Neuroimmune Cross Talk in the Gut. Neuroendocrine and neuroimmune pathways contribute to the pathophysiology of irritable bowel syndrome

O’Malley, Dervla

doi:10.1152/ajpgi.00272.2016

Cited by 19 publications

(15 citation statements)

References 87 publications

(26 reference statements)

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“…antibodies, which we have previously shown to improve IBS-like symptoms in WKY rats, 32 enhanced the therapeutic efficacy of administering a GLP-1 mimetic.…”

Section: Discussionmentioning

confidence: 85%

“…26 However, more than just being a biomarker of IBS, IL-6 has functional effects in the GI tract, activating submucosal secretomotor neurons 27,28 and modulating mucosal ion transport and epithelial permeability. 31 As cross talk between immune, endocrine, and neural systems is likely to underlie the multi-factorial nature of IBS, 32 31 As cross talk between immune, endocrine, and neural systems is likely to underlie the multi-factorial nature of IBS, 32 …”

Section: Introductionmentioning

confidence: 99%

“…29,30 Moreover, neutralization of peripheral IL-6R signaling ameliorated visceral hypersensitivity and stress-induced defecation in the WKY rat model of IBS. 31 As cross talk between immune, endocrine, and neural systems is likely to underlie the multi-factorial nature of IBS, 32 this study investigated if exendin-4 (Ex-4), a GLP-1 receptor (GLP-R) agonist, improves bowel dysfunction in WKY rats and determined if co-treatment with neutralizing monoclonal IL-6 receptor (IL-6R) antibodies modified the outcome.…”

Section: Introductionmentioning

confidence: 99%

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The Glucagon‐like peptide‐1 receptor agonist, exendin‐4, ameliorated gastrointestinal dysfunction in the Wistar Kyoto rat model of Irritable Bowel Syndrome

O’Brien

O’Malley

2019

Neurogastroenterology Motil

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Background: Glucagon-like peptide-1 (GLP-1) is beneficial in relieving pain-related symptoms of Irritable bowel syndrome (IBS), a prevalent, multi-factorial functional bowel disorder characterized by diarrhea and/or constipation, abdominal bloating, and pain. Activation of myenteric neurons has been implicated in the inhibitory effects of GLP-1 on gastrointestinal motility; however, the mechanisms of action underlying this are not clear. Methods: A rat model of IBS was used to examine physiological changes evoked by intraperitoneal administration of a GLP-1 receptor agonist, exendin-4. Behavioral and physiological analysis of stress-sensitive Wister Kyoto (WKY) rats was used to determine if administration of exendin-4, in the presence or absence of neutralizing interleukin-6 receptor monoclonal antibodies, modified IBS-like symptoms. Immunofluorescence, calcium imaging, and Western blotting techniques were used to investigate the potential role of enteric neural plexi and tight junction protein expression in this effect. Key Results: Consistent with the expression of GLP-1 and interleukin-6 receptors in both submucosal and myenteric ganglia, exendin-4 and interleukin-6 stimulated calcium responses in these neurons. In vivo administration of exendin-4 normalized stress-induced defecation and visceral pain sensitivity in WKY rats. No additional changes were noted in rats co-treated with exendin-4 and anti-interleukin-6 receptor antibodies. Mucosal expression of occludin, a tight junction protein, was decreased by exendin-4. Centrally regulated anxiety-like behaviors were not modified. Conclusions and Inferences: These data suggest that intraperitoneal injection of exendin-4 improves bowel dysfunction in WKY rats without impacting on centrally regulated anxiety-like behaviors. Modulation of enteric neuronal function and tight junction expression appear to underlie the functional benefits of this intervention. K E Y W O R D S colorectal distension, exendin-4, glucagon-like peptide-1, interleukin-6, open field, stress, Wister Kyoto

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“…antibodies, which we have previously shown to improve IBS-like symptoms in WKY rats, 32 enhanced the therapeutic efficacy of administering a GLP-1 mimetic.…”

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Glucagon‐like peptide‐1 receptor agonist, exendin‐4, ameliorated gastrointestinal dysfunction in the Wistar Kyoto rat model of Irritable Bowel Syndrome

O’Brien

O’Malley

2019

Neurogastroenterology Motil

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“…Согласно данным E. Pyleris и соавт., у больных с подтвержденным диагнозом СРК и синдромом избыточного бактериального роста (СИБР) [17], интраэпителиальных лимфоцитов и плазматических клеток [18,19] в слизистой оболочке кишечника пациентов, страдающих СРК [20]. Тучные клетки несут на своей поверхности рецепторы для IgE и при дегрануляции выделяют большое количество биологически активных веществ, таких как гепарин, лей котриены, протеазы, что приводит к активации наивных Т-клеток и дифференцировке их в функциональные эффекторные клетки: CD8 + цитотоксические Т-клетки, CD4 + Т-хелперные клетки (Th1), CD4 + Th2 и регуляторные клетки Th3 [21], а также изменению цитокинового профиля.…”

Section: национальная школа гастроэнтерологии гепатологииunclassified

Probiotics in the Complex Treatment of Various Diseases of the Gastrointestinal Tract

Ивашкин

Reshetova

Зольникова

et al. 2020

Rossijskij žurnal gastroènterologii, gepatologii, koloproktolog

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“…Interestingly, approximately 50–90% of patients with IBS also experience symptoms of anxiety and depression [ 2 ]. O’Malley [ 3 ] further reported that dysfunction within the gut-brain axis—which involves the efferent and afferent components of the peripheral nervous system, circulating hormones, and local paracrine/neurocrine factors—plays a major role in IBS.…”

Section: Introductionmentioning

confidence: 99%

Magnetic resonance imaging analysis of brain function in patients with irritable bowel syndrome

et al. 2017

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BackgroundIrritable bowel syndrome (IBS) is a common functional disease of the gastrointestinal tract. The current study aimed to examine the association between visceral hypersensitivity in IBS and cortical activation using functional magnetic resonance imaging (fMRI), and to elucidate the role of psychological factors in the pathogenesis of IBS.MethodsThe present study included 31 patients with IBS and 20 healthy controls. Cerebral function was assessed using fMRI. During imaging, a Sengstaken-Blakemore tube was placed within the rectum approximately 10 cm from the anus, following which gas was rapidly injected into the airbag using a 150-ml syringe. Images were obtained at 40 ml, 80 ml, and 120 ml of expansion. Psychological status was evaluated using the Hospital Anxiety and Depression Scale (HADS).ResultsAnxiety and depression scores were higher among patients with IBSthan among controls (both P < 0.05), although scores in both groups were below the level of clinical diagnosis. Brain activation in regions of interest (parietal areas, prefrontal cortex, cerebellum, anterior cingulate cortex, insular cortex, and thalamus) increased along with increases in rectal balloon dilation, except in women with IBS and patients with disease duration less than 5 years. Furthermore, region of interest (ROI) activation (such as the parietal region, prefrontal cortex, cerebellum, anterior cingulate cortex, insular cortex, and thalamus) differed significantly between the 40-ml and 120-ml conditions, and between the 80-ml and 120-ml conditions (P < 0.05), among patients with IBS with anxiety or depression scores less than 9 points.ConclusionsOverall, our findings indicate that changes in brain activation due to changes in rectal balloon distension can be objectively and accurately measured using fMRI. Although our results indicated that visceral hypersensitivity during IBS is associated with changes in cortical activation, further studies utilizing larger sample sizes are required to more fully elucidate the association between psychological factors and visceral hypersensitivity in IBS.

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Neuroimmune Cross Talk in the Gut. Neuroendocrine and neuroimmune pathways contribute to the pathophysiology of irritable bowel syndrome

Abstract: Access to the full text of the published version may require a subscription. Rights © 2016 the American Physiological SocietyEmbargo information Access to this item is restricted until 12 months after publication by the request of the publisher. Embargo lift date

Cited by 19 publications

References 87 publications

The Glucagon‐like peptide‐1 receptor agonist, exendin‐4, ameliorated gastrointestinal dysfunction in the Wistar Kyoto rat model of Irritable Bowel Syndrome

The Glucagon‐like peptide‐1 receptor agonist, exendin‐4, ameliorated gastrointestinal dysfunction in the Wistar Kyoto rat model of Irritable Bowel Syndrome

Probiotics in the Complex Treatment of Various Diseases of the Gastrointestinal Tract

Magnetic resonance imaging analysis of brain function in patients with irritable bowel syndrome

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