Serotonin, tryptophan metabolism and the brain-gut-microbiome axis

O’Mahony, Siobhain M.; Clarke, Gerard; Borre, Yuliya; Dinan, Timothy G.; Cryan, John F.

doi:10.1016/j.bbr.2014.07.027

Cited by 1,439 publications

(1,119 citation statements)

References 225 publications

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“…83 In another example, rats that are given Bifidobacterium infantis for 14 days showed increased concentrations of the serotonin precursor tryptophan in plasma, an effect that may be mediated by the altered expression of indoleamine-2,3-dioxygenase, a key enzyme in the kynurenine pathway of tryptophan degradation. 84,85 In addition to pathogen-specific alterations in neurotransmitters within the CNS, specific structural microbial molecules that are often referred to as microbe-associated molecular patterns (MAMPs) are found in the brain. The profile of MAMPs has been shown to be significantly influenced by the composition of gut microbiota.…”

Section: Effect Of Bacterial Metabolites On the Central Nervous Systemmentioning

confidence: 99%

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

Yarandi

Peterson

Treisman

et al. 2016

J Neurogastroenterol Motil

222

134

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Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional. Alteration in the composition of the gut microbiome can potentially lead to increased intestinal permeability and impair the function of the intestinal barrier. Subsequently, neuro-active compounds and metabolites can gain access to the areas within the central nervous system that regulate cognition and emotional responses. Deregulated inflammatory response, promoted by harmful microbiota, can activate the vagal system and impact neuropsychological functions. Some bacteria can produce peptides or short chain fatty acids that can affect gene expression and inflammation within the central nervous system. In this review, we summarize the evidence supporting the role of gut microbiota in modulating neuropsychological functions of the central nervous system and exploring the potential underlying mechanisms.

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Section: Effect Of Bacterial Metabolites On the Central Nervous Systemmentioning

confidence: 99%

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

Yarandi

Peterson

Treisman

et al. 2016

J Neurogastroenterol Motil

222

134

View full text Add to dashboard Cite

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“…[71] Serotonin is well-known as a neurotransmitter involved in mood and cognition, and disruption of the serotonergic system is a key feature of anxiety and mood disorders, for which the first-line therapeutics are selective serotonin receptor inhibitors (SSRIs). In addition to its mood regulatory function, serotonin has an important role in gastrointestinal function and is thought to facilitate communication throughout the gut-brain axis.…”

Section: Microbiota Regulates Tryptophan Metabolismmentioning

confidence: 99%

“…In addition to its mood regulatory function, serotonin has an important role in gastrointestinal function and is thought to facilitate communication throughout the gut-brain axis. [71] In fact, the vast majority of the body's serotonin is produced in the gastrointestinal tract by enterochromaffin cells. [71] Recent studies highlight the role of the microbiota in modulating both serotonin secretion and tryptophan metabolism in humans and rodents.…”

Section: Microbiota Regulates Tryptophan Metabolismmentioning

confidence: 99%

“…[71] In fact, the vast majority of the body's serotonin is produced in the gastrointestinal tract by enterochromaffin cells. [71] Recent studies highlight the role of the microbiota in modulating both serotonin secretion and tryptophan metabolism in humans and rodents. [72][73][74][75] To this end, GF animals exhibit striking alterations in circulating tryptophan levels and serotonergic neurotransmission, at least in the hippocampus.…”

Section: Microbiota Regulates Tryptophan Metabolismmentioning

confidence: 99%

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Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

et al. 2017

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The amygdala is a key brain area regulating responses to stress and emotional stimuli, so improving our understanding of how it is regulated could offer novel strategies for treating disturbances in emotion regulation. As we review here, a growing body of evidence indicates that the gut microbiota may contribute to a range of amygdala-dependent brain functions from pain sensitivity to social behavior, emotion regulation, and therefore, psychiatric health. In addition, it appears that the microbiota is necessary for normal development of the amygdala at both the structural and functional levels. While further investigations are needed to elucidate the exact mechanisms of microbiota-to-amygdala communication, ultimately, this work raises the intriguing possibility that the gut microbiota may become a viable treatment target in disorders associated with amygdala dysregulation, including visceral pain, post-traumatic stress disorder, and beyond. Also see the video abstract here: https://youtu.be/O5gvxVJjX18

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“…While this process has been associated with immunosuppression through Treg activation and effector T cell suppression,56 inflammation‐induced expression of this enzyme leads to tryptophan depletion both locally and systemically in chronic inflammatory states and has also been linked to alterations in mood 5, 53, 57. Similarly, the ability of host microbiota to control tryptophan metabolism has been functionally linked to influencing mood 58. Furthermore, polymorphisms in IDO1 have been associated with susceptibility to IFNα‐induced depression in hepatitis patients 59.…”

Section: Discussionmentioning

confidence: 99%

Effects of anti-inflammatory drugs on the expression of tryptophan-metabolism genes by human macrophages

Regan

Gill

Clohisey

et al. 2018

Journal of Leukocyte Biology

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Several lines of evidence link macrophage activation and inflammation with (monoaminergic) nervous systems in the etiology of depression. IFN treatment is associated with depressive symptoms, whereas anti‐TNFα therapies elicit positive mood. This study describes the actions of 2 monoaminergic antidepressants (escitalopram, nortriptyline) and 3 anti‐inflammatory drugs (indomethacin, prednisolone, and anti‐TNFα antibody) on the response of human monocyte‐derived macrophages (MDMs) from 6 individuals to LPS or IFN‐α. Expression profiling revealed robust changes in the MDM transcriptome (3294 genes at P < 0.001) following LPS challenge, whereas a more limited subset of genes (499) responded to IFNα. Contrary to published reports, administered at nontoxic doses, neither monoaminergic antidepressant significantly modulated the transcriptional response to either inflammatory challenge. Each anti‐inflammatory drug had a distinct impact on the expression of inflammatory cytokines and on the profile of inducible gene expression—notably on the regulation of enzymes involved in metabolism of tryptophan. Inter alia, the effect of anti‐TNFα antibody confirmed a predicted autocrine stimulatory loop in human macrophages. The transcriptional changes were predictive of tryptophan availability and kynurenine synthesis, as analyzed by targeted metabolomic studies on cellular supernatants. We suggest that inflammatory processes in the brain or periphery could impact on depression by altering the availability of tryptophan for serotonin synthesis and/or by increasing production of neurotoxic kynurenine.

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Serotonin, tryptophan metabolism and the brain-gut-microbiome axis

Cited by 1,439 publications

References 225 publications

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

Effects of anti-inflammatory drugs on the expression of tryptophan-metabolism genes by human macrophages

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