ArticleNature2012
ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 759 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
An Evaluation of a Synbiotic Formula for Symptom Improvement in Hospitalised Patients With COVID-19 Infection
Investigating the Inflammatory Cytokines and Cytokine Storm Among Bangladeshi Patients With COVID-19: a Prospective, Observational Study
Evaluation of a Synbiotic Formula in Patient With COVID-19
Who cites it
759 citing papers in PubMed, 4 syntheses or guidelines pooled it, 1,270 citations in OpenAlex.
- The Role of Aromatic Amino Acids in Polycystic Ovary Syndrome through Patients' Blood Metabolic Profiling: A Systematic Review of the Past Five Years.Journal of proteome research · 2025Pooled it
- Pooled it
- Pooled it
- COVID-19 alters human microbiomes: a meta-analysis.Frontiers in cellular and infection microbiology · 2023Pooled it
- Nicotinamide modulates gut microbial metabolic potential and accelerates recovery in mild-to-moderate COVID-19.Nature metabolism · 2025Trial
- Trial
- Gut microbial allies and adversaries in SARS-CoV-2 infection.Current research in microbial sciences · 2026Article
- Cardiovascular Disease as a Risk Amplifier of COVID-19 Severity and a Potential Correlations to Long-Term Gastrointestinal Sequelae.Journal of racial and ethnic health disparities · 2026Article
- Salidroside and mesenchymal stem cells alleviate hypobaric hypoxia-induced lung injury and are associated with alterations in the gut-lung axis.Biochemistry and biophysics reports · 2026Article
- Animal gut microbes and microbiomes in the 21st century and beyond.Science China. Life sciences · 2026Review
- Preventive and therapeutic effects of co-administration of Bacteroides thetaiotaomicron and infliximab on dextran sodium sulfate-induced colitis in mice.Intestinal research · 2026Article
- Characterization of Nasopharyngeal Microbiota Dysbiosis in Children withMicroorganisms · 2026Article
- Pathogen-Specific Regulation of Renin-Angiotensin System Genes in Epithelial Cells: A Comparative Study of SARS-CoV-2 Spike Protein N-Terminal Domain Fragment and Bacterial Lipopolysaccharide.Pathogens (Basel, Switzerland) · 2026Article
- Tryptophan pathway metabotypes associate with disease activity and immune-metabolic dysfunction in inflammatory bowel disease.medRxiv : the preprint server for health sciences · 2026Article
- Article
- VRAC coordinates the trade-off between nutrient absorption and antimicrobial defense in enterocytes against inflammation.Nature communications · 2026Article
- SARS-CoV-2 Persistence and the Gut Microbiota: New Insights into Long COVID Pathogenesis.Viruses · 2026Review
- Activation of Angiotensin-Converting Enzyme 2 Mitigates Gastrointestinal Acute Radiation Syndrome.International journal of radiation oncology, biology, physics · 2026Article
- Short Ileal Microvillus Length Phenotype Associates with Progression from Inflammatory to Complicated Disease Behavior in Pediatric Crohn's Disease.Inflammatory bowel diseases · 2026Article
- ACE2 expression by colonic epithelial cells is associated with viral infection, immunity, and energy metabolism.Scientific reports · 2026Article
699 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Malnutrition affects up to one billion people in the world and is a major cause of mortality. In many cases, malnutrition is associated with diarrhoea and intestinal inflammation, further contributing to morbidity and death. The mechanisms by which unbalanced dietary nutrients affect intestinal homeostasis are largely unknown. Here we report that deficiency in murine angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (Ace2), which encodes a key regulatory enzyme of the renin-angiotensin system (RAS), results in highly increased susceptibility to intestinal inflammation induced by epithelial damage. The RAS is known to be involved in acute lung failure, cardiovascular functions and SARS infections. Mechanistically, ACE2 has a RAS-independent function, regulating intestinal amino acid homeostasis, expression of antimicrobial peptides, and the ecology of the gut microbiome. Transplantation of the altered microbiota from Ace2 mutant mice into germ-free wild-type hosts was able to transmit the increased propensity to develop severe colitis. ACE2-dependent changes in epithelial immunity and the gut microbiota can be directly regulated by the dietary amino acid tryptophan. Our results identify ACE2 as a key regulator of dietary amino acid homeostasis, innate immunity, gut microbial ecology, and transmissible susceptibility to colitis. These results provide a molecular explanation for how amino acid malnutrition can cause intestinal inflammation and diarrhoea.
Indexed as
Identifiers
What OpenQuestion holds
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.