Hydrogen Sulfide in Physiology and Diseases of the Digestive Tract.
Hydrogen sulfide (H₂S) is a Janus-faced molecule. On one hand, several toxic functions have been attributed to H₂S and exposure to high levels of this gas is extremely hazardous to health. On the other hand, H₂S delivery based clinical therapies are being developed to combat inflammation, visceral pain, oxidative stress related tissue injury, thrombosis and cancer. Since its discovery, H₂S has been found to have pleiotropic effects on physiology and health. H₂S is a gasotransmitter that exerts its effect on different systems, such as gastrointestinal, neuronal, cardiovascular, respiratory, renal, and hepatic systems. In the gastrointestinal tract, in addition to H₂S production by mammalian cystathionine-β-synthase (CBS), cystathionine-γ-lyase (CSE), H₂S is also generated by the metabolic activity of resident gut microbes, mainly by colonic Sulfate-Reducing Bacteria (SRB) via a dissimilatory sulfate reduction (DSR) pathway. In the gut, H₂S regulates functions such as inflammation, ischemia/ reperfusion injury and motility. H₂S derived from gut microbes has been found to be associated with gastrointestinal disorders such as ulcerative colitis, Crohn's disease and irritable bowel syndrome. This underscores the importance of gut microbes and their production of H₂S on host physiology and pathophysiology.
Section of Gastroenterology, Medicine Service, New Mexico VA Health Care System, Albuquerque, NM 87108, USA. sbsingh14@salud.unm.edu.|Division of Gastroenterology and Hepatology, Department of Medicine, the University of New Mexico, Albuquerque, NM 87131, USA. sbsingh14@salud.unm.edu.
Sudha B
SB
Singh
Section of Gastroenterology, Medicine Service, New Mexico VA Health Care System, Albuquerque, NM 87108, USA. helin@salud.unm.edu.
Henry C
HC
Lin
Desulfovibrio; Hydrogen sulfide; Ischemia/reperfusion injury; gastrointestinal tract; inflammation; motility; sulfate reducing bacteria
FASEB J. 2005 Jul;19(9):1196-8
15863703
FASEB J. 2004 Jul;18(10):1165-7
15155563
Br J Pharmacol. 2013 May;169(1):34-50
23297830
Dig Dis Sci. 2012 Jun;57(6):1496-503
22271414
FEMS Microbiol Ecol. 2002 May 1;40(2):107-12
19709217
Biochem Pharmacol. 2001 Jul 15;62(2):255-9
11389886
Sci Signal. 2009 Nov 10;2(96):ra72
19903941
BMC Anesthesiol. 2015 Aug 18;15:119
26283659
Mol Cancer Res. 2006 Jan;4(1):9-14
16446402
Rev Esp Enferm Dig. 2015 Nov;107(11):659-71
26541655
Life Sci. 2013 Jul 19;93(1):24-9
23727354
Br J Pharmacol. 2014 Mar;171(6):1534-50
24345161
Antioxid Redox Signal. 2010 May 15;12(10):1147-54
19769459
J Bacteriol. 1955 Dec;70(6):735-7
13271322
J Immunol. 2014 Feb 15;192(4):1806-14
24403532
Physiol Behav. 2006 Oct 30;89(3):350-7
16887154
Inflamm Allergy Drug Targets. 2011 Apr;10(2):92-102
21275897
Dis Colon Rectum. 2005 Mar;48(3):469-75
15747080
Nature. 2012 Oct 4;490(7418):55-60
23023125
J Clin Microbiol. 2003 Jun;41(6):2752-4
12791922
Am J Clin Nutr. 1977 Nov;30(11):1770-6
920636
Gut. 2000 Jan;46(1):64-72
10601057
J Immunol. 2012 Nov 15;189(10):5047-56
23034168
J Surg Res. 2012 Jun 15;175(2):234-42
21571312
FEMS Microbiol Lett. 2003 Nov 7;228(1):137-42
14612249
Physiol Rev. 1998 Apr;78(2):393-427
9562034
J Bacteriol. 1987 Jun;169(6):2391-7
3108233
Dig Liver Dis. 2010 Feb;42(2):103-9
19570733
J Biol Chem. 1972 Nov 25;247(22):7157-62
4565078
Inflamm Bowel Dis. 2011 Sep;17(9):1971-8
21830275
Biochem Biophys Res Commun. 1997 Aug 28;237(3):527-31
9299397
Biochem Biophys Res Commun. 2012 May 4;421(2):164-9
22503984
PLoS One. 2015 Jul 28;10(7):e0134234
26218067
PLoS One. 2013 Aug 05;8(8):e71962
23940796
Am J Pathol. 2013 Apr;182(4):1188-95
23395089
Br J Pharmacol. 2005 Aug;145(8):1123-31
15937520
Am J Physiol Lung Cell Mol Physiol. 2006 Jun;290(6):L1193-201
16428267
Am J Emerg Med. 2008 May;26(4):518.e5-7
18410836
PLoS One. 2014 Aug 26;9(8):e105701
25157497
FASEB J. 2015 Apr;29(4):1591-602
25550470
J Biochem. 2009 Nov;146(5):623-6
19605461
J Pharm Pharmacol. 2009 Feb;61(2):207-12
19178768
Am J Physiol Heart Circ Physiol. 2009 Mar;296(3):H868-76
19168723
FEBS Lett. 2015 Jan 2;589(1):165-71
25479086
Case Rep Infect Dis. 2015;2015:354168
25632357
Pharmacol Res. 2015 Mar;93:52-63
25641403
Can J Microbiol. 2015 Feb;61(2):155-63
25630400
Ir J Med Sci. 2016 Aug;185(3):649-54
26141462
Inflamm Res. 2015 Oct;64(10):789-97
26249853
Oral Microbiol Immunol. 1992 Dec;7(6):378-9
1299802
Exp Cell Res. 2016 Jul 15;345(2):134-40
26163895
Aust J Biol Sci. 1974 Oct;27(5):465-71
4447490
Biochem Pharmacol. 1980 Oct 15;29(20):2885-7
7437088
ISME J. 2010 Feb;4(2):232-41
19865183
Physiol Rev. 2012 Apr;92(2):791-896
22535897
Nature. 2010 Sep 23;467(7314):426-9
20864996
J Leukoc Biol. 2007 May;81(5):1322-32
17289797
Br J Pharmacol. 2005 Jun;145(3):275-82
15778736
Eur J Pharmacol. 2014 Feb 15;725:70-8
24444438
Gastroenterology. 2006 Nov;131(5):1542-52
17101327
Am J Physiol Lung Cell Mol Physiol. 2007 Apr;292(4):L960-71
17209138
Cell Mol Biol Lett. 2003;8(4):991-1003
14668922
JAMA. 2004 Aug 18;292(7):852-8
15316000
Cell Host Microbe. 2011 Oct 20;10(4):311-23
22018232
Nat Commun. 2013;4:1366
23340406
Aliment Pharmacol Ther. 2012 Apr;35(7):828-38
22315951
Br J Pharmacol. 2002 Sep;137(2):139-45
12208769
Am J Physiol. 1998 Apr;274(4 Pt 1):G727-33
9575855
FEMS Microbiol Ecol. 2014 Feb;87(2):357-67
24117923
Biochim Biophys Acta. 1978 Feb 10;522(2):340-53
623768
Sci Rep. 2012;2:499
22787557
Eur J Pharmacol. 2010 Mar 25;630(1-3):131-6
20035745
J Exp Zool. 1998 Oct 15;282(3):310-22
9755482
Nature. 2012 Jul 5;487(7405):104-8
22722865
Infect Immun. 2011 Jul;79(7):2597-607
21536792
Biochem J. 1990 Jul 15;269(2):335-40
2201285
Br J Pharmacol. 2015 Feb;172(4):992-1004
25297699
Biochem Pharmacol. 2012 Mar 15;83(6):715-22
22222427
Microbiol Rev. 1987 Jun;51(2):192-205
3299028
Clin Exp Pharmacol Physiol. 2010 Jul;37(7):753-63
20636621
J Clin Gastroenterol. 2006 May-Jun;40(5):421-6
16721224
Br J Pharmacol. 2013 Aug;169(8):1795-809
23713790
Mol Oral Microbiol. 2011 Jun;26(3):221-7
21545699
Dig Dis Sci. 2011 May;56(5):1379-86
20981572
Nat Rev Drug Discov. 2015 May;14(5):329-45
25849904
J Biomed Res. 2015 May;29(3):203-13
26060444
ISME J. 2012 Jan;6(1):57-70
21753800
Nutrition. 2014 Jul-Aug;30(7-8):776-83.e1
24984992
Res Exp Med (Berl). 1987;187(1):9-17
3575886
FASEB J. 2006 Oct;20(12):2118-20
16912151
Int J Clin Exp Pathol. 2015 Jan 01;8(1):474-81
25755736
Obesity (Silver Spring). 2012 Nov;20(11):2257-61
22546742
Am J Physiol Gastrointest Liver Physiol. 2015 Oct 1;309(7):G590-601
26251473
Gastroenterology. 1998 Sep;115(3):584-90
9721155
Dig Dis Sci. 1998 Jan;43(1):162-5
9508519
Am J Emerg Med. 1995 Mar;13(2):199-203
7893309
Acta Physiol Scand. 1985 Aug;124(4):581-9
2996301
Gastroenterology. 1982 Jan;82(1):9-15
6273253
Mol Med Rep. 2015 Mar;11(3):1837-44
25377925
Free Radic Biol Med. 2009 Jul 1;47(1):103-13
19375498
Antioxid Redox Signal. 2009 Apr;11(4):703-14
18855522
PLoS One. 2013 Sep 13;8(9):e74422
24058562
Scand J Gastroenterol. 2003 Jan;38(1):73-9
12608468
J Neurochem. 2008 Aug;106(4):1577-85
18513201
Histochem Cell Biol. 1998 Sep;110(3):243-50
9749958
Gastroenterology. 2004 Jul;127(1):80-93
15236175
J Gastrointest Surg. 2012 Feb;16(2):334-43
22058041
Br J Pharmacol. 2010 Mar;159(6):1236-46
20128814
J Appl Bacteriol. 1988 Aug;65(2):103-11
3204069
Environ Health Perspect. 2014 Aug;122(8):817-22
24833621
Mediators Inflamm. 2014;2014:935251
24966472
Molecules. 2015 May 19;20(5):9099-123
25996214
Gastroenterology. 2005 Oct;129(4):1210-24
16230075
Nature. 2006 Dec 21;444(7122):1022-3
17183309
Biochem Biophys Res Commun. 2015 Mar 13;458(3):632-8
25684185
PLoS One. 2015 Mar 26;10(3):e0121331
25811907
Exp Ther Med. 2013 Mar;5(3):689-694
23403765
Inflamm Bowel Dis. 2015 May;21(5):1006-17
25738373
Cell Physiol Biochem. 2015;36(4):1539-51
26159361
Br J Pharmacol. 2007 Apr;150(8):996-1002
17339831
J Clin Invest. 1999 Oct;104(8):1107-14
10525049
J Pharmacol Exp Ther. 2014 Oct;351(1):96-104
25077524
Eur J Pharmacol. 2015 Oct 5;764:471-9
26201052
Genome Res. 2012 Feb;22(2):292-8
22009990
J Clin Microbiol. 2012 Jan;50(1):199-201
22075582
J Cell Mol Med. 2013 Mar;17(3):365-76
23356870
Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13582-7
23898195
FASEB J. 2007 Dec;21(14 ):4070-6
17634391
Eur J Pharmacol. 2005 Feb 21;509(2-3):171-7
15733553
Arch Oral Biol. 2010 Jul;55(7):515-22
20593542
Gastroenterology. 1993 Mar;104(3):802-9
8440437
Am J Physiol Gastrointest Liver Physiol. 2013 Oct 1;305(7):G467-73
23868410
J Bacteriol. 1961 Dec;82:933-9
14484818
Oral Microbiol Immunol. 1990 Jun;5(3):137-42
2080068
J Immunol. 2008 Sep 15;181(6):4320-31
18768890
Surg Today. 2015 Jul;45(7):892-903
25362520
Front Physiol. 2012 Nov 28;3:448
23226130
Br J Pharmacol. 2011 Sep;164(2b):485-98
21486289
Nephrol Dial Transplant. 2015 Sep;30(9):1497-506
26142397
J Am Soc Nephrol. 2013 Apr;24(5):759-70
23449534
Immunopharmacol Immunotoxicol. 1998 Aug;20(3):399-408
9736444
Gastroenterology. 2009 Aug;137(2):569-78, 578.e1
19375422
Benef Microbes. 2014 Sep;5(3):247-61
24583610
Clin Exp Pharmacol Physiol. 2008 Feb;35(2):223-8
17941893
FASEB J. 2012 Apr;26(4):1727-35
22247331
Plast Reconstr Surg. 2010 Jun;125(6):1670-8
20517090
Bull Exp Biol Med. 2014 Jul;157(3):302-6
25070160
Biochem J. 1982 Aug 15;206(2):267-77
7150244
Gut. 2004 Oct;53(10):1479-84
15361498
Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13780-5
17699621
J Clin Periodontol. 2000 Dec;27(12):943-50
11140562
Gastroenterology. 2014 Aug;147(2):303-13
24798417
Oxid Med Cell Longev. 2015;2015:186908
26064416
Antioxid Redox Signal. 2014 Feb 10;20(5):818-30
23582008
PLoS One. 2012;7(9):e46301
23029468
Neurogastroenterol Motil. 2008 Dec;20(12):1306-16
19019033
Anal Biochem. 1973 Jul;54(1):294-9
4737670
QJM. 2015 Dec;108(12 ):977-8
26031707
J Pharmacol Exp Ther. 2009 Sep;330(3):764-70
19491326
Iran J Basic Med Sci. 2015 Mar;18(3):253-8
25945238
Inflamm Bowel Dis. 2011 Jul;17(7):1620-5
21674719
Am J Physiol Gastrointest Liver Physiol. 2012 Jan 1;302(1):G44-54
21921289
Dig Dis Sci. 2000 Jul;45(7):1439-43
10961726
Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):13559-64
25187563
Am J Gastroenterol. 1998 Jan;93(1):83-7
9448181
Inflamm Bowel Dis. 2003 Jan;9(1):10-7
12656132
Antioxid Redox Signal. 2010 May 15;12(10):1167-78
19769462
Am J Physiol Gastrointest Liver Physiol. 2011 Jul;301(1):G188-93
21474649
Science. 2011 Nov 18;334(6058):986-90
22096201
Eur J Pharmacol. 2014 Oct 5;740:112-20
25008073
Forensic Sci Int. 2001 Dec 1;123(2-3):211-4
11728749