Introduction

Patients (pts) with disorders of gut–brain interaction (DGBI) frequently present with overlapping non-gastrointestinal conditions such as fibromyalgia (FM), whose prevalence in irritable bowel syndrome (IBS) varies from 28–33% to 65%. The co-presence of FM complicates clinical management and worsens outcomes. The pathophysiology of IBS is now well established, involving dysfunction of the gut-brain axis and peripheral factors including microbiome alterations, mucosal barrier disruption, and immune activation. Recently, dysfunction of the gut-musculoskeletal axis was proposed for FM. Shared pathophysiology, involving altered intestinal permeability (IP), and multidisciplinary therapeutic strategies, including dietary interventions, have been proposed for both conditions.

Aims & Methods

To evaluate the effects of a low-FODMAP diet (LFD) on clinical symptoms and IP in pts with IBS, FM, or both, and to assess correlations with serum biomarkers.
This prospective study included 35 pts (88,6% female): 45.7% had IBS+FM, 28.6% IBS-only, and 25.7% FM-only. IP was assessed using serum zonulin (ZO) levels. Clinical evaluations included: SF-36 (quality of life, QoL) for all pts; IBS Symptom Severity Score (IBS-SSS) for IBS; and both Fibromyalgia Impact Questionnaire (FIQ) and Polysymptomatic Distress Scale (PDS) for FM. Assessments occurred at baseline (T0), after 1 month of LFD (T1), at 3 months (T2, reintroduction phase), and 6 months (T3, free diet/follow-up).

Results

At baseline, QoL was significantly lower in the IBS+FM group compared to IBS-only, especially in physical functioning, social functioning, and general health domains (p<0.001). The IBS-only group showed global QoL improvement after 1 month on the LFD, with significant gains in general health (p=0.02) and emotional well-being (p=0.002). Improvements were sustained through T2, but did not increase further. In contrast, the IBS+FM group demonstrated delayed but significant improvements at T2 in physical functioning (p=0.01), energy/fatigue (p=0.02), and social functioning (p<0.001) domains. Similarly, IBS-SSS scores improved significantly at T1 in the IBS-only group (p<0.001) and remained low at T2 (p=0.006), while in the IBS+FM group, the improvement occurred later, reaching significance at T2 (p=0.02). For FM, FIQ and PDS scores improved significantly only at T3 in the IBS+FM group (p=0.03 and p=0.006, respectively), while no significant change occurred in the FM-only group. However, in this group of pts a non-significant reduction in FM symptom scores was observed at T1 and T2, but was followed by worsening symptoms during the free-diet follow-up at T3. Serum ZO levels at T0 were similar across all groups. Significant reductions were observed only in the FM-only and IBS+FM pts, both at T1 (p< 0.001 for both) and T2 (p=0.004, p=0.01, respectively), suggesting improved intestinal permeability. No significant ZO changes were instead observed in the IBS-only group.

Conclusion

The low-FODMAP diet improves gastrointestinal symptoms and quality of life in IBS patients, especially in general health and emotional well-being domains, with delayed but significant benefits also in those with FM. Reductions in zonulin levels in FM and IBS+FM groups suggest enhanced intestinal barrier function, though not directly tied to symptom relief. These findings support a role for central sensitization in FM and underscore the importance of a multidisciplinary approach for managing overlapping DGBI and FM.

Introduction

Tobacco smoke is an established risk factor for Crohn’s disease (CD) postoperative recurrence (POR), however, the effect of e-cigarettes and heat-not-burn tobacco (HNBT) remains unknown. We aimed to evaluate the impact of e-cigarettes and HNBT on postoperative recurrence in CD patients.

Aims & Methods

We retrospectively included consecutive CD patients who underwent ileocolic resection and endoscopic evaluation between 6 and 12 months after surgery across 9 centers in Italy, Spain, and France. Based on smoking habits between surgery and endoscopy, patients were categorized as non-smokers, cigarette smokers, HNBT users, or e-cigarette users. To avoid confounding, the use of HNBT and e-cigarettes was confirmed by phone call, and patients smoking multiple products were excluded.
The primary outcome was endoscopic recurrence (Rutgeerts score ≥2) within the first year. Secondary analyses were conducted on the population receiving prophylactic treatment, using the modified Rutgeerts score (≥i2b), the mean Rutgeerts score, transmural disease activity, fecal calprotectin, time from diagnosis to surgery, and multivariable regression analysis.

Results

In total, 1157 patients were included, of which 860 (75%) were non-smokers, 220 (19%) conventional cigarette smokers, 37 (3%) HNBT users, and 33 (3%) e-cigarette users. Groups were homogeneous for most clinical and demographic variables, including a history of intestinal surgery for CD, use of biologics in the 12 months before surgery, and prescription of POR prophylaxis, but not age. HNBT users were younger than other groups.
Recurrence rates were significantly higher in all smoking groups compared to non-smokers: 70%, 69%, and 68% for e-cigarette, HNBT, and cigarette users, respectively, vs. 39% for non-smokers; all p<0.01. The association persisted in patients receiving pharmacological prophylaxis, with 75%, 69%, 70%, and 40% recurrence for the same groups, and all comparisons remaining significant (all p<0.005).
Using the modified Rutgeerts score cutoff of i2b to define POR overall rates decreased, with 57% recurrence for e-cigarette and HNBT users, 54% for conventional cigarette smokers, and 29% for non-smokers. However, the relative proportions remained consistent, and the differences between groups did not change.
When analyzing the Rutgeerts score as a continuous variable, traditional cigarette smoking, HNBT use, and e-cigarette use remained associated with significantly greater endoscopic disease activity compared to non-smokers (2.02, 2.09, and 1.7,4 respectively, vs. 1.12; all p<0.05). Interestingly, the mean Rutgeerts score among e-cigarette users was numerically lower than that of conventional tobacco cigarettes and HNBT, although the difference was not statistically significant (1.74 vs. 2.02 and 2.09, respectively, both p>0.05). When restricting the analysis to patients receiving prophylactic biologics, differences persisted (p<0.05).
The average fecal calprotectin levels and imaging assessments confirmed the trends observed in endoscopy. The mean calprotectin levels at the time of endoscopy were 221 μ/g, 206 μ/g and 174 μ/g for tobacco, HNBT, and e-cigarettes, respectively, vs. 124 μ/g in non-smokers. Rates of transmural remission were 35%, 48%, 56%, and 61% for the same groups, respectively. Nevertheless, in calprotectin and radiologic analyses, only the differences between conventional smokers and non-smokers reached statistical significance (p<0.05), possibly due to the limited availability of these data and the wide variability of calprotectin levels.
After accounting for potential confounders such as sex, location and behavior of disease at diagnosis, disease duration, type of anastomosis, and previous intestinal resections, all smoking groups remained significantly associated with an increased risk of endoscopic recurrence compared to nonsmokers, e-cigarette (OR 3.06, 95% CI 1.08-9.57, p=0.041), and HNBT (OR 4.47, 95% CI 2.00-10.77, p<0.001), and conventional tobacco (OR 4.66, 95% CI 3.07-7.20, p<0.001).
Finally, we compared disease duration at the time of surgery. Compared to those who never smoked, patients who smoked traditional cigarettes and used HNBT had a significantly shorter disease duration at the time of intervention (7.2 and 5.2 years vs 9.0; p=0.029 and p=0.046, respectively), suggestive of a more aggressive disease course. Instead, the difference with e-cigarettes was not significant (7.5 years vs 9.0, p=0.76).

Conclusion

E-cigarettes and heat-not-burn tobacco are associated with increased endoscopic recurrence of CD compared to non-smoking.

Clinical Case Summary

Introduction: Evidence on endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for advanced colorectal lesions in the setting of Crohn’s Disease (CD) is limited.
Aims & methods: To assess feasibility and safety of complete endoscopic resection (ER) for advanced polyps in patients with complex perianal disease. A 55-year-old man with a 30-year CD history (Montreal A2L3B2p) and right hemicolectomy/sigmoidectomy due to intestinal strictures and enterocolic fistulas, was treated with intravenous infliximab, that switched to adalimumab and azathioprine due to drug-induced lupus. One year ago, he experienced perianal disease relapse with complex intersphincteric and transsphincteric fistulas and intensified adalimumab was initiated.
Results: Colonoscopy revealed a rectal polypoid lesion (80 mm, Paris 0-Is) involving half of lumen circumference and extending up to end-to-end surgical anastomosis. Following chromoendoscopy and narrow band imaging endoscopy performance (NICE 2, Kudo IV, JNET 2B), the lesion was removed using single-tunneling ESD technique, instead of surgical resection, because of the risk of short bowel syndrome. During the procedure, resection of two fistulas was performed with mucinous content discharge. Due to fistulas and fibrosis, ESD continuation was considered unsafe for preserving rectal muscularis propria integrity, and lesion resection proceeded with piecemeal-EMR. A scrotal emphysema was observed and resolved spontaneously. Histological examination revealed tubular adenoma with high-grade dysplasia and small foci of intramucosal adenocarcinoma removed with clear margins. Patient’s course was uneventful and he initiated treatment with subcutaneous infliximab.
Conclusion: Complete ER of large lesions in the setting of complex perianal CD requires advanced ER techniques. Although ER of fistulas in the background of polypoid rectal lesions is challenging, it may be a feasible option without postinterventional complications.

References

Image 1: Rectal polypoid lesion (80 mm, Paris 0-Is, NICE 2, Kudo IV, JNET 2B ) imaged with a. white-light endoscopy b. chromoendoscopy with indigo carmine c. NBI endoscopy
Image 2: Lesion resection using single-tunneling ESD technique
Image 3: Resection of two fistula tracts with subsequent mucinous content discharge
Image 4: Lesion resection was proceeded with piecemeal-EMR
Image 5: Scrotal emphysema
Image 6: Endoscopic view of submucosal defect following complete resection of the lesion