ACE2 - From the renin-angiotensin system to gut microbiota and malnutrition

Microbes and Infection

Volumn 15, Issue 13, 2013, Pages 866-873

  Perlot, Thomas ^a   Penninger, Josef M ^a  

^a ERICH SCHMID INSTITUTE OF MATERIALS SCIENCE   (Austria)

Author keywords

Amino acid transport; Malnutrition; Microbiota; Renin angiotensin system; Virus receptor

Indexed keywords

AMINO ACID TRANSPORTER; ANGIOTENSIN CONVERTING ENZYME 2; NICOTINAMIDE; VIRUS RECEPTOR;

ACUTE LUNG INJURY; CLINICAL TRIAL (TOPIC); DIARRHEA; ENTERITIS; HARTNUP DISEASE; HUMAN; HYPERTENSION; INNATE IMMUNITY; INTESTINE EPITHELIUM; INTESTINE FLORA; KIDNEY DISEASE; KWASHIORKOR; MALNUTRITION; NONHUMAN; PELLAGRA; PRIORITY JOURNAL; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; SARS CORONAVIRUS; SHORT SURVEY; VASOCONSTRICTION;

SARS CORONAVIRUS;

AMINO ACID TRANSPORT; MALNUTRITION; MICROBIOTA; RENIN-ANGIOTENSIN SYSTEM; VIRUS RECEPTOR;

AMINO ACID TRANSPORT SYSTEMS, NEUTRAL; GASTROINTESTINAL TRACT; HUMANS; IMMUNITY, INNATE; IMMUNOLOGIC FACTORS; MALNUTRITION; PEPTIDYL-DIPEPTIDASE A; RECEPTORS, VIRUS; RENIN-ANGIOTENSIN SYSTEM; SARS VIRUS;

EID: 84888061271     PISSN: 12864579     EISSN: 1769714X     Source Type: Journal    
DOI: 10.1016/j.micinf.2013.08.003     Document Type: Short Survey

References (81)

1. Lambert D.W., Clarke N.E., Turner A.J. Not just angiotensinases: new roles for the angiotensin-converting enzymes. Cell Mol. Life Sci. 2010, 67:89-98.
2. Kuba K., Imai Y., Penninger J.M. Multiple functions of angiotensin-converting enzyme 2 and its relevance in cardiovascular diseases. Circ. J. 2013, 77:301-308.
3. Kuba K., Imai Y., Ohto-Nakanishi T., Penninger J.M. Trilogy of ACE2: a peptidase in the renin-angiotensin system, a SARS receptor, and a partner for amino acid transporters. Pharmacol. Ther. 2010, 128:119-128.
4. Imai Y., Kuba K., Ohto-Nakanishi T., Penninger J.M. Angiotensin-converting enzyme 2 (ACE2) in disease pathogenesis. Circ. J. 2010, 74:405-410.
5. Carey R.M., Padia S.H. Angiotensin AT2 receptors: control of renal sodium excretion and blood pressure. Trends Endocrinol. Metab. 2008, 19:84-87.
6. Santos R.A., Simoes e Silva A.C., Maric C., Silva D.M., Machado R.P., de Buhr I., Heringer-Walther S., Pinheiro S.V., Lopes M.T., Bader M., Mendes E.P., Lemos V.S., Campagnole-Santos M.J., Schultheiss H.P., Speth R., Walther T. Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc. Natl. Acad. Sci. U S A 2003, 100:8258-8263.
7. Santos R.A., Ferreira A.J., Verano-Braga T., Bader M. Angiotensin-converting enzyme 2, angiotensin-(1-7) and Mas: new players of the renin-angiotensin system. J. Endocrinol. 2013, 216:R1-R17.
8. Gironacci M.M., Coba M.P., Pena C. Angiotensin-(1-7) binds at the type 1 angiotensin II receptors in rat renal cortex. Regul. Pept. 1999, 84:51-54.
9. Rowe B.P., Saylor D.L., Speth R.C., Absher D.R. Angiotensin-(1-7) binding at angiotensin II receptors in the rat brain. Regul. Pept. 1995, 56:139-146.
10. Passos-Silva D.G., Verano-Braga T., Santos R.A. Angiotensin-(1-7): beyond the cardio-renal actions. Clin. Sci. (Lond) 2013, 124:443-456.
11. Vickers C., Hales P., Kaushik V., Dick L., Gavin J., Tang J., Godbout K., Parsons T., Baronas E., Hsieh F., Acton S., Patane M., Nichols A., Tummino P. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J. Biol. Chem. 2002, 277:14838-14843.
12. Chandrasekaran B., Dar O., McDonagh T. The role of apelin in cardiovascular function and heart failure. Eur. J. Heart Fail 2008, 10:725-732.
13. Shi L., Mao C., Xu Z., Zhang L. Angiotensin-converting enzymes and drug discovery in cardiovascular diseases. Drug Discov. Today 2010, 15:332-341.
14. Tipnis S.R., Hooper N.M., Hyde R., Karran E., Christie G., Turner A.J. A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J. Biol. Chem. 2000, 275:33238-33243.
15. Donoghue M., Hsieh F., Baronas E., Godbout K., Gosselin M., Stagliano N., Donovan M., Woolf B., Robison K., Jeyaseelan R., Breitbart R.E., Acton S. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ. Res. 2000, 87:E1-E9.
16. Crackower M.A., Sarao R., Oudit G.Y., Yagil C., Kozieradzki I., Scanga S.E., Oliveira-dos-Santos A.J., da Costa J., Zhang L., Pei Y., Scholey J., Ferrario C.M., Manoukian A.S., Chappell M.C., Backx P.H., Yagil Y., Penninger J.M. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature 2002, 417:822-828.
17. Kuba K., Imai Y., Rao S., Gao H., Guo F., Guan B., Huan Y., Yang P., Zhang Y., Deng W., Bao L., Zhang B., Liu G., Wang Z., Chappell M., Liu Y., Zheng D., Leibbrandt A., Wada T., Slutsky A.S., Liu D., Qin C., Jiang C., Penninger J.M. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat. Med. 2005, 11:875-879.
18. 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., Singer D., Richter A., Kuba K., Fukamizu A., Schreiber S., Clevers H., Verrey F., Rosenstiel P., Penninger J.M. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature 2012, 487:477-481.
19. Paizis G., Tikellis C., Cooper M.E., Schembri J.M., Lew R.A., Smith A.I., Shaw T., Warner F.J., Zuilli A., Burrell L.M., Angus P.W. Chronic liver injury in rats and humans upregulates the novel enzyme angiotensin converting enzyme 2. Gut 2005, 54:1790-1796.
20. Zhang H., Wada J., Hida K., Tsuchiyama Y., Hiragushi K., Shikata K., Wang H., Lin S., Kanwar Y.S., Makino H. Collectrin, a collecting duct-specific transmembrane glycoprotein, is a novel homolog of ACE2 and is developmentally regulated in embryonic kidneys. J. Biol. Chem. 2001, 276:17132-17139.
21. Rella M., Elliot J.L., Revett T.J., Lanfear J., Phelan A., Jackson R.M., Turner A.J., Hooper N.M. Identification and characterisation of the angiotensin converting enzyme-3 (ACE3) gene: a novel mammalian homologue of ACE. BMC Genomics 2007, 8:194.
22. Inoue N., Kasahara T., Ikawa M., Okabe M. Identification and disruption of sperm-specific angiotensin converting enzyme-3 (ACE3) in mouse. PLoS One 2010, 5:e10301.
23. Towler P., Staker B., Prasad S.G., Menon S., Tang J., Parsons T., Ryan D., Fisher M., Williams D., Dales N.A., Patane M.A., Pantoliano M.W. ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J. Biol. Chem. 2004, 279:17996-18007.
24. Krege J.H., John S.W., Langenbach L.L., Hodgin J.B., Hagaman J.R., Bachman E.S., Jennette J.C., O'Brien D.A., Smithies O. Male-female differences in fertility and blood pressure in ACE-deficient mice. Nature 1995, 375:146-148.
25. Gurley S.B., Allred A., Le T.H., Griffiths R., Mao L., Philip N., Haystead T.A., Donoghue M., Breitbart R.E., Acton S.L., Rockman H.A., Coffman T.M. Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice. J. Clin. Invest. 2006, 116:2218-2225.
26. Der Sarkissian S., Grobe J.L., Yuan L., Narielwala D.R., Walter G.A., Katovich M.J., Raizada M.K. Cardiac overexpression of angiotensin converting enzyme 2 protects the heart from ischemia-induced pathophysiology. Hypertension 2008, 51:712-718.
27. Rentzsch B., Todiras M., Iliescu R., Popova E., Campos L.A., Oliveira M.L., Baltatu O.C., Santos R.A., Bader M. Transgenic angiotensin-converting enzyme 2 overexpression in vessels of SHRSP rats reduces blood pressure and improves endothelial function. Hypertension 2008, 52:967-973.
28. Yamamoto K., Ohishi M., Katsuya T., Ito N., Ikushima M., Kaibe M., Tatara Y., Shiota A., Sugano S., Takeda S., Rakugi H., Ogihara T. Deletion of angiotensin-converting enzyme 2 accelerates pressure overload-induced cardiac dysfunction by increasing local angiotensin II. Hypertension 2006, 47:718-726.
29. Nakamura K., Koibuchi N., Nishimatsu H., Higashikuni Y., Hirata Y., Kugiyama K., Nagai R., Sata M. Candesartan ameliorates cardiac dysfunction observed in angiotensin-converting enzyme 2-deficient mice. Hypertens. Res. 2008, 31:1953-1961.
30. Oudit G.Y., Kassiri Z., Patel M.P., Chappell M., Butany J., Backx P.H., Tsushima R.G., Scholey J.W., Khokha R., Penninger J.M. Angiotensin II-mediated oxidative stress and inflammation mediate the age-dependent cardiomyopathy in ACE2 null mice. Cardiovasc. Res. 2007, 75:29-39.
31. Ferreira A.J., Santos R.A., Almeida A.P. Angiotensin-(1-7): cardioprotective effect in myocardial ischemia/reperfusion. Hypertension 2001, 38:665-668.
32. Santos R.A., Ferreira A.J., Nadu A.P., Braga A.N., de Almeida A.P., Campagnole-Santos M.J., Baltatu O., Iliescu R., Reudelhuber T.L., Bader M. Expression of an angiotensin-(1-7)-producing fusion protein produces cardioprotective effects in rats. Physiol. Genomics 2004, 17:292-299.
33. Donoghue M., Wakimoto H., Maguire C.T., Acton S., Hales P., Stagliano N., Fairchild-Huntress V., Xu J., Lorenz J.N., Kadambi V., Berul C.I., Breitbart R.E. Heart block, ventricular tachycardia, and sudden death in ACE2 transgenic mice with downregulated connexins. J. Mol. Cell Cardiol. 2003, 35:1043-1053.
34. Masson R., Nicklin S.A., Craig M.A., McBride M., Gilday K., Gregorevic P., Allen J.M., Chamberlain J.S., Smith G., Graham D., Dominiczak A.F., Napoli C., Baker A.H. Onset of experimental severe cardiac fibrosis is mediated by overexpression of angiotensin-converting enzyme 2. Hypertension 2009, 53:694-700.
35. Morrell N.W., Morris K.G., Stenmark K.R. Role of angiotensin-converting enzyme and angiotensin II in development of hypoxic pulmonary hypertension. Am. J. Physiol. 1995, 269:H1186-H1194.
36. Marshall R.P., Gohlke P., Chambers R.C., Howell D.C., Bottoms S.E., Unger T., McAnulty R.J., Laurent G.J. Angiotensin II and the fibroproliferative response to acute lung injury. Am. J. Physiol. Lung Cell Mol. Physiol. 2004, 286:L156-L164.
37. Ferreira A.J., Shenoy V., Yamazato Y., Sriramula S., Francis J., Yuan L., Castellano R.K., Ostrov D.A., Oh S.P., Katovich M.J., Raizada M.K. Evidence for angiotensin-converting enzyme 2 as a therapeutic target for the prevention of pulmonary hypertension. Am. J. Respir. Crit. Care Med. 2009, 179:1048-1054.
38. Yamazato Y., Ferreira A.J., Hong K.H., Sriramula S., Francis J., Yamazato M., Yuan L., Bradford C.N., Shenoy V., Oh S.P., Katovich M.J., Raizada M.K. Prevention of pulmonary hypertension by angiotensin-converting enzyme 2 gene transfer. Hypertension 2009, 54:365-371.
39. Li X., Molina-Molina M., Abdul-Hafez A., Uhal V., Xaubet A., Uhal B.D. Angiotensin converting enzyme-2 is protective but downregulated in human and experimental lung fibrosis. Am. J. Physiol. Lung Cell Mol. Physiol. 2008, 295:L178-L185.
40. Wang R., Ibarra-Sunga O., Verlinski L., Pick R., Uhal B.D. Abrogation of bleomycin-induced epithelial apoptosis and lung fibrosis by captopril or by a caspase inhibitor. Am. J. Physiol. Lung Cell Mol. Physiol. 2000, 279:L143-L151.
41. Otsuka M., Takahashi H., Shiratori M., Chiba H., Abe S. Reduction of bleomycin induced lung fibrosis by candesartan cilexetil, an angiotensin II type 1 receptor antagonist. Thorax 2004, 59:31-38.
42. Marshall R.P., Webb S., Bellingan G.J., Montgomery H.E., Chaudhari B., McAnulty R.J., Humphries S.E., Hill M.R., Laurent G.J. Angiotensin converting enzyme insertion/deletion polymorphism is associated with susceptibility and outcome in acute respiratory distress syndrome. Am. J. Respir. Crit. Care Med. 2002, 166:646-650.
43. Raiden S., Nahmod K., Nahmod V., Semeniuk G., Pereira Y., Alvarez C., Giordano M., Geffner J.R. Nonpeptide antagonists of AT1 receptor for angiotensin II delay the onset of acute respiratory distress syndrome. J. Pharmacol. Exp. Ther. 2002, 303:45-51.
44. Imai Y., Kuba K., Rao S., Huan Y., Guo F., Guan B., Yang P., Sarao R., Wada T., Leong-Poi H., Crackower M.A., Fukamizu A., Hui C.C., Hein L., Uhlig S., Slutsky A.S., Jiang C., Penninger J.M. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature 2005, 436:112-116.
45. Warner F.J., Lew R.A., Smith A.I., Lambert D.W., Hooper N.M., Turner A.J. Angiotensin-converting enzyme 2 (ACE2), but not ACE, is preferentially localized to the apical surface of polarized kidney cells. J. Biol. Chem. 2005, 280:39353-39362.
46. Batlle D., Wysocki J., Soler M.J., Ranganath K. Angiotensin-converting enzyme 2: enhancing the degradation of angiotensin II as a potential therapy for diabetic nephropathy. Kidney Int. 2012, 81:520-528.
47. Oudit G.Y., Herzenberg A.M., Kassiri Z., Wong D., Reich H., Khokha R., Crackower M.A., Backx P.H., Penninger J.M., Scholey J.W. Loss of angiotensin-converting enzyme-2 leads to the late development of angiotensin II-dependent glomerulosclerosis. Am. J. Pathol. 2006, 168:1808-1820.
48. Tikellis C., Bialkowski K., Pete J., Sheehy K., Su Q., Johnston C., Cooper M.E., Thomas M.C. ACE2 deficiency modifies renoprotection afforded by ACE inhibition in experimental diabetes. Diabetes 2008, 57:1018-1025.
49. Wong D.W., Oudit G.Y., Reich H., Kassiri Z., Zhou J., Liu Q.C., Backx P.H., Penninger J.M., Herzenberg A.M., Scholey J.W. Loss of angiotensin-converting enzyme-2 (Ace2) accelerates diabetic kidney injury. Am. J. Pathol. 2007, 171:438-451.
50. Zimmerman D., Burns K.D. Angiotensin-(1-7) in kidney disease: a review of the controversies. Clin. Sci. (Lond.) 2012, 123:333-346.
51. Peiris J.S., Yuen K.Y., Osterhaus A.D., Stohr K. The severe acute respiratory syndrome. N. Engl. J. Med. 2003, 349:2431-2441.
52. Li W., Moore M.J., Vasilieva N., Sui J., Wong S.K., Berne M.A., Somasundaran M., Sullivan J.L., Luzuriaga K., Greenough T.C., Choe H., Farzan M. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature 2003, 426:450-454.
53. Li F., Li W., Farzan M., Harrison S.C. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science 2005, 309:1864-1868.
54. Hofmann H., Pyrc K., van der Hoek L., Geier M., Berkhout B., Pohlmann S. Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry. Proc. Natl. Acad. Sci. U S A 2005, 102:7988-7993.
55. Zaki A.M., van Boheemen S., Bestebroer T.M., Osterhaus A.D., Fouchier R.A. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N. Engl. J. Med. 2012, 367:1814-1820.
56. de Groot R.J., Baker S.C., Baric R.S., Brown C.S., Drosten C., Enjuanes L., Fouchier R.A., Galiano M., Gorbalenya A.E., Memish Z., Perlman S., Poon L.L., Snijder E.J., Stephens G.M., Woo P.C., Zaki A.M., Zambon M., Ziebuhr J. Middle East respiratory syndrome coronavirus (MERS-CoV); announcement of the coronavirus study group. J. Virol. 2013, 87:7790-7792.
57. Muller M.A., Raj V.S., Muth D., Meyer B., Kallies S., Smits S.L., Wollny R., Bestebroer T.M., Specht S., Suliman T., Zimmermann K., Binger T., Eckerle I., Tschapka M., Zaki A.M., Osterhaus A.D., Fouchier R.A., Haagmans B.L., Drosten C. Human coronavirus EMC does not require the SARS-coronavirus receptor and maintains broad replicative capability in mammalian cell lines. mBio 2012, 3. e00515-12.
58. Raj V.S., Mou H., Smits S.L., Dekkers D.H., Muller M.A., Dijkman R., Muth D., Demmers J.A., Zaki A., Fouchier R.A., Thiel V., Drosten C., Rottier P.J., Osterhaus A.D., Bosch B.J., Haagmans B.L. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 2013, 495:251-254.
59. Akpinar P., Kuwajima S., Krutzfeldt J., Stoffel M. Tmem27: a cleaved and shed plasma membrane protein that stimulates pancreatic beta cell proliferation. Cell Metab. 2005, 2:385-397.
60. Zhang Y., Wada J. Collectrin, a homologue of ACE2, its transcriptional control and functional perspectives. Biochem. Biophys. Res. Commun. 2007, 363:1-5.
61. Fukui K., Yang Q., Cao Y., Takahashi N., Hatakeyama H., Wang H., Wada J., Zhang Y., Marselli L., Nammo T., Yoneda K., Onishi M., Higashiyama S., Matsuzawa Y., Gonzalez F.J., Weir G.C., Kasai H., Shimomura I., Miyagawa J., Wollheim C.B., Yamagata K. The HNF-1 target collectrin controls insulin exocytosis by SNARE complex formation. Cell Metab. 2005, 2:373-384.
62. Pontoglio M. Hepatocyte nuclear factor 1, a transcription factor at the crossroads of glucose homeostasis. J. Am. Soc. Nephrol. 2000, 11(Suppl. 16):S140-S143.
63. Malakauskas S.M., Kourany W.M., Zhang X.Y., Lu D., Stevens R.D., Koves T.R., Hohmeier H.E., Muoio D.M., Newgard C.B., Le T.H. Increased insulin sensitivity in mice lacking collectrin, a downstream target of HNF-1alpha. Mol. Endocrinol. 2009, 23:881-892.
64. Danilczyk U., Sarao R., Remy C., Benabbas C., Stange G., Richter A., Arya S., Pospisilik J.A., Singer D., Camargo S.M., Makrides V., Ramadan T., Verrey F., Wagner C.A., Penninger J.M. Essential role for collectrin in renal amino acid transport. Nature 2006, 444:1088-1091.
65. Singer D., Camargo S.M. Collectrin and ACE2 in renal and intestinal amino acid transport. Channels (Austin) 2011, 5:410-423.
66. Malakauskas S.M., Quan H., Fields T.A., McCall S.J., Yu M.J., Kourany W.M., Frey C.W., Le T.H. Aminoaciduria and altered renal expression of luminal amino acid transporters in mice lacking novel gene collectrin. Am. J. Physiol. Ren. Physiol. 2007, 292:F533-F544.
67. Camargo S.M., Singer D., Makrides V., Huggel K., Pos K.M., Wagner C.A., Kuba K., Danilczyk U., Skovby F., Kleta R., Penninger J.M., Verrey F. Tissue-specific amino acid transporter partners ACE2 and collectrin differentially interact with hartnup mutations. Gastroenterology 2009, 136:872-882.
68. Kowalczuk S., Broer A., Tietze N., Vanslambrouck J.M., Rasko J.E., Broer S. A protein complex in the brush-border membrane explains a Hartnup disorder allele. FASEB J. 2008, 22:2880-2887.
69. Singer D., Camargo S.M., Ramadan T., Schafer M., Mariotta L., Herzog B., Huggel K., Wolfer D., Werner S., Penninger J.M., Verrey F. Defective intestinal amino acid absorption in Ace2 null mice. Am. J. Physiol. Gastrointest. Liver Physiol. 2012, 303:G686-G695.
70. Broer S. Amino acid transport across mammalian intestinal and renal epithelia. Physiol. Rev. 2008, 88:249-286.
71. Broer A., Juelich T., Vanslambrouck J.M., Tietze N., Solomon P.S., Holst J., Bailey C.G., Rasko J.E., Broer S. Impaired nutrient signaling and body weight control in a Na+ neutral amino acid cotransporter (Slc6a19)-deficient mouse. J. Biol. Chem. 2011, 286:26638-26651.
72. Kleta R., Romeo E., Ristic Z., Ohura T., Stuart C., Arcos-Burgos M., Dave M.H., Wagner C.A., Camargo S.R., Inoue S., Matsuura N., Helip-Wooley A., Bockenhauer D., Warth R., Bernardini I., Visser G., Eggermann T., Lee P., Chairoungdua A., Jutabha P., Babu E., Nilwarangkoon S., Anzai N., Kanai Y., Verrey F., Gahl W.A., Koizumi A. Mutations in SLC6A19, encoding B0AT1, cause Hartnup disorder. Nat. Genet. 2004, 36:999-1002.
73. Seow H.F., Broer S., Broer A., Bailey C.G., Potter S.J., Cavanaugh J.A., Rasko J.E. Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19. Nat. Genet. 2004, 36:1003-1007.
74. Segal I., Ou Tim L., Demetriou A., Paterson A., Hale M., Lerios M. Rectal manifestations of pellagra. Int. J. Colorectal Dis. 1986, 1:238-243.
75. Meredith D. Review. The mammalian proton-coupled peptide cotransporter PepT1: sitting on the transporter-channel fence?. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2009, 364:203-207.
76. Khan Y., Bhutta Z.A. Nutritional deficiencies in the developing world: current status and opportunities for intervention. Pediatr. Clin. North Am. 2010, 57:1409-1441.
77. Weisstaub G., Araya M. Acute malnutrition in Latin America: the challenge of ending avoidable deaths. J. Pediatr. Gastroenterol. Nutr. 2008, 47(Suppl. 1):S10-S14.
78. Reinisch W., Panes J., Lemann M., Schreiber S., Feagan B., Schmidt S., Sturniolo G.C., Mikhailova T., Alexeeva O., Sanna L., Haas T., Korom S., Mayer H. A multicenter, randomized, double-blind trial of everolimus versus azathioprine and placebo to maintain steroid-induced remission in patients with moderate-to-severe active Crohn's disease. Am. J. Gastroenterol. 2008, 103:2284-2292.
79. Smith M.I., Yatsunenko T., Manary M.J., Trehan I., Mkakosya R., Cheng J., Kau A.L., Rich S.S., Concannon P., Mychaleckyj J.C., Liu J., Houpt E., Li J.V., Holmes E., Nicholson J., Knights D., Ursell L.K., Knight R., Gordon J.I. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 2013, 339:548-554.
80. Trehan I., Goldbach H.S., LaGrone L.N., Meuli G.J., Wang R.J., Maleta K.M., Manary M.J. Antibiotics as part of the management of severe acute malnutrition. N. Engl. J. Med. 2013, 368:425-435.
81. Sommer F., Backhed F. The gut microbiota-masters of host development and physiology. Nat. Rev. Microbiol. 2013, 11:227-238.