Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour
Journal: Nature Reviews Neuroscience
Pulished: Sep 12 , 2012
Author: John F. Cryan and Timothy G. Dinan
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.
The neuroactive potential of the human gut microbiota in quality of life and depression
Journal: Nature Microbiology
Pulished: Feb 04, 2019
Author: Mireia Valles-Colomer, Gwen Falony, Youssef Darzi, et al.
Abstract: The relationship between gut microbial metabolism and mental health is one of the most intriguing and controversial topics in microbiome research. Bidirectional microbiota–gut–brain communication has mostly been explored in animal models, with human research lagging behind. Large-scale metagenomics studies could facilitate the translational process, but their interpretation is hampered by a lack of dedicated reference databases and tools to study the microbial neuroactive potential. Surveying a large microbiome population cohort (Flemish Gut Flora Project, n = 1,054) with validation in independent data sets (ntotal = 1,070), we studied how microbiome features correlate with host quality of life and depression. Butyrate-producing Faecalibacterium and Coprococcus bacteria were consistently associated with higher quality of life indicators. Together with Dialister, Coprococcus spp. were also depleted in depression, even after correcting for the confounding effects of antidepressants. Using a module-based analytical framework, we assembled a catalogue of neuroactive potential of sequenced gut prokaryotes. Gut–brain module analysis of faecal metagenomes identified the microbial synthesis potential of the dopamine metabolite 3,4-dihydroxyphenylacetic acid as correlating positively with mental quality of life and indicated a potential role of microbial γ-aminobutyric acid production in depression. Our results provide population-scale evidence for microbiome links to mental health, while emphasizing confounder importance.
Why does the microbiome affect behaviour?
Journal: Nature Reviews Microbiology
Pulished: Apr 24, 2018
Author: Katerina V.-A. Johnson and Kevin R. Foster
Growing evidence indicates that the mammalian microbiome can affect behaviour, and several symbionts even produce neurotransmitters. One common explanation for these observations is that symbionts have evolved to manipulate host behaviour for their benefit. Here, we evaluate the manipulation hypothesis by applying evolutionary theory to recent work on the gut–brain axis. Although the theory predicts manipulation by symbionts under certain conditions, these appear rarely satisfied by the genetically diverse communities of the mammalian microbiome. Specifically, any symbiont investing its resources to manipulate host behaviour is expected to be outcompeted within the microbiome by strains that do not manipulate and redirect their resources into growth and survival. Moreover, current data provide no clear evidence for manipulation. Instead, we show how behavioural effects can readily arise as a by-product of natural selection on microorganisms to grow within the host and natural selection on hosts to depend upon their symbionts. We argue that understanding why the microbiome influences behaviour requires a focus on microbial ecology and local effects within the host.
The interplay between the intestinal microbiota and the brain
Journal: Nature Reviews Microbiology
Pulished: Sep 24, 2012
Author: Stephen M. Collins., Michael Surette and Premysl Bercik
Abstract: The intestinal microbiota consists of a vast bacterial community that resides primarily in the lower gut and lives in a symbiotic relationship with the host. A bidirectional neurohumoral communication system, known as the gut–brain axis, integrates the host gut and brain activities. Here, we describe the recent advances in our understanding of how the intestinal microbiota communicates with the brain via this axis to influence brain development and behaviour. We also review how this extended communication system might influence a broad spectrum of diseases, including irritable bowel syndrome, psychiatric disorders and demyelinating conditions such as multiple sclerosis.
The mucosal immune system: master regulator of bidirectional gut–brain communications
Journal: Nature Reviews Gastroenterology & Hepatology
Pulished: Jan 18, 2017
Author: Nick Powell, Marjorie M, Walker and Nicholas J. Talley
Abstract: Communication between the brain and gut is not one-way, but a bidirectional highway whereby reciprocal signals between the two organ systems are exchanged to coordinate function. The messengers of this complex dialogue include neural, metabolic, endocrine and immune mediators responsive to diverse environmental cues, including nutrients and components of the intestinal microbiota (microbiota–gut–brain axis). We are now starting to understand how perturbation of these systems affects transition between health and disease. The pathological repercussions of disordered gut–brain dialogue are probably especially pertinent in functional gastrointestinal diseases, including IBS and functional dyspepsia. New insights into these pathways might lead to novel treatment strategies in these common gastrointestinal diseases. In this Review, we consider the role of the immune system as the gatekeeper and master regulator of brain–gut and gut–brain communications. Although adaptive immunity (T cells in particular) participates in this process, there is an emerging role for cells of the innate immune compartment (including innate lymphoid cells and cells of the mononuclear phagocyte system). We will also consider how these key immune cells interact with the specific components of the enteric and central nervous systems, and rapidly respond to environmental variables, including the microbiota, to alter gut homeostasis.
From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways
Journal: Molecular Psychiatry
Pulished: Apr 19, 2016
Author: G B Rogers, D J Keating, R L Young, et al.
Abstract: The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut–brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies.
Finding the needle in the haystack: systematic identification of psychobiotics
Journal: Br J Pharmacol
Pulished: Dec 26, 2018
Author: Bambury A, Sandhu K, Cryan JF and Dinan TG.
Abstract: The brain-gut-microbiota axis is increasingly viewed as a novel paradigm in neuroscience with the capacity to generate innovative therapies for patients with psychiatric illnesses. Psychobiotics, defined as live bacteria, which when ingested in adequate amounts, confer mental health benefits, are increasingly of interest, as preclinical trials continue to show promising results. Particularly in stress-related, anxiety and depressive disorders, there is potential for psychobiotics to deliver new therapies. The question of which microbes may prove to be the most promising psychobiotic in delivering such therapies at a clinical level is of great importance. Here we look at the characteristics of psychobiotics, in an attempt to present an outline from which the identification of potential new psychobiotics may be possible.
Psychobiotics and the Manipulation of Bacteria-Gut-Brain Signals
Journal: Trends Neurosci
Pulished: Oct 25, 2016
Author: Sarkar A, Lehto SM, Harty S, et al.
Psychobiotics were previously defined as live bacteria (probiotics) which, when ingested, confer mental health benefits through interactions with commensal gut bacteria. We expand this definition to encompass prebiotics, which enhance the growth of beneficial gut bacteria. We review probiotic and prebiotic effects on emotional, cognitive, systemic, and neural variables relevant to health and disease. We discuss gut-brain signalling mechanisms enabling psychobiotic effects, such as metabolite production. Overall, knowledge of how the microbiome responds to exogenous influence remains limited. We tabulate several important research questions and issues, exploration of which will generate both mechanistic insights and facilitate future psychobiotic development. We suggest the definition of psychobiotics be expanded beyond probiotics and prebiotics to include other means of influencing the microbiome.
Psychobiotics: An emerging probiotic in psychiatric practice
Journal: Biomed J.
Pulished: Aug 09, 2016
Author: Kali A.
Abstract: Intestinal microbial flora plays critical role in maintenance of health. Probiotic organisms have been recognized as an essential therapeutic component in the treatment of intestinal dysbiosis. Current research suggests their health benefits extends beyond intestinal disorders. The neuroactive molecules produced by the gut microbiota has been found to modulate neural signals which affect neurological and psychiatric parameters like sleep, appetite, mood and cognition. Use of these novel probiotics opens up the possibility of restructuring of intestinal microbiota for effective management of various psychiatric disorders.
Modification of the gut microbiome to combat neurodegeneration
Journal: Rev Neurosci
Pulished: May 16, 2019
Author: Sasmita AO
Abstract: The gut microbiome was extensively researched for its biological variety and its potential role in propagating diseases outside of the gastrointestinal (GI) tract. Recently, a lot of effort was focused on comprehending the gut-brain axis and the bizarre communication between the GI system and the nervous system. Ample amount of studies being carried out also revealed the involvement of the gut microbiome in enhancing the degree of many neurological disorders, including neurodegenerative diseases. It was widely observed that there were distinct microbiome profiles and dysbiosis within patients suffering from Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Various approaches to re-establish the balance of the gut microbiome, from antibiotic therapy, fecal microbiota transplant, or ingestion of psychobiotics, are discussed within this review within the specific context of combating neurodegenerative diseases. Present studies and clinical trials indicate that although there is an immense potential of gut microbiome modification to be preventive or therapeutic, there are still many intercalated components of the gut-brain axis at play and thus, more research needs to be carried out to delineate microbiome factors that may potentially alleviate symptoms of neurodegeneration.
From Probiotics to Psychobiotics: Live Beneficial Bacteria Which Act on the Brain-Gut Axis
Journal: Nutrients
Pulished: Apr 20, 2019
Author: Bermúdez-Humarán LG, Salinas E, Ortiz GG, et al.
Abstract: There is an important relationship between probiotics, psychobiotics and cognitive and behavioral processes, which include neurological, metabolic, hormonal and immunological signaling pathways; the alteration in these systems may cause alterations in behavior (mood) and cognitive level (learning and memory). Psychobiotics have been considered key elements in affective disorders and the immune system, in addition to their effect encompassing the regulation of neuroimmune regulation and control axes (the hypothalamic-pituitary-adrenal axis or HPA, the sympathetic-adrenal-medullary axis or SAM and the inflammatory reflex) in diseases of the nervous system. The aim of this review is to summarize the recent findings about psychobiotics, the brain-gut axis and the immune system. The review focuses on a very new and interesting field that relates the microbiota of the intestine with diseases of the nervous system and its possible treatment, in neuroimmunomodulation area. Indeed, although probiotic bacteria will be concentrated after ingestion, mainly in the intestinal epithelium (where they provide the host with essential nutrients and modulation of the immune system), they may also produce neuroactive substances which act on the brain-gut axis.
The gut-brain relationship: Investigating the effect of multispecies probiotics on anxiety in a randomized placebo-controlled trial of healthy young adults
Journal: J Affect Disord
Pulished: Jun 01, 2019
Author: Tran N, Zhebrak M, Yacoub C, et al.
Abstract：
Introduction: There has been an increased interest in understanding the therapeutic effect of gut-microbiota on health, particularly in mental health. However, limited research into the connection between gut-microbiota and mental health makes this study an important endeavor in exploring the effect of gut-microbiota, through probiotics intervention, on mental health like anxiety and factors related to anxiety (e.g., anxiety control, affect, negative mood regulation, and worry).
Method: Healthy college students (N = 86; 75.6% female), average age of 20.59, participated in a double-blind, placebo-control, and randomization-control study. Eligible participants completed a baseline survey before being assigned to a condition, which consisted of four probiotics conditions and one placebo condition. After 28 days of daily intake, the participants returned to complete their exit survey.
Result: Probiotics were observed to improve panic anxiety, neurophysiological anxiety, negative affect, worry, and increase negative mood regulation. Furthermore, post hoc analyses revealed that the CFU (colony-forming unit) level was more effective than species counts in accounting for the number of significant improvements. A ceiling effect was detected in the study, participants with high distress reported higher number of improvements than those with normative distress.
Conclusion: Overall, this study is the first to examine the effect of CFU and species count on probiotics' efficacy. The study's finding suggested that probiotics may have the therapeutic potential to treat anxiety, however, further research is necessary to make that determination.
From isoniazid to psychobiotics: the gut microbiome as a new antidepressant target
Journal: Br J Hosp Med (Lond)
Pulished: Mar 02, 2019
Author: Butler MI, Sandhu K, Cryan JF and Dinan TG.
Abstract: 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. Psychobioticscontaining 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.
The novel insight into anti-inflammatory and anxiolytic effects of psychobiotics in diabetic rats: possible link between gut microbiota and brain regions
Journal: Eur J Nutr.
Pulished: Mar 02, 2019
Author: Hosseinifard ES, Morshedi M, Bavafa-Valenlia K and Saghafi-Asl M
Abstract：
Purpose: Type 2 diabetes mellitus (T2DM) was associated with gut microbial impairment (dysbiosis) and neurological and behavioral disorders. The role of the gut-brain axis in the management of many diseases including T2DM has been the focus of much research activity in the recent years. However, a wide knowledge gap exists about the gut microbial effects on the function of glia cells. Hence, the present study was aimed to examine the effects of psychobatics on dysbiosis and glia cells function in enteric and central nervous system with an inflammatory insight in T2DM.
Methods: Thirty rats were treated by Lactobacillus (L.) plantarum, inulin, or their combination (synbiotic) for 8 weeks after inducing T2DM. Fecal sample was collected to evaluate gut microbial composition. Then, the rats were sacrificed, and the colon, amygdala, and prefrontal cortex (PFC) were studied.
Results: T2DM resulted in dysbiosis and increased levels of glial cell-derived neurotrophic factor (GDNF), glial fibrillary acidic protein (GFAP), and inflammatory markers (IL-17, IL-6, and TLR-2) in the colon and brain. However, concurrent supplementation of L. plantarum and inulin could improve the gut microbial composition as well as reduce the levels of inflammatory cytokines. While the administration of L. plantarum led to a significant decrease in TLR-2 as well as GDNF and GFAP only in the amygdala, the synbiotic intake could make such changes in the colon, amygdala, and PFC.
Conclusion: Our findings demonstrated an innovative approach to the beneficial effects of psychobiotics in neuroinflammation and behavioral performance through gut microbiota changes, focusing on possible role of glial cells in gut-brain axis.
Microbiota-Brain-Gut Axis and Neurodegenerative Diseases
Journal: Curr Neurol Neurosci Rep.
Pulished: Oct 17, 2017
Author: Quigley EMM
Abstract
Pupose of review: The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson's disease, and, finally, to assess the potential for microbiota-targeted therapies.
Recent findings : Work on animal models has established the microbiota-gut-brain axis as a real phenomenon; to date, the evidence for its operation in man has been limited and has been confronted by considerable logistical challenges. Animal and translational models have incriminated a disturbed gut microbiota in a number of CNS disorders, including Parkinson's disease; data from human studies is scanty. While a theoretical basis can be developed for the use of microbiota-directed therapies in neurodegenerative disorders, support is yet to come from high-quality clinical trials. In theory, a role for the microbiota-gut-brain axis is highly plausible; clinical confirmation is awaited.
Microbiota-gut-brain axis and the central nervous system
Journal: Oncotarget
Pulished: May 10, 2017
Author: Zhu X, Han Y, Du J, et al.
Abstract: The gut and brain form the gut-brain axis through bidirectional nervous, endocrine, and immune communications. Changes in one of the organs will affect the other organs. Disorders in the composition and quantity of gut microorganisms can affect both the enteric nervous system and the central nervous system (CNS), thereby indicating the existence of a microbiota-gut-brain axis. Due to the intricate interactions between the gut and the brain, gut symbiotic microorganisms are closely associated with various CNS diseases, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and multiple sclerosis. In this paper, we will review the latest advances of studies on the correlation between gut microorganisms and CNS functions & diseas
Psychobiotics: A Novel Class of Psychotropic
Journal: Biological Psychiatry
Pulished: Nov 15, 2013
Author: Timothy G. Dinan, Catherine Stanton and John F. Cryan
Abstract: Here, we define a psychobiotic as a live organism that, when ingested in adequate amounts, produces a health benefit in patients suffering from psychiatric illness. As a class of probiotic, these bacteria are capable of producing and delivering neuroactive substances such as gamma-aminobutyric acid and serotonin, which act on the brain-gut axis. Preclinical evaluation in rodents suggests that certain psychobiotics possess antidepressant or anxiolytic activity. Effects may be mediated via the vagus nerve, spinal cord, or neuroendocrine systems. So far, psychobiotics have been most extensively studied in a liaison psychiatric setting in patients with irritable bowel syndrome, where positive benefits have been reported for a number of organisms including Bifidobacterium infantis. Evidence is emerging of benefits in alleviating symptoms of depression and in chronic fatigue syndrome. Such benefits may be related to the anti-inflammatory actions of certain psychobiotics and a capacity to reduce hypothalamic-pituitary-adrenal axis activity. Results from large scale placebo-controlled studies are awaited.
Psychobiotics Highlight the Pathways to Happiness
Journal: Biological Psychiatry
Pulished: Nov 15, 2013
Author: Philip W.J. Burnet and Philip J. Cowen
Abstract: There is no doubt that enteric commensal microbiota are important benefactors of mammalian intestinal health. The professed 「good」 bacterial species, Lactobacilli and Bifidobacteria, lack the external proinflammatory lipopolysaccharide chains that are anchored to the cell walls of pathogenic bacteria such as E. coli and Salmonella. The host gut, therefore, is tolerant to extensive colonization by beneficial bacteria, which compete with the establishment of detrimental microbes and lower the risk of infection.