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Review Open access Jul 2026

Efficacy of gut-brain neuromodulators in functional esophageal disorders: a systematic review.

BACKGROUND Patients with functional esophageal disorders exhibit symptoms such as chest pain, heartburn, dysphagia, globus sensation, or reflux hypersensitivity in the absence of structural abnormalities. This is characterized by dysregulated gut-brain interactions and visceral hypersensitivity. METHODS A systematic search of the MEDLINE, EMBASE, Web of Science and the Cochrane central register of controlled trials databases was performed to December 31, 2025. Relevant randomized controlled trials (RCT) reporting the effects of gut-brain neuromodulator (GBN) therapy on functional chest pain (FCP), functional heartburn (FH), reflux hypersensitivity (RH), functional dysphagia (FD), and globus were analyzed. KEY RESULTS Among 2538 screened records, 29 RCTs were included. Neuromodulators provided symptom relief in 18-67% of patients with FCP, with 52-71% achieving ≥ 50% symptom reduction. Moreover, 46-80% of patients experienced a globus reduction of more than 50%. In contrast, the number of included studies for RH and FH was small, and the evidence was inconsistent. In healthy individuals, human experimental models indicated that central or local sensory-modulatory pathways can mitigate acid-induced hyperalgesia, thereby offering a promising therapeutic strategy for RH. Convincing evidence to support the use of GBN in the treatment of FD is lacking. However, its effects on normal human esophageal motility also provides strategies for drug selection, although these outcome indicators vary substantially. CONCLUSIONS AND INFERENCES GBNs can alleviate FCP, improve globus, and to some extent regulate esophageal sensation. However, their effectiveness for FD, FH, and RH remains controversial. Accordingly, future well-designed and phenotype-specific RCTs are required to establish the role of GBNs in clinical management.

Zimeng Wang, Zhi Zheng, Xi-Cheng Wei et al. · 0 citations
Review Aug 2026

What is new in abdominal pain-related disorders of the gut-brain interaction in children.

PURPOSE OF REVIEW This review aims to summarize recent advances in the diagnosis, epidemiology, pathophysiology, and management of pediatric abdominal pain-related disorders of gut-brain interaction (AP-DGBI), including irritable bowel syndrome (IBS) and functional abdominal pain - not otherwise specified (FAP-NOS). Emphasis is placed on emerging diagnostic tools, updated international guidelines, and novel therapeutic approaches. RECENT FINDINGS Novel diagnostic scoring systems may improve clinical evaluation. Growing evidence also supports the role of sleep, biopsychosocial model, and family dynamics in disease severity and persistence, suggesting additional targets in treatment. The recent 2025 ESPGHAN/NASPGHAN guidelines provide evidence-based recommendations for the management of AP-DGBI. Evidence for pharmacologic and nonpharmacologic therapies is promising, although data remains limited. SUMMARY Pediatric AP-DGBI are common and significantly impair quality of life. Advances in diagnostic approaches, our understanding of prevalence and pathophysiology, and growing evidence for both pharmacologic and nonpharmacologic therapies for AP-DGBI may improve future management. Larger high-quality pediatric trials are needed. A multidisciplinary, patient-centered approach using the biopsychosocial model remains at the forefront of optimizing outcomes.

Lily Barash, Carmen Lindmoen, Rachel E. Borlack · 0 citations
Aug 2026

Auricular Neurostimulation: A Novel Therapy for Abdominal Pain-Related Disorders of Gut-Brain Interaction.

Disorders of gut-brain interaction (DGBI) are highly prevalent in the pediatric population. DGBI are heterogeneous disorders with presumed multifactorial pathophysiology. Emerging studies document autonomic nervous system alterations in at least a subset. There is significant symptom overlap among the most common DGBI categories and suboptimal clinical characterization. Extraintestinal comorbidities are frequent and contribute to a rising health care burden. Most therapies are either gut-directed or empirically aimed at desensitizing brain-gut signals. There are a lack of targeted, safe, and effective therapies. Percutaneous electrical nerve field stimulation (PENFS) is a nonpharmacologic neurostimulation device that targets vagal pathways via the external auricle. Four-week cycles of PENFS therapy have demonstrated efficacy for various abdominal pain-related DGBI in children. PENFS has a high safety profile with minimal side effects in large cohort studies. Although access remains challenging because of the need for device placements by certified clinicians along with limited reimbursement, auricular PENFS is a promising, noninvasive, and targeted therapy for pediatric DGBI with underlying autonomic dysregulation.

Lauren D Hagenstein, Katja Karrento · 0 citations
Open access Jul 2026

Rome V: minimizing "functional", maximizing precision in gut-brain disorders.

Rome V represents a major conceptual and clinical evolution in the field of disorders of gut-brain interaction (DGBI). Its most important contribution is the deliberate move away from the term "functional", a label that has often implied that symptoms are less real, less biological, or merely psychological. By emphasizing DGBI, Rome V reframes these conditions as positive diagnoses arising from altered gut-brain regulation, visceral sensitivity, motility, mucosal and immune mechanisms, microbiota, autonomic function, and central processing. Beyond terminology, Rome V introduces greater diagnostic precision. In esophageal disorders, the exclusion of gastroesophageal reflux disease and major motor disorders is aligned with Lyon Consensus 2.0 and Chicago Classification v4.0, while globus and functional chest pain are refined to avoid unnecessary interventions. In gastroduodenal disorders, functional dyspepsia is better phenotyped according to meal-related symptoms, with clearer distinctions from chronic nausea and vomiting syndrome, gastroparesis, cyclic vomiting syndrome, cannabinoid hyperemesis syndrome, rumination, and inability to belch. In bowel disorders, Rome V reintroduces abdominal discomfort into IBS criteria, changes the symptom frequency threshold, renames functional constipation as chronic constipation, and redefines abdominal bloating/distension. The anorectal section is particularly relevant because it operationalizes fecal incontinence, defines dyssynergic defecation using objective testing, and formally recognizes rectal hypo- and hypersensitivity, which may guide biofeedback therapy. Rome V also raises future challenges: implementation in clinical practice, patient-centered communication, avoidance of reductionism, development of mechanism-based research, and interpretation of forthcoming epidemiological data. Overall, Rome V promotes precision, reduces stigma, and supports more rational, mechanism-based care.

J. Remes-Troche · 0 citations
Review Jul 2026

Rome V criteria for pediatric disorders of gut–brain interaction: key updates and clinical implications

ABSTRACT Introduction The Rome criteria have provided the acclaimed global standard for diagnosing pediatric functional gastrointestinal disorders. With the release of Rome criteria V in 2026, the field has undergone a major transformation. The notable changes are the replacement of the term functional gastrointestinal disorders with disorders of gut–brain interaction (DGBIs) and shifting from age-based subdivisions to an anatomical and symptom cluster framework. Area covered We reviewed pediatric Rome V documents and available evidence to cover both upper and lower gastrointestinal disorders of gut-brain interaction (DGBI). The new diagnostic entities such as reflux hypersensitivity, reflux negative esophageal pain disorder, supragastric belching, functional pediatric feeding disorders, centrally mediated abdominal pain syndrome, biliary pain syndrome, proctalgia fugax, functional diarrhea, functional bloating, and infant distress syndrome were discussed in detail. Expert opinion Rome V provides clinicians with a more precise diagnostic framework. However, many new entities remain descriptive, highlighting the urgent need for epidemiological studies, mechanistic research, and biomarker discovery. Large multicenter trials, in DGBI should be conducted using physiological studies, microbiome analysis, and psychosocial profiles to generate robust evidence on pathophysiology, and management strategies. Ultimately, Rome V should be seen as a launchpad for discovery–transforming descriptive categories into mechanically defined, therapeutically actionable disorders that improve outcomes for children worldwide.

S. Rajindrajith, N. Devanarayana, W. Hathagoda et al. · 0 citations
Review Open access Aug 2026

Mechanisms of brain-body interactions in post-stroke visceral dysfunction and recovery.

Traditionally, stroke has been characterized as an acute focal brain injury; however, its clinical consequences extend beyond neurological deficits to encompass visceral dysfunction, which substantially influences functional outcomes, quality of life, and social reintegration. Here, we advance an integrated brain-body interaction (BBI) framework that conceptualizes post-stroke visceral dysfunction as a systemic consequence of disrupted communication between the brain and peripheral organs, rather than as isolated organ-specific complications. This review synthesizes four interconnected pathways involved in this process: autonomic regulation, neuroimmune interactions, neurohumoral signalling, and the microbiota-gut-brain axis (MGBA). Additionally, we examine emerging interventions aimed at restoring visceral function through recalibration of brain-body signalling, including neural plasticity enhancement, vagus nerve stimulation (VNS), acupuncture, and microbiota-based modulation. By linking shared mechanisms to multimodal therapeutic targets, this perspective supports a transition from organ-specific complication management to systems-level, mechanism-guided rehabilitation. Although clinical evidence remains heterogeneous, future progress will require long-term physiological monitoring, multimodal imaging, multi-omics, and artificial intelligence-enabled analyses to advance clinical diagnosis and precision rehabilitation within a systems-neuroscience framework.

Xin Zhang, Ying Zhang, Shi-Hui Chen et al. · 0 citations