Mood and gut feelings

Forsythe, Paul; Sudo, Nobuyuki; Dinan, Timothy G.; Taylor, Valerie H.; Bienenstock, John

doi:10.1016/j.bbi.2009.05.058

Cited by 400 publications

(278 citation statements)

References 91 publications

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“…6,7 Interactions between the microbiota of the gut lumen and the immune system modulate mood and sensation. [8][9][10] Understanding the molecular basis of such interactions is currently the subject of intense research effort. It is clear that many newly discovered mechanisms are not ubiquitously used by all visceral sensory neurons.…”

Section: Introductionmentioning

confidence: 99%

Extrinsic primary afferent signalling in the gut

Brookes

Spencer

Costa

et al. 2013

Nat Rev Gastroenterol Hepatol

246

216

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Visceral sensory neurons activate reflex pathways that control gut function and also give rise to important sensations, such as fullness, bloating, nausea, discomfort, urgency and pain. Sensory neurons are organised into three distinct anatomical pathways to the central nervous system (vagal, thoracolumbar and lumbosacral). Although remarkable progress has been made in characterizing the roles of many ion channels, receptors, and second messengers in visceral sensory neurons, the basic aim of understanding how many classes there are, and how they differ, has proven difficult to achieve. We suggest that there are just five structurally distinct types of sensory endings in the gut wall that account for essentially all of the primary afferent neurons in the three pathways. Each of these five major structural types of endings seems to show distinctive combinations of physiological responses. These types are: 'intraganglionic laminar' endings in myenteric ganglia; 'mucosal' endings located in the subepithelial layer; 'muscular mucosal' afferents, with mechanosensitive endings close to the muscularis mucosae; 'intramuscular' endings, with endings within the smooth muscle layers; and 'vascular' afferents, with sensitive endings primarily on blood vessels. 'Silent' afferents might be a subset of inexcitable 'vascular' afferents, which can be switched on by inflammatory mediators.Extrinsic sensory neurons comprise an attractive focus for targeted therapeutic intervention in a range of gastrointestinal disorders.2

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Section: Introductionmentioning

confidence: 99%

Extrinsic primary afferent signalling in the gut

Brookes

Spencer

Costa

et al. 2013

Nat Rev Gastroenterol Hepatol

246

216

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“…The gut microbiota and the metabolites they produce may also modulate the peripheral nervous system and central nervous system (CNS) to influence brain development and function (158) . To date, numerous studies have demonstrated the importance of the gut microbiota in the stress response (159,160) and neurodevelopmental disorders (161)(162)(163) .…”

Section: Microbial Production Of Exopolysaccharidesmentioning

confidence: 99%

Gut microbiota, the pharmabiotics they produce and host health

et al. 2014

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A healthy gut microbiota plays many crucial functions in the host, being involved in the correct development and functioning of the immune system, assisting in the digestion of certain foods and in the production of health-beneficial bioactive metabolites or ‘pharmabiotics’. These include bioactive lipids (including SCFA and conjugated linoleic acid) antimicrobials and exopolysaccharides in addition to nutrients, including vitamins B and K. Alterations in the composition of the gut microbiota and reductions in microbial diversity are highlighted in many disease states, possibly rendering the host susceptible to infection and consequently negatively affecting innate immune function. Evidence is also emerging of microbially produced molecules with neuroactive functions that can have influences across the brain–gut axis. For example, γ-aminobutyric acid, serotonin, catecholamines and acetylcholine may modulate neural signalling within the enteric nervous system, when released in the intestinal lumen and consequently signal brain function and behaviour. Dietary supplementation with probiotics and prebiotics are the most widely used dietary adjuncts to modulate the gut microbiota. Furthermore, evidence is emerging of the interactions between administered microbes and dietary substrates, leading to the production of pharmabiotics, which may directly or indirectly positively influence human health.

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“…T here is increasing evidence suggesting an interaction between the intestinal microbiota, the gut, and the central nervous system (CNS) in what is recognized as the microbiome-gut-brain axis (1)(2)(3)(4). Studies in rodents have implicated dysregulation of this axis in functional bowel disorders, including irritable bowel syndrome.…”

mentioning

confidence: 99%

Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve

Bravo¹,

Forsythe

Chew

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

3,127

2,512

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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 GABA B1b 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 GABA Aα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABA Aα2 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 stressrelated disorders such as anxiety and depression.brain-gut axis | irritable bowel syndrome | probiotic | fear conditioning | cognition T here is increasing evidence suggesting an interaction between the intestinal microbiota, the gut, and the central nervous system (CNS) in what is recognized as the microbiome-gut-brain axis (1-4). Studies in rodents have implicated dysregulation of this axis in functional bowel disorders, including irritable bowel syndrome. Indeed, visceral perception in rodents can be affected by alterations in gut microbiota (5). Moreover, it has been shown that the absence and/or modification of the gut microflora in mice affects the hypothalamic-pituitary-adrenal (HPA) axis response to stress (6, 7) and anxiety behavior (8, 9), which is important given the high comorbidity between functional gastrointestinal disorders and stress-related psychiatric disorders, such as anxiety and depression (10). In addition, pathogenic bacteria in rodents can induce anxiety-like behaviors, which are mediated via vagal afferents (9, 11).GABA is the main inhibitory neurotransmitter of the CNS, the effects of which are mediated through two major classes of receptors-the ionotropic GABA A receptors, which exist as a number of subtypes formed by the coassembly of different subunits (α, β, and γ subunits; ref. 12), and the GABA B receptors, which are G protein coupled and consist of a heterodi...

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Mood and gut feelings

Cited by 400 publications

References 91 publications

Extrinsic primary afferent signalling in the gut

Extrinsic primary afferent signalling in the gut

Gut microbiota, the pharmabiotics they produce and host health

Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve

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