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Pregnancy is a transformative period marked by profound physical and emotional changes, with far-reaching consequences for both mother and child. Emerging research has illustrated the pivotal role of a mother's diet during pregnancy in influencing the prenatal gut microbiome and subsequently shaping the neurodevelopment of her offspring. The intricate interplay between maternal gut health, nutrition, and neurodevelopmental outcomes has emerged as a captivating field of investigation within developmental science. Acting as a dynamic bridge between mother and fetus, the maternal gut microbiome, directly and indirectly, impacts the offspring's neurodevelopment through diverse pathways. This comprehensive review delves into a spectrum of studies, clarifying putative mechanisms through which maternal nutrition, by modulating the gut microbiota, orchestrates the early stages of brain development. Drawing insights from animal models and human cohorts, this work underscores the profound implications of maternal gut health for neurodevelopmental trajectories and offers a glimpse into the formulation of targeted interventions able to optimize the health of both mother and offspring. The prospect of tailored dietary recommendations for expectant mothers emerges as a promising and accessible intervention to foster the growth of beneficial gut bacteria, potentially leading to enhanced cognitive outcomes and reduced risks of neurodevelopmental disorders.

Background: Recent advances have significantly expanded our understanding of the gut microbiome's influence on host physiology and metabolism. However, the specific role of certain microorganisms in gestational health and fetal development remains underexplored., Objective: This study investigates the impact of Bifidobacterium breve UCC2003 on fetal brain metabolism when colonized in the maternal gut during pregnancy., Methods: Germ-free pregnant mice were colonized with or without B. breve UCC2003 during pregnancy. The metabolic profiles of fetal brains were analyzed, focusing on the presence of key metabolites and the expression of critical metabolic and cellular pathways., Results: Maternal colonization with B. breve resulted in significant metabolic changes in the fetal brain. Specifically, ten metabolites, including citrate, 3-hydroxyisobutyrate, and carnitine, were reduced in the fetal brain. These alterations were accompanied by increased abundance of transporters involved in glucose and branched-chain amino acid uptake. Furthermore, supplementation with this bacterium was associated with elevated expression of critical metabolic pathways such as PI3K-AKT, AMPK, STAT5, and Wnt-β-catenin signaling, including its receptor Frizzled-7. Additionally, there was stabilization of HIF-2 protein and modifications in genes and proteins related to cellular growth, axogenesis, and mitochondrial function., Conclusions: The presence of maternal B. breve during pregnancy plays a crucial role in modulating fetal brain metabolism and growth. These findings suggest that Bifidobacterium could modify fetal brain development, potentially offering new avenues for enhancing gestational health and fetal development through microbiota-targeted interventions., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The prevalence of brain disorders, including stress-related neuropsychiatric disorders and conditions with cognitive dysfunction, is rising. Poor dietary habits contribute substantially to this accelerating trend. Conversely, healthy dietary intake supports mood and cognitive performance. Recently, the communication between the microorganisms within the gastrointestinal tract and the brain along the gut-brain axis has gained prominence as a potential tractable target to modulate brain health. The composition and function of the gut microbiota is robustly influenced by dietary factors to alter gut-brain signalling. To reflect this interconnection between diet, gut microbiota and brain functioning, we propose that a diet-microbiota-gut-brain axis exists that underpins health and well-being. In this Review, we provide a comprehensive overview of the interplay between diet and gut microbiota composition and function and the implications for cognition and emotional functioning. Important diet-induced effects on the gut microbiota for the development, prevention and maintenance of neuropsychiatric disorders are described. The diet-microbiota-gut-brain axis represents an uncharted frontier for brain health diagnostics and therapeutics across the lifespan., (© 2024. Springer Nature Limited.)

Obesity increases the morbidity and mortality of traumatic brain injury (TBI). Detailed analyses of transcriptomic changes in the brain and adipose tissue were performed to elucidate the interactive effects between high-fat diet-induced obesity (DIO) and TBI. Adult male mice were fed a high-fat diet (HFD) for 12 weeks prior to experimental TBI and continuing after injury. High-throughput transcriptomic analysis using Nanostring panels of the total visceral adipose tissue (VAT) and cellular components in the brain, followed by unsupervised clustering, principal component analysis, and IPA pathway analysis were used to determine shifts in gene expression patterns and molecular pathway activity. Cellular populations in the cortex and hippocampus, as well as in VAT, during the chronic phase after combined TBI-HFD showed amplification of central and peripheral microglia/macrophage responses, including superadditive changes in selected gene expression signatures and pathways. Furthermore, combined TBI and HFD caused additive dysfunction in Y-Maze, Novel Object Recognition (NOR), and Morris water maze (MWM) cognitive function tests. These novel data suggest that HFD-induced obesity and TBI can independently prime and support the development of altered states in brain microglia and VAT, including the disease-associated microglia/macrophage (DAM) phenotype observed in neurodegenerative disorders. The interaction between HFD and TBI promotes a shift toward chronic reactive microglia/macrophage transcriptomic signatures and associated pro-inflammatory disease-altered states that may, in part, underlie the exacerbation of cognitive deficits. Thus, targeting of HFD-induced reactive cellular phenotypes, including in peripheral adipose tissue immune cell populations, may serve to reduce microglial maladaptive states after TBI, attenuating post-traumatic neurodegeneration and neurological dysfunction., (© 2024. The Author(s).)

Middle age has historically been an understudied period of life compared to older age, when cognitive and brain health decline are most pronounced, but the scope for intervention may be limited. However, recent research suggests that middle age could mark a shift in brain aging. We review emerging evidence on multiple levels of analysis indicating that midlife is a period defined by unique central and peripheral processes that shape future cognitive trajectories and brain health. Informed by recent developments in aging research and lifespan studies in humans and animal models, we highlight the utility of modeling non-linear changes in study samples with wide subject age ranges to distinguish life stage-specific processes from those acting linearly throughout the lifespan., Competing Interests: Declaration of interests The authors declare no competing interests in relation to this work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Understanding the interrelationship between the gut microbiota and host physiology, although still in its relative infancy, has taken important steps forward over the past decade. In the context of brain disorders including those characterized by neurodevelopmental and neurodegenerative changes there have been important advances. However, initially research involved correlational analyses, had limited translational scope, and lacked functional assessments. Thus, largescale longitudinal clinical investigations that assess causation and underlying mechanisms via in depth analysis methods are needed. In neurodegeneration research, strong causal evidence now links the gut microbiome to Alzheimer's (AD), and Parkinson's Disease (PD), as supported by human-to-animal transplantation studies. Longitudinal interventions are being conducted in AD, PD, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Neurodevelopmental research has also seen a boon in microbiome-related clinical research including in autism, Attention-deficit/hyperactivity disorder, and schizophrenia, which is confirming prior animal model work regarding the key time-windows in the gut microbiome important for infant cognition. While recent research advances represent important progress, fundamental knowledge gaps and obstacles remain. Knowing how and why the gut microbiome changes at the extremes of life will develop our mechanistic understanding and help build the evidence base as we strive toward counteracting microbial missteps with precision therapeutic interventions.

Objective. Blood pool region of interest (ROI) data extracted from the field of view of a PET scanner can be impacted by both dispersive and background effects. This circumstance compromises the ability to correctly extract the arterial input function (AIF) signal. The paper explores a novel approach to addressing this difficulty. Approach. The method involves representing the AIF in terms of the whole-body impulse response (IR) to the injection profile. Analysis of a collection/population of directly sampled arterial data sets allows the statistical behaviour of the tracer's impulse response to be evaluated. It is proposed that this information be used to develop a penalty term for construction of a data-adaptive method of regularisation estimator of the AIF when dispersive and/or background effects maybe impacting the blood pool ROI data. Main results. Computational efficiency of the approach derives from the linearity of the impulse response representation of the AIF and the ability to substantially rely on quadratic programming techniques for numerical implementation. Data from eight different tracers, used in PET cancer imaging studies, are considered. Sample image-based AIF extractions for brain studies with: 18 F-labeled fluoro-deoxyglucose and fluoro-thymidine (FLT), 11 C-labeled carbon dioxide (CO2) and 15 O-labeled water (H2O) are presented. Results are compared to the true AIF based on direct arterial sampling. Formal numerical simulations are used to evaluate the performance of the AIF extraction method when the ROI data has varying amounts of contamination, in comparison to a direct approach that ignores such effects. It is found that even with quite small amounts of contamination, the mean squared error of the regularised AIF is significantly better than the error associated with direct use of the ROI data. Significance. The proposed IR-based AIF extraction scheme offers a practical methodological approach for situations where the available image ROI data may be contaminated by background and/or dispersion effects., (Creative Commons Attribution license.)

The blood-brain barrier (BBB) is vital for maintaining brain homeostasis by enabling an exquisite control of exchange of compounds between the blood and the brain parenchyma. Moreover, the BBB prevents unwanted toxins and pathogens from entering the brain. This barrier, however, breaks down with age and further disruption is a hallmark of many age-related disorders. Several drugs have been explored, thus far, to protect or restore BBB function. With the recent connection between the BBB and gut microbiota, microbial-derived metabolites have been explored for their capabilities to protect and restore BBB physiology. This review, will focus on the vital components that make up the BBB, dissect levels of disruption of the barrier, and discuss current drugs and therapeutics that maintain barrier integrity and the recent discoveries of effects microbial-derived metabolites have on BBB physiology., (© 2022. The Author(s).)

Gut bacteria influence the brain and behavior, but causation in humans remains unclear.

Ethanolamine is a bioactive molecule found in several cells, including those in the central nervous system (CNS). In the brain, ethanolamine and ethanolamine-related molecules have emerged as prodrug moieties that can promote drug movement across the blood-brain barrier. This improvement in the ability to target drugs to the brain may also mean that in the process, ethanolamine concentrations in the brain are increased enough for ethanolamine to exert its own neurological actions. Ethanolamine and its associated products have various positive functions ranging from cell signaling to molecular storage, and alterations in their levels have been linked to neurodegenerative conditions such as Alzheimer's disease. This mini-review focuses on the effects of ethanolamine on the CNS and highlights the possible implications of these effects for drug design., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Steroid hormones are essential biomolecules for human physiology as they modulate the endocrine system, nervous function and behaviour. Recent studies have shown that the gut microbiota is directly involved in the production and metabolism of steroid hormones in the periphery. However, the influence of the gut microbiota on levels of steroids acting and present in the brain (i.e., neuroactive steroids) is not fully understood. Therefore, using liquid chromatography-tandem mass spectrometry, we assessed the levels of several neuroactive steroids in various brain areas and the plasma of germ-free (GF) male mice and conventionally colonized controls. The data obtained indicate an increase in allopregnanolone levels associated with a decrease in those of 5α-androstane-3α, 17β-diol (3α-diol) in the plasma of GF mice. Moreover, an increase of dihydroprogesterone and isoallopregnanolone in the hippocampus, cerebellum, and cerebral cortex was also reported. Changes in dihydrotestosterone and 3α-diol levels were also observed in the hippocampus of GF mice. In addition, an increase in dehydroepiandrosterone was associated with a decrease in testosterone levels in the hypothalamus of GF mice. Our findings suggest that the absence of microbes affects the neuroactive steroids in the periphery and the brain, supporting the evidence of a microbiota-mediated modulation of neuroendocrine pathways involved in preserving host brain functioning.

The regulation of the serotonin transporter (SERT) by guanine nucleotide-binding protein alpha (Gα) q was investigated using Gαq knockout mice. In the absence of Gαq, SERT-mediated uptake of 5-hydroxytryptamine (5HT) was enhanced in midbrain and frontal cortex synaptosomes, but only in female mice. The mechanisms underlying this sexual dimorphism were investigated using quantitative western blot analysis revealing brain region-specific differences. In the frontal cortex, SERT protein expression was decreased in male knockout mice, seemingly explaining the sex-dependent variation in SERT activity. The differential expression of Gαi1 in female mice contributes to the sex differences in the midbrain. In fact, Gαi1 levels inversely correlate with 5HT uptake rates across both sexes and genotypes. Likely due to differential SERT regulation as well as sex differences in the expression of tryptophan hydroxylase 2, Gαq knockout mice also displayed sex- and genotype-dependent alterations in total 5HT tissue levels as determined by high-performance liquid chromatography. Gαq inhibitors, YM-254890 and BIM-46187, differentially affected SERT activity in both, synaptosomes and cultured cells. YM-254890 treatment mimicked the effect of Gαq knockout in the frontal cortex. BIM-46187, which promotes the nucleotide-free form of Gα proteins, substantially inhibited 5HT uptake, prompting us to hypothesise that Gαq interacts with SERT similarly as with G-protein-coupled receptors and inhibits SERT activity by modulating transport-associated conformational changes. Taken together, our findings reveal a novel mechanism of SERT regulation and impact our understanding of sex differences in diseases associated with dysregulation of serotonin transmission, such as depression and anxiety., (© 2021 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Our gut harbours trillions of microorganisms essential for the maintenance of homeostasis and host physiology in health and disease. In the last decade, there has been a growing interest in understanding the bidirectional pathway of communication between our microbiota and the central nervous system. With regard to reward processes there is accumulating evidence from both animal and human studies that this axis may be a key factor in gating reward valence. Focusing on the mesocorticolimbic pathway, we will discuss how the intestinal microbiota is involved in regulating brain reward functions, both in natural (i.e. eating, social or sexual behaviours) and non-natural reinforcers (drug addiction behaviours including those relevant to alcohol, psychostimulants, opioids and cannabinoids). We will integrate preclinical and clinical evidence suggesting that the microbiota-gut-brain axis could be implicated in the development of disorders associated with alterations in the reward system and how it may be targeted as a promising therapeutic strategy. Cover Image for this issue: https://doi.org/10.1111/jnc.15065., (© 2020 International Society for Neurochemistry.)

The gut-brain axis plays an important role in maintaining homeostasis. Many intrinsic and extrinsic factors influence signaling along this axis, modulating the function of both the enteric and central nervous systems. More recently the role of the microbiome as an important factor in modulating gut-brain signaling has emerged and the concept of a microbiota-gut-brain axis has been established. In this review, we highlight the role of this axis in modulating enteric and central nervous system function and how this may impact disorders such as irritable bowel syndrome and disorders of mood and affect. We examine the overlapping biological constructs that underpin these disorders with a special emphasis on the neurotransmitter serotonin, which plays a key role in both the gastrointestinal tract and in the brain. Overall, it is clear that although animal studies have shown much promise, more progress is necessary before these findings can be translated for diagnostic and therapeutic benefit in patient populations., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Healthy dietary intake has been acknowledged for decades as one of the main contributors to health. More recently, the field of nutritional psychiatry has progressed our understanding regarding the importance of nutrition in supporting mental health and cognitive function. Thereby, individual nutrients, including omega-3 fatty acids and polyphenols, have been recognized to be key drivers in this relationship. With the progress in appreciating the influence of dietary fiber on health, increasingly research is focusing on deciphering its role in brain processes. However, while the importance of dietary fiber in gastrointestinal and metabolic health is well established, leading to the development of associated health claims, the evidence is not conclusive enough to support similar claims regarding cognitive function. Albeit the increasing knowledge of the impact of dietary fiber on mental health, only a few human studies have begun to shed light onto the underexplored connection between dietary fiber and cognition. Moreover, the microbiota-gut-brain axis has emerged as a key conduit for the effects of nutrition on the brain, especially fibers, that are acted on by specific bacteria to produce a variety of health-promoting metabolites. These metabolites (including short chain fatty acids) as well as the vagus nerve, the immune system, gut hormones, or the kynurenine pathway have been proposed as underlying mechanisms of the microbiota-brain crosstalk. In this minireview, we summarize the evidence available from human studies on the association between dietary fiber intake and cognitive function. We provide an overview of potential underlying mechanisms and discuss remaining questions that need to be answered in future studies. While this field is moving at a fast pace and holds promise for future important discoveries, especially data from human cohorts are required to further our understanding and drive the development of public health recommendations regarding dietary fiber in brain health.

Background: The gastrointestinal microbiota has emerged as a key regulator of gut-brain axis signalling with important implications for neurogastroenterology. There is continuous bidirectional communication between the gut and the brain facilitated by neuronal, endocrine, metabolic, and immune pathways. The microbiota influences these signalling pathways via several mechanisms. Studies have shown compositional and functional alterations in the gut microbiota in stress-related psychiatric disorders. Gut microbiota reconfigurations are also a feature of irritable bowel syndrome (IBS), a gut-brain axis disorder sharing high levels of psychiatric comorbidity including both anxiety and depression. It remains unclear how the gut microbiota alterations in IBS align with both core symptoms and these psychiatric comorbidities., Methods: In this review, we highlight common and disparate features of these microbial signatures as well as the associated gut-brain axis signalling pathways. Studies suggest that patients with either IBS, depression or anxiety, alone or comorbid, present with alterations in gut microbiota composition and harbor immune, endocrine, and serotonergic system alterations relevant to the common pathophysiology of these comorbid conditions., Key Results: Research has illustrated the utility of fecal microbiota transplantation in animal models, expanding the evidence base for a potential causal role of disorder-specific gut microbiota compositions in symptom set expression. Moreover, an exciting study by Constante and colleagues in this issue highlights the possibility of counteracting this microbiota-associated aberrant behavioral phenotype with a probiotic yeast, Saccharomyces boulardii CNCM I-745., Conclusions and Inferences: Such data highlights the potential for therapeutic targeting of the gut microbiota as a valuable strategy for the management of comorbid psychiatric symptoms in IBS., (© 2021 John Wiley & Sons Ltd.)

The central nervous system (CNS) can be injured or damaged through a variety of insults including traumatic injury, stroke, and neurodegenerative or demyelinating diseases, including Alzheimer's disease, Parkinson's disease and multiple sclerosis. Existing pharmacological and other therapeutics strategies are limited in their ability to repair or regenerate damaged CNS tissue meaning there are significant unmet clinical needs facing patients suffering CNS damage and/or degeneration. Through a variety of mechanisms including neuronal replacement, secretion of therapeutic factors, and stimulation of host brain plasticity, cell-based repair offers a potential mechanism to repair and heal the damaged CNS. However, over the decades of its evolution as a therapeutic strategy, cell-based CNS repair has faced significant hurdles that have prevented its translation to widespread clinical practice. In recent years, advances in cell technologies combined with advances in biomaterial-based regenerative medicine and tissue engineering have meant there is very real potential for many of these hurdles to be overcome. This review will provide an overview of the main CNS conditions that lend themselves to cellular repair and will then outline the potential of biomaterial-based approaches for improving the outcome of cellular repair in these conditions., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Microbes colonize the human body during the first moments of life and coexist with the host throughout the lifespan. Intestinal microbiota and their metabolites aid in the programming of important bodily systems such as the immune and the central nervous system during critical temporal windows of development, with possible structural and functional implications throughout the lifespan. These critical developmental windows perinatally (during the first 1000 days) are susceptible timepoints for insults that can endure long lasting effects on the microbiota-gut-brain axis. Environmental and parental factors like host genetics, mental health, nutrition, delivery and feeding mode, exposure to antibiotics, immune activation and microbiota composition antenatally, are all factors that are able to modulate the microbiota composition of mother and infant and may thus regulate important bodily functions. Among all these factors, early life nutrition plays a pivotal role in perinatal programming and in the modulation of offspring microbiota from birth throughout lifespan. This review aims to present current data on the impact of early life nutrition and microbiota priming of important bodily systems and all the factors influencing the microbial coexistence with the host during early life development.

Purpose: Preterm twins are at higher risk of neurodisability than preterm singletons, with monochorionic-diamniotic (MCDA) twins at higher risk than dichorionic-diamniotic (DCDA) twins. The impact of genetic influences on EEG concordance in preterm twins <32 weeks of gestational age is not established. This study aims to investigate EEG concordance in preterm MCDA and dichorionic-diamniotic twins during maturation., Methods: Infants <32 weeks of gestational age had multichannel EEG recordings for up to 72 postnatal hours, with repeat recordings at 32 and 35 weeks of postmenstrual age. Twin pairs had synchronous recordings. Mathematical EEG features were generated to represent EEG power, discontinuity, and symmetry. Intraclass correlations, while controlling for gestational age, estimated similarities within twins., Results: EEGs from 10 twin pairs, 4 MCDA and 6 dichorionic-diamniotic pairs, and 10 age-matched singleton pairs were analyzed from a total of 36 preterm infants. For MCDA twins, 17 of 22 mathematical EEG features had significant (>0.6; P < 0.05) intraclass correlations at one or more time points, compared with 2 of 22 features for DCDA twins and 0 of 22 for singleton pairs. For MCDA twins, all 10 features of discontinuity and all four features of symmetry were significant at one or more time-points. Three features of the MCDA twins (spectral power at 3-8 Hz, EEG skewness at 3-15 Hz, and kurtosis at 3-15 Hz) had significant intraclass correlations over all three time points., Conclusions: Preterm twin EEG similarities are subtle but clearly evident through mathematical analysis. MCDA twins showed stronger EEG concordance across different postmenstrual ages, thus confirming a strong genetic influence on preterm EEG activity at this early development stage., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2019 by the American Clinical Neurophysiology Society.)

The dynamic population of microbes that reside in the gastrointestinal tract plays a pivotal role in orchestrating several aspects of host physiology and health, including but not limited to nutrient extraction and metabolism, as well as the regulation of intestinal epithelial barrier integrity. Gut microbes interact with the host in a bi-directional manner as the microbiota can support the development and education of the innate and adaptive immune systems, thereby conferring protection against pathogens and harmful stimuli while training the host to maintain a homeostatic tolerance towards commensal symbiotics. Recent advances in the field have highlighted the importance of the host-microbiota relationship in neurodevelopment and behaviour, with relevant implications for the onset and progression of brain disorders of inflammatory origin. Microbial modulation of brain function is achieved throughout complex neuro-immune-endocrine pathways of the microbiome-gut-brain axis. Changes in the composition of the gut microbiota or perturbation in microbial-derived metabolites and neuroactive compounds are sensed by the afferent branches of the sympathetic and vagal innervation and transmitted to the central nervous system, which in turn produces behavioural responses. Here, we focus on how the crosstalk between the gut microbiota and the immune system modulates the development and function of the peripheral and central nervous systems. Specific attention is afforded to the involvement of host-microbe neuroimmune interactions in the pathogenesis of neuro-psychiatric and neuroinflammatory disorders such as autism spectrum disorders, anxiety, and depression, as well as Parkinson's and Alzheimer's diseases., (© 2021 S. Karger AG, Basel.)

The theme of this monograph reflects the growing research interest in the contribution of the microbiome-gut-brain axis to mental health. This chapter introduces readers to the study of the microbiome in psychiatric research and emphasises how research into the gut microbiome has had a significant impact on our understanding of mental health. A brief summary of the historical background for microbiome research in mental health is followed by examples of evidence linking gut microorganisms to changes in brain function. As novel technological developments have played a major role in providing the evidence for microbiome modulation of brain function, an overview of modern techniques and technologies is then provided. These have broadened our understanding of the range of microorganisms, in addition to bacteria, which contribute to the changes initiated by the microbiome. In addition, common experimental models are reviewed in light of the important role that animal studies, particularly in germ-free rodents, have played in establishing microbiome-gut-brain interactions. This introduction concludes with a summary of the challenges for future microbiome research, providing a forward-thinking perspective echoed in many of the following chapters., (© 2021 S. Karger AG, Basel.)

Since the beginning of life on earth, microorganisms have played a significant role in evolution. Throughout the history of Homo sapiens and its precursor humanoid forms, microorganisms have been present at birth and proliferated until death. It is at these extremes of life that the microbiome, especially that within the gastrointestinal tract, is most dynamic and perhaps has its greatest influence on host health. Here, we focus on the role of the gut microbiome as a regulator of brain and behaviour through key points in the human lifespan. We first describe trajectories of the microbiome in early life and ageing, before providing evidence for the existence of sensitive periods in the microbiome-gut-brain axis at these extremes of the lifespan. Finally, we briefly examine potential mechanisms for interactions between the microbiome and the brain during development and ageing., (© 2021 S. Karger AG, Basel.)

Male middle age is a transitional period where many physiological and psychological changes occur leading to cognitive and behavioural alterations, and a deterioration of brain function. However, the mechanisms underpinning such changes are unclear. The gut microbiome has been implicated as a key mediator in the communication between the gut and the brain, and in the regulation of brain homeostasis, including brain immune cell function. Thus, we tested whether targeting the gut microbiome by prebiotic supplementation may alter microglia activation and brain function in ageing. Male young adult (8 weeks) and middle-aged (10 months) C57BL/6 mice received diet enriched with a prebiotic (10% oligofructose-enriched inulin) or control chow for 14 weeks. Prebiotic supplementation differentially altered the gut microbiota profile in young and middle-aged mice with changes correlating with faecal metabolites. Functionally, this translated into a reversal of stress-induced immune priming in middle-aged mice. In addition, a reduction in ageing-induced infiltration of Ly-6C hi monocytes into the brain coupled with a reversal in ageing-related increases in a subset of activated microglia (Ly-6C + ) was observed. Taken together, these data highlight a potential pathway by which targeting the gut microbiome with prebiotics can modulate the peripheral immune response and alter neuroinflammation in middle age. Our data highlight a novel strategy for the amelioration of age-related neuroinflammatory pathologies and brain function.

Dysbindin-1 is implicated in several aspects of schizophrenia, including cognition and both glutamatergic and dopaminergic neurotransmission. Targeted knockout of dysbindin-1A (Dys-1A KO), the most abundant and widely expressed isoform in the brain, is associated with deficits in delay/interference-dependent working memory. Using an ethologically based approach, the following behavioural phenotypes were examined in Dys-1A KO mice: exploratory activity, social interaction, anxiety and problem-solving ability. Levels of monoamines and their metabolites were measured in striatum, hippocampus and prefrontal cortex using high-performance liquid chromatography with electrochemical detection. The ethogram of initial exploration in Dys-1A KO mice was characterised by increased rearing from a seated position; over subsequent habituation, stillness was decreased relative to wildtype. In a test of dyadic social interaction with an unfamiliar conspecific in a novel environment, female KO mice showed an increase in investigative social behaviours. Marble burying behaviour was unchanged. Using the puzzle-box test to measure general problem-solving performance, no effect of genotype was observed across nine trials of increasing complexity. Dys-1A KO demonstrated lower levels of 5-HT in ratio to its metabolite 5-HIAA in the prefrontal cortex. These studies elaborate the behavioural and neurochemical phenotype of Dys-1A KO mice, revealing subtle genotype-related differences in non-social and social exploratory behaviours and habituation of exploration in a novel environment, as well as changes in 5-HT activity in brain areas related to schizophrenia., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose of Review: Probiotics are living bacteria, which when ingested in adequate amounts, confer health benefits. Gut microbes are suggested to play a role in many psychiatric disorders and could be a potential therapeutic target. Between the gut and the brain, there is a bi-directional communication pathway called the microbiota-gut-brain axis. The purpose of this review is to examine data from recent interventional studies focusing on probiotics and the gut-brain axis for the treatment of depression, anxiety and schizophrenia., Recent Findings: Probiotics are likely to improve depression but not schizophrenia. Regarding anxiety, there is only one trial which showed an effect of a multispecies probiotic. However, determinants like the duration of treatment, dosage and interactions have not been thoroughly investigated and deserve more scientific attention. Microbiome-based therapies such as probiotics could be cautiously recommended for depression to enhance beneficial bacteria in the gut and to improve mood through the gut-brain axis.

Chronic stress and ageing are two of the most important factors that negatively affect cognitive processes such as learning and memory across the lifespan. To date, pharmacological agents have been insufficient in reducing the impact of both on brain health, and thus, novel therapeutic strategies are required. Recent research has focused on nutritional interventions to modify behaviour and reduce the deleterious consequences of both stress and ageing. In this context, emerging evidence indicate that phospholipids, a specific type of fat, are capable of improving a variety of cognitive processes in both animals and humans. The mechanisms underlying these positive effects are actively being investigated but as of yet are not fully elucidated. In this review, we summarise the preclinical and clinical studies available on phospholipid-based strategies for improved brain health across the lifespan. Moreover, we summarize the hypothesized direct and indirect mechanisms of action of these lipid-based interventions which may be used to promote resilience to stress and improve age-related cognitive decline in vulnerable populations., Competing Interests: Declaration of Competing Interest APC Microbiome Ireland has conducted studies in collaboration with several companies, including GSK, Pfizer, Cremo, Suntory, Wyeth, Mead Johnson, Nutricia, 4D Pharma, and DuPont. B. L. Roy is an employee of Cremo SA. T. G. Dinan has been an invited speaker at meetings organized by Servier, Lundbeck, Janssen, and AstraZeneca and has received research funding from Mead Johnson, Cremo, Nutricia, and 4D Pharma. J. F. Cryan has been an invited speaker at meetings organized by Mead Johnson, Yakult, Alkermes, and Janssen and has received research funding from Mead Johnson Nutrition, Cremo, Nutricia, DuPont, and 4D Pharma., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The microbiota-gut-brain axis encompasses a bidirectional mode of communication between the microorganisms residing in our gut, and our brain function and behavior. The composition of the gut microbiota is subject to diurnal variation and is entrained by host circadian rhythms. In turn, a diverse microbiota is essential for optimal regulation of host circadian pathways. Disruption of the cyclical nature of this microbe-host interaction profoundly influences disease pathology and severity. This review aims to summarize current knowledge on this bidirectional relationship. Indeed, the past few years have revealed promising data regarding the relationship between the microbiota-gut-brain axis and circadian rhythms and how they act in concert to influence disease, but further research needs to be done to examine how they coalesce to modulate severity of, and risk for, certain diseases. Moreover, there is a need for a greater understanding of the molecular mechanisms underlying the close relationship between circadian-microbiome-brain interactions., Competing Interests: Declaration of Interests The authors are not aware of any affiliations, memberships, funding, or financial holdings that might be perceived as affecting the objectivity of this review. However, T.G.D. and J.F.C. have been invited speakers at meetings organized by Yakult, Alkermes, Ordesa, Servier, Lundbeck, Janssen, and AstraZeneca, and have received research funding from Mead Johnson, Cremo, Nutricia, Dupont, Pharmavite, and 4D Pharma. All other authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The gut microbiota is a vast, complex, and fascinating ecosystem of microorganisms that resides in the human gastrointestinal tract. As an integral part of the microbiota-gut-brain axis, it is now being recognized that the microbiota is a modulator of brain and behavior, across species. Intriguingly, periods of change in the microbiota coincide with the development of other body systems and particularly the brain. We hypothesize that these times of parallel development are biologically relevant, corresponding to 'sensitive periods' or 'critical windows' in the development of the microbiota-gut-brain axis. Specifically, signals from the microbiota during these periods are hypothesized to be crucial for establishing appropriate communication along the axis throughout the life span. In other words, the microbiota is hypothesized to act like an expected input to calibrate the development of the microbiota-gut-brain axis. The absence or disruption of the microbiota during specific developmental windows would therefore be expected to have a disproportionate effect on specific functions or potentially for regulation of the system as a whole. Evidence for microbial modulation of neurocognitive development and neurodevelopmental risk is discussed in light of this hypothesis, finishing with a focus on the challenges that lay ahead for the future study of the microbiota-gut-brain axis during development., (© 2019 Association for Child and Adolescent Mental Health.)

Multisensory integration strongly depends on the temporal proximity between two inputs. In the audio-visual domain, stimulus pairs with delays up to a few hundred milliseconds can be perceived as simultaneous and integrated into a unified percept. Previous research has shown that the size of this temporal window of integration can be narrowed by feedback-guided training on an audio-visual simultaneity judgment task. Yet, it has remained uncertain how the neural network that processes audio-visual asynchronies is affected by the training. In the present study, participants were trained on a 2-interval forced choice audio-visual simultaneity judgment task. We recorded their neural activity with magnetoencephalography in response to three different stimulus onset asynchronies (0 ms, each participant's individual binding window, 300 ms) before, and one day following training. The Individual Window stimulus onset asynchrony condition was derived by assessing each participant's point of subjective simultaneity. Training improved performance in both asynchronous stimulus onset conditions (300 ms, Individual Window). Furthermore, beta-band amplitude (12-30 Hz) increased from pre-compared to post-training sessions. This increase moved across central, parietal, and temporal sensors during the time window of 80-410 ms post-stimulus onset. Considering the putative role of beta oscillations in carrying feedback from higher to lower cortical areas, these findings suggest that enhanced top-down modulation of sensory processing is responsible for the improved temporal acuity after training. As beta oscillations can be assumed to also preferentially support neural communication over longer conduction delays, the widespread topography of our effect could indicate that training modulates not only processing within primary sensory cortex, but rather the communication within a large-scale network., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Whereas the diagnosis of moderate and severe traumatic brain injury (TBI) is readily visible on current medical imaging paradigms (magnetic resonance imaging [MRI] and computed tomography [CT] scanning), a far greater challenge is associated with the diagnosis and subsequent management of mild TBI (mTBI), especially concussion which, by definition, is characterized by a normal CT. To investigate whether the integrity of the blood-brain barrier (BBB) is altered in a high-risk population for concussions, we studied professional mixed martial arts (MMA) fighters and adolescent rugby players. Additionally, we performed the linear regression between the BBB disruption defined by increased gadolinium contrast extravasation on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on MRI and multiple biomechanical parameters indicating the severity of impacts recorded using instrumented mouthguards in professional MMA fighters. MMA fighters were examined pre-fight for a baseline and again within 120 h post-competitive fight, whereas rugby players were examined pre-season and again post-season or post-match in a subset of cases. DCE-MRI, serological analysis of BBB biomarkers, and an analysis of instrumented mouthguard data, was performed. Here, we provide pilot data that demonstrate disruption of the BBB in both professional MMA fighters and rugby players, dependent on the level of exposure. Our data suggest that biomechanical forces in professional MMA and adolescent rugby can lead to BBB disruption. These changes on imaging may serve as a biomarker of exposure of the brain to repetitive subconcussive forces and mTBI.

The traditional fields of pharmacology and toxicology are beginning to consider the substantial impact our gut microbiota has on host physiology. The microbiota-gut-brain axis is emerging as a particular area of interest and a potential new therapeutic target for effective treatment of central nervous system disorders, in addition to being a potential cause of drug side effects. Microbiota-gut-brain axis signaling can occur via several pathways, including via the immune system, recruitment of host neurochemical signaling, direct enteric nervous system routes and the vagus nerve, and the production of bacterial metabolites. Altered gut microbial profiles have been described in several psychiatric and neurological disorders. Psychobiotics, live biotherapeutics or substances whose beneficial effects on the brain are bacterially mediated, are currently being investigated as direct and/or adjunctive therapies for psychiatric and neurodevelopmental disorders and possibly for neurodegenerative disease, and they may emerge as new therapeutic options in the clinical management of brain disorders.

There is mounting evidence that the trillions of microbes that inhabit our gut are a substantial contributing factor to mental health and, equally, to the progression of neuropsychiatric disorders. The extraordinary complexity of the gut ecosystem, and how it interacts with the intestinal epithelium to manifest physiological changes in the brain to influence mood and behaviour, has been the subject of intense scientific scrutiny over the last 2 decades. To further complicate matters, we each harbour a unique microbiota community that is subject to change by a number of factors including diet, exercise, stress, health status, genetics, medication, and age, amongst others. The microbiota-gut-brain axis is a dynamic matrix of tissues and organs including the gastrointestinal (GI) microbiota, immune cells, gut tissue, glands, the autonomic nervous system (ANS), and the brain that communicate in a complex multidirectional manner through a number of anatomically and physiologically distinct systems. Long-term perturbations to this homeostatic environment may contribute to the progression of a number of disorders by altering physiological processes including hypothalamic-pituitary-adrenal axis activation, neurotransmitter systems, immune function, and the inflammatory response. While an appropriate, co-ordinated physiological response, such as an immune or stress response, is necessary for survival, a dysfunctional response can be detrimental to the host, contributing to the development of a number of central nervous system disorders., (© 2019 S. Karger AG, Basel.)

Sex is a critical factor in the diagnosis and development of a number of mental health disorders including autism, schizophrenia, depression, anxiety, Parkinson's disease, multiple sclerosis, anorexia nervosa and others; likely due to differences in sex steroid hormones and genetics. Recent evidence suggests that sex can also influence the complexity and diversity of microbes that we harbour in our gut; and reciprocally that our gut microbes can directly and indirectly influence sex steroid hormones and central gene activation. There is a growing emphasis on the role of gastrointestinal microbiota in the maintenance of mental health and their role in the pathogenesis of disease. In this review, we introduce mechanisms by which gastrointestinal microbiota are thought to mediate positive health benefits along the gut-brain axis, we report how they may be modulated by sex, the role they play in sex steroid hormone regulation, and their sex-specific effects in various disorders relating to mental health., Competing Interests: Declaration of Competing Interest J.F.C, and T.G.D have research support from Mead Johnson, Cremo, 4D Pharma, Suntory Wellness, and Nutricia. These authors have spoken at meetings sponsored by food and pharmaceutical companies. All other authors report no potential conflicts of interest., (Copyright © 2019. Published by Elsevier Inc.)

New frontiers for host-microbe interactions continue to emerge as our knowledge of the adult gut microbiome in health and disease is continually supplemented and improved. Alterations in the gut microbiota composition in irritable bowel syndrome (IBS) are now linked to symptom severity while population-based evidence linking gut microbiome signatures to depression is an important new landmark. The effects of drugs on gut microbiome composition are also becoming clearer. Meanwhile, preclinical studies have delineated the influence of the gut microbiome at a structural and activity level in distinct brain regions. Bacterial metabolites, such as tryptamine, can activate specific receptors to impact gastrointestinal motility. These recent studies bring into focus the future implications for therapeutic targeting of the microbiome-gut-brain axis., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Sociability can facilitate mutually beneficial outcomes such as division of labor, cooperative care, and increased immunity, but sociability can also promote negative outcomes, including aggression and coercion. Accumulating evidence suggests that symbiotic microorganisms, specifically the microbiota that reside within the gastrointestinal system, may influence neurodevelopment and programming of social behaviors across diverse animal species. This relationship between host and microbes hints that host-microbiota interactions may have influenced the evolution of social behaviors. Indeed, the gastrointestinal microbiota is used by certain species as a means to facilitate communication among conspecifics. Further understanding of how microbiota influence the brain in nature may be helpful for elucidating the causal mechanisms underlying sociability and for generating new therapeutic strategies for social disorders in humans, such as autism spectrum disorders (ASDs)., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson's disease, and Alzheimer's disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.

The gut-brain axis is a bidirectional communication system between the central nervous system and the gastrointestinal tract, in which serotonin (5-HT) functions as a key neurotransmitter. Recent research has increasingly concentrated on tryptophan, the precursor to 5-HT and on the microbial regulation of tryptophan metabolism, with an emphasis on host-microbe control over kynurenine pathway metabolism and microbial-specific pathways that generate bioactive tryptophan metabolites. Here, we critically assess recent progress made towards a mechanistic understanding of the microbial regulation of tryptophan metabolism and microbiota-gut-brain axis homeostasis highlighting the role tryptophan metabolism plays in preclinical and clinical neuroscience and in the challenge to improve our understanding of how perturbed tryptophan metabolism contributes to stress-related psychiatric disorders., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The gut microbiome facilitates a consistent transfer of information between the gut and the brain and microRNAs may now represent a key signalling molecule that facilitates this relationship. This review will firstly examine how these small non-coding RNAs influence the gut microbiome, and secondly how the microbiome, when disturbed, may influence miRNA expression in the brain. In addition, we will examine the consequence that microbiome-related changes in miRNA expression have on neurodevelopment, behaviour and cognition. We will also discuss novel data that suggests miRNAs contained in our diet may influence our immune system in a positive manner, offering a further potential pathway for treatment of disorders of the gut-brain axis that are influenced by the microbiome., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Stress negatively impacts gut and brain health. Individual differences in response to stress have been linked to genetic and environmental factors and more recently, a role for the gut microbiota in the regulation of stress-related changes has been demonstrated. However, the mechanisms by which these factors influence each other are poorly understood, and there are currently no established robust biomarkers of stress susceptibility. To determine the metabolic and microbial signatures underpinning physiological stress responses, we compared stress-sensitive Wistar Kyoto (WKY) rats to the normo-anxious Sprague Dawley (SD) strain. Here we report that acute stress-induced strain-specific changes in brain lipid metabolites were a prominent feature in WKY rats. The relative abundance of Lactococcus correlated with the relative proportions of many brain lipids. In contrast, plasma lipids were significantly elevated in response to stress in SD rats, but not in WKY rats. Supporting these findings, we found that the greatest difference between the SD and WKY microbiomes were the predicted relative abundance of microbial genes involved in lipid and energy metabolism. Our results provide potential insights for developing novel biomarkers of stress vulnerability, some of which appear genotype specific.

Microbial colonization of the gastrointestinal tract plays a crucial role in the development of enteric and central nervous system functionality. The serotonergic system has been heavily implicated in microbiota-gut-brain axis signaling, particularly in proof-of-principle studies in germ-free (GF) animals. One aspect of the serotonergic system that has been left unexplored in relation to the microbiota is the unique ability of the serotonin receptor 2C (5-HT 2C ) to undergo post-transcriptional editing, which has been implicated in decreased receptor functionality. We investigated whether GF mice, with absent microbiota from birth, have altered 5-HT 2C receptor expression and editing in the brain, and if colonization of the microbiota is able to restore editing patterns. Next, we investigated whether microbiota depletion later in life using a chronic antibiotic treatment could affect 5-HT 2C receptor editing patterns in rats. We found that GF mice have an increased prevalence of the edited 5-HT 2C receptor isoforms in the amygdala, hypothalamus, prefrontal cortex, and striatum, which was partially normalized upon colonization post-weaning. However, no alterations were observed in the hypothalamus after microbiota depletion using an antibiotic treatment in adult rats. This suggests that alterations in the microbiome during development, but not later in life, could influence 5-HT 2C receptor editing patterns. Overall, these results demonstrate that the microbiota affects 5-HT 2C receptor editing in the brain and may inform novel therapeutic strategies in conditions in which 5-HT 2C receptor editing is altered, such as depression.

The gut microbiota, acting via the gut-brain axis, modulates key neurobiological systems that are dysregulated in stress-related disorders. Preclinical studies show that the gut microbiota exerts an influence over neuroimmune and neuroendocrine signaling pathways, in addition to epigenetic modification, neurogenesis, and neurotransmission. In humans, preliminary evidence suggests that the gut microbiota profile is altered in depression. The full impact of microbiota-based treatments, at different neurodevelopmental time points, has yet to be fully explored. The integration of the gut microbiota, as a mediator, in the complex trajectory of depression, may enhance the possibility of personalized precision psychiatry., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Recently it has been proposed to expand the definition of psychobiotics (beneficial bacteria (probiotics) or support for such bacteria (prebiotics) that positively impact mental health) to any exogenous influence whose effect on the brain is bacterially-mediated. This definition would include inactivated microorganisms with anxiolytic and antidepressant effects. The use of inactivated microorganisms has several advantages over living organisms, including no risk of infection in vulnerable individuals and ease of use in terms of storage and delivery options. It has been reported that consumption of inactivated microorganisms can affect behaviour, particularly in chronic or prolonged stress situations, but effects on healthy populations have not been investigated to the same extent. Also, only limited data is available on the effects of inactivated microorganisms on the microbiota of healthy individuals (animal or human). Therefore, we investigated the effect of feeding a standard mouse chow which incorporates ADR-159, a heat-killed fermentate generated by two Lactobacillus strains, on the behaviour and microbiota of healthy mice. Prolonged consumption of ADR-159 diet had no adverse effect on anthropometrics or general health, but the ADR-159 fed animals demonstrated increased sociability and lower baseline corticosterone levels (stress hormone). The diet also led to subtle but significant changes in the microbiota, with less abundant taxa being most affected. The behavioural, biochemical and microbiological results provide a new light on the impact of inactivated microorganisms and their metabolites on the social behaviour and microbiota of healthy mice., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Transition immediately after birth is a complex physiological process. The neonate has to establish sufficient ventilation to ensure significant changes from intra-uterine to extra-uterine circulation. If hypoxia or bradycardia or both occur, as commonly happens during immediate transition in preterm neonates, cerebral hypoxia-ischemia may cause perinatal brain injury. The primary objective of the COSGOD phase III trial is to investigate whether it is possible to increase survival without cerebral injury in preterm neonates of less than 32 weeks of gestation by targeting cerebral tissue oxygen saturation (crSO 2 ) using specified clinical treatment guidelines during the immediate transition period after birth (the first 15 min) in addition to the routine monitoring of arterial oxygen saturation (SpO 2 ) and heart rate (HR)., Methods/design: COSGOD III is an investigator-initiated, randomized, multi-center, multi-national, phase III clinical trial. Inclusion criteria are neonates of less than 32 weeks of gestation, decision to provide full life support, and parental informed consent. Exclusion criteria are severe congenital malformations of brain, heart, lung, or prenatal cerebral injury or a combination of these. The premature infants will be randomly assigned to study or control groups. Both groups will have a near-infrared spectroscopy (NIRS) device (left frontal), pulse oximeter (right palm/wrist), and electrocardiogram placed immediately after birth. In the study group, the crSO 2 , SpO 2 , and HR readings are visible, and the infant will receive treatment in accordance with defined treatment guidelines. In the control group, only SpO 2 and HR will be visible, and the infant will receive routine treatment. The intervention period will last for the first 15 min after birth during the immediate transition period and resuscitation. Thereafter, each neonate will be followed up for primary outcome to term date or discharge. The primary outcome is mortality or cerebral injury (or both) defined as any intra-ventricular bleeding or cystic periventricular leukomalacia (or both). Secondary outcomes are neonatal morbidities., Discussion: crSO 2 monitoring during immediate transition has been proven to be feasible and improve cerebral oxygenation during immediate transition. The additional monitoring of crSO 2 with dedicated interventions may improve outcome of preterm neonates as evidenced by increased survival without cerebral injury., Trial Registration: ClinicalTrials.gov Identifier: NCT03166722 . Registered March 5, 2017.

The gut microbiota has emerged as a key player in health and disease. Here we discuss the vagus nerve, which connects the visceral organs and the brain, as an important communication pathway for the gut microbiota to influence brain and behavior., (Copyright © 2019 Elsevier Inc. All rights reserved.)

For the premature newborn, little is known about changes in brain activity during transition to extra-uterine life. We aim to quantify these changes in relation to the longer-term maturation of the developing brain. We analysed EEG for up to 72 hours after birth from 28 infants born <32 weeks of gestation. These infants had favourable neurodevelopment at 2 years of age and were without significant neurological compromise at time of EEG monitoring. Quantitative EEG was generated using features representing EEG power, discontinuity, spectral distribution, and inter-hemispheric connectivity. We found rapid changes in cortical activity over the 3 days distinct from slower changes associated with gestational age: for many features, evolution over 1 day after birth is equivalent to approximately 1 to 2.5 weeks of maturation. Considerable changes in the EEG immediately after birth implies that postnatal adaption significantly influences cerebral activity for early preterm infants. Postnatal age, in addition to gestational age, should be considered when analysing preterm EEG within the first few days after birth.

An awareness of the importance of the gut-brain axis in psychiatric disorders such as depression is increasing. The gut microbiome is a key component of this axis. Gut bacteria can communicate with the brain through a variety of pathways including the hypothalamic-pituitary-adrenal axis, immune modulation, tryptophan metabolism and the production of various neuroactive compounds. Patients with depression, and other mood and anxiety disorders, show distinct compositional changes in their gut bacteria profile, raising the question about a possible aetiological role for the microbiome in these disorders. Evidence is emerging that the gut microbiome may represent a new potential antidepressant target and the term 'psychobiotic' has been coined to describe bacteria which confer mental health benefits. Gut bacteria are easily accessible and can be altered in a variety of ways including through the use of probiotics, prebiotics and dietary change. Psychobiotics containing various Lactobacillus and Bifidobacterium species have demonstrated the ability to improve mood, reduce anxiety and enhance cognitive function in both healthy populations and patient groups. This article provides an overview of the identification and development of antidepressant psychobiotics, from the preclinical evidence in the laboratory to the more recent encouraging results from human trials.