Abstract
Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection first emerged in Wuhan, Hubei Province, China, in December 2019 and spread rapidly to other provinces and other countries. Angiotensin I converting enzyme 2 (ACE2) is the receptor for SARS-CoV and has been suggested to be also the receptor for SARS-CoV-2. Paradoxically, ACE2 expression in the lung protects mice from SARS-CoV spike protein induced lung injury by attenuating the renin-angiotensin system. In the intestine, ACE2 also suppresses intestinal inflammation by maintaining amino acid homeostasis, antimicrobial peptide expression and ecology of the gut microbiome. We performed analysis of single cell-RNA sequencing data from control subjects and those with colitis or inflammatory bowel disease (6 controls, 6 colitis cases, 2 ulcerative colitis cases and 3 Crohn’s disease cases). The single cell-RNA sequencing data was also used to conduct co-expression analysis and GO enrichment analysis. Multiplex immunofluorescence (mIF) was performed to assess the expression of ACE2, IFNA4, and RSAD2 on colon specimens obtained from patients, including non‑diseased (control) tissue, ulcerative colitis (UC) tissue and Crohn’s disease (CD) tissue. We revealed that ACE2 exhibited specific and high expression levels in colonocytes. Furthermore, genes implicated in viral infection and anti-infection immunity were also found to be highly expressed in colonocytes. Additionally, we conducted an analysis of genes co-expressed with ACE2 within colonocytes, and total of 3420 and 2136 genes were identified as being positively and negatively correlated with ACE2 expression. Concurrently, through Gene Ontology (GO) enrichment analysis, it was observed that genes positively associated with ACE2 expression were significantly enriched in pathways related to viral infection, organismal immunity, and energy metabolism. Accordingly, mIF showed a significant increase in IFNA4 and RSAD2 expression in the colonic epithelial ACE2⁺ cells of UC and CD patients relative to controls. Integrated data from single cell-RNA sequencing and patient’s mIF highlighted the expression profile of ACE2 in colonic epithelial cells, suggesting the possible involvement of ACE2 in the intestinal tract of patients with SARS-CoV-2 pneumonia in enteroviral infection, immunity and energy metabolism functions.
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Data availability
The data generated in this study have been deposited in two public repositories. The processed gene expression and raw sequencing data are available under controlled access from the Genome Sequence Archive (GSA) of the Beijing Institute of Genomics, Chinese Academy of Sciences under accession number HRA000072 (application guidance: http://bigd.big.ac.cn/gsa-human). The processed data from the pooling dataset are publicly available in the Gene Expression Omnibus (GEO) under accession number GSE121380.
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Acknowledgements
The authors are quite grateful for the available data used in this study provided by Zhang Lab.
Funding
Natural Science Foundation of China (91742109, 31770978, 31722003, 31770925, 31370847, 81770552), National Key Research and Development Program (2016YFC0900102), National Science and Technology Major Project (2018ZX10302205), Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease (2019B030301004), Guangzhou Women and Children’s Medical Center Fund (5001-3001032) and National Health and Medical Research Council of Australia (1037321, 1105209, 1143976, and 1080321 to A.M.L.) funded this study. Guangdong Province Science and Technology Innovation Strategy Special Fund (Guangdong-Hong Kong Joint Funding Programme) (2025A0505080010). Guangzhou Science and Technology fund (2024A04J3928).
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Y.Z., Q.T. and W.X. conceived of and supervised the project. Y.Q., H.C. and Q.T. performed the bioinformatic analysis. Y.H. performed the experiment with assistance from H.C., J. L.. Y.Z. wrote the manuscript with significant assistance from Q.T., W.X. and M.L. All authors read, discussed and approved the manuscript.
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Qi, Y., Huang, Y., Chen, H. et al. ACE2 expression by colonic epithelial cells is associated with viral infection, immunity, and energy metabolism. Sci Rep (2026). https://doi.org/10.1038/s41598-026-36052-w
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DOI: https://doi.org/10.1038/s41598-026-36052-w
