Prebiotic feeding elevates central brain derived neurotrophic factor, N-methyl-d-aspartate receptor subunits and d-serine
TL;DR: The GOS prebiotic increased cortical NR1, d-serine, and hippocampal NR2A subunits and BDNF and NR1subunit mRNAs, in the rat hippocampus, and increased plasma levels of the gut peptide PYY.
About: This article is published in Neurochemistry International.The article was published on 2013-12-01 and is currently open access. It has received 284 citations till now. The article focuses on the topics: Brain-derived neurotrophic factor & Peptide YY.
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TL;DR: 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.
Abstract: 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 ...
1,775 citations
TL;DR: This Review summarizes existing knowledge on the potential of SCFAs to directly or indirectly mediate microbiota–gut–brain interactions and their interaction with gut–brain signalling pathways including immune, endocrine, neural and humoral routes.
Abstract: Short-chain fatty acids (SCFAs), the main metabolites produced by bacterial fermentation of dietary fibre in the gastrointestinal tract, are speculated to have a key role in microbiota-gut-brain crosstalk. However, the pathways through which SCFAs might influence psychological functioning, including affective and cognitive processes and their neural basis, have not been fully elucidated. Furthermore, research directly exploring the role of SCFAs as potential mediators of the effects of microbiota-targeted interventions on affective and cognitive functioning is sparse, especially in humans. This Review summarizes existing knowledge on the potential of SCFAs to directly or indirectly mediate microbiota-gut-brain interactions. The effects of SCFAs on cellular systems and their interaction with gut-brain signalling pathways including immune, endocrine, neural and humoral routes are described. The effects of microbiota-targeted interventions such as prebiotics, probiotics and diet on psychological functioning and the putative mediating role of SCFA signalling will also be discussed, as well as the relationship between SCFAs and psychobiological processes. Finally, future directions to facilitate direct investigation of the effect of SCFAs on psychological functioning are outlined.
1,206 citations
TL;DR: How the development of future treatments for central nervous system (CNS) disorders can take advantage of the intimate and mutual interactions of the gut microbiota with the brain by exploring the role of SCFAs in the regulation of neuro-immunoendocrine function is highlighted.
Abstract: A substantial body of evidence supports that the gut microbiota plays a pivotal role in the regulation of metabolic, endocrine and immune functions. In recent years, there has been growing recognition of the involvement of the gut microbiota in the modulation of multiple neurochemical pathways through the highly interconnected gut-brain axis. Although amazing scientific breakthroughs over the last few years have expanded our knowledge on the communication between microbes and their hosts, the underpinnings of microbiota-gut-brain crosstalk remain to be determined. Short-chain fatty acids (SCFAs), the main metabolites produced in the colon by bacterial fermentation of dietary fibers and resistant starch, are speculated to play a key role in neuro-immunoendocrine regulation. However, the underlying mechanisms through which SCFAs might influence brain physiology and behavior have not been fully elucidated. In this review, we outline the current knowledge about the involvement of SCFAs in microbiota-gut-brain interactions. We also highlight how the development of future treatments for central nervous system (CNS) disorders can take advantage of the intimate and mutual interactions of the gut microbiota with the brain by exploring the role of SCFAs in the regulation of neuro-immunoendocrine function.
966 citations
TL;DR: This review will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted, and draw on both clinical and preclinical evidence to support this concept.
Abstract: The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a "leaky gut" may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function.
719 citations
Cites background from "Prebiotic feeding elevates central ..."
...GOS, for example, increased hippocampal neurotrophin levels and the expression N-methyl-d-aspartate receptor subunits in the rat frontal cortex (Savignac et al., 2013)....
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TL;DR: O Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate speculations.
Abstract: The discovery of the size and complexity of the human microbiome has resulted in an ongoing reevaluation of many concepts of health and disease, including diseases affecting the CNS. A growing body of preclinical literature has demonstrated bidirectional signaling between the brain and the gut microbiome, involving multiple neurocrine and endocrine signaling mechanisms. While psychological and physical stressors can affect the composition and metabolic activity of the gut microbiota, experimental changes to the gut microbiome can affect emotional behavior and related brain systems. These findings have resulted in speculation that alterations in the gut microbiome may play a pathophysiological role in human brain diseases, including autism spectrum disorder, anxiety, depression, and chronic pain. Ongoing large-scale population-based studies of the gut microbiome and brain imaging studies looking at the effect of gut microbiome modulation on brain responses to emotion-related stimuli are seeking to validate these speculations. This article is a summary of emerging topics covered in a symposium and is not meant to be a comprehensive review of the subject.
666 citations
Cites background from "Prebiotic feeding elevates central ..."
...Surprisingly, there has been a paucity of studies in animals or humans with prebiotics, although specific prebiotics have been shown to increase brain BDNF levels (Savignac et al., 2013)....
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References
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Book•
01 Jan 1983
TL;DR: This paper presents a meta-analyses of the determinants of earthquake-triggered landsliding in the Czech Republic over a period of 18 months in order to establish a probabilistic framework for estimating the intensity of the earthquake.
Abstract: Preface. Acknowledgements. Introduction. References. List of Structures. Index of Abbreviations. Diagrams.
57,116 citations
"Prebiotic feeding elevates central ..." refers methods in this paper
...8 mm from Bregma, (Paxinos and Watson, 1986)], were pre-treated as described (Eastwood et al....
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...Slides containing sections of the dorsal hippocampus [ 3.2 to 3.8 mm from Bregma, (Paxinos and Watson, 1986)], were pre-treated as described (Eastwood et al., 1995)....
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TL;DR: The emerging concept of a microbiota–gut–brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders.
Abstract: Recent years have witnessed the rise of the gut microbiota as a major topic of research interest in biology. Studies are revealing how variations and changes in the composition of the gut microbiota influence normal physiology and contribute to diseases ranging from inflammation to obesity. Accumulating data now indicate that the gut microbiota also communicates with the CNS — possibly through neural, endocrine and immune pathways — and thereby influences brain function and behaviour. Studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. Thus, the emerging concept of a microbiota-gut-brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders.
3,058 citations
"Prebiotic feeding elevates central ..." refers background in this paper
...The proliferation of the Bifidobacteria and Lactobacilli strains in the large intestine, have anxiolytic and mnemonic effects in both rodents (Li et al., 2009; Bravo et al., 2011) and humans (Messaoudi et al., 2011a,b; Rao et al., 2009; Cryan and Dinan, 2012)....
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TL;DR: Chronic treatment with L. rhamnosus induced region-dependent alterations in GABAB1b mRNA in the brain with increases in cortical regions and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice, highlighting the important role of bacteria in the bidirectional communication of the gut–brain axis.
Abstract: There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABAB1b mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced GABAAα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABAAα2 in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut–brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression.
2,713 citations
"Prebiotic feeding elevates central ..." refers background in this paper
...The proliferation of the Bifidobacteria and Lactobacilli strains in the large intestine, have anxiolytic and mnemonic effects in both rodents (Li et al., 2009; Bravo et al., 2011) and humans (Messaoudi et al., 2011a,b; Rao et al., 2009; Cryan and Dinan, 2012)....
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...The proliferation of the Bifidobacteria and Lactobacilli strains in the large intestine, have anxiolytic and mnemonic effects in both rodents (Li et al., 2009; Bravo et al., 2011) and humans (Messaoudi et al....
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TL;DR: Exposure to microbes at an early developmental stage is required for the HPA system to become fully susceptible to inhibitory neural regulation, and results suggest that commensal microbiota can affect the postnatal development of the Hpa stress response in mice.
Abstract: Indigenous microbiota have several beneficial effects on host physiological functions; however, little is known about whether or not postnatal microbial colonization can affect the development of brain plasticity and a subsequent physiological system response. To test the idea that such microbes may affect the development of neural systems that govern the endocrine response to stress, we investigated hypothalamic–pituitary–adrenal (HPA) reaction to stress by comparing germfree (GF), specific pathogen free (SPF) and gnotobiotic mice. Plasma ACTH and corticosterone elevation in response to restraint stress was substantially higher in GF mice than in SPF mice, but not in response to stimulation with ether. Moreover, GF mice also exhibited reduced brain-derived neurotrophic factor expression levels in the cortex and hippocampus relative to SPF mice. The exaggerated HPA stress response by GF mice was reversed by reconstitution with Bifidobacterium infantis. In contrast, monoassociation with enteropathogenic Escherichia coli, but not with its mutant strain devoid of the translocated intimin receptor gene, enhanced the response to stress. Importantly, the enhanced HPA response of GF mice was partly corrected by reconstitution with SPF faeces at an early stage, but not by any reconstitution exerted at a later stage, which therefore indicates that exposure to microbes at an early developmental stage is required for the HPA system to become fully susceptible to inhibitory neural regulation. These results suggest that commensal microbiota can affect the postnatal development of the HPA stress response in mice.
2,023 citations
"Prebiotic feeding elevates central ..." refers background in this paper
...Mice devoid of gut microbiota from birth have reduced levels of N-methyl-D-aspartate receptors (NMDARs), specifically the NR1 and NR2A subunits, in the hippocampus (Sudo et al., 2004), or NR2B subunits in the amygdala (Neufeld et al., 2011; Kiss et al., 2012)....
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...Mice devoid of gut microbiota from birth have reduced levels of N-methyl-D-aspartate receptors (NMDARs), specifically the NR1 and NR2A subunits, in the hippocampus (Sudo et al., 2004), or NR2B subunits in the amygdala (Neufeld et al....
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TL;DR: The intestinal microbiota influences brain chemistry and behavior independently of the autonomic nervous system, gastrointestinal-specific neurotransmitters, or inflammation.
1,366 citations
"Prebiotic feeding elevates central ..." refers background or result in this paper
...…study has shown that plasma from mice administered with Bifidobacterium longum, did not change the expression of BDNF mRNA in cultured SH-SY5Y cells (Bercik et al., 2011b), and this was reasoned to be further evidence of a vagal, rather than a ‘blood-borne’ mediation of probiotic central effects....
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...A similar elevation of BDNF mRNA after FOS and GOS administration is, therefore, in keeping with a potential antidepressant/anxiolytic property of gut bacteria (Bercik et al., 2011a)....
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...Interestingly, selective antimicrobials which elevate the levels of intrinsic gut Lactobacilli, also increase brain BDNF concentrations in mice (Bercik et al., 2011a)....
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...The elevated expression of BDNF and encoded protein in rats fed with FOS, is consistent with the effect of a Bifidobacterium probiotic (Bercik et al., 2011a; O’Sullivan et al., 2011) and the selective proliferation of these species with antimicrobials (Bercik et al., 2011a)....
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...For instance, the oral administration of Bifidobacteria to rats elevated hippocampal brain-derived neurotrophic factor (BDNF) (Bercik et al., 2011a; O’Sullivan et al., 2011), which may underlie some antidepressant actions (Kerman, 2012)....
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