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Microbes & Immunity A disruptive solution for endometriosis

of knowledge in the pathophysiology of endometriosis, sharing of variants associated with endometriosis and
this distinction is rather ambitious, since endometriotic migraine) as well as in case of threatening inflammation
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lesion can grow very slowly and the diagnosis is often with Emergency Use Authorization from the FDA in July
delayed. Nevertheless, as the bidirectional microbiota- of 2020 for patients with known or suspected coronavirus
gut-brain axis is known to involve the vagus nerve 19,37,64-66 disease 2019 (COVID-19). We are seeing a paradigm
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and as severe endometriosis leads to a reduced vagal tone shift in our understanding of how disease is modulated by
in women, the rationale for using non-invasive VNS in infection and/or inflammation across numerous disorders
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endometriosis is very much appealing. from the use of electroceuticals in the treatment of IBD
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and rheumatoid arthritis to the treatment of cytokine
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4. Rationale for using VNS in endometriosis storm associated with COVID-19. 105
In a nutshell, gut dysbiosis and estrobolome activity The benefits of non-invasive VNS are potentially
seem to be essential to initiate endometriosis. 20,33,34,68 plethora for women with endometriosis. First and foremost,
Although preliminary, antibiotic and probiotic treatments non-invasive VNS can provide a significant reduction
have demonstrated efficacy in treating endometriosis, of side effects, compared to the actual drugs (from non-
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modulating the gut and/or genital microbiota by other steroidal anti-inflammatory drugs whose anticipated side
means, potentially including non-invasive VNS, has effects are relatively mild to progestins whose prolonged
been suggested as a novel therapeutic strategy to improve use has been linked with a malignant transformation of
outcomes in patients with chronic endometriosis. 29,69,70 ovarian endometrioma). Indeed, non-invasive VNS has
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Indeed, minimally or non-invasive VNS is already known proven to be very well tolerated and is likely to be more
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to mitigate gut dysbiosis and is currently advocated for ethical for young ladies than dienogest. 108,109
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managing both IBS and IBD. 73-76
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Second, most current drugs merely alleviate symptoms
VNS appears particularly promising to help delay or without reversing the progression of endometriosis.
even prevent severe endometriosis, since in a mouse model, Guo even stated in 2014 that “no blockbuster drug for
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vagotomy has been shown to promote the progression of endometriosis seems to be on the horizon yet”, probably
endometriosis, whereas VNS could relieve it. Actually, because interdisciplinary clinical research, fully funded
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besides mitigation of gut dysbiosis and estrobolome by non-industrial sources, is lacking. The same author
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activity, non-invasive VNS is likely to be helpful to has even called for a paradigm shift in drug research
several therapeutic mechanisms: (i) decreasing local and and development in endometriosis lately. Remarkably,
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systemic inflammation (by stimulating alpha 7 nicotinic non-invasive VNS has all the requisites to become an
receptors (α7nAChR), 77,78 involved in the cholinergic all-in-one tool (both etiological and symptomatic) in
anti-inflammatory pathway, 79-84 which are significantly endometriosis (that is the main aim of this article). Indeed,
reduced in endometriotic lesions); (ii) counteracting non-invasive VNS has already been successfully used in
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VIP-induced increase of intestinal and brain barrier different types of chronic pain (chronic pain being an
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permeability; 86-88 (iii) decreasing the central symptoms of interdisciplinary clinical research field by essence), has
endometriosis, i.e., stress, pain, anxiety, and depression; 89-92 shown promising results not only in chronic pelvic pain,
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(iv) protecting from hypoxia; 93,94 (v) acting through but also in a wide array of comorbidities of endometriosis
epigenetic regulatory mechanisms (histone deacetylation, (FDA-approved for preventing migraine attacks, stress,
micro-RNA and methylation of DNA), 11,95-98 and (vi) finally anxiety, and depression), and has the potential to reverse
modulating the downstream MAPK or NF-κB pathways the several pathophysiologic mechanisms involved in
signaling pathways, which are known to be involved in endometriosis. Non-invasive VNS does not modify one
endometriosis. 98-100 but a variety of factors, both peripherally and centrally,
Traditionally, VNS was achieved through surgical and has demonstrated an expanded scope and value for
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implantation. In 2017, however, non-invasive approaches holistic therapy. This ability relies mainly not only on
that involve stimulating the cervical vagus nerve and the the widespread innervation of the vagus nerve but also on
auricular branch of the vagus nerve were approved by the its ability to shift the body and brain from a sympathetic
U.S. Food and Drug Administration (FDA) for cluster to a parasympathetic dominance. Indeed, another
headache and abdominal pain, respectively. Since then, therapeutical approach (a fluid therapy comprising
numerous new indications have been cleared by the FDA, adenosine, lidocaine, and magnesium) allowing a similar
and remarkably for the treatment and the prevention shift from sympathetic to parasympathetic tone has
of migraine attacks 101,102 (this is of highest importance been intitled “Revolution in sepsis: a symptoms-based
since multitrait genetic analyses identified substantial to a systems-based approach?” as it enables to “maintain

Volume 1 Issue 2 (2024) 49 doi: 10.36922/mi.4389