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.

Clinical Case Summary

Introduction: Gastric siderosis (GS) refers to the abnormal deposition of iron within the gastric mucosa, a condition that can be associated with various underlying pathologies. Our case depicts a case of gastric siderosis with iron deposition in the stomach in association with excessive oral iron intake, presenting unusually with chronic diarrhea. Such association has been mentioned previously in the literature but not established.
Case: A 70-year-old lady with a history of iron deficiency anemia and chronic kidney disease presented with 3 weeks of progressively worsening diarrhea. Home medicines included iron pills. She denied any blood in stool, abdominal pain, recent travel, or antibiotic use. Her vitals and her abdominal exam were unremarkable. Stool studies, including stool parasite, C. difficile toxin, calprotectin, and bacterial PCR, were negative.
Colonoscopy showed a normal macroscopic appearance with random biopsies negative for microscopic colitis. An upper endoscopy was performed demonstrating normal esophagus but pitted brown spots mucosa in the gastric body, and antrum. Biopsies were taken, with antral ones demonstrating antral mucosa with iron deposition in the glands and lamina propria concerning gastric siderosis. Oral iron was discontinued and the patient endorsed improvement in symptoms upon outpatient follow-up with endoscopic resolution at 6 months.
Discussion: Iron deposition in gastric mucosa induces a highly oxidative state, producing injury. However, siderosis due to oral iron use is less commonly associated with mucosal injury, with cases seen with changes ranging from erythema to mucosal erosions. Our patient had pattern B on biopsy involving stroma, whereas A involves macrophages in gastric inflammation, and C involves glands in hemochromatosis. No association with the duration or amount of exposure is associated with differences in symptoms. Non-bloody diarrhea occurs without active ulceration being reported, making our patient unique.

References

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2. Abraham SC, Yardley JH, Wu TT. Erosive injury to the upper gastrointestinal tract in patients receiving iron medication: an underrecognized entity. Am J Surg Pathol. 1999 Oct;23(10):1241-7. doi: 10.1097/00000478-199910000-00009. PMID: 10524525.
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Clinical Case Summary

We present the case of a 50-year-old man with six months of persistent, non-bloody watery diarrhea (8–10 episodes/day), unresponsive to antibiotics and probiotics. His past medical history was unremarkable, he took no home medications, and denied raw meat or fish consumption. Notably, he had recently started working in an animal feed production facility one month before symptom onset. Initial labs showed mild leukocytosis (10.04 x 10³/µL; ULN: 8.77) and mildly elevated CRP (7.5 mg/L; ULN: 3.4). Extensive infectious workup, including CMV serology, Quantiferon, stool cultures for Salmonella, and tests for fungi and parasites (e.g., Giardia), fecal elastase, rectal swabs for Klebsiella pneumoniae carbapenemase and Clostridium difficile returned negative. Colonoscopy and upper GI endoscopy were normal, and biopsies from all intestinal segments showed no pathological findings. He was discharged with partial improvement (3–4 bowel movements/day) and normalized CRP, but was readmitted a week later for worsening symptoms. Repeat blood work, thyroid function, serum calcitonin and inflammatory markers were within normal limits. Intestinal ultrasound showed a tubular descending colon suggestive of nonspecific left-sided colitis; other bowel segments were normal. Stool tests remained negative.Urine toxicology was positive for cannabinoids. Upon further questioning, the patient admitted to regular use over the past eight months, including during both hospitalisations (CUDIT-R score = 12). After cessation of cannabinoid use, diarrhea resolved completely. At 3-month follow-up, he was asymptomatic, with normal bowel habits and labs. He reported only sporadic cannabinoid use at present (CUDIT-R score 7). This case illustrates the potential for chronic cannabinoid use to induce persistent diarrhea mimicking infectious or inflammatory disease. Screening for substance use should be considered in chronic unexplained diarrhea.

Introduction

Microplastics are unavoidable in our current environment and can enter the human body through ingestion, inhalation, and skin contact. Gut microbes play a role in plastic degradation, breaking down polymers into smaller molecules through enzymatic processes like depolymerization and oxidation, which can then be used as a carbon source (1). However, there is mounting alarming evidence that implicates microplastics in causing oxidative stress, DNA damage, and chronic inflammation, potentially leading to various health issues, including gastrointestinal disorders (2-4). In individuals with digestive disorders such as DGBI (disorders of gut-brain interaction), microplastics may exacerbate symptoms by disrupting gut microbiome and immune responses. Previously, within a functional dyspepsia (FD) cohort we identified a strong positive correlation between plastic degrading Exiguobacterium genus (5) within the duodenal mucosa and mucosa Th2 immune cells (6).

Aims & Methods

We aimed to investigate the differential abundance of microbes and metabolic pathways known to degrade plastics in patients with FD. Previously, we have published the 16S duodenal mucosa associated microbiome sequence data for FD (n=17) and asymptomatic control (n=11) groups (6), in addition we conducted a systematic review and retrieved 1 raw duodenal mucosa-associated microbiome 16S sequence dataset (FD n=61, controls n=38) for re-analysis with a consistent bioinformatic pipeline. This included quality assessment, demultiplexing and denoising with QIIME2 and taxonomic assignment with SILVA database. Functional differences in the microbiome were predicted with PICRUSt2. Differentially abundant plastic utilising genes were assessed in R, after CLR-transformation.

Results

As the two 16S upper gastrointestinal mucosa microbiome FD studies were sequenced separately, and the batch effect are pronounced we could not combine them for pooled analysis. When we examined the first study for predicted metabolic pathways for differential polyethylene terephthalate (PET) utilization when comparing FD patients to controls in the duodenum mucosa-associated microbiome, we did not identify any significant differences. An increase in the "partial TCA cycle (obligate autotrophs)" was observed in the gastric mucosa-associated microbiome of FD patients vs controls; PET by-products have been linked to the TCA cycle (7).
The study retrieved through our systematic review identified several significantly increased predicted functional polyethylene-associated genes, primarily from later stages of degradation. The findings revealed that the gene 3-oxoadipate enol-lactonase [EC:3.1.1.24] was significantly increased in FD patients. Furthermore, the genes 5-carboxymethyl-2-hydroxymuconic-semialdehyde dehydrogenase [EC:1.2.1.60] and 5-oxopent-3-ene-1,2,5-tricarboxylate decarboxylase/2-hydroxyhepta-2,4-diene-1,7-dioate isome were significantly increased in controls. Finally, 5-carboxymethyl-2-hydroxymuconate isomerase [EC:5.3.3.10] was also increased in controls though not significantly.

Conclusion

Our recent microbiome analysis reveals a significant enrichment of PET-degrading microbes colonising the upper gastrointestinal tract of patients with FD compared to controls. These findings provide new insights into the microbial and immune landscape of FD patients, highlighting potential microbial biomarkers and immune associations that warrant further investigation.

References

1. Yang X-G, Wen P-P, Yang Y-F, Jia P-P, Li W-G, Pei D-S. 2023. Plastic biodegradation by in vitro environmental microorganisms and in vivo gut microorganisms of insects. Frontiers in Microbiology
2. Jayavel S, Govindaraju B, Michael JR, Viswanathan B. 2024. Impacts of micro and nanoplastics on human health. Bulletin of the National Research Centre
3. Cheng Y, Yang Y, Bai L, Cui J. 2024. Microplastics: an often-overlooked issue in the transition from chronic inflammation to cancer. J Transl Med
4. Han Q, Gao X, Wang S, Wei Z, Wang Y, Xu K, Chen M. 2023. Co-exposure to polystyrene microplastics and di-(2-ethylhexyl) phthalate aggravates allergic asthma through the TRPA1-p38 MAPK pathway. Toxicology Letters
5. Parthasarathy A, Miranda RR, Eddingsaas NC, Chu J, Freezman IM, Tyler AC, Hudson AO. 2022. Polystyrene Degradation by Exiguobacterium sp. RIT 594: Preliminary Evidence for a Pathway Containing an Atypical Oxygenase. Microorganisms
6. Hoedt EC, Burns GL, Kang S, Bruce J, Morrison M, Keely S, Talley NJ. 2025. Altered Duodenal Mucosa-Associated Microbiota and Immune Profiles in Functional Dyspepsia: A Study of Host-Microbiome Homeostasis. bioRxiv doi:10.1101/2025.04.10.648308:2025.04.10.648308.
7. Carr CM, Clarke DJ, Dobson ADW. 2020. Microbial Polyethylene Terephthalate Hydrolases: Current and Future Perspectives. Front Microbiology

Disclosure

Keely reports consultancy and positions held on advisory boards for: Gossamer Bio (Scientific Advisory Board), Anatara Lifescience (Scientific Advisory Board), Microba Life Science (Consultancy) and Immuron Ltd. (Consultancy).
Talley reports personal fees from Biocodex (FD) (2024), Brown University (fiber and laxation), Microba (microbiome), outside the submitted work. NJT has a patent Licensing Questionnaires Talley Bowel Disease Questionnaire licensed to Mayo/Talley and Nepean Dyspepsia Index (NDI) 1998, patent “Diagnostic marker for functional gastrointestinal disorders” Australian Provisional Patent Application 2021901692, “Methods and compositions for treating age-related neurodegenerative disease associated with dysbiosis” US Application No. 63/537,725.

Clinical Case Summary

We present a rare case of protein losing gastropathy.A 60-year-old female presented to our clinic with 10 years history of intermittent dyspepsia with no alarm features and peripheral oedema for 6 months.Physical examination was unremarkable except mild bilateral pitting oedema.Pertinent investigations suggested normal albumin,urine analysis,renal&liver profiles and a normal echocardiogram.Subsequent testing with esophagogastroduodenoscopy(EGD) for dyspepsia showed hypertrophied mucosal folds predominantly in gastric corpus while sparing the antrum.Full thickness biopsies were taken and sent for histopathology with differentials of Lymphoma,adenocarcinoma,sarcoidosis and Menetrier’s disease.Stool antigen for Helicobacter Pylori(H.Pylori)thereafter,was positive while Contrast enhanced CT abdomen was consistent with mildly thickened gastric walls.Histological examination demostrated foveolar hyperplasia,elongated gastric pits and cystically dilated gastric glands without any features of malignancy.Hence a diagnosis of Menetrier’s disease(underlying H.Pylori) was made.
Patient then had H.Pylori eradication therapy as well as a diet rich in medium-chain fatty acids and proteins.H.Pylori eradication was confirmed.6 months follow up revealed partial resolution of her symptoms but no change in endoscopic findings.Patient could not undergo further treatment with biologics(cetuximab)due to financial constraints and octreotide for its local unavailability.She is now on a yearly endoscopic surveillance for future high risk of gastric malignancies.

References

​​Fig1A.Haematoxylin & Eosin staining shows foveolar & mucous cell hyperplasia,elongated gastric pits and lymphocytic infiltration.
Fig1B.Haematoxylin & ​Eosin staining shows cystic dilation of gastric glands
1.Pepa P, Uehara T, Wonaga A, Redondo A, Avagnina A, Mazzocchi O, Antelo P, Waldbaum C, Sorda J. Menetrier's disease. A diagnostic and therapeutic challenge. Medicina (B Aires). 2021;81(3):470-473. English. PMID: 34137712.
2.Gore M, Bansal K, Jadhav N. Menetrier Disease. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan– [updated 2023 Jun 25].

Disclosure

No conflicts