Recent studies have highlighted the potential influence of gut dysbiosis on traumatic brain injury (TBI) outcomes. Alterations in the abundance and diversity of Lactobacillus species may affect immune dysregulation, neuroinflammatory responses, anxiety- and depressive-like behaviors, and neuroprotective mechanisms activated in response to TBI.

This study aims to evaluate the protective and preventive effects of Pan-probiotic (PP) treatment on the inflammatory response during both the acute and chronic phases of TBI.

Males and female mice underwent controlled cortical impact (CCI) injury or sham. They received a PP mixture in drinking water containing strains of Lactobacillus plantarum, L. reuteri, L. helveticas, L. fermentum, L. rhamnosus, L. gasseri, and L. casei. In the acute group, mice received PP or vehicle (VH) treatment for 7 weeks before TBI, continuing until 3 days post-injury (dpi). In the chronic group, treatment began 2 weeks before TBI and was extended through 35 dpi. The taxonomic microbiome profiles of fecal samples were evaluated using 16S rRNA V1-V3 sequencing analysis, and Short-chain fatty acids (SCFAs) were measured. Immunohistochemical, in situ hybridization, and histological analyses were performed to assess neuroinflammation post-TBI, while behavioral assessments were conducted to evaluate sensorimotor and cognitive functions.

Our findings suggest that a 7-week PP administration induces specific microbial changes, including increased abundance of beneficial bacteria such as Lactobacillaceae, Limosilactobacillus, and Lactiplantibacillus. PP treatment reduces lesion volume and cell death at 3 dpi, elevates SCFA levels at 35 dpi, and decreases microglial activation at both time points, particularly in males. Additionally, PP treatment improved motor recovery in males and alleviated depressive-like behaviors in females.

Our findings indicate that PP administration modulates microbiome composition, reduces neuroinflammation, and improves motor deficits following TBI, with these effects being particularly pronounced in male mice.

The current discovery that the gut microbiome, which contains roughly 100 trillion microbes, affects health and disease has catalyzed a boom in multidisciplinary research efforts focused on understanding this relationship. Also, it is commonly demonstrated that the gut and the CNS are closely related in a bidirectional pathway. A balanced gut microbiome is essential for regular brain activities and emotional responses. On the other hand, the CNS regulates the majority of GI physiology. Any disruption in this bidirectional pathway led to a progression of health problems in both directions, neurological and gastrointestinal diseases. In this review, we hope to shed light on the complicated connections of the microbiome-gut-brain axis and the critical roles of gut microbiome in the early development of the brain in order to get a deeper knowledge of microbiome-mediated pathological conditions and management options through rebalancing of gut microbiome.

2'-Fucosyllactose (2'-FL) is one of the major oligosaccharides found in human breast milk, with several recognized beneficial effects on the host. Extensive research has indicated positive effects of 2'-FL on cognitive development in the brain, yet its molecular mechanisms have remained elusive. This study aimed to assess the impact of 2'-FL on the gut-brain axis microbiota and cognitive function in growing mice, along with its potential mechanisms of action.

Following long-term supplementation for 4 weeks, 2'-FL was found to enhance cognitive memory function in growing mice (3 weeks old) as assessed through Y-maze, novel object recognition, and water maze tests. Analysis via 16S rRNA sequencing revealed significant alterations in gut microbiota diversity and composition induced by 2'-FL, notably increasing the relative abundance of Bacteroides and Lactobacillus genera. Additionally, 2'-FL significantly elevated levels of 5-hydroxytryptamine (5-HT) and 5-hydroxytryptophan (5-HTP) in the hippocampal tissue. However, antibiotic intervention abolished the cognitive advantage conferred by 2'-FL, highlighting the critical role of gut microbiota in mediating its effects. Similarly, short-term supplementation with 2'-FL for 7 days indicated rapid changes in gut microbiota composition preceding cognitive improvements, further suggesting a potential causal relationship between gut microbiota characteristics and cognition. Further, in vitro experiments with mouse feces suggested that 2'-FL may influence tryptophan hydroxylase levels in the gut microbiota and inhibit the activity of 5-hydroxytryptophan decarboxylase, potentially leading to increased accumulation of 5-HTP. Additionally, 2'-FL may indirectly impact tryptophan hydroxylase levels in enterochromaffin cells by promoting short-chain fatty acid production, which could support 5-HTP synthesis. Elevated 5-HTP produced by the gut system enters the bloodstream, crosses the blood-brain barrier, and may potentially enhance brain 5-HT levels.

This study offers preliminary evidence that the cognitive-promoting effects of 2'-FL in mice may be closely associated with gut microbiota and 5-HT. The findings suggest that 2'-FL contribute to cognitive development in growing mice, potentially by modulating gut microbiota and enhancing 5-HT levels in the brain. Video Abstract.

Autism spectrum disorder (ASD) is characterized by deficits in social communication and restricted, repetitive behavioral patterns. Although other physiological presentations in individuals with ASD are heterogeneous, neuroimaging studies have consistently revealed a developmental pattern of initial white matter hypermyelination followed by reduced myelination compared with typically developing peers. Multiple studies have demonstrated that core ASD symptoms, including impairments in social skills, language acquisition, learning capabilities, motor performance, and sensory processing, correlate significantly with white matter dysregulation measured through diffusion tensor imaging (DTI). Longitudinal studies have shown that decreased gut microbiome diversity, particularly reductions in beneficial bacteria such as Bifidobacterium and Lactobacillus, correlates with symptom severity. Emerging mechanistic evidence suggests bidirectional relationships between microbiome composition and white matter development, both directly through metabolites like short-chain fatty acids (SCFAs) that regulate oligodendrocyte function and subsequent myelination, and indirectly through modulation of neuroinflammatory pathways. By integrating molecular-level gut physiology findings with macro-level brain imaging data, we may identify novel therapeutic approaches targeting the gut-brain axis in ASD management.

The gastrointestinal tract is inhabited by trillions of micro-organisms that form the gut microbiome, which serves various functions that can influence neurological pathways. It can release metabolites that could affect the nervous system. The bidirectional communication between the intestine and the central nervous system is known as the gut-brain axis. This communication can be impacted by the microbiota in various direct and indirect ways. There has been a suggested connection between the microbiome and many neurological disorders, including epilepsy, Alzheimer's disease, Parkinson's disease and multiple sclerosis. This has been explored in human and animal studies. While no microbial biomarkers have been identified yet, alterations in several taxa have been suggested to be associated with disease states. The potential of the microbiome to modulate neurological function has sparked multiple clinical trials using gut-altering treatments, some with positive preliminary results.

Recent evidence supports the hypothesis of an association between gut microbiota and the pathogenesis of retinal and eye diseases, suggesting the existence of a gut-eye axis. However, no data are available on the possible effect of the gut microbiota on the optic nerve fiber maturation and myelin development.

We investigated the impact of gut microbiota on the optic nerves collected from neonatal and young adult germ-free (GF), gnotobiotic (stably colonized with 12 bacteria strains, OMM12) and control (colonized with a complex gut microbiota, CGM) mice, by performing stereological and morphoquantitative analyses with transmission electron microscopy and gene expression analysis by quantitative real-time PCR.

Young adult GF and OMM12 optic nerve axons are smaller and hypermyelinated compared to CGM ones, while no such differences were detected in neonatal optic nerves. The transcription factors Olig1, Olig2, and Sox10 (oligodendrocyte myelination positive regulators) are downregulated in CGM and OMM12 young adult mice compared to the respective neonates. Such developmental downregulation was not observed in GF optic nerves, suggesting that the absence of the gut microbiota prolongs the stimulation of optic nerve fiber myelination, possibly through mechanisms that are yet to be identified.

Altogether, these data underscore the gut microbiota pivotal role in driving optic nerve myelination, contributing to our knowledge about both the gut-eye axis and the gut-brain axis, and opening new horizons for further investigations that will explore the role of the microbiota also in pathologies, injuries and regeneration associated with the optic nerve.

The maternal microbiome is emerging as an important factor that influences the neurological health of mothers and their children. Recent studies highlight how microbial communities in the maternal gut can shape early-life development in ways that inform long-term health trajectories. Research on the neurodevelopmental effects of maternal microbiomes is expanding our understanding of the microbiome-gut-brain axis to include signaling across the maternal-offspring unit during the perinatal period. In this Review, we synthesize existing literature on how the maternal microbiome modulates brain function and behavior in both mothers and their developing offspring. We present evidence from human and animal studies showing that the maternal microbiome interacts with environmental factors to impact risk for neurodevelopmental abnormalities. We further discuss molecular and cellular mechanisms that facilitate maternal-offspring crosstalk for neuromodulation. Finally, we consider how advancing understanding of these complex interactions could lead to microbiome-based interventions for promoting maternal and offspring health.

Most brain development occurs in the "first 1000 days", a critical period from conception to a child's second birthday. Critical brain processes that occur during this time include synaptogenesis, myelination, neural pruning, and the formation of functioning neuronal circuits. Perturbations during the first 1000 days likely contribute to later-life neurodegenerative disease, including sporadic amyotrophic lateral sclerosis (ALS). Neurodevelopment is determined by many events, including the maturation and colonization of the infant microbiome and its metabolites, specifically neurotransmitters, immune modulators, vitamins, and short-chain fatty acids. Successful microbiome maturation and gut-brain axis function depend on maternal factors (stress and exposure to toxins during pregnancy), mode of delivery, quality of the postnatal environment, diet after weaning from breast milk, and nutritional deficiencies. While the neonatal microbiome is highly plastic, it remains prone to dysbiosis which, once established, may persist into adulthood, thereby inducing the development of chronic inflammation and abnormal excitatory/inhibitory balance, resulting in neural excitation. Both are recognized as key pathophysiological processes in the development of ALS.

The microbiota-gut-brain axis (MGBA) plays a significant role in the maintenance of brain structure and function. The MGBA serves as a conduit between the CNS and the ENS, facilitating communication between the emotional and cognitive centers of the brain via diverse pathways. In the initial stages of this review, we will examine the way how MGBA affects neurogenesis, neuronal dendritic morphology, axonal myelination, microglia structure, brain blood barrier (BBB) structure and permeability, and synaptic structure. Furthermore, we will review the potential mechanistic pathways of neuroplasticity through MGBA influence. The short-chain fatty acids (SCFAs) play a pivotal role in the MGBA, where they can modify the BBB. We will therefore discuss how SCFAs can influence microglia, neuronal, and astrocyte function, as well as their role in brain disorders such as Alzheimer's disease (AD), and Parkinson's disease (PD). Subsequently, we will examine the technical strategies employed to study MGBA interactions, including using germ-free (GF) animals, probiotics, fecal microbiota transplantation (FMT), and antibiotics-induced dysbiosis. Finally, we will examine how particular bacterial strains can affect brain structure and function. By gaining a deeper understanding of the MGBA, it may be possible to facilitate research into microbial-based pharmacological interventions and therapeutic strategies for neurological diseases.

The microbiota-gut-brain axis is a complex bidirectional communication system that involves multiple interactions between intestinal functions and the emotional and cognitive centers of the brain. These interactions are mediated by molecules (metabolites) produced in both areas, which are considered mediators. To shed light on this complex mechanism, which is still largely unknown, a reliable characterization of the mediators is essential. Here, we review the most studied metabolites in the microbiota-gut-brain axis, the metabolic pathways in which they are involved, and their functions. This review focuses mainly on the use of mass spectrometry for their determination, reporting on the latest analytical methods, their limitations, and future perspectives. The analytical strategy for the qualitative-quantitative characterization of mediators must be reliable in order to elucidate the molecular mechanisms underlying the influence of the above-mentioned axis on stress resilience or vulnerability.

The gut microbiome is a complex system that directly interacts with and influences many systems in the body. This delicate balance of microbiota plays an important role in health and disease and is highly influenced by lifestyle factors and the surrounding environment. As further research emerges, understanding the full potential of the gut microbiome and the impact of using nutraceuticals to positively influence its function may open the door to greater therapeutic outcomes in the treatment and prevention of disease. Curcumin, a bioactive compound derived from the turmeric rhizome, has been studied in depth for its influence on human health as a potent anti-inflammatory and antioxidant properties. However, the therapeutic activity of curcumin is limited by its low oral bioavailability. While most available research has primarily focused on the curcuminoid compounds of turmeric, the non-curcuminoid compounds hold promise to offer therapeutic benefits while synergistically enhancing the bioavailability of curcumin and supporting the gut microbiome. This review summarizes current knowledge of the relationship between the gut and the various systems within the body, and how dysbiosis, or disruption in the gut microbial balance, leads to inflammation and increased risk of chronic disease. The review also summarizes recent research that focuses on the bioactivity of both the curcuminoid and non-curcuminoid compounds that comprise the whole turmeric root and their synergistic role in enhancing bioavailability to support a healthy gut microbiome and promising use in the treatment and prevention of disease.

The primary source of short-chain fatty acids (SCFAs), now recognized as critical mediators of host health, particularly in the context of neurobiology and cancer development, is the gut microbiota's fermentation of dietary fibers. Recent research highlights the complex influence of SCFAs, such as acetate, propionate, and butyrate, on brain cancer progression. These SCFAs impact immune modulation and the tumor microenvironment, particularly in brain tumors like glioma. They play a critical role in regulating cellular processes, including apoptosis, cell differentiation, and inflammation. Moreover, studies have linked SCFAs to maintaining the integrity of the blood-brain barrier (BBB), suggesting a protective role in preventing tumor infiltration and enhancing anti-tumor immunity. As our understanding of the gut-brain axis deepens, it becomes increasingly important to investigate SCFAs' therapeutic potential in brain cancer management. Looking into how SCFAs affect brain tumor cells and the environment around them could lead to new ways to prevent and treat these diseases, which could lead to better outcomes for people who are dealing with these challenging cancers.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder. Increasing evidence suggests that it is potentially related to gut microbiota, but no prior bibliometric analysis has been performed to explore the most influential works in the relationships between ASD and gut microbiota. In this study, we conducted an in-depth analysis of the most-cited articles in this field, aiming to provide insights to the existing body of research and guide future directions.

A search strategy was constructed and conducted in the Web of Science database to identify the 100 most-cited papers in ASD and gut microbiota. The Biblioshiny package in R was used to analyze and visualize the relevant information, including citation counts, country distributions, authors, journals, and thematic analysis. Correlation and comparison analyses were performed using SPSS software.

The top 100 influential manuscripts were published between 2000 and 2021, with a total citation of 40,662. The average number of citations annually increased over the years and was significantly correlated to the year of publication (r = 0.481, p < 0.01, Spearman's rho test). The United States was involved in the highest number of publications (n = 42). The number of publications in the journal was not significantly related to the journal's latest impact factor (r = 0.016, p > 0.05, Spearman's rho test). Co-occurrence network and thematic analysis identified several important areas, such as microbial metabolites of short-chain fatty acids and overlaps with irritable bowel syndrome.

This bibliometric analysis provides the key information of the most influential studies in the area of ASD and gut microbiota, and suggests the hot topics and future directions. The findings of this study can serve as a valuable reference for researchers and policymakers, guiding the development and implementation of the scientific research strategies in this area.

Malnutrition affects over 30 million children annually and has profound immediate and enduring repercussions. Survivors often suffer lasting neurocognitive consequences that impact academic performance and socioeconomic outcomes. Mechanistic understanding of the emergence of these consequences is poorly understood. Using multi-system SHAP interpreted random forest models and network analysis, we show that Moderate Acute Malnutrition (MAM) associates with enrichment of faecal Rothia mucilaginosa, Streptococcus salivarius and depletion of Bacteroides fragilis in a cohort of one-year-old children in Dhaka, Bangladesh. These microbiome changes form interconnected pathways that involve reduced plasma odd-chain fatty acid levels, decreased gamma and beta electroencephalogram power in temporal and frontal brain regions, and reduced vocalization. These findings support the hypothesis that prolonged colonization by oral commensal species delay gut microbiome and brain development. While causal links require empirical validation, this study provides insights to improve interventions targeting MAM-associated neurodevelopmental deficits.

Post-streptococcal autoimmune neuropsychiatric disorders (PANDAS) are a group of pathological condition characterized by sudden-onset obsessive-compulsive and tic disorders following beta-hemolytic Streptococcus group A (GAS) infection, hypothesized to be caused by autoimmune mechanisms targeting the basal ganglia. Scant literature is available regarding the microbiota composition in children with PANDAS, however few studies support the hypothesis that streptococcal infections may alter gut microbiota composition in these patients, leading to chronic inflammation that may impact the brain function and behavior. Notable changes include reduced microbial diversity and shifts in bacterial populations, which affect metabolic functions crucial for neuroinflammation. Elevated serum levels of sNOX2-dp and isoprostanes indicate oxidative stress, while the presence of lipopolysaccharides (LPS) may contribute to neuroinflammation. The aim of this narrative review is to explore the link between PANDAS and gut microbiota composition. The potential connection between gut microbiota and neuropsychiatric symptoms in PANDAS might suggest the importance of dietary interventions, such as promoting the Mediterranean diet and fiber intake, to reduce the inflammatory state of this patients and therefore improve their outcome.

Glial cells are key players in the regulation of nervous system functioning in both the central and enteric nervous systems. Glial cells are dynamic and respond to environmental cues to modulate their activity. Increasing evidence suggests that these signals include those originating from the gut microbiota, the community of microorganisms, including bacteria, viruses, archaea, and protozoa, that inhabit the gut. The gut microbiota and the brain communicate in a bidirectional manner across multiple signaling pathways and interfaces that together comprise the microbiota-gut-brain axis. Here, we detail the role of glial cells, including astrocytes, microglia, and oligodendrocytes in the central nervous system, and glial cells in the enteric nervous system along this gut-brain axis. We review what is known regarding the modulation of glia by microbial signals, in particular by microbial metabolites which signal to the brain through systemic circulation and via the vagus nerve. In addition, we highlight what is yet to be discovered regarding the role of other gut microbiota signaling pathways in glial cell modulation and the challenges of research in this area.

Schizophrenia is a complex heterogenous disorder thought to be caused by interactions between genetic and environmental factors. The theories developed to explain the etiology of schizophrenia have focused largely on the dysfunction of neurotransmitters such as dopamine, serotonin and glutamate with their receptors, although research in the past several decades has indicated strongly that other factors are also involved and that the role of neuroglial cells in psychotic disorders including schizophrenia should be given more attention. Although glia were originally thought to be present in the brain only to support neurons in a physical, metabolic and nutritional capacity, it has become apparent that these cells have a variety of important physiological roles and that abnormalities in their function may make significant contributions to the symptoms of schizophrenia. In the present paper, we review the interactions of brain microglia, astrocytes and oligodendroglia with aspects such as transmitter dysregulation, neuro-inflammation, oxidative stress, synaptic function, the gut microbiome, myelination and the blood-brain barrier that appear to affect the cause, development and treatment of schizophrenia. We also review crosstalk between microglia, astrocytes and oligodendrocytes and the effects of antipsychotics on neuroglia. Problems associated with studies on specific biomarkers for glia in schizophrenia are discussed.

Several lines of evidence demonstrate that microbiota influence brain development. Using high-resolution ex vivo magnetic resonance imaging (MRI), this study examined the impact of microbiota status on brain volume and revealed microbiota-related differences that were sex and brain region dependent. Cortical and hippocampal regions demonstrate increased sensitivity to microbiota status during the first 5 weeks of postnatal life, effects that were greater in male germ-free mice. Conventionalization of germ-free mice at puberty did not normalize brain volume changes. These data add to the existing literature and highlight the need to focus more attention on early-life microbiota-brain axis mechanisms in order to understand the regulatory role of the microbiome in brain development.

Traumatic brain injury (TBI) represents a multifaceted pathological condition resulting from external forces that disrupt neuronal integrity and function. This narrative review explores the intricate relationship between dietary macronutrients, gut microbiota (GM), and neuroinflammation in the TBI. We delineate the dual aspects of TBI: the immediate mechanical damage (primary injury) and the subsequent biological processes (secondary injury) that exacerbate neuronal damage. Dysregulation of the gut-brain axis emerges as a critical factor in the neuroinflammatory response, emphasizing the role of the GM in mediating immune responses. Recent evidence indicates that specific macronutrients, including lipids, proteins, and probiotics, can influence microbiota composition and in turn modulate neuroinflammation. Moreover, specialized dietary interventions may promote resilience against secondary insults and support neurological recovery post-TBI. This review aims to synthesize the current preclinical and clinical evidence on the potential of dietary strategies in mitigating neuroinflammatory pathways, suggesting that targeted nutrition and gut health optimization could serve as promising therapeutic modalities in TBI management.

The combination of hypertension with systemic inflammation during pregnancy is a hallmark of preeclampsia, but both processes also convey dynamic information about its antecedents and correlates (e.g., fetal growth restriction) and potentially related offspring sequelae. Causal inferences are further complicated by the increasingly frequent overlap of preeclampsia, fetal growth restriction, and multiple indicators of acute and chronic inflammation, with decreased gestational length and its correlates (e.g., social vulnerability). This complexity prompted our group to summarize information from mechanistic studies, integrated with key clinical evidence, to discuss the possibility that sustained or intermittent systemic inflammation-related phenomena offer hints about viable therapeutic targets, not only for the prevention of preeclampsia, but also the neurobehavioral and other developmental deficits that appear to be overrepresented in surviving offspring. Importantly, we feel that carefully designed hypothesis-driven observational studies are necessary if we are to translate the mechanistic evidence into child health benefits, namely because multiple pregnancy disorders might contribute to heightened risks of neuroinflammation, arrested brain development, or dysconnectivity in survivors who exhibit developmental problems later in life.

Anxiety disorders represent one of the most common and debilitating illnesses worldwide. However, the development of novel therapeutics for anxiety disorders has lagged compared to other mental illnesses. A growing body of research suggests the gut microbiota plays a role in the etiopathology of anxiety disorders and may, therefore, serve as a novel target for their treatment through the use of probiotics. The use of dietary supplements like probiotics is increasing and their interaction with pharmacotherapies is not well understood. Utilizing the chick social-separation stress test, the primary aim of this study was to evaluate the commercially-available multi-strain probiotic found in VSL#3 for potential anxiolytic-like and/or antidepressant-like effects in the stress-vulnerable Black Australorp genetic line. A secondary aim was to evaluate the interaction between probiotics and the SSRI fluoxetine. Animals were treated with either saline, probiotics, fluoxetine, or probiotics + fluoxetine for 8 days prior to exposure to a 90-min isolation stressor that produces both a panic-like (i.e., anxiety-like) state followed by a state of behavioral despair (i.e., depression-like). The 8-day probiotic regimen produced anxiolytic-like effects but did not attenuate behavioral despair. Fluoxetine failed to significantly alter behavior in either of the two phases. Moreover, the combination of fluoxetine with probiotics attenuated the anxiolytic-like effects of probiotics. The fluoxetine + probiotics combination had no effect on behavioral despair. The results of the current study align with other preclinical studies and some clinical trials suggesting probiotics may offer beneficial effects on anxiety. Investigations examining the anxiolytic-like mechanism of probiotics are needed before any conclusions can be made. Additionally, as the use of probiotics becomes more popular, research on the interactions between probiotic-microbiota and psychotropic medications is necessary.

Welfare in commercial livestock farming is becoming increasingly important in current agriculture research. Unfortunately, there is a lack of understanding about the neuronal mechanisms that underlie well-being on an individual level. Neuroplasticity in the hippocampus, the subventricular zone (SVZ), the olfactory bulb (OB) and the hypothalamus may be essential regulatory components in the context of farm animal behaviour and welfare that may be altered by providing environmental enrichment (EE). The importance of pre-and probiotics as a form of EE and the microbiota-gut-brain axis (MGBA) has come under the spotlight in the last 20 years, particularly in the contexts of research into stress and of stress resilience. However, it could also be an important regulatory system for animal welfare in livestock farming. This review aims to present a brief overview of the effects of EE on physiology and behaviour in farm animals and briefly discusses literature on behavioural flexibility, as well as inter-individual stress-coping styles and their relationship to animal welfare. Most importantly, we will summarise the literature on different forms of neural plasticity in farm animals, focusing on neurogenesis in various relevant brain regions. Furthermore, we will provide a brief outlook connecting these forms of neuroplasticity, stress, EE, the MGBA and welfare measures in modern livestock farming, concentrating on pigs.

Growing evidence demonstrates the connection between gut microbiota, neurodevelopment, and adult brain function. Microbial colonization occurs before the maturation of neural systems and its association with brain development. The early microbiome interactions with the gut-brain axis evolved to stimulate cognitive activities. Gut dysbiosis can lead to impaired brain development, growth, and function. Docosahexaenoic acid (DHA) is critically required for brain structure and function, modulates gut microbiota, and impacts brain activity. This review explores how gut microbiota influences early brain development and adult functions, encompassing the modulation of neurotransmitter activity, neuroinflammation, and blood-brain barrier integrity. In addition, it highlights processes of how the gut microbiome affects fetal neurodevelopment and discusses adult brain disorders.

The microbiota-gut-brain axis involves complex bidirectional communication through neural, immune, and endocrine pathways. Microbial metabolites, such as short-chain fatty acids, influence gut motility and brain function by interacting with gut receptors and modulating hormone release. Additionally, microbial components such as lipopolysaccharides and cytokines can cross the gut epithelium and the blood-brain barrier, impacting immune responses and cognitive function. Ex vivo models, which preserve gut tissue and neural segments, offer insight into localized gut-brain communication by allowing for detailed study of nerve excitability in response to microbial signals, but they are limited in systemic complexity. Miniaturized in vitro models, including organ-on-chip platforms, enable precise control of the cellular environment and simulate complex microbiota-host interactions. These systems allow for the study of microbial metabolites, immune responses, and neuronal activity, providing valuable insights into gut-brain communication. Despite challenges such as replicating long-term biological processes and integrating immune and hormonal systems, advancements in bioengineered platforms are enhancing the physiological relevance of these models, offering new opportunities for understanding the mechanisms of the microbiota-gut-brain axis. This review aims to describe the ex vivo and miniaturized in vitro models which are used to mimic the in vivo conditions and facilitate more precise studies of gut brain communication.

Crib-biting is a stereotyped oral behavior with poorly understood etiology and pathophysiology. The relationship between the gut microbiome and brain function has been described in behavioral disorders such as schizophrenia, depression and anxiety in humans. In horses, studies of behavioral problems and the microbiome are very limited. This study aimed to characterize the fecal microbiome and the predicted functional profile of horses with and without aerophagia. Fecal samples were collected from 12 Colombian Creole Horses of both sexes, divided into two groups: group 1, composed of six horses with crib-biting (3 females and 3 males), average body weight of 330 ± 10 kg, age of 7.0 ± 1.2 years and body condition score (BCS) of 5/9 ± 1 and group 2, consisting of six horses without crib-biting (3 females and 3 males), average body weight of 335 ± 5 kg, age 6.5 ± 1 years and BCS of 6/9 ± 1. From each horse in both groups fecal total DNA was obtained and 16S ribosomal RNA gene amplicons were sequenced to characterize the bacterial community structure. Community structure and differential abundance analyses revealed significant differences between the two conditions (p < 0.05). Specifically, the fecal microbiota at the family level in crib-biting horses, showing a decrease in Bacteroidales and an increase in Bacillota and Clostridia, differed from that of healthy horses without crib-biting, consistent with findings from previous studies. Furthermore, metagenome prediction suggests metabolic profile changes in bacterial communities between both conditions in horses. Further studies are required to validate the role of the microbiota-gut-brain axis in the etiology of crib-biting and other abnormal and stereotyped behaviors.

Depression is a global health concern affecting nearly 280 million individuals. It not only imposes a significant burden on economies and healthcare systems but also manifests complex physiological connections and consequences. Agmatine, a putative neuromodulator derived primarily from beneficial gut microbes specially Lactobacillus, has emerged as a potential therapeutic agent for mental health. The microbiota-gut-brain axis is involved in the development of depression through the peripheral nervous system, endocrine system, and immune system and may be a key factor in the effect of agmatine. Therefore, this study aimed to investigate the potential mechanism of agmatine in antibiotic-induced dysbiosis and depression-like behavior in rats, focusing on its modulation of the gut-brain axis. Depression-like behavior associated with dysbiosis was induced through a seven-day regimen of the broad-spectrum antibiotic, comprising ampicillin and metronidazole and validated through microbial, biochemical, and behavioral alterations. On day 8, antibiotic-treated rats exhibited loose fecal consistency, altered fecal microbiota, and depression-like behavior in forced swim test. Pro-inflammatory cytokines were elevated, while agmatine and monoamine levels decreased in the hippocampus and prefrontal cortex. Antibiotic administration disrupted tight junction proteins in the ileum, affecting gut architecture. Oral administration of agmatine alone or combined with probiotics significantly reversed antibiotic-induced dysbiosis, restoring gut microbiota and mitigating depression-like behaviors. This intervention also restored neuro-inflammatory markers, increased agmatine and monoamine levels, and preserved gut integrity. The study highlights the regulatory role of endogenous agmatine in the gut-brain axis in broad-spectrum antibiotic induced dysbiosis and associated depression-like behavior.

The developing central nervous system is highly sensitive to nutrient changes during the perinatal period, emphasising the potential impact of alterations of maternal diet on offspring brain development and behaviour. A growing body of research implicates the gut microbiota in neurodevelopment and behaviour. Maternal overweight and obesity during the perinatal period has been linked to changes in neurodevelopment, plasticity and affective disorders in the offspring, with implications for microbial signals from the maternal gut. Here we investigate the impact of maternal high-fat diet (mHFD)-induced changes in microbial signals on offspring brain development, and neuroimmune signals, and the enduring effects on behaviour into adolescence. We first demonstrate that maternal caecal microbiota composition at term pregnancy (embryonic day 18: E18) differs significantly in response to maternal diet. Moreover, mHFD resulted in the upregulation of microbial genes in the maternal intestinal tissue linked to alterations in quinolinic acid synthesis and elevated kynurenine levels in the maternal plasma, both neuronal plasticity mediators related to glutamate metabolism. Metabolomics of mHFD embryonic brains at E18 also detected molecules linked to glutamate-glutamine cycle, including glutamic acid, glutathione disulphide, and kynurenine. During adolescence, the mHFD offspring exhibited increased locomotor activity and anxiety-like behaviour in a sex-dependent manner, along with upregulation of glutamate-related genes compared to controls. Overall, our results demonstrate that maternal exposure to high-fat diet results in microbiota changes, behavioural imprinting, altered brain metabolism, and glutamate signalling during critical developmental windows during the perinatal period.

The rising global prevalence of microplastics (MPs) has highlighted their diverse toxicological effects. The oxytocin (OT) system in mammals, deeply intertwined with social behaviors, is recognized to be vulnerable to environmental stressors. We hypothesized that MP exposure might disrupt this system, a topic not extensively studied. We investigated the effects of MPs on behavioral neuroendocrinology via the gut-brain axis by exposing adolescent male C57BL/6 mice to varied sizes (5 μm and 50 μm) and concentrations (100 μg/L and 1000 μg/L) of polystyrene MPs over 10 weeks. The results demonstrated that exposure to 50 μm MPs significantly reduced colonic mucin production and induced substantial alterations in gut microbiota. Notably, the 50 μm-100 μg/L group showed a significant reduction in OT content within the medial prefrontal cortex and associated deficits in sociality, along with damage to the blood-brain barrier. Importantly, blocking the vagal pathway ameliorated these behavioral impairments, emphasizing the pivotal role of the gut-brain axis in mediating neurobehavioral outcomes. Our findings confirm the toxicity of MPs on sociality and the corresponding neuroendocrine systems, shedding light on the potential hazards and adverse effects of environmental MPs exposure on social behavior and neuroendocrine frameworks in social mammals, including humans.

The bidirectional regulation between the gut microbiota and brain, known as gut-brain axis, has received significant attention. The myelin sheath, produced by oligodendrocytes or Schwann cells, is essential for efficient nervous signal transmission and the maintenance of brain function. Growing evidence shows that both oligodendrogenesis and myelination are modulated by gut microbiota and its metabolites, and when dysbiosis occurs, changes in the microbiota composition and/or associated metabolites may impact developmental myelination and the occurrence of neurodevelopmental disabilities. Although the link between the microbiota and demyelinating disease such as multiple sclerosis has been extensively studied, our knowledge about the role of the microbiota in other myelin-related disorders, such as neurodegenerative diseases, is limited. Mechanistically, the microbiota-oligodendrocyte axis is primarily mediated by factors such as inflammation, the vagus nerve, endocrine hormones, and microbiota metabolites as evidenced by metagenomics, metabolomics, vagotomy, and morphological and molecular approaches. Treatments targeting this axis include probiotics, prebiotics, microbial metabolites, herbal bioactive compounds, and specific dietary management. In addition to the commonly used approaches, viral vector-mediated tracing and gene manipulation, integrated multiomics and multicenter clinical trials will greatly promote the mechanistic and interventional studies and ultimately, the development of new preventive and therapeutic strategies against gut-oligodendrocyte axis-mediated brain impairments. Interestingly, recent findings showed that microbiota dysbiosis can be induced by hippocampal myelin damage and is reversible by myelin-targeted drugs, which provides new insights into understanding how hippocampus-based functional impairment (such as in neurodegenerative Alzheimer's disease) regulates the peripheral homeostasis of microbiota and associated systemic disorders.

Microbes have inhabited the earth for hundreds of millions of years longer than humans. The microbiota-gut-brain axis (MGBA) represents a bidirectional communication pathway. These communications occur between the central nervous system (CNS), the enteric nervous system (ENS), and the emotional and cognitive centres of the brain. The field of research on the gut-brain axis has grown significantly during the past two decades. Signalling occurs between the gut microbiota and the brain through the neural, endocrine, immune, and humoral pathways. A substantial body of evidence indicates that the MGBA plays a pivotal role in various neurological diseases. These include Alzheimer's disease (AD), autism spectrum disorder (ASD), Rett syndrome, attention deficit hyperactivity disorder (ADHD), non-Alzheimer's neurodegeneration and dementias, fronto-temporal lobe dementia (FTLD), Wilson-Konovalov disease (WD), multisystem atrophy (MSA), Huntington's chorea (HC), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), temporal lobe epilepsy (TLE), depression, and schizophrenia (SCZ). Furthermore, the bidirectional correlation between therapeutics and the gut-brain axis will be discussed. Conversely, the mood of delivery, exercise, psychotropic agents, stress, and neurologic drugs can influence the MGBA. By understanding the MGBA, it may be possible to facilitate research into microbial-based interventions and therapeutic strategies for neurological diseases.

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.

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.

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.

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.

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.

Along with mounting evidence that gut microbiota and their metabolites migrate endogenously to distal organs, the 'gut-lung axis,' 'gut-brain axis,' 'gut-liver axis' and 'gut-renal axis' have been established. Multiple animal recent studies have demonstrated gut microbiota may also be a key susceptibility factor for neurological disorders such as Alzheimer's disease, Parkinson's disease and autism. The gastrointestinal tract is innervated by the extrinsic sympathetic and vagal nerves and the intrinsic enteric nervous system, and the gut microbiota interacts with the nervous system to maintain homeostatic balance in the host gut. A total of 1507 publications on the interactions between the gut microbiota, the gut-brain axis and neurological disorders are retrieved from the Web of Science to investigate the interactions between the gut microbiota and the nervous system and the underlying mechanisms involved in normal and disease states. We provide a comprehensive overview of the effects of the gut microbiota and its metabolites on nervous system function and neurotransmitter secretion, as well as alterations in the gut microbiota in neurological disorders, to provide a basis for the possibility of targeting the gut microbiota as a therapeutic agent for neurological disorders.

The gut-brain axis is the communication mechanism between the gut and the central nervous system, and the intestinal flora and lipopolysaccharide (LPS) play a crucial role in this mechanism. Exercise regulates the gut microbiota composition and metabolite production (i.e., LPS). We aimed to investigate the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on cognitive function in C57BL/6 J mice through gut-brain axis regulation of gut microbiota composition and LPS displacement.

C57BL/6 J male mice were randomly divided into sedentary, HIIT, and MICT groups. After 12 weeks of exercise intervention, the cognitive function of the brain and mRNA levels of related inflammatory factors were measured. RNA sequencing, Golgi staining, intestinal microbial 16 s rDNA sequencing, and ELISA were performed.

HIIT and MICT affect brain cognitive function by regulating the gut microbiota composition and its metabolite, LPS, through the gut microbiota-gut-brain axis. HIIT is suspected to have a risk: it can induce "intestinal leakage" by regulating intestinal permeability-related microbiota, resulting in excessive LPS in the blood and brain and activating M1 microglia in the brain, leading to reduced dendritic spine density and affecting cognitive function.

This study revealed a potential link between changes in the gut microbiota and cognitive function. It highlighted the possible risk of HIIT in reducing dendritic spine density and affecting cognitive function.

The human intestine is colonized by a variety of microorganisms that influence the immune system, the metabolic response, and the nervous system, with consequences for brain function and behavior. Unbalance in this microbial ecosystem has been shown to be associated with psychiatric disorders, and altered gut microbiome composition related to bacteria, viruses, and fungi has been well established in patients with alcohol use disorder. This review describes the gut microbiome-brain communication pathways, including the ones related to the vagus nerve, the inflammatory cytokines, and the gut-derived metabolites. Finally, the potential benefits of microbiota-based therapies for the management of alcohol use disorder, such as probiotics, prebiotics, and fecal microbiota transplantation, are also discussed.

White matter injury (WMI) is thought to be a major contributor to long-term cognitive dysfunctions after traumatic brain injury (TBI). This damage occurs partly due to apoptotic death of oligodendrocyte lineage cells (OLCs) after the injury, triggered directly by the trauma or in response to degenerating axons. Recent research suggests that the gut microbiota modulates the inflammatory response through the regulation of peripheral immune cell infiltration after TBI. Additionally, T-cells directly impact OLCs differentiation and proliferation. Therefore, we hypothesized that the gut microbiota plays a critical role in regulating the OLC response to WMI influencing T-cells differentiation and activation. Gut microbial depletion early after TBI chronically reduced re-myelination, acutely decreased OLCs proliferation, and was associated with increased myelin debris accumulation. Surprisingly, the absence of T-cells in gut microbiota depleted mice restored OLC proliferation and remyelination after TBI. OLCs co-cultured with T-cells derived from gut microbiota depleted mice resulted in impaired proliferation and increased expression of MHC-II compared with T cells from control-injured mice. Furthermore, MHC-II expression in OLCs appears to be linked to impaired proliferation under gut microbiota depletion and TBI conditions. Collectively our data indicates that depletion of the gut microbiota after TBI impaired remyelination, reduced OLCs proliferation with concomitantly increased OLC MHCII expression, and required the presence of T cells. This data suggests that T cells are an important mechanistic link by which the gut microbiota modulate the oligodendrocyte response and white matter recovery after TBI.

Early life adversity has a profound impact on physical and mental health. Because the central nervous and immune systems are not fully mature at birth and continue to mature during the postnatal period, a bidirectional interaction between the central nervous system and the immune system has been hypothesized, with traumatic stressors during childhood being pivotal in priming individuals for later adult psychopathology. Similarly, the microbiome, which regulates both neurodevelopment and immune function, also matures during childhood, rendering this interaction between the brain and the immune system even more complex. In this review, we provide evidence for the role of the immune response and the microbiome in the deleterious effects of early life adversity, both in humans and rodent models.

The microbes in breast milk are critical for the early establishment of infant gut microbiota and have important implications for infant health. Breast milk microbes primarily derive from the migration of maternal intestinal microbiota. This review suggests that the regulation of maternal diet on gut microbiota may be an effective strategy to improve infant health.

This article reviews the impact of breast milk microbiota on infant development and intestinal health. The close relationship between the microbiota in the maternal gut and breast through the entero-mammary pathway is discussed. Based on the effect of diet on gut microbiota, it is proposed that changing the maternal dietary structure is a new strategy for regulating breast milk microbiota and infant intestinal microbiota, which would have a positive impact on infant health.

Breast milk microbes have beneficial effects on infant development and regulation of the immune system. The mother's gut and breast can undergo certain bacterial migration through the entero-mammary pathway. Research has shown that intervening in a mother's diet during breastfeeding can affect the composition of the mother's gut microbiota, thereby regulating the microbiota of breast milk and infant intestines, and is closely related to infant health.

Alcohol use disorder (AUD) is commonly associated with distressing psychological symptoms. Pathologic changes associated with AUD have been described in both the gut microbiome and brain, but the mechanisms underlying gut-brain signaling in individuals with AUD are unknown. This study examined associations among the gut microbiome, brain morphometry, and clinical symptoms in treatment-seeking individuals with AUD.

We performed a secondary analysis of data collected during inpatient treatment for AUD in subjects who provided gut microbiome samples and had structural brain magnetic resonance imaging (MRI; n = 16). Shotgun metagenomics sequencing was performed, and the morphometry of brain regions of interest was calculated. Clinical symptom severity was quantified using validated instruments. Gut-brain modules (GBMs) used to infer neuroactive signaling potential from the gut microbiome were generated in addition to microbiome features (e.g., alpha diversity and bacterial taxa abundance). Bivariate correlations were performed between MRI and clinical features, microbiome and clinical features, and MRI and microbiome features.

Amygdala volume was significantly associated with alpha diversity and the abundance of several bacteria including taxa classified to Blautia, Ruminococcus, Bacteroides, and Phocaeicola. There were moderate associations between amygdala volume and GBMs, including butyrate synthesis I, glutamate synthesis I, and GABA synthesis I & II, but these relationships were not significant after false discovery rate (FDR) correction. Other bacterial taxa with shared associations to MRI features and clinical symptoms included Escherichia coli and Prevotella copri.

We identified gut microbiome features associated with MRI morphometry and AUD-associated symptom severity. Given the small sample size and bivariate associations performed, these results require confirmation in larger samples and controls to provide meaningful clinical inferences. Nevertheless, these results will inform targeted future research on the role of the gut microbiome in gut-brain communication and how signaling may be altered in patients with AUD.

Interactions between the gut microbiota and host immunity are sophisticated, dynamic, and host-dependent. Scientists have recently conducted research showing that disturbances in the gut bacterial community can lead to a decrease in some metabolites and, consequently, to behaviors such as depression. Exposure to stressors dropped the relative abundance of bacteria in the genus Bacteroides while soaring the relative abundance of bacteria in the genus Clostridium, Coprococcus, Dialister, and Oscillibacter, which were also reduced in people with depression. Microbiota and innate immunity are in a bilateral relationship. The gut microbiota has been shown to induce the synthesis of antimicrobial proteins such as catalysidins, type C lectins, and defensins. Probiotic bacteria can modulate depressive behavior through GABA signaling. The gut microbiome produces essential metabolites such as neurotransmitters, tryptophan metabolites, and short-chain fatty acids (SCFAs) that can act on the CNS. In the case of dysbiosis, due to mucin changes, the ratio of intestinal-derived molecules may change and contribute to depression. Psychotropics, including Bifidobacterium longum NCC3001, Clostridium butyricum CBM588, and Lactobacillus acidophilus, have mental health benefits, and can have a positive effect on the host-brain relationship, and have antidepressant effects. This article reviews current studies on the association between gut microbiota dysbiosis and depression. Comprehensively, these findings could potentially lead to novel approaches to improving depressive symptoms via gut microbiota alterations, including probiotics, prebiotics, and fecal microbiota transplantation.

The formation of the human gut microbiome initiates in utero, and its maturation is established during the first 2-3 years of life. Numerous factors alter the composition of the gut microbiome and its functions, including mode of delivery, early onset of breastfeeding, exposure to antibiotics and chemicals, and maternal stress, among others. The gut microbiome-brain axis refers to the interconnection of biological networks that allow bidirectional communication between the gut microbiome and the brain, involving the nervous, endocrine, and immune systems. Evidence suggests that the gut microbiome and its metabolic byproducts are actively implicated in the regulation of the early brain development. Any disturbance during this stage may adversely affect brain functions, resulting in a variety of neurodevelopmental disorders (NDDs). In the present study, we reviewed recent evidence regarding the impact of the gut microbiome on early brain development, alongside its correlation with significant NDDs, such as autism spectrum disorder, attention-deficit/hyperactivity disorder, Tourette syndrome, cerebral palsy, fetal alcohol spectrum disorders, and genetic NDDs (Rett, Down, Angelman, and Turner syndromes). Understanding changes in the gut microbiome in NDDs may provide new chances for their treatment in the future.

Psychosis, defined as a set of symptoms that results in a distorted sense of reality, is observed in several psychiatric disorders in addition to schizophrenia. This paper reviews the literature relevant to the underlying neurobiology of psychosis. The dopamine hypothesis has been a major influence in the study of the neurochemistry of psychosis and in development of antipsychotic drugs. However, it became clear early on that other factors must be involved in the dysfunction involved in psychosis. In the current review, it is reported how several of these factors, namely dysregulation of neurotransmitters [dopamine, serotonin, glutamate, and γ-aminobutyric acid (GABA)], neuroinflammation, glia (microglia, astrocytes, and oligodendrocytes), the hypothalamic-pituitary-adrenal axis, the gut microbiome, oxidative stress, and mitochondrial dysfunction contribute to psychosis and interact with one another. Research on psychosis has increased knowledge of the complexity of psychotic disorders. Potential new pharmacotherapies, including combinations of drugs (with pre- and probiotics in some cases) affecting several of the factors mentioned above, have been suggested. Similarly, several putative biomarkers, particularly those related to the immune system, have been proposed. Future research on both pharmacotherapy and biomarkers will require better-designed studies conducted on an all stages of psychotic disorders and must consider confounders such as sex differences and comorbidity.

The gut microbiota can influence human behavior. However, due to the massive multiple-testing problem, research into the relationship between microbiome ecosystems and the human brain faces drawbacks. This problem arises when attempting to correlate thousands of gut bacteria with thousands of brain voxels.

We performed brain magnetic resonance imaging (MRI) scans on 133 participants and applied machine-learning algorithms (Ridge regressions) combined with permutation tests. Using this approach, we were able to correlate specific gut bacterial families with brain MRI signals, circumventing the difficulties of massive multiple testing while considering sex, age, and body mass index as confounding factors.

The relative abundance (RA) of the Selenomonadaceae, Clostridiaceae, and Veillonellaceae families in the gut was associated with altered cerebellar, visual, and frontal T2-mapping and diffusion tensor imaging measures. Conversely, decreased relative abundance of the Eubacteriaceae family was also linked to T2-mapping values in the cerebellum. Significantly, the brain regions associated with the gut microbiome were also correlated with depressive symptoms and attentional deficits.

Our analytical strategy offers a promising approach for identifying potential brain biomarkers influenced by gut microbiota. By gathering a deeper understanding of the microbiota-brain connection, we can gain insights into the underlying mechanisms and potentially develop targeted interventions to mitigate the detrimental effects of dysbiosis on brain function and mental health.