دورية أكاديمية
5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-γ Signaling in the Intestinal Epithelium.
| العنوان: | 5-Aminosalicylic Acid Ameliorates Colitis and Checks Dysbiotic Escherichia coli Expansion by Activating PPAR-γ Signaling in the Intestinal Epithelium. |
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| المؤلفون: | Cevallos SA; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA., Lee JY; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA., Velazquez EM; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA., Foegeding NJ; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Shelton CD; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Tiffany CR; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA., Parry BH; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA., Stull-Lane AR; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA., Olsan EE; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA., Savage HP; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA., Nguyen H; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA., Ghanaat SS; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA., Byndloss AJ; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA., Agu IO; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA., Tsolis RM; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA., Byndloss MX; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, Tennessee, USA.; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Bäumler AJ; Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, California, USA ajbaumler@ucdavis.edu. |
| المصدر: | MBio [mBio] 2021 Jan 19; Vol. 12 (1). Date of Electronic Publication: 2021 Jan 19. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, D.C. : American Society for Microbiology |
| مواضيع طبية MeSH: | Anti-Inflammatory Agents, Non-Steroidal/*pharmacology , Colitis/*drug therapy , Dysbiosis/*drug therapy , Escherichia coli/*drug effects , Mesalamine/*pharmacology , PPAR gamma/*genetics, Animals ; Colitis/genetics ; Colitis/microbiology ; Colitis/pathology ; Colon/drug effects ; Colon/microbiology ; Colon/pathology ; Cytochrome b Group/genetics ; Cytochrome b Group/metabolism ; Dextran Sulfate/administration & dosage ; Dysbiosis/genetics ; Dysbiosis/microbiology ; Dysbiosis/pathology ; Electron Transport Chain Complex Proteins/genetics ; Electron Transport Chain Complex Proteins/metabolism ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Escherichia coli/pathogenicity ; Escherichia coli Proteins/genetics ; Escherichia coli Proteins/metabolism ; Female ; Gene Expression Regulation ; Inflammation ; Male ; Mice ; Mice, Inbred C57BL ; Microfilament Proteins/genetics ; Microfilament Proteins/metabolism ; Nitrate Reductase/genetics ; Nitrate Reductase/metabolism ; Oxidoreductases/genetics ; Oxidoreductases/metabolism ; PPAR gamma/agonists ; PPAR gamma/metabolism ; Treatment Outcome |
| مستخلص: | 5-Aminosalicylic acid (5-ASA), a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist, is a widely used first-line medication for the treatment of ulcerative colitis, but its anti-inflammatory mechanism is not fully resolved. Here, we show that 5-ASA ameliorates colitis in dextran sulfate sodium (DSS)-treated mice by activating PPAR-γ signaling in the intestinal epithelium. DSS-induced colitis was associated with a loss of epithelial hypoxia and a respiration-dependent luminal expansion of Escherichia coli , which could be ameliorated by treatment with 5-ASA. However, 5-ASA was no longer able to reduce inflammation, restore epithelial hypoxia, or blunt an expansion of E. coli in DSS-treated mice that lacked Pparg expression specifically in the intestinal epithelium. These data suggest that the anti-inflammatory activity of 5-ASA requires activation of epithelial PPAR-γ signaling, thus pointing to the intestinal epithelium as a potential target for therapeutic intervention in ulcerative colitis. IMPORTANCE An expansion of Enterobacterales in the fecal microbiota is a microbial signature of dysbiosis that is linked to many noncommunicable diseases, including ulcerative colitis. Here, we used Escherichia coli , a representative of the Enterobacterales , to show that its dysbiotic expansion during colitis can be remediated by modulating host epithelial metabolism. Dextran sulfate sodium (DSS)-induced colitis reduced mitochondrial activity in the colonic epithelium, thereby increasing the amount of oxygen available to fuel an E. coli expansion through aerobic respiration. Activation of epithelial peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling with 5-aminosalicylic acid (5-ASA) was sufficient to restore mitochondrial activity and blunt a dysbiotic E. coli expansion. These data identify the host's epithelial metabolism as a potential treatment target to remediate microbial signatures of dysbiosis, such as a dysbiotic E. coli expansion in the fecal microbiota. (Copyright © 2021 Cevallos et al.) |
| References: | J Immunol. 2007 Mar 1;178(5):2940-9. (PMID: 17312139) J Antibiot (Tokyo). 2018 Nov;71(11):950-961. (PMID: 30050110) mBio. 2019 Oct 1;10(5):. (PMID: 31575772) Cell Host Microbe. 2010 Sep 16;8(3):292-300. (PMID: 20833380) Gut. 2006 Aug;55(8):1104-13. (PMID: 16547072) Am J Physiol Gastrointest Liver Physiol. 2007 Feb;292(2):G657-66. (PMID: 17095756) Int J Syst Evol Microbiol. 2016 Dec;66(12):5575-5599. (PMID: 27620848) Scand J Gastroenterol. 2009;44(11):1323-31. (PMID: 19891583) Gastroenterology. 2003 May;124(5):1265-76. (PMID: 12730867) Science. 2013 Feb 8;339(6120):708-11. (PMID: 23393266) J Biol Chem. 1999 Sep 10;274(37):26448-53. (PMID: 10473604) Aliment Pharmacol Ther. 2006 Sep;24 Suppl 1:2-9. (PMID: 16939423) Scand J Gastroenterol. 1988 Jan;23(1):107-12. (PMID: 2894070) ISME J. 2013 Jul;7(7):1256-61. (PMID: 23677008) Lancet. 1977 Oct 29;2(8044):892-5. (PMID: 72239) Gastroenterology. 1978 Oct;75(4):638-40. (PMID: 30669) Drugs. 1989 Oct;38(4):500-23. (PMID: 2684592) Trends Biotechnol. 2015 Sep;33(9):496-503. (PMID: 26210164) Gastroenterology. 2008 Mar;134(3):688-95. (PMID: 18325386) Dis Markers. 2014;2014:932530. (PMID: 25548431) Nature. 2012 Jun 13;486(7402):207-14. (PMID: 22699609) Cell Host Microbe. 2015 May 13;17(5):662-71. (PMID: 25865369) Cell Host Microbe. 2017 Feb 8;21(2):208-219. (PMID: 28182951) Biochem Pharmacol. 2016 Apr 15;106:70-81. (PMID: 26947454) J Exp Med. 2001 May 7;193(9):1027-34. (PMID: 11342587) J Exp Med. 2005 Apr 18;201(8):1205-15. (PMID: 15824083) Lancet. 1962 May 26;1(7239):1094-6. (PMID: 13865153) World J Gastroenterol. 2008 Jan 7;14(1):114-9. (PMID: 18176972) Front Immunol. 2019 May 14;10:1070. (PMID: 31139192) World J Gastrointest Pathophysiol. 2014 Nov 15;5(4):579-88. (PMID: 25401001) Nature. 2018 Jan 11;553(7687):208-211. (PMID: 29323293) N Engl J Med. 2002 Aug 8;347(6):417-29. (PMID: 12167685) Histochem Cell Biol. 2007 Sep;128(3):253-61. (PMID: 17680263) Front Microbiol. 2018 Jun 13;9:1274. (PMID: 29951050) Clin Ther. 2000 Oct;22(10):1151-68; discussion 1149-50. (PMID: 11110228) Cancer Sci. 2009 Aug;100(8):1366-73. (PMID: 19459851) Biomed Res Int. 2017;2017:9351507. (PMID: 29230419) Gut. 2006 Sep;55(9):1341-9. (PMID: 16905700) Science. 2017 Aug 11;357(6351):570-575. (PMID: 28798125) Nat Microbiol. 2019 Jun;4(6):1057-1064. (PMID: 30911125) Science. 2018 Nov 30;362(6418):. (PMID: 30498100) |
| معلومات مُعتمدة: | T32 DK007673 United States DK NIDDK NIH HHS; R56 AI112949 United States AI NIAID NIH HHS; R01 AI044170 United States AI NIAID NIH HHS; R01 AI149632 United States AI NIAID NIH HHS; R21 AI146432 United States AI NIAID NIH HHS; R01 AI096528 United States AI NIAID NIH HHS; R01 AI112949 United States AI NIAID NIH HHS; R21 AI153069 United States AI NIAID NIH HHS; R01 AI109799 United States AI NIAID NIH HHS; R21 AI143253 United States AI NIAID NIH HHS; TL1 TR000133 United States TR NCATS NIH HHS; UL1 TR000002 United States TR NCATS NIH HHS; P50 CA236733 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: Escherichia coli; dysbiosis; gut inflammation; inflammatory bowel disease; microbial communities |
| المشرفين على المادة: | 0 (Anti-Inflammatory Agents, Non-Steroidal) 0 (Cytochrome b Group) 0 (Electron Transport Chain Complex Proteins) 0 (Escherichia coli Proteins) 0 (Microfilament Proteins) 0 (PPAR gamma) 0 (Pparg protein, mouse) 0 (Vil1 protein, mouse) 4Q81I59GXC (Mesalamine) 9042-14-2 (Dextran Sulfate) EC 1.- (Oxidoreductases) EC 1.7.99.4 (NarG protein, E coli) EC 1.7.99.4 (Nitrate Reductase) EC 1.7.99.4 (napA protein, E coli) EC 1.7.99.4 (narZ protein, E coli) EC 1.9.3.- (cytochrome bd terminal oxidase complex, E coli) |
| تواريخ الأحداث: | Date Created: 20210120 Date Completed: 20210910 Latest Revision: 20210910 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC7845635 |
| DOI: | 10.1128/mBio.03227-20 |
| PMID: | 33468700 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2150-7511 |
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| DOI: | 10.1128/mBio.03227-20 |