Vagus nerve stimulation and sacral nerve stimulation for inflammatory bowel disease

The prevalence of inflammatory bowel disease (IBD) in the United States is approximately 0.9% of the general population, with ulcerative colitis (UC) affecting 0.4% and Crohn’s disease (CD) affecting 0.5%. The direct cost of IBD care in the US amounts to $60 billion annually, primarily focused on managing symptoms such as diarrhea, blood in stool, weight loss, fever, and abdominal pain. The etiology of IBD is complex, involving genetic predisposition and immunologic disturbances, particularly an exaggerated mucosal immune response to the native microbiota. While anti-inflammatory medications and biologics exist, they are primarily symptomatic, often ineffective for a large proportion of patients, and can have significant side effects.

Given these limitations, there is a pressing need for more effective, patient-adherent, and cost-effective IBD treatments. Recently, two neuromodulation therapies have emerged as potential alternatives: vagus nerve stimulation (VNS) and sacral nerve stimulation (SNS). This systematic review assesses the efficacy, potential mechanisms, and safety of these therapies in patients with IBD.

Background and Objectives

In this systematic review, we evaluated the effectiveness of VNS and SNS therapies in patients with IBD, focusing on Crohn’s disease and ulcerative colitis. We aimed to determine the impact of these therapies on IBD symptoms, disease activity, severity of intestinal lesions, and intestinal pain, as well as their potential mechanisms of action and safety profiles.

Methods

We conducted a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The PubMed database was comprehensively searched for studies evaluating VNS and SNS in patients with IBD. Studies were rigorously assessed for inclusion and exclusion criteria.

Results

Our analysis encompassed five clinical studies, three on VNS and two on SNS. The VNS studies included two implantable VNS (iVNS) studies and one transcutaneous auricular VNS (taVNS) study. Similarly, the SNS studies included both implantable and percutaneous approaches.

VNS Studies

The iVNS studies showed significant improvements in IBD symptoms, including disease activity indices (CDAI, pC-DAI, and pUCDAI), endoscopic severity scores (CDEIS), and gastrointestinal pain scores (VAS). Importantly, these improvements were sustained over long-term follow-up periods, up to 12 months. The taVNS study, conducted in pediatric and young adult patients, also demonstrated improvements in disease activity indices, though to a lesser extent.

SNS Studies

The SNS studies demonstrated similar beneficial effects on IBD symptoms, with reductions in disease activity and improvement in intestinal pain. These findings suggest that SNS may also be an effective therapy for IBD.

Mechanisms of Action

Both VNS and SNS therapies appear to work by normalizing the sympathetic and parasympathetic signaling in the gut, mitigating sympathetic dominance during IBD flares. This normalization of the autonomic balance leads to reduced intestinal mucosal inflammation, as evidenced by decreased levels of inflammatory biomarkers (such as CRP and fecal calprotectin).

Safety

Importantly, none of the evaluated VNS or SNS methods resulted in long-term adverse effects. The procedures are typically performed using minimally invasive techniques, with implantable devices receiving FDA approval for various indications, demonstrating a well-established safety profile.

Conclusions

Cumulative evidence from the evaluated studies indicates that VNS and SNS therapies effectively alleviate IBD symptoms and may hold promise in addressing the underlying pathophysiologies of IBD, including intestinal mucosal inflammation and sympathetic dominance. These therapies represent valuable options for individualized IBD treatment, offering alternatives to traditional medical and surgical approaches.

Future research should focus on expanding the patient population, comparing different neuromodulation modalities, and elucidating the precise mechanisms of action of VNS and SNS in IBD. With continued investigation, these therapies may become standard of care for IBD patients.

Full text

https://www.xiahepublishing.com/2994-8754/JTG-2023-00098

The study was recently published in the Journal of Translational Gastroenterology.

Journal of Translational Gastroenterology (JTG) dedicates to improving clinical diagnosis and treatment, advancing understanding of the molecular mechanisms, and promoting translation from bench to bedside of gastrointestinal, hepatobiliary, and pancreatic diseases. The aim of JTG is to provide a forum for the exchange of ideas and concepts on basic, translational, and clinical aspects of gastroenterology, and promote cross-disciplinary research and collaboration.

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