ArticleGastroenterology2021
Altered Intestinal ACE2 Levels Are Associated With Inflammation, Severe Disease, and Response to Anti-Cytokine Therapy in Inflammatory Bowel Disease.
Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Risk of adverse outcomes in inflammatory bowel disease patients infected with SARS-CoV-2: a systematic review and meta-analysis.International journal of colorectal disease · 2022Pooled it
- Preventive and therapeutic effects of co-administration of Bacteroides thetaiotaomicron and infliximab on dextran sodium sulfate-induced colitis in mice.Intestinal research · 2026Article
- Yeast Display Technology Enables Rapid Discovery of Low-Nanomolar Macrocyclic Peptide Inhibitors of Human Angiotensin-Converting Enzyme 2.Journal of medicinal chemistry · 2026Article
- Short Ileal Microvillus Length Phenotype Associates with Progression from Inflammatory to Complicated Disease Behavior in Pediatric Crohn's Disease.Inflammatory bowel diseases · 2026Article
- Pioglitazone mitigates acetic acid-induced colitis in rats via epigenetic-modulation and antioxidant mechanisms.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Risk for COVID-19 Vulnerability in Patients with Inflammatory Bowel Disease: Assessing Alterations in ACE2 and TMPRSS2.Biomedicines · 2025Review
- Angiotensin‑converting enzyme 2 expression in human tumors: Implications for prognosis and therapy (Review).Oncology reports · 2025Review
- The role of gut-islet axis in pancreatic islet function and glucose homeostasis.Diabetes, obesity & metabolism · 2025Review
- Impact of Glucose, Inflammation and Phytochemicals onAntioxidants (Basel, Switzerland) · 2025Article
- Recurrent calf myositis as revealing manifestation of Crohn disease: a case report.Frontiers in pediatrics · 2025Article
- Altered plasma levels of the SARS-CoV-2-related proteins ACE2 and TMPRSS2 in patients with Crohn's disease.Scientific reports · 2024Article
- Comprehensive Association Analyses of Extraintestinal Manifestations in Inflammatory Bowel Disease.Gastroenterology · 2024Article
- ACE2 mediates tryptophan alleviation on diarrhea by repairing intestine barrier involved mTOR pathway.Cellular & molecular biology letters · 2024Article
- One-year post-acute COVID-19 syndrome and mortality in South Korea: a nationwide matched cohort study using claims data.Frontiers in public health · 2024Article
- Bioadhesive Microcarriers Encapsulated with IL-27 High Expressive MSC Extracellular Vesicles for Inflammatory Bowel Disease Treatment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Profiling the inflammatory bowel diseases using genetics, serum biomarkers, and smoking information.iScience · 2023Article
- COVID-19 Outcomes in Inflammatory Bowel Disease Hospitalized Patients: A Comprehensive Analysis Using the National Inpatient Sample.Gastroenterology research · 2023Article
- COVID-19 and Gastrointestinal Tract: From Pathophysiology to Clinical Manifestations.Medicina (Kaunas, Lithuania) · 2023Review
- ACE2 in chronic disease and COVID-19: gene regulation and post-translational modification.Journal of biomedical science · 2023Review
- Repurposing of RAS-Pathway Mediated Drugs for Intestinal Inflammation Related Diseases for Treating SARS-CoV-2 Infection.Current microbiology · 2023Review
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
aimsThe host receptor for severe acute respiratory syndrome coronavirus 2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small bowel (SB). Our aim was to identify factors influencing intestinal ACE2 expression in Crohn's disease (CD), ulcerative colitis (UC), and non-inflammatory bowel disease (IBD) controls.
methodsUsing bulk RNA sequencing or microarray transcriptomics from tissue samples (4 SB and 2 colonic cohorts; n = 495; n = 387 UC; n = 94 non-IBD), we analyzed the relationship between ACE2 with demographics and disease activity and prognosis. We examined the outcome of anti-tumor necrosis factor and anti-interleukin-12/interleukin-23 treatment on SB and colonic ACE2 expression in 3 clinical trials. Univariate and multivariate regression models were fitted.
resultsACE2 levels were consistently reduced in SB CD and elevated in colonic UC compared with non-IBD controls. Elevated SB ACE2 was also associated with demographic features (age and elevated body mass index) associated with poor coronavirus disease 2019 outcomes. Within CD, SB ACE2 was reduced in patients subsequently developing complicated disease. Within UC, colonic ACE2 was elevated in active disease and in patients subsequently requiring anti-tumor necrosis factor rescue therapy. SB and colonic ACE2 expression in active CD and UC were restored by anti-cytokine therapy, most notably in responders.
conclusionsReduced SB but elevated colonic ACE2 levels in IBD are associated with inflammation and severe disease, but normalized after anti-cytokine therapy, suggesting compartmentalization of ACE2-related biology in SB and colonic inflammation. The restoration of ACE2 expression with anti-cytokine therapy might be important in the context of severe acute respiratory syndrome coronavirus 2 infection and potentially explain reports of reduced morbidity from coronavirus disease 2019 in IBD patients treated with anti-cytokines.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.