Cited by 1,271Gut microbiota and healthInflammatory Bowel DiseaseAnimal Nutrition and Physiology

The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.

ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation

Open access

Hashimoto, Tatsuo, Perlot, Thomas, Rehman, Ateequr, Trichereau, Jean, Ishiguro, Hiroaki, Paolino, Magdalena, Sigl, Verena, Hanada, Toshikatsu, Hanada, Reiko, Lipinski, Simone, Wild, Birgit, Camargo, Simone M. R., Singer, Dustin, Richter, Andreas, Kuba, Keiji, Fukamizu, Akiyoshi, Schreiber, Stefan, Clevers, Hans, Verrey, Francois, Rosenstiel, Philip, Penninger, Josef M.·2012·Nature

DOI 10.1038/nature11228PMC PMC7095315

Open this paper in CoChat — free account Open PDF

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1038/nature11228

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Introducing mothur: Open-Source, Platform-Independent, Community-Supported Software for Describing and Comparing Microbial Communities
Schloss, P. D., Westcott, S. L., Ryabin, T., Hall, J. R., Hartmann, M., Hollister, E. B., Lesniewski, R. A., Oakley, B. B., Parks, D. H., Robinson, C. J., et al. (2009) · Applied and Environmental Microbiology · doi:10.1128/aem.01541-09 · Cited by 21,481
Naive Bayesian Classifier for Rapid Assignment of rRNA Sequences into the New Bacterial Taxonomy
Wang, Q., Garrity, G. M., Tiedje, J. M., & Cole, J. R. (2007) · Applied and Environmental Microbiology · doi:10.1128/aem.00062-07 · Cited by 20,145
PAST: PALEONTOLOGICAL STATISTICAL SOFTWARE PACKAGE FOR EDUCATION AND DATA ANALYSIS
Hammer, Ø., Harper, D. A. T., & Ryan, P. D. (2001) · Palaeontologia Electronica · Cited by 17,871
UCHIME improves sensitivity and speed of chimera detection
Edgar, R. C., Haas, B. J., Clemente, J. C., Quince, C., & Knight, R. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr381 · Cited by 15,114
Non‐parametric multivariate analyses of changes in community structure
Clarke, K. R. (1993) · Australian Journal of Ecology · doi:10.1111/j.1442-9993.1993.tb00438.x · Cited by 14,449
SILVA: a comprehensive online resource for quality checked and aligned ribosomal RNA sequence data compatible with ARB
Pruesse, E., Quast, C., Knittel, K., Fuchs, B. M., Ludwig, W., Peplies, J., & Glöckner, F. O. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm864 · Cited by 6,682
A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury
Kuba, K., Imai, Y., Rao, S., Gao, H., Guo, F., Guan, B., Huan, Y., Yang, P., Zhang, Y., Deng, W., et al. (2005) · Nature Medicine · doi:10.1038/nm1267 · Cited by 3,445
Self-citation
A Novel Angiotensin-Converting Enzyme–Related Carboxypeptidase (ACE2) Converts Angiotensin I to Angiotensin 1-9
Donoghue, M., Hsieh, F., Baronas, E., Godbout, K., Gosselin, M., Stagliano, N., Donovan, M., Woolf, B., Robison, K., Jeyaseelan, R., et al. (2000) · Circulation Research · doi:10.1161/01.res.87.5.e1 · Cited by 2,485
Angiotensin-converting enzyme 2 protects from severe acute lung failure
Imai, Y., Kuba, K., Rao, S., Huan, Y., Guo, F., Guan, B., Yang, P., Sarao, R., Wada, T., Leong-Poi, H., et al. (2005) · Nature · doi:10.1038/nature03712 · Cited by 2,453
Self-citation
A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice
Okayasu, I., Hatakeyama, S., Yamada, M., Ohkusa, T., Inagaki, Y., & NAKAYA, R. (1990) · Gastroenterology · doi:10.1016/0016-5085(90)90290-h · Cited by 2,408

Flagged first, then by citations

Show all 44 references

Sorted by citations

Items 901–998 of 998

Gordian Knot: Gastrointestinal lesions caused by three highly pathogenic coronaviruses from SARS-CoV and MERS-CoV to SARS-CoV-2
Meng, X. L., Lou, Q., Yang, W.-Y., Chen, R., Xu, W.-H., Yang, Y., Zhang, L., Xu, T., & Xiang, H. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173659 · Cited by 7
Expression and Possible Significance of ACE2 in the Human Liver, Esophagus, Stomach, and Colon
Liu, Y., Wu, Q., Wan, D., He, H., Lin, H., Wang, K., Que, G., Wang, Y., Chen, Y., Tang, X., et al. (2021) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2021/6949902 · Cited by 7
Retracted
Risk, Course, and Effect of SARS-CoV-2 Infection in Children and Adults with Chronic Inflammatory Bowel Diseases
Corrias, A., Cortes, G. M., Bardanzellu, F., Melis, A., Fanos, V., & Marcialis, M. A. (2021) · Children · doi:10.3390/children8090753 · Cited by 7
Transmission of severe acute respiratory syndrome coronavirus 2 via fecal-oral: Current knowledge
da Silva, F. A. F., de Brito, B. B., Santos, M. L. C., Marques, H. S., Júnior, R. T. D. S., de Carvalho, L. S., Cruz, S. D. S., Rocha, G. R., Santos, G. L. C., de Souza, K. C., et al. (2021) · World Journal of Clinical Cases · doi:10.12998/wjcc.v9.i28.8280 · Cited by 7
Evaluation of botanicals as potential COVID-19 symptoms terminator
Çalışkan, U. K., & KARAKUŞ, M. M. (2021) · World Journal of Gastroenterology · doi:10.3748/wjg.v27.i39.6551 · Cited by 7
Importance of gut microbiome regulation for the prevention and recovery process after SARS‑CoV‑2 respiratory viral infection (Review)
Najmi, N., Megantara, I., Andriani, L., Goenawan, H., & Lesmana, R. (2022) · Biomedical Reports · doi:10.3892/br.2022.1508 · Cited by 8
Wound Healing Is a First Response in a Cancerous Pathway: Hyperplasia Developments to 4n Cell Cycling in Dysplasia Linked to Rb-Inactivation
Walen, K. H. (2015) · Journal of Cancer Therapy · doi:10.4236/jct.2015.610099 · Cited by 8
Nutritional influences of overfeeding on experimental outcomes in laboratory mice: consequences for gut microbiota and other functional studies
Bischoff, S. C., & Volynets, V. (2016) · International Journal of Medical Microbiology · doi:10.1016/j.ijmm.2016.05.018 · Cited by 7
Adjustment of triple shellac coating for precise release of bioactive substances with different physico-chemical properties in the ileocolonic region
Theismann, E., Keppler, J. K., Knipp, J.-R., Fangmann, D., Appel, E., Gorb, S. N., Waetzig, G. H., Schreiber, S., Laudes, M., & Schwarz, K. (2019) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2019.04.039 · Cited by 9
Self-citation
Undernutrition—Looking Within for Answers
Relman, D. A. (2013) · Science · doi:10.1126/science.1234723 · Cited by 7
Gastrointestinal disturbance and effect of fecal microbiota transplantation in discharged COVID-19 patientsPreprint
Deng, Z., Liu, F., Ye, S., Zhu, X., He, X., Wang, S., Li, Y., Jiang, L., Wang, J., Lin, Y., et al. (2020) · Research Square · doi:10.21203/rs.3.rs-54135/v1 · Cited by 7
Systems biology and microbiome innovations for personalized diabetic retinopathy management
Aminian-Dehkordi, J., Montazeri, F., Tamadon, A., & Mofrad, M. R. K. (2025) · npj Systems Biology and Applications · doi:10.1038/s41540-025-00607-w · Cited by 6
SARS-CoV-2 infection-associated detrimental effects on the various human organs
Haleema, N., Mahnoor, A., Saeed, U., Piracha, Z. Z., Rafia, T., Noor-, U.-A., Farrah, M., Rida, F. E., & Uppal, R. (2021) · International Journal of Clinical Virology · doi:10.29328/journal.ijcv.1001038 · Cited by 6
Increased ACE2 and TMPRSS2 expression in ulcerative colitis
Hamamoto, Y., Kawamura, M., Uchida, H., Hiramatsu, K., Katori, C., Asai, H., Egawa, S., & Yoshida, K. (2024) · Pathology - Research and Practice · doi:10.1016/j.prp.2024.155108 · Cited by 6
ACE2 Knockout Mice Are Resistant to High-Fat Diet-Induced Obesity in an Age-Dependent Manner
Nunes-Souza, V., Alenina, N. V., Qadri, F., Mosienko, V., Santos, R. A. S., Bäder, M., & Rabelo, L. A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179515 · Cited by 6
Bioinformatic characterization of ENPEP, the gene encoding a potential cofactor for SARS-CoV-2 infection
Arppo, A., Barker, H. R., & Parkkila, S. (2024) · PLoS ONE · doi:10.1371/journal.pone.0307731 · Cited by 6
Dietary tryptophan depletion alters the faecal bacterial community structure of compulsive drinker rats in schedule-induced polydipsia
Merchán, A., Pérez-Fernández, C., López, M. J., Moreno, J., Moreno, M., Sánchez-Santed, F., & Flores, P. (2021) · Physiology & Behavior · doi:10.1016/j.physbeh.2021.113356 · Cited by 6
Global occurrence of SARS-CoV-2 in environmental aquatic matrices and its implications for sanitation and vulnerabilities in Brazil and developing countries
Castro, G. B., Bernegossi, A. C., Sousa, B. J. D. O., Silva, M. R. D. L. E., Silva, F. R. D., Freitas, B. L. S., Ogura, A. P., & Corbi, J. J. (2021) · International Journal of Environmental Health Research · doi:10.1080/09603123.2021.1949437 · Cited by 6
Pharmacotherapy Based on ACE2 Targeting and COVID-19 Infection
Vitiello, A., & Ferrara, F. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126644 · Cited by 6
L-Tryptophan Differentially Regulated Glucose and Amino Acid Transporters in the Small Intestine of Rat Challenged with Lipopolysaccharide
Wang, B., Jiang, L., Wu, Z., & Dai, Z. (2022) · Animals · doi:10.3390/ani12213045 · Cited by 6
Association of Dietary Niacin Intake with Diabetes in Adults in the United States
Liu, C., Duan, W., & Xu, W. (2023) · Experimental and Clinical Endocrinology & Diabetes · doi:10.1055/a-2038-0476 · Cited by 6
Design and Synthesis of Imine Derivatives: DFT, Molecular Docking and Antimicrobial Analysis
Kumari, B., & Ahmad, K. (2023) · ChemistrySelect · doi:10.1002/slct.202300734 · Cited by 6
Characterization of the angiotensin-converting enzyme 2 (ACE2), the main receptor for the SARS-CoV-2 virus.
Jami, G., Ataee, M., Esmaeili, V., Chamani, S., Rezaei, A., & Naghizadeh, A. (2023) · PubMed Central · Cited by 6
Metabolomic and Transcriptomic Correlative Analyses in Germ-Free Mice Link Lacticaseibacillus rhamnosus GG-Associated Metabolites to Host Intestinal Fatty Acid Metabolism and β-Oxidation
Suntornsaratoon, P., Ferraris, R. P., Ambat, J., Antonio, J. M., Flores, J., Jones, A., Su, X., Gao, N., & Li, W. V. (2024) · Laboratory Investigation · doi:10.1016/j.labinv.2024.100330 · Cited by 6
Exploring the Mystery of Angiotensin-Converting Enzyme II (ACE2) in the Battle against SARS-CoV-2
Sharma, D., Sharma, J., & Singh, A. (2021) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1155/2021/9939929 · Cited by 6
Double Deletion of Angiotensin II Type 2 and Mas Receptors Accelerates Aging‐Related Muscle Weakness in Male Mice
Takeshita, H., Yamamoto, K. I., Mogi, M., Wang, Y., Nozato, Y., Fujimoto, T., Yokoyama, S., Hongyo, K., Nakagami, F., Akasaka, H., et al. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.021030 · Cited by 6
Gastrointestinal manifestations and possible mechanisms of COVID ‐19 in different periods
Zhang, M. M., Chen, L. N., & Qian, J. (2021) · Journal of Digestive Diseases · doi:10.1111/1751-2980.13065 · Cited by 6
Relation of ACE2 with co-morbidity factors in SARS-CoV-2 pathogenicity
Santra, D., Banerjee, A., De, S. K., Thatoi, H., & Maiti, S. (2023) · Comparative Clinical Pathology · doi:10.1007/s00580-023-03434-9 · Cited by 6
Nutrients, herbal bioactive derivatives and commensal microbiota as tools to lower the risk of SARS-CoV-2 infection
Romani, A., Sergi, D., Zauli, E., Voltan, R., Lodi, G., Vaccarezza, M., Caruso, L., Previati, M., & Zauli, G. (2023) · Frontiers in Nutrition · doi:10.3389/fnut.2023.1152254 · Cited by 6
A systematic review of the prevalence of persistent gastrointestinal symptoms and incidence of new gastrointestinal illness after acute SARS-CoV-2 infectionPreprint
Hawkings, M. J., Vaselli, N. M., Charalampopoulos, D., Brierley, L., Elliot, A. J., Buchan, I. E., & Hungerford, D. (2023) · medRxiv · doi:10.1101/2023.04.26.23289142 · Cited by 6
A metabolic constraint in the kynurenine pathway drives mucosal inflammation in IBDPreprint
Welz, L., Harris, D. M. M., Kim, N., Alsaadi, A. I., Wu, Q., Oumari, M., Taubenheim, J., Volk, V., Credido, G., Koncina, E., et al. (2024) · medRxiv · doi:10.1101/2024.08.08.24311598 · Cited by 6
Self-citation
Untargeted metabolomics uncovers metabolic dysregulation and tissue sensitivity in ACE2 knockout mice
Zhao, L., Yang, W., Ji, W., Pan, Q., Yang, J., & Cao, X. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e27472 · Cited by 5
An overview of gastrointestinal diseases in patients with COVID-19: A narrative review
Lin, C.-Y., Su, S., & Chen, K. (2022) · Medicine · doi:10.1097/md.0000000000030297 · Cited by 5
What do we know about the renin angiotensin system and inflammatory bowel disease?
Lo, S. W., Segal, J. P., Lubel, J. S., & Garg, M. (2022) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2022.2157261 · Cited by 5
SARS-CoV-2 pathogenesis in the gastrointestinal tract mediated by Spike-induced intestinal inflammation
Li, Z., He, J., Yin, Y., Tang, L., Liu, Y., Monteiro, O., & Zeng, F. (2023) · Precision Clinical Medicine · doi:10.1093/pcmedi/pbad034 · Cited by 5
Multiomics analysis reveals the potential mechanism of high‐fat diet in dextran sulfate sodium‐induced colitis mice model
Zhao, Y., Chen, Z., Dong, R., Liu, Y., Zhang, Y., Guo, Y., Yu, M., Li, X., & Wang, J. (2024) · Food Science & Nutrition · doi:10.1002/fsn3.4426 · Cited by 6
Effects of adding niacinamide to diets with normal and low protein levels on the immunity, antioxidant, and intestinal microbiota in growing-finishing pigs
Lan, T., Cai, M., Wang, S., Lü, Y., Tang, Z., Tang, Q., Gao, J., Xu, Y., Peng, X., & Sun, Z. (2024) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2024.109809 · Cited by 5
Long-Term Prospects of Extrapulmonary Persistence of SARS-COV-2 Coronavirus
", Литвинов, А. С., LLP", M., L., U., Savin, A. V., & Kukhtina, A. A. (2020) · Medicina · doi:10.29234/2308-9113-2020-8-1-51-73 · Cited by 5
A child infected with severe acute respiratory syndrome coronavirus 2 presenting with diarrhea without fever and cough
Liu, Q., Zhang, Y., & Long, Y. (2020) · Medicine · doi:10.1097/md.0000000000021427 · Cited by 5
Angiotensin Converting Enzyme-2 (ACE-2) role in disease and future in research
Abdul‐Hafez, A., Mohamed, T., & Uhal, B. D. (2021) · Journal of Lung Pulmonary & Respiratory Research · doi:10.15406/jlprr.2021.08.00251 · Cited by 5
Susceptibility to Metabolic Diseases in COVID-19: To be or Not to be an Issue
Kaviani, M., Keshtkar, S., Soleimanian, S., Sarvestani, F. S., Azarpira, N., & Pakbaz, S. (2022) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2022.803314 · Cited by 6
Simian Immunodeficiency Virus Infection Mediated Changes in Jejunum and Peripheral SARS-CoV-2 Receptor ACE2 and Associated Proteins or Genes in Rhesus Macaques
Boby, N., Cao, X., Williams, K. M., Gadila, S. K. G., Shroyer, M. N., Didier, P. J., Srivastav, S., Das, A., Baker, K. C., Sha, Q., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.835686 · Cited by 5
Overexpression of angiotensin-converting enzyme 2 contributes to the amelioration of Streptococcus uberis-induced inflammatory injury in mammary epithelial cells
Yan, S., Xie, N., Aleem, M. T., Ji, X., Zhang, C., Cao, X., & Zhang, Y. (2022) · Veterinary Microbiology · doi:10.1016/j.vetmic.2022.109398 · Cited by 5
Features of the intestine conditions at patients with a new coronavirus infection
Topchiy, T. B., Ardatskaya, M. D., Butorova, L. I., Maslovskii, L. V., & Minushkin, O. N. (2022) · Terapevticheskii arkhiv · doi:10.26442/00403660.2022.07.201768 · Cited by 5
A case of massive refractory diarrhea in a patient with COVID ‐19
Shimizu, K., Hirata, H., Tokuhira, N., Ueda, A., Motooka, D., Nakamura, S., & Ogura, H. (2022) · Acute Medicine & Surgery · doi:10.1002/ams2.793 · Cited by 5
Multiomics profiling of the impact of an angiotensin (1–7)-expressing probiotic combined with exercise training in aged male rats
Baptista, L. C. P., Zumbro, E. L., Graham, Z., Hernandez, A. R., Buchanan, T., Sun, Y., Yang, Y., Banerjee, A., Verma, A., Li, Q., et al. (2023) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00508.2022 · Cited by 5
SARS-CoV-2 Variant-Specific Gastrointestinal Symptoms of COVID-19: 2023 Update
Slabakova, Y., Gerasoudis, S., Miteva, D., Peshevska-Sekulovska, M., Batselova, H., Snegarova, V., Vasilev, G., Vasilev, G., Sekulovski, M., Lazova, S., et al. (2023) · Gastroenterology Insights · doi:10.3390/gastroent14040032 · Cited by 5
Manifestaciones gastrointestinales de pacientes infectados con el nuevo Coronavirus SARS-CoV-2
Luis Antonio Díaz, P., & Espino, A. (2020) · Revista Gastroenterología Latinoamericana · doi:10.46613/gastrolat202001-05 · Cited by 5
Alimentary system is directly attacked by SARS‐COV‐2 and further prevents immune dysregulation caused by COVID‐19
Chen, S., Zhou, J., Ou, X., Cheng, W., Qin, Y., Guo, Y., & Jiang, Y. (2020) · International Journal of Clinical Practice · doi:10.1111/ijcp.13893 · Cited by 5
COVID-19 and the small intestine
Дмитривич, Б. С., Васильевна, Б. Е., Владимировна, Б. С., Романовна, Д. С., & Parfenov, A. I. (2021) · Terapevticheskii arkhiv · doi:10.26442/00403660.2021.03.200662 · Cited by 5
The Impact of COVID-19 in Gastroenterology and Hepatology
Ramkissoon, R. A., & Wang, X. (2021) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000001600 · Cited by 6
Ulcerative colitis after SARS-CoV-2 infection
Kartsoli, S., Vrakas, S., Kalomoiris, D., Manoloudaki, K., & Xourgias, V. (2022) · Autopsy and Case Reports · doi:10.4322/acr.2021.378 · Cited by 5
Inflammatory Bowel Disease
Young, W., Jester, T., Stoll, M. L., & Ízcue, A. (2018) · Springer eBooks · doi:10.1007/978-3-319-79026-8_19 · Cited by 5
Angiotensin Converting Enzyme 2 in Coronavirus Disease (COVID-19): Evidence from Bioinformatics AnalysisPreprint
Yang, X., Zhao, H., Li, Y., & Zhang, P. (2020) · Preprints.org · doi:10.20944/preprints202004.0466.v1 · Cited by 5
Amino acid transporter B 0 AT1 influence on ADAM17 interactions with SARS-CoV-2 receptor ACE2 putatively expressed in intestine, kidney, and cardiomyocytesPreprint
Andring, J. T., McKENNA, R. V., & Stevens, B. R. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.10.30.361873 · Cited by 5
Role of microbiota in pain: From bench to bedside
Ren, H., Cao, B., Xu, Q., Zhao, R., Li, H., & Wei, B. (2025) · iMetaOmics. · doi:10.1002/imo2.58 · Cited by 7
Genetically Predicted Higher Levels of Caffeic Acid Are Protective Against Ulcerative Colitis: A Comprehensive Metabolome Analysis
Naito, T., Osaka, R., Kakuta, Y., Kawai, Y., Khor, S., Umeno, J., Tokunaga, K., Ishibashi-Ueda, H., Tomita, T., Noguchi, M., et al. (2024) · Inflammatory Bowel Diseases · doi:10.1093/ibd/izae143 · Cited by 4
Sarcopenic Obesity: The Underlying Molecular Pathophysiology and Prospect Therapies
Meiliana, A., Dewi, N. M., Defi, I. R., Rosdianto, A. M., Qiantori, A. A., & Wijaya, A. (2024) · The Indonesian Biomedical Journal · doi:10.18585/inabj.v16i4.3176 · Cited by 4
Human microbiome in post-acute COVID-19 syndrome (PACS)
Fallah, A., Sedighian, H., Kachuei, R., & Fooladi, A. A. I. (2024) · Current Research in Microbial Sciences · doi:10.1016/j.crmicr.2024.100324 · Cited by 6
ACE2, From the Kidney to SARS-CoV-2: Donald Seldin Award Lecture 2023
BATLLE, D. C., Hassler, L., & Wysocki, J. A. (2024) · Hypertension · doi:10.1161/hypertensionaha.124.22064 · Cited by 4
The Triad of COVID-19 in Children: Acute COVID-19, Multisystem Inflammatory Syndrome, and Long COVID—Part I
Gupte, A., Sriram, S., Gunasekaran, V., Chaudhari, K., & Kamat, D. (2024) · Pediatric Annals · doi:10.3928/19382359-20241003-03 · Cited by 4
Senolytic Treatment Alleviates Corneal Allograft Rejection Through Upregulation of Angiotensin-Converting Enzyme 2 (ACE2)
Chi, H., Ma, L., Zeng, F., Wang, X., Peng, P., Bai, X., Zhang, T., Yin, W., Yu, Y., Yang, L., et al. (2025) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.66.2.15 · Cited by 4
The intestine and cardiovascular disease
Delk, S. C., Reddy, S. T., & Fogelman, A. M. (2025) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000001001 · Cited by 4
ACE2 Activation in Intestinal Epithelial Cells Prevents Radiation-Induced Intestinal Injury
Song, X., Peng, R., Chen, Z., Dai, J., Zhang, Y., Dong, S., Wang, S., Yu, H., Jiang, Q., Li, W., et al. (2026) · Antioxidants and Redox Signaling · doi:10.1177/15230864261428120 · Cited by 4
Muscle mass, muscle strength and the renin-angiotensin system
Takeshita, H., Yamamoto, K. I., Mogi, M., & Rakugi, H. (2024) · Clinical Science · doi:10.1042/cs20220501 · Cited by 4
Mechanisms of action and adaptive responses to diclofenac and meloxicam during the early life stages of Oryzias melastigma
Liang, C., Chen, Y., Ling, Y., Li, P., Liu, J., Li, X., Xu, Y., & Liu, Z. (2025) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2025.178927 · Cited by 4
Effects of 3-indoleacrylic acid on alleviating lipopolysaccharide-induced liver inflammatory damage in laying hens
Zhang, Q., Wang, Y., Wang, Y., Yuan, J., Wang, Y., Zeng, Y., Zhang, H., Yang, H., Ma, Q., Shi, D., et al. (2025) · Poultry Science · doi:10.1016/j.psj.2025.105307 · Cited by 5
Methodologies for bioactivity assay: animal study
Xu, F., & de Mejı́a, E. G. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821389-6.00022-4 · Cited by 4
Does COVID-19 Affect Adult Neurogenesis? A Neurochemical Perspective
Saikarthik, J., Saraswathi, I., & Al-Atram, A. A. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.101179 · Cited by 4
Intestinal viral infections of nSARS‐CoV2 in the Indian community: Risk of virus spread in India
Maan, H. S., Chaurasia, D., Kapoor, G. T., Dave, L., Siddiqui, A., Pal, S., Singh, H. O., Biswas, D., & Chowdhary, R. (2021) · Journal of Medical Virology · doi:10.1002/jmv.27480 · Cited by 4
The COVID-19 "Bad Tryp" Syndrome: NAD/NADH+, Tryptophan Phenylalanine Metabolism and Thermogenesis like Hecatomb - The Hypothesis of Pathophysiology Based on a Compared COVID-19 and Yellow Fever Inflammatory Skeleton
Zanella, L. G. F. D. A. B. D. (2022) · Journal of Infectious Diseases and Epidemiology · doi:10.23937/2474-3658/1510243 · Cited by 4
ACE2 Receptor: A Potential Pharmacological Target in COVID-19
Zhu, Y., Zhang, S., Wang, Z., Wang, Z., & Zhu, S. (2023) · Current Protein and Peptide Science · doi:10.2174/1389203724666230816092518 · Cited by 4
COVID-19 and Nutrition: Focus on Chronic Kidney Disease
Mafra, D., Kemp, J. A., Cardozo, L., Borges, N. A., Nerbass, F. B., Alvarenga, L., & Kalantar‐Zadeh, K. (2023) · Journal of Renal Nutrition · doi:10.1053/j.jrn.2023.01.004 · Cited by 4
Group B Vitamins: From Homeostasis to Pathogenesis and Treatment of Multiple Sclerosis
Abdurasulova, I. N., & Dmitriev, A. V. (2023) · Успехи физиологических наук · doi:10.31857/s0301179823010034 · Cited by 4
SIR+ models: accounting for interaction-dependent disease susceptibility in the planning of public health interventions
Martignoni, M. M., Raulo, A., Linkovski, O., & Kolodny, O. (2024) · Scientific Reports · doi:10.1038/s41598-024-63008-9 · Cited by 3
Niacin deficiency and cutaneous immunity
Ikenouchi, A., & Sugita, K. (2015) · Japanese Journal of Clinical Immunology · doi:10.2177/jsci.38.37 · Cited by 4
Molekulare Darmmikrobiomdiagnostik
Rosenstiel, P. C. (2017) · Die Gastroenterologie · doi:10.1007/s11377-016-0129-x · Cited by 4
Self-citation
Skeletal Muscle System
Acuña, M. J., Brandan, E., & Motta‐Santos, D. (2019) · Springer eBooks · doi:10.1007/978-3-030-22696-1_11 · Cited by 4
[The clinical importance of keratin 18 in breast cancer].
Schaller, G., Fuchs, I., Ebert, A. D., Gstettenbauer, M., Herbst, H., & Lengyel, E. R. (1999) · PubMed · Cited by 4
Gut mycobiota alterations in patients with COVID-19 and H1N1 and associations with immune and gastrointestinal symptomsPreprint
Lv, L., Gu, S., Jiang, H., Ren, Y., Chen, Y., chen, Y., Luo, R., Huang, C., Lu, H., Zheng, B., et al. (2020) · doi:10.21203/rs.3.rs-33152/v1 · Cited by 4
Evaluation of Tryptophan and Its Metabolites in Predicting Disease Activation in Inflammatory Bowel Disease
Karataş, A., Karakan, T., Ekmen, N., Ünsal, Y., Türkeş, G. F., Gülbahar, Ö., Cindoruk, M., Ergin, M., Kılıç, G., İbi̇ş, M., et al. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14031016 · Cited by 3
Underweight was associated with increased mortality in adults with latent tuberculosis infection
Liao, J.-Z., Liu, X., & Qi, M. (2025) · Frontiers in Nutrition · doi:10.3389/fnut.2025.1607507 · Cited by 3
Angiotensin‑converting enzyme 2 expression in human tumors: Implications for prognosis and therapy (Review)
Rizopoulos, T., & Assimakopoulou, M. (2025) · Oncology Reports · doi:10.3892/or.2025.8934 · Cited by 3
Global surge of human metapneumovirus (hMPV) and its interactions with microbiome to disease severity
Meher, M. M., & Afrin, M. (2025) · Journal of Infection and Public Health · doi:10.1016/j.jiph.2025.103024 · Cited by 4
ACE2: Friend or Foe in Post-COVID-19 Neurodegeneration?
Kononova, S. V., Бобкова, Н. В., Полтавцева, Р. А., Leonov, S. V., & Sukhikh, G. T. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262211104 · Cited by 5
Plant-derived angiotensin-converting enzyme regulatory peptides: Potential sources, mechanisms and applications
Huang, Z., Shao, Q., Li, P., Wang, J., Cai, M., Ma, J., Yang, K., Bu, T., & Yang, H. (2025) · Food Chemistry · doi:10.1016/j.foodchem.2025.147603 · Cited by 3
Post‐Coronavirus Disease ( COVID )‐19 Irritable Bowel Syndrome: What We've Learned So Far
Ghoshal, U. C., Singh, R., & Goenka, M. K. (2026) · Neurogastroenterology & Motility · doi:10.1111/nmo.70250 · Cited by 3
VRAC coordinates the trade-off between nutrient absorption and antimicrobial defense in enterocytes against inflammation
Yi, X., Zhang, S., Gu, X., Wu, X., Ma, L., Xu, Y., Lv, S., Huang, J., Zhi, Y., Cao, Y., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-69963-3 · Cited by 3
Multi-Organ System Dysfunction in Covid-19 – A Review
Bhadoria, P., & Rathore, H. (2021) · Journal of Evolution of Medical and Dental Sciences · doi:10.14260/jemds/2021/135 · Cited by 3
Inequality: The Dangers of Meat Haves and Have-Nots in a Nicotinamide-Adenine-Dinucleotide World
Williams, A. C., & Hill, L. J. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.96748 · Cited by 4
Gastrointestinal symptoms in 609 Japanese patients with COVID-19: a single-center retrospective study
Kuriki, S., Nishida, T., Chang, L.-S., Hosokawa, K., Fujii, Y., Osugi, N., Nakamatsu, D., Matsumoto, K., Yamamoto, M., Morimura, O., et al. (2023) · Scandinavian Journal of Gastroenterology · doi:10.1080/00365521.2023.2204387 · Cited by 3
The causal relationship between gut microbiota and COVID-19: A two-sample Mendelian randomization analysis
Tian, S., & Huang, W. (2024) · Medicine · doi:10.1097/md.0000000000036493 · Cited by 3
The association of three vaccination doses with reduced gastrointestinal symptoms after severe acute respiratory syndrome coronavirus 2 infections in patients with inflammatory bowel disease
Hong, Y., Che, T., Shen, X., Chen, J., Wang, K., Zhao, L., Gao, W., Zhang, Y., Ge, W., Gu, Y., et al. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1377926 · Cited by 3
Probiotic Chocolate Containing Lactobacillus plantarum Dad‐13 Alters the Gut Microbiota Composition of Undernourished Children in Lombok: A Randomized Double‐Blind Trial
Rahayu, E. S., Yoga, W. K., Komalasari, H., Mariyatun, M., Yuda, W. A., Manurung, N. E. P., Hasan, P. N., Suharman, S., Pamungkaningtyas, F. H., Nurfiana, D. A., et al. (2024) · International Journal of Food Science · doi:10.1155/2024/9493797 · Cited by 3
Low Protein Diet Exacerbates Experimental Mouse Models of Colitis through Epithelial Autonomous and Nonautonomous Mechanisms
Solanki, S. A., Taranto, J., Rebernick, R. J., Castillo, C., Ponnusamy, V., Sykes, M. M., Leiser, S. F., Lee, J. H., Schmidt, T. M., & Shah, Y. M. (2025) · Journal of Nutrition · doi:10.1016/j.tjnut.2025.03.031 · Cited by 3
Feeding the cattle on the Temora common: The public atonement and death of the Punjabi hawker Gujjar Singh in 1902
Spennemann, D. H. R. (2020) · Sikh Formations · doi:10.1080/17448727.2020.1804198 · Cited by 3
Public Database-Driven Insights Into Aging Stress-Associated Defective Gut Barrier With Low SARS-CoV-2 Receptors
Moon, Y. (2020) · Frontiers in Medicine · doi:10.3389/fmed.2020.606991 · Cited by 3
The Significance of Angiotensin-Converting Enzyme-2 (ACE2) in SARSCov- 2 Infection and COVID-19
Restini, C. B. A., Belavek, T., Bernal, R., Ibrahim, V., Irwin, K., Kim, M., & Merlo, C. (2020) · Coronaviruses · doi:10.2174/2666796701999201218141035 · Cited by 3

Authors: Hashimoto, T., Perlot, T., Rehman, A., Trichereau, J., Ishiguro, H., Paolino, M., Sigl, V., Hanada, T., Hanada, R., Lipinski, S., Wild, B., Camargo, S. M. R., Singer, D., Richter, A., Kuba, K., Fukamizu, A., Schreiber, S., Clevers, H., Verrey, F., Rosenstiel, P., & Penninger, J. M.
Affiliations: Institute of Molecular Biotechnology (AT)
University Medical Center Freiburg (DE)
Yokohama City University (JP)
Christian-Albrechts-Universität zu Kiel (DE)
University of Vienna (AT)
University of Zurich (CH)
Akita University (JP)
University of Tsukuba (JP)
Royal Netherlands Academy of Arts and Sciences (NL)
Corresponding author: Rosenstiel, Philip
Penninger, Josef M.
ORCID: Hashimoto, Tatsuo
Rehman, Ateequr
Paolino, Magdalena
Sigl, Verena
Hanada, Toshikatsu
Hanada, Reiko
Lipinski, Simone
Wild, Birgit
Camargo, Simone M. R.
Singer, Dustin
Richter, Andreas
Kuba, Keiji
Fukamizu, Akiyoshi
Schreiber, Stefan
Clevers, Hans
Rosenstiel, Philip
Penninger, Josef M.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2012-07-25
Volume: 487
Issue: 7408
Pages: 477-481
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature11228
PMC: PMC7095315
OpenAlex: W2017614891
Cited by: 1,271
References: 44
Citations by year: 2026: 35 · 2025: 70 · 2024: 96 · 2023: 135 · 2022: 180 · 2021: 229 · 2020: 259 · 2019: 39 · 2018: 44 · 2017: 31 · 2016: 35 · 2015: 28 · 2014: 32 · 2013: 46 · 2012: 11
FWCI: 15.03
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
Data Archiving and Networked Services (DANS) (submittedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
Zurich Open Repository and Archive (University of Zurich)
Funders: European Respiratory Society
Deutsche Forschungsgemeinschaft (SFB 877, SPP 1399)
Österreichischen Akademie der Wissenschaften
Bundesministerium für Bildung und Forschung
Exzellenzclusters Entzündungsforschung
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Nutrition and Physiology
Keywords: ACE2, angiotensin-converting enzyme 2, protein malnutrition, colitis, intestinal inflammation, gut microbiota, tryptophan metabolism, nicotinamide, renin-angiotensin system, innate immunity, antimicrobial peptides, microbial ecology, epithelial damage, germ-free mice, microbiota transplantation
MeSH terms: Angiotensin-Converting Enzyme 2, Animals, Colitis, Diarrhea, Dietary Proteins, Female, Germ-Free Life, Homeostasis, Immunity, Innate, Intestines, Peptidyl-Dipeptidase A, Male, Models, Biological, Niacinamide, Renin-Angiotensin System, Trinitrobenzenesulfonic Acid, Tryptophan, Dextran Sulfate, Gene Deletion, Genetic Predisposition to Disease, Malnutrition, Mice, Metagenome, Biocatalysis, TOR Serine-Threonine Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks