Psychological stress‐induced colonic barrier dysfunction: Role of immune‐mediated mechanisms

Hattay, Priya; Prusator, Dawn K.; Tran, Lee; Meerveld, B. Greenwood-Van

doi:10.1111/nmo.13043

Cited by 27 publications

(27 citation statements)

References 55 publications

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“…Although the experimenter was not blinded to the experimental treatments, the histologist was blinded. While a power analysis was not conducted, n -values for this study were similar to our previously published reports using the same techniques (Venkova et al, 2004 ; Venkova and Greenwood-van Meerveld, 2006 ; Tran and Greenwood-Van Meerveld, 2013 ; Hattay et al, 2017 ). For the I sc and TEER calculations, individual chambers were excluded when the PD was >−10 mV or < −1 mV—indicating either an error with the electrodes or a damaged tissue preparation; when excluding chambers due to PD measurement, the I sc , calculated TEER, and the HRP flux for that chamber were also excluded from analysis.…”

Section: Methodssupporting

confidence: 84%

“…Additionally, a layer of mucus covering the mucosal epithelium represents an “unstirred” layer and barrier to movement of contents between intestinal epithelial cells (Camilleri et al, 2012 ). A growing body of evidence suggests that alterations in barrier function may be an important factor in the pathogenesis of IBS, and we recently demonstrated that in response to a chronic psychological stressor there are increases in permeability, mucosal mast cells, and expression of pro-inflammatory cytokines along with altered TJ protein expression within the rat colon (Hattay et al, 2017 ); however, due to the systemic nature of the chronic stressor, the role of specific central and/or peripheral factors could not be determined, although there is evidence that corticotropin-releasing hormone via its type 2 receptors can play a role (Ducarouge et al, 2013 , 2017 ). The goal of the present study was to test the hypothesis that a centrally driven facilitation of the stress axis via corticosterone (CORT)-induced activation of the CeA would be sufficient to induce abnormalities in colonic barrier function and increase colonic permeability.…”

Section: Introductionmentioning

confidence: 99%

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Stereotaxic Exposure of the Central Nucleus of the Amygdala to Corticosterone Increases Colonic Permeability and Reduces Nerve-Mediated Active Ion Transport in Rats

et al. 2018

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Background: Irritable bowel syndrome (IBS) is characterized by visceral pain and abnormal bowel habits that are worsened during stress. Evidence also suggests altered intestinal barrier function in IBS. Previously, we demonstrated that stereotaxic application of the stress hormone corticosterone (CORT) onto the central nucleus of the amygdala (CeA) induces colonic hyperalgesia and anxiety-like behavior in a rat model, however the effect on intestinal permeability and mucosal function remain to be evaluated.Methods: Male Fischer 344 rats underwent bilateral stereotaxic implantation of CORT or inert cholesterol (CHOL)-containing micropellets (30 μg) onto the dorsal margin of the CeA. Seven days later, colonic tissue was isolated to assess tissue permeability in modified Ussing chambers via transepithelial electrical resistance (TEER) and macromolecular flux of horseradish peroxidase (HRP). Secretory responses to electrical field stimulation (EFS) of submucosal enteric nerves as well as activation with forskolin were used to assess movements of ions across the isolated colonic tissues. In a separate cohort, colonic histology, and mast cell infiltration was assessed.Key Results: Compared to CHOL-implanted controls, we determined that exposing the CeA to elevated levels of CORT significantly increased macromolecular flux across the colonic epithelial layer without changing TEER. Nerve-mediated but not cAMP-mediated active transport was inhibited in response to elevated amygdala CORT. There were no histological changes or increases in mast cell infiltration within colonic tissue from CORT treated animals.Conclusion and Inferences: These observations support a novel role for the CeA as a modulator of nerve-mediated colonic epithelial function.

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Section: Methodssupporting

confidence: 84%

Section: Introductionmentioning

confidence: 99%

Stereotaxic Exposure of the Central Nucleus of the Amygdala to Corticosterone Increases Colonic Permeability and Reduces Nerve-Mediated Active Ion Transport in Rats

et al. 2018

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“…Our study and others depict an environment wherein stress can be both pro-and anti-inflammatory 76,86 , systemically and at the gastrointestinal epithelium. Resultant outcomes include relaxed or elevated macrophage trafficking and antigenic presentation activity [87][88][89][90] and barrier dysfunction 91,92 , all of which may act profoundly upon microbial abundances. However, an understanding of why Parasutterella is a frequent target is presently incomplete.…”

Section: Discussionmentioning

confidence: 99%

Unique maternal immune and functional microbial profiles during prenatal stress

Antonson

Evans

Galley

et al. 2020

Preprint

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Maternal stress during pregnancy is widespread and stress-induced fetal neuroinflammation is thought to derive from a disruption in intrauterine immune homeostasis, though the exact origins are incompletely defined. We aimed to identify divergent immune and microbial metagenome profiles of stressed gestating mice that may underlie detrimental inflammatory signaling at the maternal-fetal interface. In response to stress, maternal glucocorticoid circuit activation corresponded with diminished spleen mass and IL-1β production, reflecting systemic immunosuppression. At the maternal-fetal interface, density of placental mononuclear leukocytes decreased with stress. Yet maternal whole blood leukocyte analysis indicated monocytosis and classical M1 phenotypic shifts. Genome-resolved microbial metagenomic analyses revealed reductions in genes, microbial strains, and metabolic pathways in stressed dams that are primarily associated with pro-inflammatory function. Overall, these data indicate that stress disrupts maternal immunological and microbial regulation during pregnancy, characterized by concurrent anti-and pro-inflammatory signatures, which may displace immune equilibrium at the maternal-fetal interface.

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“…Since NLR are important in maintaining intestinal physiology (38) that can be detrimentally impacted by exposure to stress (61, 62), we assessed ileal and colonic mucosal barrier function in WT(±WAS) and NodDKO(±WAS) mice. While baseline ion transport (Isc) and permeability (G, FITC flux) were intact in NodDKO(-WAS), stress significantly increased Isc, G, and FITC flux in the ileum and/or the colon of NodDKO(+WAS) mice vs WT(+WAS) controls.…”

Section: Discussionmentioning

confidence: 99%

Nod-like receptors are critical for gut-brain axis signaling

Pusceddu

Barboza

Schneider

et al. 2019

Preprint

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Gut-brain axis signaling is critical for maintaining health and homeostasis. Stressful life events can impact gut-brain signaling, leading to altered mood, cognition and intestinal dysfunction. Here we identify nucleotide binding oligomerization domain (Nod)-like receptors (NLR), Nod1 and Nod2, as novel regulators for gut-brain signaling. NLR are innate immune pattern recognition receptors expressed in the gut and brain, important in the regulation of gastrointestinal (GI) physiology. We found that mice deficient in both Nod1 and Nod2 (NodDKO) demonstrate signs of stress-induced anxiety, cognitive impairment and depression in the context of a hyperactive hypothalamic-pituitary-adrenal axis. These deficits were coupled with impairments in the serotonergic pathway in the brain, decreased hippocampal neurogenesis, and reduced neural activation. In addition, NodDKO mice had increased GI permeability and altered serotonin signaling in the gut following exposure to acute stress. Administration of the selective serotonin reuptake inhibitor, fluoxetine, abrogated behavioral impairments and restored serotonin signaling. We also identified that intestinal epithelial cell-specific deletion of Nod1 (VilCre+Nod1f/f), but not Nod2, increased susceptibility to stress-induced anxiety-like behavior and cognitive impairment following exposure to stress. Together these data suggest that intestinal epithelial NLR are novel modulators of gut-brain communication and may serve as potential novel therapeutic targets for the treatment of gut-brain disorders.

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Psychological stress‐induced colonic barrier dysfunction: Role of immune‐mediated mechanisms

Abstract: Our findings suggest that chronic stress increases colonic permeability via sub-inflammatory cytokine-mediated remodeling of TJ protein expression.

Cited by 27 publications

References 55 publications

Stereotaxic Exposure of the Central Nucleus of the Amygdala to Corticosterone Increases Colonic Permeability and Reduces Nerve-Mediated Active Ion Transport in Rats

Stereotaxic Exposure of the Central Nucleus of the Amygdala to Corticosterone Increases Colonic Permeability and Reduces Nerve-Mediated Active Ion Transport in Rats

Unique maternal immune and functional microbial profiles during prenatal stress

Nod-like receptors are critical for gut-brain axis signaling

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