Host-microbiome interactions: the aryl hydrocarbon receptor and the central nervous system

Lee, Hae Ung; McPherson, Zachary E.; Tan, Bryan C.; Korecka, Agata; Pettersson, Sven

doi:10.1007/s00109-016-1486-0

Cited by 51 publications

(39 citation statements)

References 111 publications

(137 reference statements)

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“…Analogously, the ovarian development of Ahr KO mice presents similarities with PCOS models and the disease is associated with exposure to environmental pollutants . AHR also plays a role in neurodegenerative disorders …”

Section: Disturbed Circadian Clock Gh and Sexual Development: An Unmentioning

confidence: 95%

At the Intersection of Microbiota and Circadian Clock: Are Sexual Dimorphism and Growth Hormones the Missing Link to Pathology?

2019

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Reciprocal interactions between the host circadian clock and the microbiota are evidenced by recent literature. Interestingly, dysregulation of either the circadian clock or microbiota is associated with common human pathologies such as obesity, type 2 diabetes, or neurological disorders. However, it is unclear to what extent a perturbation of pathways regulated by both the circadian clock and microbiota is involved in the development of these disorders. It is speculated that these perturbations are associated with impaired growth hormone (GH) secretion and sexual development. The GH axis is a broadly neglected pathway and could be the main converging point for the interaction of both circadian clock and microbiota. Here, the links between the circadian clock and microbiota are reviewed. Finally, the effects of chronodisruption and dysbiosis on physiology and pathology are discussed and it is speculated whether a common deregulation of the GH pathway could mediates those effects.

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Section: Disturbed Circadian Clock Gh and Sexual Development: An Unmentioning

confidence: 95%

At the Intersection of Microbiota and Circadian Clock: Are Sexual Dimorphism and Growth Hormones the Missing Link to Pathology?

2019

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“…Termed “ the holobiont ,” the microbiome of each host and its organs forms a close functional entity having evolutionarily designed interactions that support nutritional intake, defense mechanisms, and reproduction (Lee et al , 2016). AHR is considered as an evolutionarily highly-conserved “sensor” capable of recognizing endogenous as well as foreign chemicals/signals — including many ligands that are metabolites produced directly, or indirectly, by the microbiome .…”

Section: Ahr and Cell-signaling Pathwaysmentioning

confidence: 99%

Aryl hydrocarbon receptor (AHR): “pioneer member” of the basic-helix/loop/helix per - Arnt - sim (bHLH/PAS) family of “sensors” of foreign and endogenous signals

Nebert

2017

Progress in Lipid Research

220

191

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The basic-helix-loop-helix Per-Arnt-Sim (bHLH/PAS) family comprises many transcription factors, found throughout all three kingdoms of life; bHLH/PAS members “sense” innumerable intracellular and extracellular “signals” — including endogenous compounds, foreign chemicals, gas molecules, redox potential, photons (light), gravity, heat, and osmotic pressure. These signals then initiate downstream signaling pathways involved in responding to that signal. The term “PAS”, abbreviation for “Per-Arnt-Sim” was first coined in 1991. Although the mouse Arnt gene was not identified until 1991, evidence of its co-transcriptional binding partner, aryl hydrocarbon receptor (AHR), was first reported in 1974 as a “sensor” of foreign chemicals, up-regulating cytochrome P450 family 1 (CYP1) and other enzyme activities that usually metabolize the signaling chemical. Within a few years, AHR was proposed also to participate in inflammation. The mouse [Ah] locus was shown (1973–1989) to be relevant to chemical carcinogenesis, mutagenesis, toxicity and teratogenesis, the mouse Ahr gene was cloned in 1992, and the first Ahr(−/−) knockout mouse line was reported in 1995. After thousands of studies from the early 1970s to present day, we now realize that AHR participates in dozens of signaling pathways involved in critical-life processes, affecting virtually every organ and cell-type in the animal, including many invertebrates.

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“…[ 5 ] The aryl hydrocarbon receptor integrates sensing of toxins, microbial factors, and host kynurenine metabolites for induction of immune genes. [ 18 ] Kynurenines generated via IDO activity bind to the aryl hydrocarbon receptor, which in turn mediates generation of FOXP3‐expressing regulatory T cells, which have an inhibitory role on other cells of the immune system. [ 14–15,19 ] Interestingly, pigment from M. tuberculosis can also bind directly to the aryl hydrocarbon receptor, [ 20 ] presumably inducing the same downstream effects as kynurenines.…”

Section: Ido Catalyzes the Kynurenine‐tryptophan‐nicotinamide Pathwaymentioning

confidence: 99%

Evolutionary Views of Tuberculosis: Indoleamine 2,3‐Dioxygenase Catalyzed Nicotinamide Synthesis Reflects Shifts in Macrophage Metabolism

et al. 2020

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Indoleamine 2,3-dioxygenase (IDO) is the rate-limiting enzyme in conversion of tryptophan to kynurenines, feeding de novo nicotinamide synthesis. IDO orchestrates materno-foetal tolerance, increasing human reproductive fitness. IDO mediates immune suppression through depletion of tryptophan required by T lymphocytes and other mechanisms. IDO is expressed by alternatively activated macrophages, suspected to play a key role in tuberculosis (TB) pathogenesis. Unlike its human host, Mycobacterium tuberculosis can synthesize tryptophan, suggesting possible benefit to the host from infection with the microbe. Intriguingly, nicotinamide analogues are used to treat TB. In reviewing this field, it is postulated that flux through the nicotinamide synthesis pathway reflects switching between aerobic glycolysis and oxidative phosphorylation in M. tuberculosis-infected macrophages. The evolutionary cause of such shifts may be ancient mitochondrial behavior related to reproductive fitness. Evolutionary perspectives on the IDO pathway may elucidate why, after centuries of co-existence with the Tubercle bacillus, humans still remain susceptible to TB disease.

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Host-microbiome interactions: the aryl hydrocarbon receptor and the central nervous system

Cited by 51 publications

References 111 publications

At the Intersection of Microbiota and Circadian Clock: Are Sexual Dimorphism and Growth Hormones the Missing Link to Pathology?

At the Intersection of Microbiota and Circadian Clock: Are Sexual Dimorphism and Growth Hormones the Missing Link to Pathology?

Aryl hydrocarbon receptor (AHR): “pioneer member” of the basic-helix/loop/helix per - Arnt - sim (bHLH/PAS) family of “sensors” of foreign and endogenous signals

Evolutionary Views of Tuberculosis: Indoleamine 2,3‐Dioxygenase Catalyzed Nicotinamide Synthesis Reflects Shifts in Macrophage Metabolism

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