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Article ; Online: Targeting the Vagus Nerve to Treat Inflammatory Bowel Disease?

Bonaz, Bruno / Sinniger, Valérie

2023 Volume 17, Issue 12, Page(s) 1893–1894

MeSH term(s)	Humans ; Crohn Disease ; Vagus Nerve Stimulation ; Prospective Studies ; Inflammatory Bowel Diseases/drug therapy ; Inflammatory Bowel Diseases/immunology ; Vagus Nerve/immunology
Language	English
Publishing date	2023-09-22
Publishing country	England
Document type	Editorial ; Comment
ZDB-ID	2390120-2
ISSN	1876-4479 ; 1873-9946
ISSN (online)	1876-4479
ISSN	1873-9946
DOI	10.1093/ecco-jcc/jjad149
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Article ; Online: The burden of early life stress in chronic inflammatory bowel diseases.

Minjoz, Séphora / Sinniger, Valérie / Hot, Pascal / Bonaz, Bruno / Pellissier, Sonia

Journal of health psychology

2023 Volume 28, Issue 13, Page(s) 1204–1216

Abstract: The aim of this study was to evaluate the prevalence of early life stress (ELS) in a population with inflammatory bowel diseases (IBD) and to estimate its burden on mental, physical, and digestive health. Ninety-three participants with IBD were asked to ... ...

Abstract	The aim of this study was to evaluate the prevalence of early life stress (ELS) in a population with inflammatory bowel diseases (IBD) and to estimate its burden on mental, physical, and digestive health. Ninety-three participants with IBD were asked to anonymously complete questionnaires (Childhood Trauma Questionnaire-Short Form, Early Life Event Scale, Perceived Stress Scale, Hospital Anxiety and Depression Scale, Ways of Coping Checklist, Gastro-Intestinal Quality of Life Index questionnaire, and ad hoc questions about symptoms). The prevalence of patients with IBD who were exposed to at least one childhood abuse was 53%. Mental health and quality of life were significantly poorer in patients with IBD who were exposed to early abuse than in those who were not. Patients exposed to ELS had also more digestive perturbations and fatigue. These results suggest that early abuse should be considered a component of IBD care.
MeSH term(s)	Humans ; Child ; Quality of Life/psychology ; Adverse Childhood Experiences ; Inflammatory Bowel Diseases/psychology ; Adaptation, Psychological ; Surveys and Questionnaires ; Anxiety ; Depression/psychology
Language	English
Publishing date	2023-05-19
Publishing country	England
Document type	Journal Article
ZDB-ID	2021897-7
ISSN	1461-7277 ; 1359-1053
ISSN (online)	1461-7277
ISSN	1359-1053
DOI	10.1177/13591053231173918
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Article: Therapeutic Potential of Vagus Nerve Stimulation for Inflammatory Bowel Diseases.

Bonaz, Bruno / Sinniger, Valérie / Pellissier, Sonia

Frontiers in neuroscience

2021 Volume 15, Page(s) 650971

Abstract: The vagus nerve is a mixed nerve, comprising 80% afferent fibers and 20% efferent fibers. It allows a bidirectional communication between the central nervous system and the digestive tract. It has a dual anti-inflammatory properties via activation of the ...

Abstract	The vagus nerve is a mixed nerve, comprising 80% afferent fibers and 20% efferent fibers. It allows a bidirectional communication between the central nervous system and the digestive tract. It has a dual anti-inflammatory properties via activation of the hypothalamic pituitary adrenal axis, by its afferents, but also through a vago-vagal inflammatory reflex involving an afferent (vagal) and an efferent (vagal) arm, called the cholinergic anti-inflammatory pathway. Indeed, the release of acetylcholine at the end of its efferent fibers is able to inhibit the release of tumor necrosis factor (TNF) alpha by macrophages via an interneuron of the enteric nervous system synapsing between the efferent vagal endings and the macrophages and releasing acetylcholine. The vagus nerve also synapses with the splenic sympathetic nerve to inhibit the release of TNF-alpha by splenic macrophages. It can also activate the spinal sympathetic system after central integration of its afferents. This anti-TNF-alpha effect of the vagus nerve can be used in the treatment of chronic inflammatory bowel diseases, represented by Crohn's disease and ulcerative colitis where this cytokine plays a key role. Bioelectronic medicine, via vagus nerve stimulation, may have an interest in this non-drug therapeutic approach as an alternative to conventional anti-TNF-alpha drugs, which are not devoid of side effects feared by patients.
Language	English
Publishing date	2021-03-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2021.650971
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Targeting the cholinergic anti-inflammatory pathway with vagus nerve stimulation in patients with Covid-19?

Bonaz, Bruno / Sinniger, Valérie / Pellissier, Sonia

Bioelectronic medicine

2020 Volume 6, Page(s) 15

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), at the origin of the worldwide COVID-19 pandemic, is characterized by a dramatic cytokine storm in some critical patients with COVID-19. This storm is due to the release of high levels of pro- ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), at the origin of the worldwide COVID-19 pandemic, is characterized by a dramatic cytokine storm in some critical patients with COVID-19. This storm is due to the release of high levels of pro-inflammatory cytokines such as interleukin (IL)-1 β, IL-6, tumor necrosis factor (TNF), and chemokines by respiratory epithelial and dendritic cells, and macrophages. We hypothesize that this cytokine storm and the worsening of patients' health status can be dampened or even prevented by specifically targeting the vagal-driven cholinergic anti-inflammatory pathway (CAP). The CAP is a concept that involves an anti-inflammatory effect of vagal efferents by the release of acetylcholine (ACh). Nicotinic acetylcholine receptor alpha7 subunit (α7nAChRs) is required for ACh inhibition of macrophage-TNF release and cytokine modulation. Hence, targeting the α7nAChRs through vagus nerve stimulation (VNS) could be of interest in the management of patients with SARS-CoV-2 infection. Indeed, through the wide innervation of the organism by the vagus nerve, especially the lungs and gastrointestinal tract, VNS appears as a serious candidate for a few side effect treatment that could dampen or prevent the cytokine storm observed in COVID-19 patients with severe symptoms. Finally, a continuous vagal tone monitoring in patients with COVID-19 could be used as a predictive marker of COVID-19 illness course but also as a predictive marker of response to COVID-19 treatment such as VNS or others.
Keywords	covid19
Language	English
Publishing date	2020-07-29
Publishing country	England
Document type	Journal Article
ZDB-ID	2929561-0
ISSN	2332-8886 ; 2332-8886
ISSN (online)	2332-8886
ISSN	2332-8886
DOI	10.1186/s42234-020-00051-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Vagus Nerve Stimulation at the Interface of Brain-Gut Interactions.

Bonaz, Bruno / Sinniger, Valérie / Pellissier, Sonia

Cold Spring Harbor perspectives in medicine

2019 Volume 9, Issue 8

Abstract: The vagus nerve, a key component of the cross-communication between the gut and the brain, is a major element of homeostasis sensing the "milieu intérieur" and boosting the nervous and endocrine responses to maintain the gastrointestinal health status. ... ...

Abstract	The vagus nerve, a key component of the cross-communication between the gut and the brain, is a major element of homeostasis sensing the "milieu intérieur" and boosting the nervous and endocrine responses to maintain the gastrointestinal health status. This nerve has anti-inflammatory properties regulating the gut through the activation of the hypothalamic-pituitary-adrenal axis and the release of cortisol and through a vagovagal reflex, which has an anti-tumor necrosis factor (TNF) effect called the cholinergic anti-inflammatory pathway. Stimulating this nerve is an interesting tool as a nondrug therapy for the treatment of gastrointestinal diseases in which brain-gut communication is dysfunctional, such as inflammatory bowel disorders and others. This review presents the rationale of vagal gastrointestinal physiology and diseases and the most recent advances in vagus nerve stimulation. It also highlights the main issues to be addressed in the future to improve this bioelectronic therapy for gastrointestinal disorders.
MeSH term(s)	Animals ; Epilepsy/therapy ; Gastrointestinal Diseases/physiopathology ; Gastrointestinal Diseases/therapy ; Humans ; Inflammation/physiopathology ; Inflammation/therapy ; Neuroimmunomodulation ; Obesity/therapy ; Vagus Nerve/physiology ; Vagus Nerve Stimulation
Language	English
Publishing date	2019-08-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	2157-1422
ISSN (online)	2157-1422
DOI	10.1101/cshperspect.a034199
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Targeting the cholinergic anti-inflammatory pathway with vagus nerve stimulation in patients with Covid-19?

Bonaz, Bruno / Sinniger, Valérie Pellissier / Sonia,

Bioelectronic Medicine

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), at the origin of the worldwide COVID-19 pandemic, is characterized by a dramatic cytokine storm in some critical patients with COVID-19 This storm is due to the release of high levels of pro- ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), at the origin of the worldwide COVID-19 pandemic, is characterized by a dramatic cytokine storm in some critical patients with COVID-19 This storm is due to the release of high levels of pro-inflammatory cytokines such as interleukin (IL)-1 β, IL-6, tumor necrosis factor (TNF), and chemokines by respiratory epithelial and dendritic cells, and macrophages We hypothesize that this cytokine storm and the worsening of patients’ health status can be dampened or even prevented by specifically targeting the vagal-driven cholinergic anti-inflammatory pathway (CAP) The CAP is a concept that involves an anti-inflammatory effect of vagal efferents by the release of acetylcholine (ACh) Nicotinic acetylcholine receptor alpha7 subunit (α7nAChRs) is required for ACh inhibition of macrophage-TNF release and cytokine modulation Hence, targeting the α7nAChRs through vagus nerve stimulation (VNS) could be of interest in the management of patients with SARS-CoV-2 infection Indeed, through the wide innervation of the organism by the vagus nerve, especially the lungs and gastrointestinal tract, VNS appears as a serious candidate for a few side effect treatment that could dampen or prevent the cytokine storm observed in COVID-19 patients with severe symptoms Finally, a continuous vagal tone monitoring in patients with COVID-19 could be used as a predictive marker of COVID-19 illness course but also as a predictive marker of response to COVID-19 treatment such as VNS or others
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #679597
Database	COVID19

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Article ; Online: Targeting the cholinergic anti-inflammatory pathway with vagus nerve stimulation in patients with Covid-19?

Bonaz, Bruno / Sinniger, Valérie / Pellissier, Sonia

Bioelectronic Medicine

2020 Volume 6, Issue 1

Keywords	covid19
Language	English
Publisher	Springer Science and Business Media LLC
Publishing country	us
Document type	Article ; Online
ZDB-ID	2929561-0
ISSN	2332-8886
ISSN	2332-8886
DOI	10.1186/s42234-020-00051-7
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Altered parabrachial nucleus nociceptive processing may underlie central pain in Parkinson's disease.

Pautrat, Arnaud / Al Tannir, Racha / Pernet-Gallay, Karin / Soutrenon, Rémi / Vendramini, Estelle / Sinniger, Valérie / Overton, Paul G / David, Olivier / Coizet, Véronique

NPJ Parkinson's disease

2023 Volume 9, Issue 1, Page(s) 78

Abstract: The presence of central neuropathic pain in Parkinson's disease suggests that the brain circuits that allow us to process pain could be dysfunctional in the disorder. However, there is to date no clear pathophysiological mechanism to explain these ... ...

Abstract	The presence of central neuropathic pain in Parkinson's disease suggests that the brain circuits that allow us to process pain could be dysfunctional in the disorder. However, there is to date no clear pathophysiological mechanism to explain these symptoms. In this work, we present evidence that the dysfunction of the subthalamic nucleus and/or substantia nigra pars reticulata may impact nociceptive processing in the parabrachial nucleus (PBN), a low level primary nociceptive structure in the brainstem, and induce a cellular and molecular neuro-adaptation in this structure. In rat models of Parkinson's disease with a partial dopaminergic lesion in the substantia nigra compacta, we found that the substantia nigra reticulata showed enhanced nociceptive responses. Such responses were less impacted in the subthalamic nucleus. A total dopaminergic lesion produced an increase in the nociceptive responses as well as an increase of the firing rate in both structures. In the PBN, inhibited nociceptive responses and increased expression of GABA
Language	English
Publishing date	2023-05-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2819218-7
ISSN	2373-8057
ISSN	2373-8057
DOI	10.1038/s41531-023-00516-x
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Article: The Vagus Nerve in the Neuro-Immune Axis: Implications in the Pathology of the Gastrointestinal Tract.

Bonaz, Bruno / Sinniger, Valérie / Pellissier, Sonia

Frontiers in immunology

2017 Volume 8, Page(s) 1452

Abstract: The vagus nerve (VN) is the longest nerve of the organism and a major component of the parasympathetic nervous system which constitutes the autonomic nervous system (ANS), with the sympathetic nervous system. There is classically an equilibrium between ... ...

Abstract	The vagus nerve (VN) is the longest nerve of the organism and a major component of the parasympathetic nervous system which constitutes the autonomic nervous system (ANS), with the sympathetic nervous system. There is classically an equilibrium between the sympathetic and parasympathetic nervous systems which is responsible for the maintenance of homeostasis. An imbalance of the ANS is observed in various pathologic conditions. The VN, a mixed nerve with 4/5 afferent and 1/5 efferent fibers, is a key component of the neuro-immune and brain-gut axes through a bidirectional communication between the brain and the gastrointestinal (GI) tract. A dual anti-inflammatory role of the VN is observed using either vagal afferents, targeting the hypothalamic-pituitary-adrenal axis, or vagal efferents, targeting the cholinergic anti-inflammatory pathway. The sympathetic nervous system and the VN act in synergy, through the splenic nerve, to inhibit the release of tumor necrosis factor-alpha (TNFα) by macrophages of the peripheral tissues and the spleen. Because of its anti-inflammatory effect, the VN is a therapeutic target in the treatment of chronic inflammatory disorders where TNFα is a key component. In this review, we will focus on the anti-inflammatory role of the VN in inflammatory bowel diseases (IBD). The anti-inflammatory properties of the VN could be targeted pharmacologically, with enteral nutrition, by VN stimulation (VNS), with complementary medicines or by physical exercise. VNS is one of the alternative treatments for drug resistant epilepsy and depression and one might think that VNS could be used as a non-drug therapy to treat inflammatory disorders of the GI tract, such as IBD, irritable bowel syndrome, and postoperative ileus, which are all characterized by a blunted autonomic balance with a decreased vagal tone.
Language	English
Publishing date	2017-11-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2017.01452
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Article ; Online: Anti-inflammatory properties of the vagus nerve: potential therapeutic implications of vagus nerve stimulation.

Bonaz, Bruno / Sinniger, Valérie / Pellissier, Sonia

The Journal of physiology

2016 Volume 594, Issue 20, Page(s) 5781–5790

Abstract: Brain and viscera interplay within the autonomic nervous system where the vagus nerve (VN), containing approximately 80% afferent and 20% efferent fibres, plays multiple key roles in the homeostatic regulations of visceral functions. Recent data have ... ...

Abstract	Brain and viscera interplay within the autonomic nervous system where the vagus nerve (VN), containing approximately 80% afferent and 20% efferent fibres, plays multiple key roles in the homeostatic regulations of visceral functions. Recent data have suggested the anti-inflammatory role of the VN. This vagal function is mediated through several pathways, some of them still debated. The first one is the anti-inflammatory hypothalamic-pituitary-adrenal axis which is stimulated by vagal afferent fibres and leads to the release of cortisol by the adrenal glands. The second one, called the cholinergic anti-inflammatory pathway, is mediated through vagal efferent fibres that synapse onto enteric neurons which release acetylcholine (ACh) at the synaptic junction with macrophages. ACh binds to α-7-nicotinic ACh receptors of those macrophages to inhibit the release of tumour necrosis (TNF)α, a pro-inflammatory cytokine. The last pathway is the splenic sympathetic anti-inflammatory pathway, where the VN stimulates the splenic sympathetic nerve. Norepinephrine (noradrenaline) released at the distal end of the splenic nerve links to the β2 adrenergic receptor of splenic lymphocytes that release ACh. Finally, ACh inhibits the release of TNFα by spleen macrophages through α-7-nicotinic ACh receptors. Understanding of these pathways is interesting from a therapeutic point of view, since they could be targeted in various ways to stimulate anti-inflammatory regulation in TNFα-related diseases such as inflammatory bowel disease and rheumatoid arthritis. Among others, VN stimulation, either as an invasive or non-invasive procedure, is becoming increasingly frequent and several clinical trials are ongoing to evaluate the potential effectiveness of this therapy to alleviate chronic inflammation.
MeSH term(s)	Acetylcholine/metabolism ; Animals ; Humans ; Hypothalamo-Hypophyseal System/metabolism ; Hypothalamo-Hypophyseal System/physiology ; Inflammation/physiopathology ; Pituitary-Adrenal System/metabolism ; Pituitary-Adrenal System/physiology ; Receptors, Nicotinic/metabolism ; Spleen/metabolism ; Vagus Nerve/metabolism ; Vagus Nerve/physiology ; Vagus Nerve Stimulation/methods
Chemical Substances	Receptors, Nicotinic ; Acetylcholine (N9YNS0M02X)
Language	English
Publishing date	2016-10-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP271539
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