Introduction

Gut microbiota appear to play a role in the pathogenesis of disorders of gut-brain interaction. Established evidence supports the association between gastrointestinal (GI) infections and irritable bowel syndrome (post-infection irritable bowel syndrome, PI-IBS), although the impact of specific taxa has not been clearly assessed yet. Moreover, data associating GI infection and functional dyspepsia (post-infection functional dyspepsia, PI-FD) are emerging.

Aims & Methods

We conducted a systematic review and meta-analysis to determine prevalence of PI-IBS and PI-FD after GI infection and to evaluate if specific microbial taxa differ in their likelihood of precipitating these disorders. We searched PubMed, Scopus, and Web of Science through 17 April 2023. Observational studies recruiting ≥20 adults and reporting prevalence of IBS and/or FD after GI infection with a minimum follow-up duration of 6 months were included. We used a random effects model to calculate pooled prevalence (PP) of IBS and FD as well as odd ratios (OR) with 95% confidence intervals (CIs).

Results

From 8469 papers evaluated, we identified 47 eligible studies (28,071 people) reporting prevalence of PI-IBS and 14 studies of PI-FD (15,253 people), respectively.
Overall, PP of PI-IBS after GI infection was 12.5% (95% CI 11.9%-13.0%, I²= 97,9%) and PP of PI-FD was 12.6% (95% CI 6.3%-20.6%, I²= 94.2%). The PP of PI-IBS was 19.8% for bacteria, 10.7% for viruses, 22.3% for parasites and, notably, 25.7 % for Clostridioides difficile and 22.5% for Campylobacter infections. The PP of PI-FD was 13.6 % for bacteria and 9.6 % for viruses.
Those with a history of GI infection had a significantly higher odds of developing IBS (OR 3.9, 95% CI 2.8-5.4, p<0.0001) or FD (OR 3.03, 95% CI 1.9-4.7, p<0.0001) than controls without.
In subgroup analysis, ORs for developing PI-IBS were 4.8 (95% CI 2.8-8.0, p<0.0001) for bacteria, 3.2 (95% CI 0.9-11,2, p= 0.06) for viruses, and 5.4 (95% CI 4.4-6.7, p < 0.0001) for parasites. Notably, Gram-negative bacteria (Enterobacteriaceae + Campylobacter) were associated with a higher odds (OR 5.5, 95% CI 2.5-11.9, p<0.0001). The OR for developing PI-FD was 3.8 (95% CI 0.98-14.7, p=0.05) for bacteria and 2.0 (95% CI 0.77 to 5.2, p=0.15) for virus, respectively.

Conclusion

In a systematic review and meta-analysis of 61 studies and 43,324 people we found that one-in-eight people who experience a GI infection developed PI-IBS or PI-FD. Bacterial infections, mainly Clostridioides difficile, and parasitic infections were associated with a higher prevalence of PI-IBS or PI-FD. In case-control studies, bacteria, mainly Gram-negatives, and parasites were associated with the highest odds of PI-IBS. Conclusive data on PI-FD are not yet available.

Disclosure

G.I. has received personal fees for acting as speaker for Biocodex, Danone, Sofar, Malesci, Metagenics and Tillotts Pharma, and for acting as consultant and/or advisor for Ferring Therapeutics, Giuliani, Malesci and Tillotts Pharma. A.G. reports personal fees for consultancy from Eisai Srl, 3PSolutions, Real Time Meeting, Fondazione Istituto Danone, SinergieSrl, Board MRGE and Sanofi SpA personal fees for acting as a speaker for Takeda SpA, AbbVie and Sandoz SpA and personal fees for acting on advisory boards for VSL3 and Eisai. G.C. has received personal fees for acting as advisor for Ferring Therapeutics. All other authors have no conflicts of interest to disclose.

Introduction

Celiac disease (CD) is an autoimmune enteropathy induced by the ingestion of gluten in genetically predisposed individuals. Although its clinical expression is most often digestive, extra-digestive manifestations can occur, among which thromboembolic complications, although rare, deserve particular attention.
The aim of this study is to describe the profiles of coeliac patients with thromboembolic complications, analyze their clinical, paraclinical and etiological characteristics, and discuss the underlying pathophysiological mechanisms.

Aims & Methods

This is a retrospective, descriptive, monocentric study conducted in the hepato-gastroenterology department of Ibn Sina Hospital in Rabat over a 30-year period, from 1995 to 2025. The records of 344 patients followed for celiac disease were reviewed. Patients with one or more documented thromboembolic complications during follow-up were included in the study. Clinical, biological, endoscopic and histological data were collected and analyzed.

Results

Of a total of 344 patients followed for celiac disease in the department, 5.5% (n=19) developed a thromboembolic complication during follow-up. The population concerned was predominantly female, with 89.5% women (n=17) versus only 10.5% men (n=2). The mean age at the time of complication was 39.6 years, with a median of 35.5 years, and extremes ranging from 18 to 62 years.
Endoscopic exploration (oesogastro duodenal fibroscopy) in these patients showed lesions suggestive of celiac disease in 68.4% (n=12), while it was non-specific in 31.6% (n=6), and normal in 5.3% (n=1). Histologically, villous atrophy was found in all patients, with 78.9% (n=15) showing total atrophy (Marsh IIIc) and 21.1% (n=4) subtotal atrophy (Marsh IIIb).
As regards thromboembolic manifestations, portal vein thrombosis was the most frequent complication, observed in 57.9% of cases (n=11). It was followed by deep vein thrombosis of the lower limbs, reported in 15.8% of cases (n=3), and ischemic stroke in 10.5% (n=2). Isolated cases of thrombosis of the inferior vena cava, axillary vein and femoral vein were recorded, each accounting for 5.3% of cases (n=1).
The etiological study revealed hyperhomocysteinemia in 36.8% of patients (n=7) and protein C and/or S deficiency in 21.1% (n=4). In the remaining 42.1% of patients (n=8), the thrombophilia work-up was normal, suggesting that celiac disease itself was the cause of the thrombotic event.
Therapeutically, all patients were treated with oral anticoagulation. One patient required a vena cava filter because of the risk of bleeding on anticoagulation, and another underwent surgical treatment for axillary thrombosis. The outcome was favorable in all cases, with no recurrence or major complication during follow-up.

Conclusion

Thromboembolic complications in celiac disease are rare but potentially serious. This study highlights the predominance of women, the diversity of thrombotic localizations, and the possible involvement of hyperhomocysteinemia and C/S protein deficiencies. In almost half the cases, no thrombophilic cause has been identified, suggesting a role for celiac disease in the genesis of these events. Clinical vigilance is essential, particularly in cases of late diagnosis or poor compliance with the gluten-free diet.