Introduction

Gastro-oesophageal reflux disease (GORD) is characterised by visceral pain hypersensitivity, manifesting as heartburn, and distal oesophageal inflammation. In the oesophageal mucosa of GORD patients, even without visible inflammation (non-erosive reflux disease; NERD) there is increased innervation of sensory nerve fibres containing Substance P (SP) (Xu et al., 2013). SP may be released in response to luminal refluxate or inflammatory mediators to potentiate neuro-immune pathways relevant to GORD pathogenesis. We aimed to investigate the contribution of SP and its receptor NK1R to GORD symptoms.

Aims & Methods

To assess expression of NK1R on native tissue epithelium, biopsies were collected from healthy controls (HC), functional heartburn (FH), NERD and erosive reflux disease (ERD) patients following informed consent (Royal London Hospital ethics number: 19/LO/1506) and prepared for immunohistochemistry. NK1R was co-stained with epithelial cell marker E-Cadherin, pan-leukocyte marker CD45, and general T lymphocyte marker CD3. NK1R protein level was determined by mean fluorescence intensity of 3 FOVs. Cells of the NE-1 oesophageal epithelial cell line were incubated with media containing 100 nM and 300 nM SP for 30 minutes. Cells were lysed and intracellular inflammatory pathway activation was determined by p-NF-κB/NF-κB ratio through Western blot. mRNA levels of the inflammatory cytokine CXCL8 were determined via qPCR with 18S rRNA as a housekeeping gene.

Results

Quantification of mucosal tissue samples showed NK1R mean fluorescence intensity was significantly higher in NERD (fold-change 1.52; p<0.05) and ERD (fold change 1.70; p<0.01) oesophageal mucosa compared to healthy control (n=6-8). Interestingly, NK1R was also found expressed in a sub-group of CD3+ T lymphocytes specifically in the papillae and epithelium of GORD patients. in NE-1 oesophageal epithelial cells, 30 minutes exposure to 100 nM (fold change 1.41; p<0.05) and 300 nM (fold change 1.92; p<0.0001) SP induced phosphorylation of NF-κB in a dose dependent manner (n=7-8). CXCL8 expression in NE-1 cells exposed to 30 nM, 100 nM, or 300 nM SP for 30 minutes resulted in significantly higher mRNA expression at the highest concentration (fold change 6.29; p<0.05), although a dose-dependent trend was observed at lower concentrations (n=3).

Conclusion

The significant increase in NK1R expression in NERD and ERD patients compared to healthy volunteers, combined with expression on T lymphocytes provides evidence, for the first time, that SP may have a critical role in potentiating pain sensation in the oesophagus. Indeed, SP directly induces NF-κB phosphorylation and increases transcription of inflammatory cytokine IL-8 in oesophageal epithelial cells. This demonstrates a novel neuroimmune pathway regulated by SP and NK1R that may be critical in GORD symptom generation.

References

Xu, X., Li, Z., Zou, D., Yang, M., Liu, Z., & Wang, X. (2013). High expression of calcitonin gene-related peptide and substance P in esophageal mucosa of patients with non-erosive reflux disease. Dig Dis Sci, 58(1), 53-60. doi:10.1007/s10620-012-2308-z

Introduction

Nonalcoholic fatty liver disease (NAFLD) is a widespread metabolic disorder associated with intestinal dysbiosis, low-grade systemic inflammation, and small intestinal bacterial overgrowth (SIBO). Targeting the gut-liver axis through microbiome-modulating therapies may represent a promising approach to disease management.

Aims & Methods

The aim was to investigate gut microbiota alterations in NAFLD patients and assess the efficacy of microbiota-based therapy on metabolic, inflammatory, and structural liver parameters. The study included 152 NAFLD patients and 47 controls. Gut microbiota composition was evaluated using qRT-PCR, and SIBO was diagnosed via hydrogen breath testing. The therapeutic protocol included rifaximin (200 mg TID for 14 days), Saccharomyces boulardii CNCM I-745 (1 capsule BID for 30 days), and essential phospholipids (600 mg TID for 30 days). Liver function tests, inflammatory markers, and steatometry were assessed before and after treatment.

Results

Alterations in gut microbiota composition indicative of dysbiosis—including increased Firmicutes/Bacteroides ratio and Actinobacteria abundance—were identified in NAFLD. Strong correlations emerged between the F/B index and triglycerides (r = 0.78), TNF-α (r = 0.77), and between Actinobacteria and hsCRP (r = 0.66). SIBO rates declined significantly post-treatment (51% → 17%). Liver enzymes, inflammatory markers, and steatometric parameters improved substantially (p<0.05).

Conclusion

Microbiota-targeted therapy combining rifaximin, S. boulardii, and phospholipids effectively corrected dysbiosis, reduced inflammation, improved metabolic parameters, and promoted liver structural recovery in NAFLD patients. These findings support incorporating microbiome-focused interventions into routine clinical practice for NAFLD. ​

Introduction

Functional dyspepsia (FD) is a common yet complex gastrointestinal disorder, characterised by postprandial fullness, early satiety, epigastric pain, and burning. With growing evidence linking diet to inflammation and symptoms, our objective was to review the evidence for the impact of dietary factors on FD symptomatology.

Aims & Methods

A systematic review was conducted to identify dietary components influencing FD symptoms in adults. Databases searched included MEDLINE, EMBASE, PsycINFO, Scopus, and Cochrane, covering January 2000 to December 2024. A total of 14 studies met eligibility criteria, with findings synthesised through narrative analysis.

Results

The search strategy yielded 18,424 articles, of which 14 met the inclusion criteria. Analysis identified seven key dietary components associated with FD: (1) a low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet significantly improved symptoms (p = 0.04), while gluten intake was linked to early satiety (p = 0.03); (2) probiotics or prebiotics provided symptom relief (RR 1.15, p = 0.52), with probiotics alone showing a trend toward improved FD scores (RR 1.35, p = 0.061); (3) capsaicin significantly exacerbated symptoms (p < 0.001), and spicy foods were associated with increased gastric fullness (p = 0.001); (4) both peppermint-caraway oil (p < 0.00001) and cinnamon oil (p < 0.001) demonstrated significant symptom relief; (5) ginseng-based herbal porridge led to a higher rate of epigastric symptom remission by day 90 compared to placebo (45.71% vs. 20.69%, p = 0.036), while the STW 5-II formulation (a nine-herb extract) also yielded significant improvement (p = 0.008); (6) prokinetic agents reduced symptom severity (RR 0.81, p < 0.0001), while amitriptyline outperformed both placebo (40%) and escitalopram (38%), relieving symptoms in 53% of patients—particularly those with ulcer-like FD; and (7) ginger/artichoke capsules improved symptoms within 14 days (p = 0.017), while ginger/perilla tablets offered progressive relief over one to two weeks (p < 0.05 and p < 0.01, respectively). Study quality was assessed using ROBIS, RoB 2.0, and ROBINS-I tools. Of the included studies, three were rated as low risk of bias, eight as moderate, and three as serious. Despite adherence to a standardised PRISMA-based search strategy, variability in outcome reporting limited direct comparability across studies.

Table 1

Conclusion

This review highlights dietary interventions as a promising strategy for managing FD. Our findings show that specific dietary components can be implicated in inducing inflammation and symptoms in FD. Since the symptoms are related to inflammation, we propose using “inflammatory dyspepsia” to represent the true presentation of this form of dyspepsia. Large-scale randomised trials are needed to confirm findings and refine dietary guidelines.

Introduction

Chronic intestinal pseudo-obstruction (CIPO) is a rare, heterogeneous, and challenging gastrointestinal motility disorder lacking clinical guidelines in adults.

Aims & Methods

We aimed to develop an international consensus among international experts in gut motility on the diagnosis and management of CIPO based on existing literature and expert opinion. Two experts from each continental motility society and experts on pathology, surgery, and nutritional aspects of CIPO were selected for participation. A list of >130 statements was drafted, subdivided into 11 topics. After revisions and validation by the experts of the list of statements, a systematic literature review was performed to summarize available data on every statement. Using a Delphi process of 3 voting rounds, consensus statements were identified (defined as >80% agreement).

Results

Consensus was reached for 77/139 statements. The panel defined CIPO as symptoms caused by severe small bowel dysmotility without mechanical obstruction, and with documented dilated intestine or air/fluid levels, mimicking mechanical obstruction. Pseudo-obstructive episodes or continuous pseudo-obstructive symptoms were considered a cardinal feature of CIPO. Abdominal pain, bloating, and distension were also considered cardinal symptoms, while nausea/vomiting, diarrhea, or constipation were considered associated symptoms.
Radiographic imaging was considered mandatory in the diagnostic work-up, to confirm intestinal dilation or air/fluid levels and to rule out mechanical obstruction.. No other diagnostic test was considered indispensable for the diagnosis, including endoscopy, manometry, or laparoscopy. Screening for secondary causes of CIPO, including systemic sclerosis, paraneoplastic disease, or infectious disease, was supported, with a possible role for transmural histology. Differential diagnoses, including drug adverse effects, adhesions, or enteric radiation, should be ruled out. The experts also recommended screening for complications such as nutritional deficiencies and osteoporosis.
Management requires dietary adjustment, with supplementation for deficiencies, and setting up home parenteral nutrition if enteral nutrition fails. Small intestinal bacterial overgrowth was recognized as a main contributor to symptom aggravation and should be treated by intermittent antibiotics without the need for breath testing confirmation in patients with CIPO. There was no consensus regarding choice or efficacy of drug therapy, including prokinetics (e.g. pyridostigmine, prucalopride), laxatives, or somatostatin analogs. Opioids and surgical resections should be avoided; although endoscopic or surgical decompression procedures may be helpful in acute or persisting pseudo-obstructive symptoms.

Conclusion

This expert consensus developed key statements for the definition, diagnosis, and treatment of CIPO in adult patients. It provides the opportunity to harmonize the management of these patients and to highlight the gaps in the current literature.

Disclosure

Jan Tack has given Scientific advice to Aclipse, Adare, AlfaSigma, Clasado, Danone, Falk, FitForMe, Ironwood, Kyowa Kirin, Menarini, Promed, Ricordati, Takeda, Truvion, Tsumura, Zealand Pharmaceuticals, has received research support from Biohit, Kiowa Kirin, ProMed, Sofar and Takeda, and has served on the Speaker bureau for Abbott, Bio-Codex, Mayoly, Menarini, ProMed, Reckitt-Benckiser, Schwabe, Takeda, Thai Meiji and Truvion Pharmaceuticals.