The GUT and GABA

[[je...]]

Thanks smiff, lots of info for my slow brain to process. I wouldn't be surprised if I have a histamine intolerance too. Every time I eat sugar my sinuses will flare up. Do you know if the coconut kefir water has the safer strain of bacteria?

[[Sm...]]

Thanks smiff, lots of info for my slow brain to process. I wouldn't be surprised if I have a histamine intolerance too. Every time I eat sugar my sinuses will flare up. Do you know if the coconut kefir water has the safer strain of bacteria?

 

No idea on the coconut kefir. I think you try it Jenny and if it makes you feel good go with it - it means the bacteria is working for you. If it starts making you feel foggy or itchy then it doesn't work for you.

 

Yea histamine intolerance is an interesting one. I don't think I fully understand it, still Im now on the diet. I've only been on a low histamine diet a few days but it seems to be helpful at least for me.

[[Pe...]]

Hey Smiff,

 

Just read over the article and also found a more recent one:

 

 

Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents

Azucena Perez-Burgos , Bingxian Wang , Yu-Kang Mao , Bhavik Mistry , Karen-Anne McVey Neufeld , John Bienenstock , Wolfgang Kunze

American Journal of Physiology - Gastrointestinal and Liver Physiology Published 15 January 2013 Vol. 304 no.  2,  G211-G220 DOI: 10.1152/ajpgi.00128.2012

http://ajpgi.physiology.org/content/304/2/G211#sec-16

 

This is an interesting line of research.  It appears to be in its infancy and that they are still trying to figure out whether the changes to GABA mRNA is a direct or secondary effect.  The article above suggests it may be due to the bacteria changing the firing rate of the vagus nerve resulting in a change in the afferent inputs to the brain.  It may take some time before they figure out the precise mechanisms involved but it is definitely interesting. I have heard that it is a good idea to get fermented foods into the diet.  I often say that when it comes to the body everything affects everything, LOL...thanks for showing this to me.

[[Sm...]]

I'm putting these here partly for future if I get time to read them 

 

 

Current Opinion in Gastroenterology:

November 2012 - Volume 28 - Issue 6 - p 557–562

doi: 10.1097/MOG.0b013e3283572ffa

IMMUNOLOGY: Edited by W. Allan Walker

On communication between gut microbes and the brain

 

Forsythe, Paula,b; Kunze, Wolfgang A.a,c; Bienenstock, Johna,d

Collapse Box

Abstract

 

Purpose of review: Interest in the microbiota–gut–brain axis is increasing apace and what was, not so long ago, a hypothetical relationship is emerging as a potentially critical factor in the regulation of intestinal and mental health. Studies are now addressing the neural circuitry and mechanisms underlying the influence of gut bacteria on the central nervous system and behavior.

 

Recent findings: Gut bacteria influence development of the central nervous systems (CNS) and stress responses. In adult animals, the overall composition of the microbiota or exposure to specific bacterial strains can modulate neural function, peripherally and centrally. Gut bacteria can provide protection from the central effects of infection and inflammation as well as modulate normal behavioral responses. Behavioral effects described to date are largely related to stress and anxiety and an altered hypothalamus–pituitary–adrenal axis response is a common observation in many model systems. The vagus nerve has also emerged as an important means of communicating signals from gut microbes to the CNS.

 

Summary: Studies of microbiota–gut–brain communication are providing us with a deeper understanding of the relationship between the gut bacteria and their hosts while also suggesting the potential for microbial-based therapeutic strategies that may aid in the treatment of mood disorders.

 

 

 

 

Bifidobacterium longum NCC3001 inhibits AH neuron excitability

 

    A. Khoshdel1,

    E. F. Verdu1,

    W. Kunze2,

    P. McLean3,

    G. Bergonzelli3 and

    J. D. Huizinga1,*

Neurogastroenterology & Motility

 

Volume 25, Issue 7, pages e478–e484, July 2013

Article first published online: 12 MAY 2013

 

DOI: 10.1111/nmo.12147

 

© 2013 John Wiley & Sons Ltd

 

Abstract

Background

 

Bifidobacterium longum (B. longum) NCC3001 can affect behavior and brain biochemistry, but identification of the cellular targets needs further investigation. Our hypothesis was that the communication with the brain might start with action on enteric sensory neurons.

Methods

 

Ileal segments from adult mice were used to create a longitudinal muscle-myenteric-plexus preparation to expose sensory after-hyperpolarizing (AH) neurons in the myenteric plexus to allow access with microelectrodes. The intrinsic excitability of AH neurons was tested in response to the perfusion of conditioned media (B. longum culture supernatant) or unconditioned media (growth medium, MRS).

Key Results

 

B. longum conditioned medium significantly reduced the excitability of AH neurons compared to perfusion with the unconditioned medium. Specifically, a reduction was seen in the number of action potentials fired per depolarizing test pulse, the instantaneous and time-dependent input resistances and the magnitude of the hyperpolarization-activated cationic current (Ih).

Conclusions & Inferences

 

The probiotic B. longum reduces excitability of AH sensory neurons likely via opening of potassium channels and closing of hyperpolarization-activated cation channels.

 

 

Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice

 

    H. M. Savignac1,

    B. Kiely2,

    T. G. Dinan3 and

    J. F. Cryan4,*

Neurogastroenterology & Motility

 

Volume 26, Issue 11, pages 1615–1627, November 2014

 

Abstract

Background

 

Accumulating evidence suggests that commensal bacteria consumption has the potential to have a positive impact on stress-related psychiatric disorders. However, the specific bacteria influencing behaviors related to anxiety and depression remain unclear. To this end, we compared the effects of two different Bifidobacteria on anxiety and depression-like behavior; an antidepressant was also used as a comparator.

Methods

 

Innately anxious BALB/c mice received daily Bifidobacterium longum (B.) 1714, B. breve 1205, the antidepressant escitalopram or vehicle treatment for 6 weeks. Behavior was assessed in stress-induced hyperthermia test, marble burying, elevated plus maze, open field, tail suspension test, and forced swim test. Physiological responses to acute stress were also assessed.

Key Results

 

Both Bifidobacteria and escitalopram reduced anxiety in the marble burying test; however, only B. longum 1714 decreased stress-induced hyperthermia. B. breve 1205 induced lower anxiety in the elevated plus maze whereas B. longum 1714 induced antidepressant-like behavior in the tail suspension test. However, there was no difference in corticosterone levels between groups.

Conclusions & Inferences

 

These data show that these two Bifidobacteria strains reduced anxiety in an anxious mouse strain. These results also suggest that each bacterial strain has intrinsic effects and may be beneficially specific for a given disorder. These findings strengthen the role of gut microbiota supplementation as psychobiotic-based strategies for stress-related brain-gut axis disorders, opening new avenues in the field of neurogastroenterology.

Article first published online: 24 SEP 2014

 

 

 

Regulation of the stress response by the gut microbiota: Implications for psychoneuroendocrinology

 

    Timothy G. Dinan, ,

    John F. Cryan

Psychoneuroendocrinology

 

Volume 37, Issue 9, September 2012, Pages 1369–1378

Summary

 

There is now an expanding volume of evidence to support the view that commensal organisms within the gut play a role in early programming and later responsivity of the stress system. The gut is inhabited by 1013–1014 micro-organisms, which is ten times the number of cells in the human body and contains 150 times as many genes as our genome. It has long been recognised that gut pathogens such as Escherichia coli, if they enter the gut can activate the HPA. However, animals raised in a germ-free environment show exaggerated HPA responses to psychological stress, which normalises with monocolonisation by certain bacterial species including Bifidobacterium infantis. Moreover, increased evidence suggests that animals treated with probiotics have a blunted HPA response. Stress induces increased permeability of the gut allowing bacteria and bacterial antigens to cross the epithelial barrier and activate a mucosal immune response, which in turn alters the composition of the microbiome and leads to enhanced HPA drive. Increasing data from patients with irritable bowel syndrome and major depression indicate that in these syndromes alteration of the HPA may be induced by increased gut permeability. In the case of irritable bowel syndrome the increased permeability can respond to probiotic therapy. Detailed prospective studies in patients with mood disorders examining the gut microbiota, immune parameters and HPA activity are required to throw further light on this emerging area. It is however clear that the gut microbiota must be taken into account when considering the factors regulating the HPA.

 

 

Gut–brain axis: how the microbiome influences anxiety and depression

 

    Jane A. Foster ,

    Karen-Anne McVey Neufeld

 

Within the first few days of life, humans are colonized by commensal intestinal microbiota. Here, we review recent findings showing that microbiota are important in normal healthy brain function. We also discuss the relation between stress and microbiota, and how alterations in microbiota influence stress-related behaviors. New studies show that bacteria, including commensal, probiotic, and pathogenic bacteria, in the gastrointestinal (GI) tract can activate neural pathways and central nervous system (CNS) signaling systems. Ongoing and future animal and clinical studies aimed at understanding the microbiota–gut–brain axis may provide novel approaches for prevention and treatment of mental illness, including anxiety and depression.

 

 

 

Melancholic microbes: a link between gut microbiota and depression?

 

    T. G. Dinan* and

    J. F. Cryan*

Neurogastroenterology & Motility

 

Volume 25, Issue 9, pages 713–719, September 2013

Article first published online: 1 AUG 2013

 

Abstract

 

There is a growing awareness of the potential for microbiota to influence gut-brain communication in health and disease. A variety of strategies have been used to study the impact of the microbiota on brain function and these include antibiotic use, probiotic treatments, fecal microbiota transplantation, gastrointestinal infection studies, and germ-free studies. All of these approaches provide evidence to support the view that the microbiota can influence brain chemistry and consequently behavior. Efforts are now turning to investigate the role of microbiota in animal models of psychopathology. Animal models of depression are thus essential in studying the complex interplay between the microbiota and brain. Recent studies published in this Journal and elsewhere demonstrate that there is a distinct perturbation of the composition of gut microbiota in animal models of depression and chronic stress. This has direct implications for the development of psychobiotic-based therapeutic strategies for psychiatric disorders. Moreover, given that affective co-morbidities, such as major depression and anxiety states, are common in patients presenting with irritable bowel syndrome (IBS), it may have implications for functional bowel disorders also. Further studies require appropriately phenotyped patients with depression and/or IBS using a judicious use of techniques including functional imaging and in depth microbial pyrosequencing.

 

It is increasingly recognized that the brain-gut axis provides a bidirectional homeostatic route of communication which if dysfunctional can have important pathophysiological consequences. This axis is regulated at neural, hormonal, and immunological levels.[1] Whilst much focus on this axis has been on the central regulation of digestive function and satiety; there has been increasing emphasis on its role in other aspects of physiology. It is now clear that alterations in brain–gut interactions are associated with gut inflammation, chronic abdominal pain syndromes, and eating disorders.[1] Indeed, modulation of brain-gut axis function is associated with specific alterations in the stress-response and overall behavior (see Fig. 1). The high co-morbidity between stress-related psychiatric symptoms such as anxiety with gastrointestinal (GI) disorders including irritable bowel syndrome (IBS) and inflammatory bowel disorder (IBD) is further evidence of the importance of this axis.[2] Thus modulation of the brain-gut axis is being seen as an attractive target for the development of novel treatments for a wide variety of disorders ranging from obesity, mood, and anxiety disorders to GI disorders such as IBS.

There is also a growing appreciation that gut microbiota can play a crucial role in maintaining homeostasis in health and contribute to the pathogenesis of a variety of diseases. This is now even extending to disorders of the central nervous system. Indeed, the importance of emotional state and stress processing in the brain has received increasing recognition in the study of GI disorders, and microbiota-gut brain axis dysregulation in stress-related CNS disorders has been the subject of a number of excellent recent reviews.[3-7] Major depression is a common, debilitating stress-related disorder whereby patients frequently have hypothalamic-pituitary-adrenal (HPA) alterations such as elevated cortisol levels in plasma, elevated corticotropin releasing factor (CRF) levels in the cerebrospinal fluid coupled with a failure to suppress cortisol in response to dexamethasone challenge.[8] Moreover, marked increases in the concentrations of pro-inflammatory cytokines are also common biological hallmark of the disease (see Fig. 1).[8]

 

Microbes can influence the functioning of the HPA and immune system and thus it is perhaps not so surprising that there could be a link between microbiota and depression. It is now almost a decade since Sudo et al. demonstrated that germ-free (GF) mice with a sterile GI tract have an overactive HPA in response to stress. This hyper-response of the HPA is reversed by monoassociation with a single organism, Bifidobacterium infantis, which is a predominant bacterium in the infant gut and a commonly used probiotic organism.[9] More recent studies from three independent research groups in Sweden, Canada and Ireland[10-12] have all showed alterations in the levels of key monoamines (or their receptors) involved in depression (noradrenaline [NA] and 5-hydroxytryptamine [5-HT; serotonin]) in corticolimbic regions of the brain. Moreover, there is also evidence for alterations in key neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), involved in depression in the hippocampus of GF mice.[10, 13] However, there has been limited direct evidence linking depression and gut microbiota to date.

Probiotic studies are among the most commonly carried out to support a relationship between gut microbiota and brain and behavior. We examined the impact of Lactobacillus rhamnosus on behavior and central GABA receptors in mice.[36] Animals fed L. rhamnosus demonstrated reduced anxiety on a variety of behavioral measures and altered central expression of both GABAA and GABAB receptors. In order to determine the mechanism of action, animals underwent vagotomy or sham surgery and were treated either with L. rhamnosus or inactive broth. Vagotomy prevented the emergence of an anxiolytic effect from the probiotic and prevented changes in GABA receptor expression. The study provides compelling evidence to indicate that the vagus mediates the behavioral and neurochemical effects of L. rhamnosus.[36] A growing body of data is emerging using different models to support the contention that a variety of other potential probiotics can exert psychotropic potential. Specifically, B. Infantis has been shown to reverse maternal-separation-induced increases in immobility in the forced swim test[37] and also increased plasma tryptophan levels.[38] More recently, L. helveticus was shown to prevent diet-induced anxiety-like behavior and memory[39] and B. longum NCC3001 reversed colitis-induced anxiety in the mouse via the vagus nerve.[40] Moreover, a cocktail of probiotics (L. acidophilus, B. lactis and L. Fermentum) reversed diabetes-induced cognitive and electrophysiologiocal changes[41] whereas a combination of L. helveticus and B. longum decreased anxiety[42] and reversed postmyocardial infarction-induced depression in the rat.[43]

 

Clinical validation of these findings is essential and a recent neuroimaging study has been very important in illuminating the promise of translating the preclinical data into a potential therapeutic reality. Healthy women were recruited with no GI or psychiatric symptoms and randomly assigned them to receive either fermented milk product containing B. animalis, Streptococcus thermophiles, L. bulgaricus, and Lactococcus lactis or a non-fermented milk product or no intervention twice daily for 4 weeks.[44] Participants underwent functional magnetic resonance imaging before and after the intervention to measure brain response to an emotional faces attention task and resting brain activity. Multivariate and region of interest analyses were performed. Probiotic intake was associated with reduced task-related response of a distributed functional network containing affective, viscerosensory, and somatosensory cortices. Alterations in the intrinsic activity of resting brain indicated that ingestion of probiotics was associated with changes in midbrain connectivity, which could explain the observed differences in activity during the task. The data suggest that probiotics can alter brain regions that control central processing of emotion and sensation.[44] Recently, a study assessing the effect of a combination of L. helveticus and B. longum on both human subjects had beneficial psychological effects with a decrease in serum cortisol.[41] Probiotics with the capacity to positively impact on symptoms of depression or anxiety have recently been termed psychobiotics.[45

 

 

Psychobiotics: A Novel Class of Psychotropic

 

    Timothy G. Dinan, ,

    Catherine Stanton,

    John F. Cryan

Biological Psychiatry

 

Volume 74, Issue 10, 15 November 2013, Pages 720–726

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.

 

 

The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut–brain communication

 

    P. Bercik1,

    A. J. Park1,

    D. Sinclair1,

    A. Khoshdel1,

    J. Lu1,

    X. Huang1,

    Y. Deng1,

    P. A. Blennerhassett1,

    M. Fahnestock2,

    D. Moine3,

    B. Berger3,

    J. D. Huizinga1,

    W. Kunze1,

    P. G. McLean4,

    G. E. Bergonzelli4,

    S. M. Collins1 and

    E. F. Verdu1

 

Neurogastroenterology & Motility

 

Volume 23, Issue 12, pages 1132–1139, December 2011

Background  The probiotic Bifidobacterium longum NCC3001 normalizes anxiety-like behavior and hippocampal brain derived neurotrophic factor (BDNF) in mice with infectious colitis. Using a model of chemical colitis we test whether the anxiolytic effect of B. longum involves vagal integrity, and changes in neural cell function.

 

Methods  Mice received dextran sodium sulfate (DSS, 3%) in drinking water during three 1-week cycles. Bifidobacterium longum or placebo were gavaged daily during the last cycle. Some mice underwent subdiaphragmatic vagotomy. Behavior was assessed by step-down test, inflammation by myeloperoxidase (MPO) activity and histology. BDNF mRNA was measured in neuroblastoma SH-SY5Y cells after incubation with sera from B. longum- or placebo-treated mice. The effect of B. longum on myenteric neuron excitability was measured using intracellular microelectrodes.

 

Key Results  Chronic colitis was associated with anxiety-like behavior, which was absent in previously vagotomized mice. B. longum normalized behavior but had no effect on MPO activity or histological scores. Its anxiolytic effect was absent in mice with established anxiety that were vagotomized before the third DSS cycle. B. longum metabolites did not affect BDNF mRNA expression in SH-SY5Y cells but decreased excitability of enteric neurons.

 

Conclusions & Inferences  In this colitis model, anxiety-like behavior is vagally mediated. The anxiolytic effect of B. longum requires vagal integrity but does not involve gut immuno-modulation or production of BDNF by neuronal cells. As B. longum decreases excitability of enteric neurons, it may signal to the central nervous system by activating vagal pathways at the level of the enteric nervous system.

 

 

 

The intestinal microbiome, probiotics and prebiotics in neurogastroenterology

Delphine M. Saulniera*, Yehuda Ringelb, Melvin B. Heymanc, Jane A. Fosterde, Premysl Bercikde, Robert J. Shulmanf, James Versalovicgh, Elena F. Verdud, Ted G. Dinani, Gail Hechtj & Francisco Guarnerk

 

pages 17-27

Publishing models and article dates explained

 

    Published online: 27 Oct 2014

Abstract

 

The brain-gut axis allows bidirectional communication between the central nervous system (CNS) and the enteric nervous system (ENS), linking emotional and cognitive centers of the brain with peripheral intestinal functions. Recent experimental work suggests that the gut microbiota have an impact on the brain-gut axis. A group of experts convened by the International Scientific Association for Probiotics and Prebiotics (ISAPP) discussed the role of gut bacteria on brain functions and the implications for probiotic and prebiotic science. The experts reviewed and discussed current available data on the role of gut microbiota on epithelial cell function, gastrointestinal motility, visceral sensitivity, perception and behavior. Data, mostly gathered from animal studies, suggest interactions of gut microbiota not only with the enteric nervous system but also with the central nervous system via neural, neuroendocrine, neuroimmune and humoral links. Microbial colonization impacts mammalian brain development in early life and subsequent adult behavior. These findings provide novel insights for improved understanding of the potential role of gut microbial communities on psychological disorders, most particularly in the field of psychological comorbidities associated with functional bowel disorders like irritable bowel syndrome (IBS) and should present new opportunity for interventions with pro- and prebiotics.

 

 

 

The microbiome-gut-brain axis: from bowel to behavior

 

    J. F. Cryan and

    S. M. O’Mahony

 

Article first published online: 8 FEB 2011

 

DOI: 10.1111/j.1365-2982.2010.01664.x

Neurogastroenterology & Motility

 

Volume 23, Issue 3, pages 187–192, March 2011

The ability of gut microbiota to communicate with the brain and thus modulate behavior is emerging as an exciting concept in health and disease. The enteric microbiota interacts with the host to form essential relationships that govern homeostasis. Despite the unique enteric bacterial fingerprint of each individual, there appears to be a certain balance that confers health benefits. It is, therefore, reasonable to note that a decrease in the desirable gastrointestinal bacteria will lead to deterioration in gastrointestinal, neuroendocrine or immune relationships and ultimately disease. Therefore, studies focusing on the impact of enteric microbiota on the host and in particular on the central nervous system are essential to our understanding of the influence of this system. Recent studies published in this Journal demonstrate that germ-free mice display alterations in stress-responsivity, central neurochemistry and behavior indicative of a reduction in anxiety in comparison to conventional mice. Such data offer the enticing proposition that specific modulation of the enteric microbiota may be a useful strategy for stress-related disorders and for modulating the co-morbid aspects of gastrointestinal disorders such as irritable bowel syndrome and inflammatory bowel disease.

 

 

 

Nature Reviews Neuroscience 13, 701-712 (October 2012) | doi:10.1038/nrn3346

 

Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour

 

John F. Cryan1,2 & Timothy G. Dinan1,3  About the authors

Top of page

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.

 

 

 

Microbes and the gut-brain axis

 

    P. Bercik,

    S. M. Collins and

    E. F. Verdu

 

Article first published online: 8 MAR 2012

Neurogastroenterology & Motility

 

Volume 24, Issue 5, pages 405–413, May 2012

Background The ‘gut-brain’ or ‘brain-gut axis’, depending on whether we emphasize bottom-up or top-bottom pathways, is a bi-directional communication system, comprised of neural pathways, such as the enteric nervous system (ENS), vagus, sympathetic and spinal nerves, and humoral pathways, which include cytokines, hormones, and neuropeptides as signaling molecules. Recent evidence, mainly arising from animal models, supports a role of microbes as signaling components in the gut-brain axis.

 

Aims The purpose of this review is to summarize our current knowledge regarding the role of microbes, including commensals, probiotics and gastrointestinal pathogens, in bottom-up pathways of communication in the gut-brain axis. Although this has clear implications for psychiatric co-morbidity in functional and inflammatory conditions of the gut, the focus of this review will be to discuss the current evidence for a role of bacteria (commensals, probiotics, and pathogens) as key modulators of gut-brain communication.

 

Results & Conclusions The strongest evidence for a role of microbes as signaling components in the gut-brain axis currently arises from animal studies and indicate that mechanisms of communication are likely to be multiple. There is need for the concepts generated in animal models to be translated to the human in the future.

 

 

Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents

Azucena Perez-Burgos , Bingxian Wang , Yu-Kang Mao , Bhavik Mistry , Karen-Anne McVey Neufeld , John Bienenstock , Wolfgang Kunze

American Journal of Physiology - Gastrointestinal and Liver PhysiologyPublished 15 January 2013Vol. 304no. 2

 

Mounting evidence supports the influence of the gut microbiome on the local enteric nervous system and its effects on brain chemistry and relevant behavior. Vagal afferents are involved in some of these effects. We previously showed that ingestion of the probiotic bacterium Lactobacillus rhamnosus (JB-1) caused extensive neurochemical changes in the brain and behavior that were abrogated by prior vagotomy. Because information can be transmitted to the brain via primary afferents encoded as neuronal spike trains, our goal was to record those induced by JB-1 in vagal afferents in the mesenteric nerve bundle and thus determine the nature of the signals sent to the brain. Male Swiss Webster mice jejunal segments were cannulated ex vivo, and serosal and luminal compartments were perfused separately. Bacteria were added intraluminally. We found no evidence for translocation of labeled bacteria across the epithelium during the experiment. We recorded extracellular multi- and single-unit neuronal activity with glass suction pipettes. Within minutes of application, JB-1 increased the constitutive single- and multiunit firing rate of the mesenteric nerve bundle, but Lactobacillus salivarius (a negative control) or media alone were ineffective. JB-1 significantly augmented multiunit discharge responses to an intraluminal distension pressure of 31 hPa. Prior subdiaphragmatic vagotomy abolished all of the JB-1-evoked effects. This detailed exploration of the neuronal spike firing that encodes behavioral signaling to the brain may be useful to identify effective psychoactive bacteria and thereby offer an alternative new perspective in the field of psychiatry and comorbid conditions.

The intestinal microbiome influences gut-brain communication (1, 7, 9, 14, 19, 38, 47). This is further supported by observations that the enteric nervous system and brain differ between germ-free and conventional animals (1, 15, 25, 40, 41). However, the underlying mechanisms are unknown, and most studies focus on the impact of altered signaling on the brain (9, 13, 19, 38) and not on the intervening pathways from gut luminal microbiome to the brain. Our data are incompatible with the hypothesis we initially offered in the Introduction. Indeed, we present the first evidence that in a normal mouse jejunum a single probiotic (L. rhamnosus JB-1) provokes an increase of the constitutive mesenteric nerve multi- and single-unit firing rate within minutes of luminal application. In addition, JB-1 further augmented distension-evoked increases in multi- and single-unit firing of mesenteric vagal afferents. These effects were due to single fibers that increase their firing frequency rather than an increase in the number of active fibers recruited.

 

The vagus nerve is an important afferent signaling pathway between the gastrointestinal tract and the brain (24, 47). This pathway is bidirectional, and clear evidence for a vagal efferent anti-inflammatory pathway exists (50). There are several lines of evidence that suggest that the vagus is involved in both mood regulation and gut inflammation (13, 23). Because low-grade, even unrecognizable gut inflammation, induced by pathogenic bacteria appears to promote anxiety-like behavior (36), the introduction of bacteria such as probiotics, many of which themselves induce anti-inflammatory circuits (18, 29), cannot be assumed to be acting on the brain independently from their effects on inflammation. There is also evidence that changes in the gut microbiota and/or ingestion of probiotics can experimentally influence behavior in animals that have undergone some experimental manipulations (1, 3), but these occurred separately from influences of the autonomic nervous system. The anxiolytic effect of B. longum also inhibited the generation of anxiety-like behavior in a chemical colitis model, and this effect, however, was inhibited by prior vagotomy (2).

 

We have recently published that chronic feeding of conventionally housed healthy mice with L. rhamnosus (JB-1) induced anxiolytic changes in behavior and in the level of GABAAα2, GABAAα1, and GABAB1b receptor mRNA expression in several brain structures (hippocampus, prefrontal cortex, cingulate cortex, amygdala, and locus coeruleus). These effects were abrogated after vagotomy (7). These data establish the importance in this model of the intact afferent vagus for the brain GABA receptor mRNA changes and related anxiolytic effects (12), but they provide no information about how afferent signals are altered by the probiotic. Our present data show the nature of the change that one anxiolytic probiotic bacteria produces in afferent vagal firing. This contrasts with the effects of another Lactobacillus, L. salivarius, which is not neuroactive in the gut (55) and also did not alter vagal firing. The evidence suggests that neuroactive and psychoactive effects are bacterial strain specific (16). Also, we have found that if we apply JB-1 when the muscle is paralyzed by nicardipine, an L-type calcium channel blocker, the degree of effects on the spontaneous firing frequency is still present although lower than with JB-1 administered alone. Even so, we cannot discard the possibility that JB-1 may modify the constitutive firing frequency partially through changes in the peristaltic reflexes that we have previously reported (55). However, because the degree of changes in the constitutive firing frequency induced by JB-1 on single fibers is very similar with and without nicardipine, we conclude that our results with multiunit recordings were probably obscured by the number of nonresponsive single fibers.

 

Our experiments could not directly address the underlying mechanisms of cellular transduction and signaling between JB-1 and the vagal primary afferents within the mucosa. However, commensals produce a large range of molecules, including fatty acids, cell wall oligosaccharides, and neurotransmitters (17, 30, 42). Some of these may interact with mucosal epithelial cells that release paracrine mediators to act on neuronal processes (38); certain molecules such as hydronium ions could also act directly on vagal afferents. A cogent approach to the study of which bacterial molecule(s) mediate neural effects on the host awaits genomic and metabolomic analysis of the probiotic (10). JB-1 did not facilitate the vagal response to CCK, suggesting that these bacteria probably did not act via the CCK pathway. It is not clear which of these effects might explain the neuronal effects with onset latencies of 10–15 min that we report here.

 

It remains to be elucidated exactly how the increase in the constitutive vagal firing frequency and the augmentation of its response to gut distension may change brain neurochemistry and behavior. However, electrical stimulation of vagal fibers alters concentrations of serotonin, norepinephrine, GABA, and glutamate within the brain (46), and, although controversial, vagal stimulation is a Food and Drug Administration (FDA)-approved treatment for patients with depression who do not respond to classical drug therapy (11, 46) and is also FDA approved for the adjunctive treatment of epilepsy (21).

 

In summary, we have shown that, within minutes of introduction of probiotic bacteria in the jejunal lumen of mice, vagal afferents were activated and that this activation was recorded as an increase in the spontaneous frequency of both multi- and single-unit firing frequency. This procedure further augmented the distension-evoked increases of firing frequency that in turn were all abrogated by prior subdiaphragmatic vagotomy. Thus, the mechanisms whereby some probiotic bacteria influence brain and behavior may critically involve the facilitation of vagal firing. It is therefore plausible that certain bacteria might be useful and safe adjuncts to therapy in some conditions. Our results support the fact that use of this pathway is bacterial strain dependent as has been also shown for bacterial effects on behavior. Further detailed exploration of the neuronal spike trains that encode behavioral signaling to the brain may be useful to identify those psychoactive bacteria that are effective. It may also help uncover how they signal the brain and thus offer novel approaches to the development of new forms of treatment for some psychiatric and other comorbid disorders.

 

 

The Anxiolytic Effect of Bifidobacterium Longum Ncc3001 Requires Vagal Integrity for Gut-Brain Communication

Amber J. Park

,

Premysl Bercik

,

XianXi Huang

,

Patricia Blennerhassett

,

Daniel D. Sinclair

,

Jun Lu

,

Yikang Deng

,

Gabriela Bergonzelli

,

Peter McLean

,

Stephen M. Collins

,

Elena F. Verdu

[[Sm...]]

Hey Smiff,

 

Just read over the article and also found a more recent one:

 

 

Psychoactive bacteria Lactobacillus rhamnosus (JB-1) elicits rapid frequency facilitation in vagal afferents

Azucena Perez-Burgos , Bingxian Wang , Yu-Kang Mao , Bhavik Mistry , Karen-Anne McVey Neufeld , John Bienenstock , Wolfgang Kunze

American Journal of Physiology - Gastrointestinal and Liver Physiology Published 15 January 2013 Vol. 304 no.  2,  G211-G220 DOI: 10.1152/ajpgi.00128.2012

http://ajpgi.physiology.org/content/304/2/G211#sec-16

 

This is an interesting line of research.  It appears to be in its infancy and that they are still trying to figure out whether the changes to GABA mRNA is a direct or secondary effect.  The article above suggests it may be due to the bacteria changing the firing rate of the vagus nerve resulting in a change in the afferent inputs to the brain.  It may take some time before they figure out the precise mechanisms involved but it is definitely interesting. I have heard that it is a good idea to get fermented foods into the diet.  I often say that when it comes to the body everything affects everything, LOL...thanks for showing this to me.

 

Thanks for that P. Though it did send me on another little soujourn around article land with the preliminary results above. I wont get a chance to read them properly till the new year. Still I'm getting closer to believing new psychiatric treatment will include treatment of inflammation and gut microbia.

[[Fo...]]

I have been interested in ths for some time. L rhamnosus normalises BDNF , as does B Biffidum. Then there are strains like L Plantarum (specifically L Plantarum 299v) that are found in saliva (this is one of the reasons you should chew your food properly) that promote BDNF. Single strain is a good way to go to start out, L rhamnosus in particular, and I am interested in Custom Probiotics D Lactate free formula.

 

I had the same problems with kefir and histamine. I've read though that antidepressants like fluoxetine degrade DAO enzymes and this can lead to histamine intolerance. I will go back to kefir when off these insidious drugs, and am able to clear my liver better. Just to note, cook some potatoes and chill them in the fridge, then eat them cold with your probiotics. Cold potatoes are high in resistant starch which is fuel for the probiotics. Prebiotics are where it is at as well.

 

http://www.prebiotin.com/foods-containing-prebiotics/

 

 

 

[[th...]]

I was having some trouble with constipation (HARD, difficult bowel movements every other day - I was very regular prior to withdrawal) and have been gaining weight despite watching my diet and exercising every day. I bought some kefir today - how many servings/how long did it take everyone to notice any benefits?

[Guest [jc...]]

I'm drinking 8 oz. a day and have had really great results with stomach pain and irregularity.  I noticed improvement within days.

[[th...]]

I'm drinking the Lifeway brand and they list a serving size as 1oz. Should I be drinking 8oz.? This is going to get very expensive if that's the case... 

[[Sm...]]

Ah what to do about getting the good bacteria into your gut

 

 

Well it is altogether an individual answer

 

I ended up having to ditch the kefir. It was great for a few days but then it became clear I was having a histamine reaction to it and it was making it worse. Kefir, and any other fermented product, will NOT be for everyone in withdrawal. There is likely a histamine issue with many people in withdrawal and fermented products, and dairy, will set that  off.

 

Similarly there is likely an inflammation of the gut issue with most people in withdrawal. Dairy is not for everyone on the inflammation front. It is reasonably inflammatory though not for everyone.

 

Another down side is you never know what strains you are getting, plus most kefirs have a candida yeast in it. Some strains are worse for people with inflammation/intolerant stomachs. Candida yeast can be bad too

 

So what to do?

 

Well you can try kefir and other fermented foods.

 

Ideally that would be great if that was the best for you.

 

If it doesn't than you don't use it and nothing is overly lost.

 

In that case you have to get your good bacteria from probiotics and even here it is not altogether simple (and yes I've come to believe you NEED the good bacteria particularly in chronic inflammation states like we are in).

 

There are a number of strains. Some are more inflammatory to sensitive stomachs due to the acid, others cause histamine release. Then on the other hand some reduce histamine release and stimulate GABA.

 

So here you play around again...

 

But if you want to err on the side of caution D-Lactate free strains are better on the inflammation/acidic front. The standout strains for GABA, vagus nerve, histamine reduction and inflammation of the gut reduction are: L. Rhamnosus and L.Planatarum.

 

If you get a poor brand of probiotics don't be surprised if (a) it does nothing (b) it does something but that something is irritation, bloating and pain.

 

Finally start of slow. We are so sensitive that 'normal' doses may be too much for us initially. Start with a child serve for a few weeks and slowly increase. As good bacteria repopulate your gut other bacteria die off and that releases a lot of yuck. Too much of that at once isn't good. So slow is a good option.

[[Sm...]]

This guy is positively fascinating on gut/brain axis

Watch it and be prepared for wow

http://digestionsessions.com/dr-datis-kharrazian/

 

[[Lo...]]

thought you guys would enjoy this.....remember to eat organic too.

http://articles.mercola.com/sites/articles/archive/2013/07/25/probiotics-new-prozac.aspx

[[Sm...]]

thought you guys would enjoy this.....remember to eat organic too.

http://articles.mercola.com/sites/articles/archive/2013/07/25/probiotics-new-prozac.aspx

 

[[Bl...]]

Has anyone been revved up by this strain.? I am afraid to try it as my histamine and anxiety are very high. Also I don't tolerate kefir or saurcraut.  Any thoughts?