Clinical Case Summary

Intestinal pseudo-obstruction (IPO) represents an unclarified dysmotility disorder featured by clinic-radiological signs of intestinal obstruction not associated with a well-identifiable organic gastroenterological disease. IPO may occur as a rare complication of autoimmune connectivopathies, including Systemic Lupus Erythematosus (SLE).
We present an SLE-affected 44-year-old man with a history of recurring nonspecific abdominal prokinetics not-responder sub-obstructive episodes.
The patient was admitted to our department for constipation, vomiting, and unintentional weight loss. Clinical examination revealed a family history of eosinophilic gastroenteritis (EG). SLE, diagnosed 5 years before with the onset of LSE-related hepatitis controlled by immunosuppressive therapy (prednisone 0.5 mg/kg/die/4 weeks; prednisone tapering + azathioprine 1 mg/kg/die/12 weeks). Except for LSE serology and malnutrition parameters, laboratory tests, including Systemic Sclerosis screening, presented no significant alterations. Radiologically, X-ray highlighted multiple air-fluid levels; contrast-enhanced CT showed fluid surrounding dilated loops, and fluid-filled ileal loops, without evidence of organic intrinsic/ab-extrinsic obstruction, perforation, or extraluminal gas.
In light of these findings, stenosing-pattern Crohn's disease (CD) and strictures-complicated EG were mainly suspected. Therefore, we confidently performed a colonoscopy with the histological examination resulting inconclusive for CD and EG. He was managed conservatively with nasogastric decompression, immunosuppressive therapy, and parenteral nutrition. Unfortunately, two weeks after, the worsening symptoms required a lifesaving right hemicolectomy with an ileostomy. Surgical histology showed an SLE fibro-inflammatory pattern, not-sparing the enteric plexus, suggestive of IPO.
IPO should be suspected in SLE patients presenting treated-unresponsive GI symptoms. Its early recognition is prognostically crucial.

References

• Downes TJ, Cheruvu MS, Karunaratne TB, De Giorgio R, Farmer AD. Pathophysiology, Diagnosis, and Management of Chronic Intestinal Pseudo-Obstruction. J Clin Gastroenterol. 2018 Jul;52(6):477-489. doi: 10.1097/MCG.0000000000001047. PMID: 29877952.
• Ohri AJ, Shah CG, Udani AH. Intestinal Pseudo-Obstruction - An Under-Recognized Presentation of Systemic Lupus Erythematosus. Indian J Nephrol. 2022 Sep-Oct;32(5):476-479. doi: 10.4103/ijn.IJN_494_20. Epub 2022 Aug 8. PMID: 36568587; PMCID: PMC9775609.
• Mok MY, Wong RW, Lau CS. Intestinal pseudo-obstruction in systemic lupus erythematosus: an uncommon but important clinical manifestation. Lupus. 2000;9(1):11-8. doi: 10.1177/096120330000900104. PMID: 10713642.

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.

Introduction

EUS-guided gastroenterostomy(EUS-GE) with lumen-apposing metal stent(LAMS) has emerged as a mini-invasive, effective and safe alternative to surgical gastrojejunostomy and endoluminal stenting to treat malignant gastric outlet obstruction(MGOO).Currently, intra-abdominal carcinomatosis represents a relative contraindication to this procedure, due to a possible higher risk of clinical failure.

Aims & Methods

The primary aim was to compare clinical success of EUS-GE in patients (pts) with MGOO with vs without concomitant intra-abdominal carcinomatosis.Secondary aims was to compare between the same subgroups of pts the clinical and procedural characteristics, the technical success rate and long-term outcomes.All pts undergoing EUS-GE for MGOO at our institution from Jun.2018 to Dec.2024 were retrospectively enrolled.Technical success was defined as successfully establishing EUS-GE and clinical success as oral diet tolerance without re-intervention for 14 days after the procedure. Inclusion criteria: 1)age>18 years; 2)MGOO; 3)complete clinical records. Exclusion criterium:missing data. Intra-abdominal carcinomatosis was defined according to CT/MRI imaging. Adverse events (AEs) recorded and classified (AGREE). Obstructive symptoms graded according to the GOOSS score. Data expressed as median [range], comparisons by the Student-t-test, Mann-Whitney-u test and X² test as appropriate.

Results

EUS-GE for MGOO was performed in 74 pts (36 [48.6%] males, age 71 [30-92]), with ECOG performance status ≥2 in 29(39.2%). Obstructive symptoms were reported by 72(97.3%) pts (GOOSS: 1 [0-3]). Intra-abdominal carcinomatosis was present in 29(39.2%) pts. Ascites was more frequent in pts with vs without carcinomatosis (19[65.5%] vs 12[26.7%], p=0.02). Other clinical characteristics were comparable between groups.All EUS-GE were performed in deep sedation. LAMS included Axios and Spaxus (Axios: 37[82.2%] vs 25[86.2%],p=0.89). 20mm LAMS were used in a comparable proportion of pts with vs without carcinomatosis (25[86.2%] vs 37[83.2%], p=0.89). Technical success rates and procedural time did not differ between groups (28[96.6%] vs 43[95.6%],p=0.69; 33[16-85] vs 40[20-106],p=0.52). Overall, 9 misdeployments were observed (carcinomatosis: 3[10.3%] vs no-carcinomatosis: 6[13.3%], p=0.98). AEs were 4 (19.8%) and 9 (20%) in pts with vs without carcinomatosis (p=0.71), all grade III. Time to refeeding (days) was comparable between groups (1[1-5] vs 1[1-5], p=0.96), while hospital stay (days) was longer in patients with carcinomatosis (8[2-18] vs 4[2-15],p=0.0009). Clinical success rate did not differ in pts with vs without carcinomatosis (25[86.2%] vs 43[95.6%],p=0.31). All 6 failures were due to malignancy progression. Median follow-up duration was 51[21-622] days. During follow-up, 27(93.1%) pts with and 38(84.4%) without carcinomatosis died(p=0.45). Median survival (days) and oral diet toleration until last follow-up/death were comparable between pts with vs without carcinomatosis (42[21-398] vs 66[26-622],p=0.07; 26[89.6%] vs 42[93.3%],p=0.89). Oncological treatments were resumed in 11(37.9%) pts with and 23(51.1%)without carcinomatosis (p=0.38). Rehospitalization rate for any cause was comparable in both groups (14[48.3%] vs 26[57.7%],p=0.57), requiring reintervention in 1case.

Conclusion

In our study population high technical and clinical success rates of EUS-GE were comparable in pts with and without intra-abdominal carcinomatosis. The major outcomes were comparable between these 2 subgroups of pts, suggesting the long-term efficacy of this procedure also in those with more advanced malignancy.