the ileum concomitantly with their increase in the spinal cord. Altogether, these data unveil a crosstalk between intestinal and central inflammation in EAE and support the use of molecular MRI of intestinal MAdCAM-1 as a new biomarker for prognostic in MS patients. [ABSTRACT FROM AUTHOR]

[Display omitted] • Emulsifier Polysorbate 80 exposure significantly exacerbated age-related cognitive decline, along with increased brain pathological proteins deposition and neuroinflammation, as well as disruption of the blood–brain barrier. • Emulsifier Polysorbate 80 exposure contributed to gut microbiota dysbiosis and the increased of deoxycholic acid in plasma and brain. • Emulsifier Polysorbate 80 induced cognitive decline and neuroinflammation via gut microbiota. • Mechanically, deoxycholic acid activates microglial cells may involve the upregulation of ABCA1-mediated cholesterol transport on lysosomes, thereby promotes the senescence-associated secretory phenotype. Gut microbial homeostasis is crucial for the health of cognition in elderly. Previous study revealed that polysorbate 80 (P80) as a widely used emulsifier in food industries and pharmaceutical formulations could directly alter the human gut microbiota compositions. However, whether long-term exposure to P80 could accelerate age-related cognitive decline via gut-brain axis is still unknown. Accordingly, in this study, we used the senescence accelerated mouse prone 8 (SAMP8) mouse model to investigate the effects of the emulsifier P80 intake (1 % P80 in drinking water for 12 weeks) on gut microbiota and cognitive function. Our results indicated that P80 intake significantly exacerbated cognitive decline in SAMP8 mice, along with increased brain pathological proteins deposition, disruption of the blood–brain barrier and activation of microglia and neurotoxic astrocytes. Besides, P80 intake could also induce gut microbiota dysbiosis, especially the increased abundance of secondary bile acids producing bacteria, such as Ruminococcaceae , Lachnospiraceae , and Clostridium scindens. Moreover, fecal microbiota transplantation from P80 mice into 16-week-old SAMP8 mice could also exacerbated cognitive decline, microglia activation and intestinal barrier impairment. Intriguingly, the alterations of gut microbial composition significantly affected bile acid metabolism profiles after P80 exposure, with markedly elevated levels of deoxycholic acid (DCA) in serum and brain tissue. Mechanically, DCA could activate microglial and promote senescence-associated secretory phenotype production through adenosine triphosphate-binding cassette transporter A1 (ABCA1) importing lysosomal cholesterol. Altogether, the emulsifier P80 accelerated cognitive decline of aging mice by inducing gut dysbiosis, bile acid metabolism alteration, intestinal barrier and blood brain barrier disruption as well as neuroinflammation. This study provides strong evidence that dietary-induced gut microbiota dysbiosis may be a risk factor for age-related cognitive decline. [ABSTRACT FROM AUTHOR]