Feeding the brain and nurturing the mind: Linking nutrition and the gut microbiota to brain development

The human gut contains a microbial community composed of tens of trillions of organisms that normally assemble during the first 2–3 y of postnatal life. We propose that brain development needs to be viewed in the context of the developmental biology of this “microbial organ” and its capacity to metabolize the various diets we consume. We hypothesize that the persistent cognitive abnormalities seen in children with undernutrition are related in part to their persistent gut microbiota immaturity and that specific regions of the brain that normally exhibit persistent juvenile (neotenous) patterns of gene expression, including those critically involved in various higher cognitive functions such as the brain’s default mode network, may be particularly vulnerable to the effects of microbiota immaturity in undernourished children. Furthermore, we postulate that understanding the interrelationships between microbiota and brain metabolism in childhood undernutrition could provide insights about responses to injury seen in adults. We discuss approaches that can be used to test these hypotheses, their ramifications for optimizing nutritional recommendations that promote healthy brain development and function, and the potential societal implications of this area of investigation.

Download Full-text

Microbiota-immune interactions: from gut to brain

LymphoSign Journal ◽

10.14785/lymphosign-2019-0018 ◽

2020 ◽

Vol 7 (1) ◽

pp. 1-23 ◽

Cited By ~ 1

Author(s):

Eloisa Salvo-Romero ◽

Patricia Stokes ◽

Mélanie G. Gareau

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Immune System ◽

Gut Microbiota ◽

Brain Development ◽

Immune Cells ◽

Autism Spectrum ◽

Immune System Development ◽

And Function ◽

The Brain

The vast diversity of bacteria that inhabit the gastrointestinal tract strongly influence host physiology, not only nutrient metabolism but also immune system development and function. The complexity of the microbiota is matched by the complexity of the host immune system, where they have coevolved to maintain homeostasis ensuring the mutualistic host-microbial relationship. Numerous studies in recent years investigating the gut-brain axis have demonstrated an important role for the gut microbiota in modulating brain development and function, with the immune system serving as an important coordinator of these interactions. Gut bacteria can modulate not only gut-resident immune cells but also brain-resident immune cells. Activation of the immune system in the gut and in the brain are implicated in responses to neuroinflammation, brain injury, as well as changes in neurogenesis and plasticity. Impairments in this bidirectional communication are implicated in the etiopathogenesis of psychiatric and neurodevelopmental diseases and disorders, including autism spectrum disorders, or comorbidities associated with Gastrointestinal diseases, including inflammatory bowel diseases, where dysbiosis is commonly seen. Consequently, probiotics, or beneficial microbes, are being recognized as promising therapeutic targets to modulate behavior and brain development by modulating the gut microbiota. Here we review the role of microbiota-immune interactions in the gut and the brain during homeostasis and disease and their impact on gut-brain communication, brain function, and behavior as well as the use of probiotics in central nervous system alterations. Statement of novelty: The microbiota-gut-brain axis is increasingly recognized as an important physiological pathway for maintaining health and impacting the brain and central nervous system. Increasing evidence suggests that the immune system is crucial for gut-brain signaling. In this review, we highlight the critical studies in the literature that identify the key immune pathways involved.

Download Full-text

Neurodevelopment in the first three years: implications for child development, professional practice and policy

Journal of Children s Services ◽

10.1108/jcs-01-2014-0005 ◽

2014 ◽

Vol 9 (2) ◽

pp. 154-164 ◽

Cited By ~ 4

Author(s):

Danya Glaser

Keyword(s):

Brain Development ◽

Brain Activity ◽

Brain Maturation ◽

Policy And Practice ◽

Content Type ◽

Key Issues ◽

And Function ◽

The Relationship ◽

The Brain ◽

Brain Connections

Purpose – The purpose of this paper is to outline brain structure and development, the relationship between environment and brain development and implications for practice. Design/methodology/approach – The paper is based on a selected review of the literature and clinical experience. Findings – While genetics determine the sequence of brain maturation, the nature of brain development and functioning is determined by the young child's caregiving environment, to which the developing brain constantly adapts. The absence of input during sensitive periods may lead to later reduced functioning. There is an undoubted immediate equivalence between every mind function – emotion, cognition, behaviour and brain activity, although the precise location of this in the brain is only very partially determinable, since brain connections and function are extremely complex. Originality/value – This paper provides an overview of key issues in neurodevelopment relating to the development of young children, and implications for policy and practice.

Download Full-text

Microglia, Cytokines, and Neural Activity: Unexpected Interactions in Brain Development and Function

Frontiers in Immunology ◽

10.3389/fimmu.2021.703527 ◽

2021 ◽

Vol 12 ◽

Author(s):

Austin Ferro ◽

Yohan S. S. Auguste ◽

Lucas Cheadle

Keyword(s):

Brain Development ◽

Signaling Pathways ◽

Immune Cells ◽

Neural Activity ◽

Signaling Molecules ◽

Evolutionary Strategy ◽

Inflammatory Signaling ◽

Peripheral Tissues ◽

And Function ◽

The Brain

Intercellular signaling molecules such as cytokines and their receptors enable immune cells to communicate with one another and their surrounding microenvironments. Emerging evidence suggests that the same signaling pathways that regulate inflammatory responses to injury and disease outside of the brain also play powerful roles in brain development, plasticity, and function. These observations raise the question of how the same signaling molecules can play such distinct roles in peripheral tissues compared to the central nervous system, a system previously thought to be largely protected from inflammatory signaling. Here, we review evidence that the specialized roles of immune signaling molecules such as cytokines in the brain are to a large extent shaped by neural activity, a key feature of the brain that reflects active communication between neurons at synapses. We discuss the known mechanisms through which microglia, the resident immune cells of the brain, respond to increases and decreases in activity by engaging classical inflammatory signaling cascades to assemble, remodel, and eliminate synapses across the lifespan. We integrate evidence from (1) in vivo imaging studies of microglia-neuron interactions, (2) developmental studies across multiple neural circuits, and (3) molecular studies of activity-dependent gene expression in microglia and neurons to highlight the specific roles of activity in defining immune pathway function in the brain. Given that the repurposing of signaling pathways across different tissues may be an important evolutionary strategy to overcome the limited size of the genome, understanding how cytokine function is established and maintained in the brain could lead to key insights into neurological health and disease.

Download Full-text

Targeting the gut microbiota to influence brain development and function in early life

Neuroscience & Biobehavioral Reviews ◽

10.1016/j.neubiorev.2018.09.002 ◽

2018 ◽

Vol 95 ◽

pp. 191-201 ◽

Cited By ~ 13

Author(s):

Shugui Wang ◽

Louise Harvey ◽

Rocio Martin ◽

Eline M. van der Beek ◽

Jan Knol ◽

...

Keyword(s):

Gut Microbiota ◽

Brain Development ◽

Early Life ◽

And Function

Download Full-text

Necrotizing Enterocolitis, Gut Microbiota, and Brain Development: Role of the Brain-Gut Axis

Neonatology ◽

10.1159/000497420 ◽

2019 ◽

Vol 115 (4) ◽

pp. 423-431 ◽

Cited By ~ 11

Author(s):

Hendrik J. Niemarkt ◽

Tim G. De Meij ◽

Christ-jan van Ganzewinkel ◽

Nanne K.H. de Boer ◽

Peter Andriessen ◽

...

Keyword(s):

Gut Microbiota ◽

Brain Development ◽

Necrotizing Enterocolitis ◽

The Brain

Download Full-text

Soul searching: a brief history of the mind/body debate in the neurosciences

Neurosurgical FOCUS ◽

10.3171/foc-07/07/e2 ◽

2007 ◽

Vol 23 (1) ◽

pp. 1-7 ◽

Cited By ~ 13

Author(s):

Brian Dolan

Keyword(s):

Early Modern ◽

Structure And Function ◽

The Self ◽

History Of Neuroscience ◽

History Of ◽

And Function ◽

The Mind ◽

The Brain ◽

The Way

✓Anatomical and physiological understandings of the structure and function of the brain have worked to establish it as the “seat of the soul.” As an organ of reflection, meditation, and memory, the brain becomes synonymous with what defines the “self” through the existence of consciousness—of mind. Thus, the brain has been associated with a range of transcendent concepts—the soul, spirit, mind, and consciousness—that all relate in fundamental ways to each other both in terms of their perceived location within the brain and because of the way each works ultimately to define the person to whom the brain belongs. In this article, the author provides a brief exploration of how interrelated these categories have been when seen in the context of ancient, Renaissance, early modern, and modern philosophical and medical concerns; how the brain has variously been perceived as home to these intimate states of being; and how practitioners from the neurosciences have reflected on these questions. The author provides novel insights into the interrelationships of philosophy, theology, and medicine by examining these issues through the lens of the history of neuroscience.

Download Full-text

Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide

mBio ◽

10.1128/mbio.02481-14 ◽

2015 ◽

Vol 6 (2) ◽

Cited By ~ 254

Author(s):

Kymberleigh A. Romano ◽

Eugenio I. Vivas ◽

Daniel Amador-Noguez ◽

Federico E. Rey

Keyword(s):

Gut Microbiota ◽

Intestinal Microbiota ◽

Human Life ◽

Water Soluble ◽

Human Gut ◽

Choline Intake ◽

Low Levels ◽

And Function ◽

Dietary Choline

ABSTRACT Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which upon absorption by the host is converted in the liver to trimethylamine-N-oxide (TMAO). Recent studies revealed that TMAO exacerbates atherosclerosis in mice and positively correlates with the severity of this disease in humans. However, which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., genotype) and diet affect TMA production and colonization of these microbes, and the effects TMA-producing microbes have on the bioavailability of dietary choline remain largely unknown. We screened a collection of 79 sequenced human intestinal isolates encompassing the major phyla found in the human gut and identified nine strains capable of producing TMA from choline in vitro. Gnotobiotic mouse studies showed that TMAO accumulates in the serum of animals colonized with TMA-producing species, but not in the serum of animals colonized with intestinal isolates that do not generate TMA from choline in vitro. Remarkably, low levels of colonization by TMA-producing bacteria significantly reduced choline levels available to the host. This effect was more pronounced as the abundance of TMA-producing bacteria increased. Our findings provide a framework for designing strategies aimed at changing the representation or activity of TMA-producing bacteria in the human gut and suggest that the TMA-producing status of the gut microbiota should be considered when making recommendations about choline intake requirements for humans. IMPORTANCE Cardiovascular disease (CVD) is the leading cause of death and disability worldwide, and increased trimethylamine N-oxide (TMAO) levels have been causally linked with CVD development. This work identifies members of the human gut microbiota responsible for both the accumulation of trimethylamine (TMA), the precursor of the proatherogenic compound TMAO, and subsequent decreased choline bioavailability to the host. Understanding how to manipulate the representation and function of choline-consuming, TMA-producing species in the intestinal microbiota could potentially lead to novel means for preventing or treating atherosclerosis and choline deficiency-associated diseases.

Download Full-text

Differential Effects of Antibiotic Therapy on the Structure and Function of Human Gut Microbiota

PLoS ONE ◽

10.1371/journal.pone.0080201 ◽

2013 ◽

Vol 8 (11) ◽

pp. e80201 ◽

Cited By ~ 106

Author(s):

Ana Elena Pérez-Cobas ◽

Alejandro Artacho ◽

Henrik Knecht ◽

María Loreto Ferrús ◽

Anette Friedrichs ◽

...

Keyword(s):

Gut Microbiota ◽

Antibiotic Therapy ◽

Structure And Function ◽

Human Gut ◽

Differential Effects ◽

Human Gut Microbiota ◽

And Function

Download Full-text

Assessment of behavioral, morphological and electrophysiological changes in prenatal and postnatal valproate induced rat models of autism spectrum disorder

Scientific Reports ◽

10.1038/s41598-021-02994-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Katarine Fereshetyan ◽

Vergine Chavushyan ◽

Margarita Danielyan ◽

Konstantin Yenkoyan

Keyword(s):

Autism Spectrum Disorders ◽

Brain Development ◽

Structural Changes ◽

Brain Plasticity ◽

Autism Spectrum ◽

Postnatal Life ◽

Adult Rats ◽

Spectrum Disorders ◽

Core Symptoms ◽

The Brain

AbstractAutism spectrum disorders (ASD) are neurodevelopmental disorders, that are characterized by core symptoms, such as alterations of social communication and restrictive or repetitive behavior. The etiology and pathophysiology of disease is still unknown, however, there is a strong interaction between genetic and environmental factors. An intriguing point in autism research is identification the vulnerable time periods of brain development that lack compensatory homeostatic corrections. Valproic acid (VPA) is an antiepileptic drug with a pronounced teratogenic effect associated with a high risk of ASD, and its administration to rats during the gestation is used for autism modeling. It has been hypothesized that valproate induced damage and functional alterations of autism target structures may occur and evolve during early postnatal life. Here, we used prenatal and postnatal administrations of VPA to investigate the main behavioral features which are associated with autism spectrum disorders core symptoms were tested in early juvenile and adult rats. Neuroanatomical lesion of autism target structures and electrophysiological studies in specific neural circuits. Our results showed that prenatal and early postnatal administration of valproate led to the behavioral alterations that were similar to ASD. Postnatally treated group showed tendency to normalize in adulthood. We found pronounced structural changes in the brain target regions of prenatally VPA-treated groups, and an absence of abnormalities in postnatally VPA-treated groups, which confirmed the different severity of VPA across different stages of brain development. The results of this study clearly show time dependent effect of VPA on neurodevelopment, which might be explained by temporal differences of brain regions’ development process. Presumably, postnatal administration of valproate leads to the dysfunction of synaptic networks that is recovered during the lifespan, due to the brain plasticity and compensatory ability of circuit refinement. Therefore, investigations of compensatory homeostatic mechanisms activated after VPA administration and directed to eliminate the defects in postnatal brain, may elucidate strategies to improve the course of disease.

Download Full-text

Typical and atypical brain development: a review of neuroimaging studies

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2013.15.3/edennis ◽

2013 ◽

Vol 15 (3) ◽

pp. 359-384 ◽

Cited By ~ 18

Keyword(s):

Brain Development ◽

Neurodevelopmental Disorders ◽

Fragile X ◽

Early Adulthood ◽

22Q11.2 Deletion Syndrome ◽

Developmental Trajectory ◽

Deletion Syndrome ◽

Effective Interventions ◽

And Function ◽

The Brain

In the course of development, the brain undergoes a remarkable process of restructuring as it adapts to the environment and becomes more efficient in processing information. A variety of brain imaging methods can be used to probe how anatomy, connectivity, and function change in the developing brain. Here we review recent discoveries regarding these brain changes in both typically developing individuals and individuals with neurodevelopmental disorders. We begin with typical development, summarizing research on changes in regional brain volume and tissue density, cortical thickness, white matter integrity, and functional connectivity. Space limits preclude the coverage of all neurodevelopmental disorders; instead, we cover a representative selection of studies examining neural correlates of autism, attention deficit/hyperactivity disorder, Fragile X, 22q11.2 deletion syndrome, Williams syndrome, Down syndrome, and Turner syndrome. Where possible, we focus on studies that identify an age by diagnosis interaction, suggesting an altered developmental trajectory. The studies we review generally cover the developmental period from infancy to early adulthood. Great progress has been made over the last 20 years in mapping how the brain matures with MR technology. With ever-improving technology, we expect this progress to accelerate, offering a deeper understanding of brain development, and more effective interventions for neurodevelopmental disorders.

Download Full-text