Role of oxygen gradients in shaping redox relationships between the human intestine and its microbiota.

The unique anatomy and physiology of the intestine in conjunction with its microbial content create the steepest oxygen gradients in the body, which plunge to near anoxia at the luminal midpoint. Far from static, intestinal oxygen gradients ebb and flow with every meal. This in turn governs the redox effectors nitric oxide, hydrogen sulfide, and reactive oxygen species of both host and bacterial origin. This review illustrates how the intestine and microbes utilize oxygen gradients as a backdrop for mechanistically shaping redox relationships and a functional coexistence.

[1]  R. Knight,et al.  Worlds within worlds: evolution of the vertebrate gut microbiota , 2008, Nature Reviews Microbiology.

[2]  F. Blachier,et al.  Sulfide, the first inorganic substrate for human cells , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[3]  T. Sobko,et al.  Generation of NO by probiotic bacteria in the gastrointestinal tract. , 2006, Free radical biology & medicine.

[4]  B. Bielski REEVALUATION OF THE SPECTRAL AND KINETIC PROPERTIES OF HO2 AND O2‐ FREE RADICALS , 1978 .

[5]  J. Roth,et al.  Gut inflammation provides a respiratory electron acceptor for Salmonella , 2010, Nature.

[6]  A. Kettle,et al.  Inside the neutrophil phagosome: oxidants, myeloperoxidase, and bacterial killing. , 1998, Blood.

[7]  E. Goode,et al.  Familial Correlations, Segregation Analysis, and Nongenetic Correlates of Soy Isoflavone–Metabolizing Phenotypes , 2004, Experimental biology and medicine.

[8]  P. Mortensen,et al.  Hydrogen Sulfide and Colonic Epithelial Metabolism , 2001, Digestive Diseases and Sciences.

[9]  B. Crane,et al.  Bacterial nitric oxide synthases: what are they good for? , 2009, Trends in microbiology.

[10]  K. Krause,et al.  NADPH Oxidase 1 Modulates WNT and NOTCH1 Signaling To Control the Fate of Proliferative Progenitor Cells in the Colon , 2010, Molecular and Cellular Biology.

[11]  R. Ley,et al.  The Antibacterial Lectin RegIIIγ Promotes the Spatial Segregation of Microbiota and Host in the Intestine , 2011, Science.

[12]  W. Roediger Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man. , 1980, Gut.

[13]  Jonathan A. Eisen,et al.  Human gut microbiome adopts an alternative state following small bowel transplantation , 2009, Proceedings of the National Academy of Sciences.

[14]  Jan Gerritse,et al.  Mixed chemostat cultures of obligately aerobic and fermentative or methanogenic bacteria grown under oxygen‐limiting conditions , 1990 .

[15]  D. Stahl,et al.  Natural relationships among sulfate-reducing eubacteria , 1989, Journal of bacteriology.

[16]  T. Leto,et al.  Proteins Homologous to p47phox and p67phox Support Superoxide Production by NAD(P)H Oxidase 1 in Colon Epithelial Cells* , 2003, Journal of Biological Chemistry.

[17]  M. Wilson,et al.  Regulation of intestinal blood flow. , 2000, The Journal of surgical research.

[18]  M. P. Cole,et al.  Nitrated oleic acid up-regulates PPARgamma and attenuates experimental inflammatory bowel disease. , 2010, Free Radical Biology & Medicine.

[19]  A. Thomson,et al.  Bacterial nitrite-reducing enzymes. , 1992, European journal of biochemistry.

[20]  M. Washington,et al.  Colon-specific delivery of a probiotic-derived soluble protein ameliorates intestinal inflammation in mice through an EGFR-dependent mechanism. , 2011, The Journal of clinical investigation.

[21]  James Versalovic,et al.  Human microbiome in health and disease. , 2012, Annual review of pathology.

[22]  W. Rabsch,et al.  Motility allows S. Typhimurium to benefit from the mucosal defence , 2008, Cellular microbiology.

[23]  J. A. Cole,et al.  Modulation of Shigella virulence in response to available oxygen in vivo , 2010, Nature.

[24]  James H. Brown,et al.  Microbial biogeography: putting microorganisms on the map , 2006, Nature Reviews Microbiology.

[25]  N. Murthy,et al.  Enteric commensal bacteria potentiate epithelial restitution via reactive oxygen species-mediated inactivation of focal adhesion kinase phosphatases , 2011, Proceedings of the National Academy of Sciences.

[26]  T. Fenchel,et al.  Survey of Motile Microaerophilic Bacterial Morphotypes in the Oxygen Gradient above a Marine Sulfidic Sediment , 2005, Applied and Environmental Microbiology.

[27]  R. Berg,et al.  The indigenous gastrointestinal microflora. , 1996, Trends in microbiology.

[28]  M. Fukumoto,et al.  NADPH oxidase subunit, gp91(phox) homologue, preferentially expressed in human colon epithelial cells. , 2000, Gene.

[29]  T. Sobko,et al.  Intestinal Hydrogen and Nitric Oxide Gases in Preterm Infants – Effects of Antibiotic Therapy , 2008, Neonatology.

[30]  R. Coatney,et al.  Nutrient-induced changes in intestinal blood flow in the dog. , 1994, The British veterinary journal.

[31]  O. P. Dinnick,et al.  UNSAFE ANÆSTHETIC SUPPLY SYSTEMS , 1975, The Lancet.

[32]  Woojin Jeong,et al.  Reversible Inactivation of the Tumor Suppressor PTEN by H2O2 * , 2002, The Journal of Biological Chemistry.

[33]  E. Zoetendal,et al.  Microbial Community Development in a Dynamic Gut Model Is Reproducible, Colon Region Specific, and Selective for Bacteroidetes and Clostridium Cluster IX , 2010, Applied and Environmental Microbiology.

[34]  M. Pearce,et al.  Influence of dietary factors on the clinical course of ulcerative colitis: a prospective cohort study , 2004, Gut.

[35]  T. Herlin,et al.  Energy metabolism of human neutrophils during phagocytosis. , 1982, The Journal of clinical investigation.

[36]  A. Neish,et al.  Reactive oxygen production induced by the gut microbiota: pharmacotherapeutic implications. , 2012, Current medicinal chemistry.

[37]  E. Sato,et al.  Oxygen‐dependent regulation of the respiration and growth of Escherichia coli by nitric oxide , 1997, FEBS letters.

[38]  M. Chapman,et al.  In vivo colonic butyrate metabolism and colonic permeability in extensive ulcerative colitis. , 1998, Gastroenterology.

[39]  H. Morita,et al.  Synthesis of nitric oxide from the two equivalent guanidino nitrogens of L-arginine by Lactobacillus fermentum , 1997, Journal of bacteriology.

[40]  S. Fanaro,et al.  Intestinal microflora in early infancy: composition and development , 2003, Acta paediatrica (Oslo, Norway : 1992). Supplement.

[41]  S. Falkow,et al.  Identification and characterization of a Salmonella typhimurium oxygen-regulated gene required for bacterial internalization , 1994, Infection and immunity.

[42]  P. Stewart,et al.  Spatial Patterns of DNA Replication, Protein Synthesis, and Oxygen Concentration within Bacterial Biofilms Reveal Diverse Physiological States , 2007, Journal of bacteriology.

[43]  P. Rosenstiel,et al.  DUOX2-derived reactive oxygen species are effectors of NOD2-mediated antibacterial responses , 2009, Journal of Cell Science.

[44]  J. Furne,et al.  Oxidation of hydrogen sulfide and methanethiol to thiosulfate by rat tissues: a specialized function of the colonic mucosa. , 2001, Biochemical pharmacology.

[45]  S. Krishnan,et al.  Butyrate and glucose metabolism by colonocytes in experimental colitis in mice , 2000, Gut.

[46]  G. Cooper,et al.  Changes in gastric tissue oxygenation during mobilisation for oesophageal replacement. , 1995, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[47]  T. Hirayama,et al.  Role of Nicotinamide Adenine Dinucleotide Phosphate Oxidase 1 in Oxidative Burst Response to Toll-Like Receptor 5 Signaling in Large Intestinal Epithelial Cells 1 , 2004, The Journal of Immunology.

[48]  J. Imlay Cellular defenses against superoxide and hydrogen peroxide. , 2008, Annual review of biochemistry.

[49]  H. Petty,et al.  Apparent role of traveling metabolic waves in oxidant release by living neutrophils , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[50]  N. Pace,et al.  Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases , 2007, Proceedings of the National Academy of Sciences.

[51]  B. Jørgensen,et al.  Distribution of sulfate-reducing bacteria, O2, and H2S in photosynthetic biofilms determined by oligonucleotide probes and microelectrodes , 1993, Applied and environmental microbiology.

[52]  Jeffrey I. Gordon,et al.  Reciprocal Gut Microbiota Transplants from Zebrafish and Mice to Germ-free Recipients Reveal Host Habitat Selection , 2006, Cell.

[53]  D. Stuehr,et al.  Electron Transfer, Oxygen Binding, and Nitric Oxide Feedback Inhibition in Endothelial Nitric-oxide Synthase* , 2000, The Journal of Biological Chemistry.

[54]  S. Kjelleberg,et al.  Ribosomes exist in large excess over the apparent demand for protein synthesis during carbon starvation in marine Vibrio sp. strain CCUG 15956 , 1992, Journal of bacteriology.

[55]  L. T. Angenent,et al.  Succession of microbial consortia in the developing infant gut microbiome , 2010, Proceedings of the National Academy of Sciences.

[56]  V. Tremaroli,et al.  Analysis of gut microbial regulation of host gene expression along the length of the gut and regulation of gut microbial ecology through MyD88 , 2011, Gut.

[57]  W. Roediger,et al.  THE COLONIC EPITHELIUM IN ULCERATIVE COLITIS: AN ENERGY-DEFICIENCY DISEASE? , 1980, The Lancet.

[58]  P. Hall,et al.  Regulation of cell number in the mammalian gastrointestinal tract: the importance of apoptosis. , 1994, Journal of cell science.

[59]  H. Bohlen Intestinal tissue PO2 and microvascular responses during glucose exposure. , 1980, The American journal of physiology.

[60]  H. Verspaget,et al.  Imbalanced secondary mucosal antioxidant response in inflammatory bowel disease , 2003, The Journal of pathology.

[61]  J. Clemente,et al.  Diet Drives Convergence in Gut Microbiome Functions Across Mammalian Phylogeny and Within Humans , 2011, Science.

[62]  M. Grisham,et al.  Role of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease. , 2002, Free radical biology & medicine.

[63]  Kunitomo Watanabe,et al.  Molecular epidemiological study of vertical transmission of vaginal Lactobacillus species from mothers to newborn infants in Japanese, by arbitrarily primed polymerase chain reaction , 2002, Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy.

[64]  A. Brune,et al.  Microecology of the termite gut: structure and function on a microscale. , 2000, Current opinion in microbiology.

[65]  S. Colgan,et al.  Hypoxia and metabolic factors that influence inflammatory bowel disease pathogenesis. , 2011, Gastroenterology.

[66]  A. Kettle,et al.  Myeloperoxidase associated with neutrophil extracellular traps is active and mediates bacterial killing in the presence of hydrogen peroxide , 2012, Journal of leukocyte biology.

[67]  Y. Atlasi Wnt Signaling in Stem Cells and Cancer , 2013 .

[68]  J. Handelsman,et al.  Molecular biological access to the chemistry of unknown soil microbes: a new frontier for natural products. , 1998, Chemistry & biology.

[69]  Tetsuya Nakamura,et al.  Crosstalk between Wnt and Notch signaling in intestinal epithelial cell fate decision , 2007, Journal of Gastroenterology.

[70]  E. Ogier-Denis,et al.  NOX enzymes and Toll-like receptor signaling , 2008, Seminars in Immunopathology.

[71]  I. Kaplan,et al.  Limits of the Natural Environment in Terms of pH and Oxidation-Reduction Potentials , 1960, The Journal of Geology.

[72]  P. Bork,et al.  A human gut microbial gene catalogue established by metagenomic sequencing , 2010, Nature.

[73]  A. Guz,et al.  Small Bowel Tonometry : Assessment of Small Gut Mucosal Oxygen Tension in Dog and Man , 1965, Nature.

[74]  A. Stams,et al.  The ecology and biotechnology of sulphate-reducing bacteria , 2008, Nature Reviews Microbiology.

[75]  K. Morimura,et al.  Hypoxia-inducible factor augments experimental colitis through an MIF-dependent inflammatory signaling cascade. , 2008, Gastroenterology.

[76]  E. Nudler,et al.  Endogenous Nitric Oxide Protects Bacteria Against a Wide Spectrum of Antibiotics , 2009, Science.

[77]  Robert E. Wolf,et al.  Serial review: reactive oxygen and nitrogen in inflammationRole of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease1,2 , 2002 .

[78]  A. Onderdonk,et al.  Production of experimental ulcerative colitis in gnotobiotic guinea pigs with simplified microflora , 1981, Infection and immunity.

[79]  W. Roediger,et al.  Reducing sulfur compounds of the colon impair colonocyte nutrition: implications for ulcerative colitis. , 1993, Gastroenterology.

[80]  Philip S. Stewart,et al.  Diffusion in Biofilms , 2003, Journal of bacteriology.

[81]  J. Lambeth,et al.  The Superoxide-Generating Oxidase Nox1 Is Functionally Required for Ras Oncogene Transformation , 2004, Cancer Research.

[82]  T. Sobko,et al.  Gastrointestinal nitric oxide generation in germ-free and conventional rats. , 2004, American journal of physiology. Gastrointestinal and liver physiology.

[83]  T. Aw Intestinal glutathione: determinant of mucosal peroxide transport, metabolism, and oxidative susceptibility. , 2005, Toxicology and applied pharmacology.

[84]  R. Amann,et al.  Fate of Heterotrophic Microbes in Pelagic Habitats: Focus on Populations , 2005, Microbiology and Molecular Biology Reviews.

[85]  H. Clevers,et al.  Wnt signalling in stem cells and cancer , 2005, Nature.

[86]  Hongzhu Li,et al.  Hydrogen sulfide (H2S) metabolism in mitochondria and its regulatory role in energy production , 2012, Proceedings of the National Academy of Sciences.

[87]  D. Binion,et al.  Acquired microvascular dysfunction in inflammatory bowel disease: Loss of nitric oxide-mediated vasodilation. , 2003, Gastroenterology.

[88]  E. Nudler,et al.  NO-mediated cytoprotection: instant adaptation to oxidative stress in bacteria. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[89]  J. Kristjánsson,et al.  Substrate binding site for nitrate reductase of Escherichia coli is on the inner aspect of the membrane , 1979, Journal of bacteriology.

[90]  C. Chaumontet,et al.  Oxidation of hydrogen sulfide remains a priority in mammalian cells and causes reverse electron transfer in colonocytes. , 2010, Biochimica et biophysica acta.

[91]  J. Zweier,et al.  Noninvasive measurement of anatomic structure and intraluminal oxygenation in the gastrointestinal tract of living mice with spatial and spectral EPR imaging. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[92]  A. Schramm,et al.  Fluorescence in situ hybridization (FISH) detection of nitrite reductase transcripts (nirS mRNA) in Pseudomonas stutzeri biofilms relative to a microscale oxygen gradient. , 2012, Systematic and applied microbiology.

[93]  B. Crane,et al.  Bacterial nitric oxide synthases. , 2010, Annual review of biochemistry.

[94]  K. U. Kjeldsen,et al.  Oxygen tolerance of sulfate-reducing bacteria in activated sludge. , 2004, Environmental science & technology.

[95]  Tatjana M. Hildebrandt,et al.  Three enzymatic activities catalyze the oxidation of sulfide to thiosulfate in mammalian and invertebrate mitochondria , 2008, The FEBS journal.

[96]  S. Kang,et al.  Cellular regulation by hydrogen peroxide. , 2003, Journal of the American Society of Nephrology : JASN.

[97]  I. Beech,et al.  Screening of sulfate-reducing bacteria in colonoscopy samples from healthy and colitic human gut mucosa. , 2000, FEMS microbiology ecology.

[98]  W. Verstraete,et al.  Evaluation of nitric oxide production by lactobacilli , 2001, Applied Microbiology and Biotechnology.

[99]  C. Coban,et al.  Host innate immune receptors and beyond: making sense of microbial infections. , 2008, Cell host & microbe.

[100]  P. Vaupel,et al.  Blood flow and oxygenation status of gastrointestinal tumors. , 2012, Advances in experimental medicine and biology.

[101]  D. W. Giles,et al.  The aerobic and peroxide-induced coupling of aqueous thiols. II: Reaction mechanisms, model analysis, and a comparison of the model and experimental results , 1986 .

[102]  C. Yabe-Nishimura,et al.  A crucial role for Nox 1 in redox‐dependent regulation of Wnt‐β‐catenin signaling , 2012, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[103]  S. Tannenbaum,et al.  Nitrite and nitrate are formed by endogenous synthesis in the human intestine. , 1978, Science.

[104]  P. Bork,et al.  Enterotypes of the human gut microbiome , 2011, Nature.

[105]  J. Cummings,et al.  Hydrogen sulphide: a bacterial toxin in ulcerative colitis? , 1996, Gut.

[106]  W. Zumft Cell biology and molecular basis of denitrification. , 1997, Microbiology and molecular biology reviews : MMBR.

[107]  F. Mcintosh,et al.  Differences between human subjects in the composition of the faecal bacterial community and faecal metabolism of linoleic acid. , 2009, Microbiology.

[108]  D. Savage,et al.  Influences of Dietary and Environmental Stress on Microbial Populations in the Murine Gastrointestinal Tract , 1974, Infection and immunity.

[109]  W. Lee,et al.  Dual oxidase in mucosal immunity and host-microbe homeostasis. , 2010, Trends in immunology.

[110]  H. Cypionka,et al.  Influence of oxygen on sulfate reduction and growth of sulfate-reducing bacteria , 1993, Archives of Microbiology.

[111]  J. Cole Nitrate reduction to ammonia by enteric bacteria: redundancy, or a strategy for survival during oxygen starvation? , 1996, FEMS microbiology letters.

[112]  J. Fuhrman,et al.  Wide‐ranging abundances of aerobic anoxygenic phototrophic bacteria in the world ocean revealed by epifluorescence microscopy and quantitative PCR , 2005 .

[113]  H. L. Young,et al.  Intraoperative tissue oximetry in the human gastrointestinal tract. , 1990, American journal of surgery.

[114]  J. Alverdy,et al.  Laser capture microdissection and metagenomic analysis of intact mucosa-associated microbial communities of human colon , 2010, Applied Microbiology and Biotechnology.

[115]  R. Benamouzig,et al.  Luminal sulfide and large intestine mucosa: friend or foe? , 2010, Amino Acids.

[116]  Giovambattista Pani,et al.  Reactive oxygen species as essential mediators of cell adhesion , 2003, The Journal of cell biology.

[117]  J F Gross,et al.  Analysis of oxygen transport to tumor tissue by microvascular networks. , 1993, International journal of radiation oncology, biology, physics.

[118]  Daniel B. DiGiulio,et al.  Development of the Human Infant Intestinal Microbiota , 2007, PLoS biology.

[119]  Rui Wang,et al.  The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener , 2001 .

[120]  P. Naaber,et al.  Inhibition of Clostridium difficile strains by intestinal Lactobacillus species. , 2004, Journal of medical microbiology.

[121]  M. Wilson,et al.  Glucose-induced intestinal hyperemia is mediated by nitric oxide. , 1997, The Journal of surgical research.

[122]  J. Lambeth NOX enzymes and the biology of reactive oxygen , 2004, Nature Reviews Immunology.

[123]  D. Harrison,et al.  The effect of growth conditions on respiratory activity and growth efficiency in facultative anaerobes grown in chemostat culture. , 1971, Journal of general microbiology.

[124]  H. Bohlen Mechanism of increased vessel wall nitric oxide concentrations during intestinal absorption. , 1998, American journal of physiology. Heart and circulatory physiology.

[125]  G. Macfarlane,et al.  Short chain fatty acids in human large intestine, portal, hepatic and venous blood. , 1987, Gut.

[126]  T. Leto,et al.  Oxidative innate immune defenses by Nox/Duox family NADPH oxidases. , 2008, Contributions to microbiology.

[127]  D. Savage Factors involved in colonization of the gut epithelial surface. , 1978, The American journal of clinical nutrition.

[128]  N. McGovern,et al.  Hypoxia Selectively Inhibits Respiratory Burst Activity and Killing of Staphylococcus aureus in Human Neutrophils , 2011, The Journal of Immunology.

[129]  G. Macfarlane,et al.  Use of a three-stage continuous culture system to study the effect of mucin on dissimilatory sulfate reduction and methanogenesis by mixed populations of human gut bacteria , 1988, Applied and environmental microbiology.

[130]  B. Babior,et al.  Effects of oxygen tension and pH on the respiratory burst of human neutrophils. , 1979 .

[131]  K. Krause,et al.  The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. , 2007, Physiological reviews.

[132]  Michael Wilson,et al.  Bacteriology of Humans: An Ecological Perspective , 2008 .

[133]  M. Grisham,et al.  Effects of neutrophil-derived oxidants on intestinal permeability, electrolyte transport, and epithelial cell viability , 1990, Inflammation.

[134]  Kap-Seok Yang,et al.  Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins. , 2005, Current opinion in cell biology.

[135]  K. Morita,et al.  Interferon-γ activates transcription of NADPH oxidase 1 gene and upregulates production of superoxide anion by human large intestinal epithelial cells , 2006 .

[136]  T. Sharp,et al.  Mucosal reactive oxygen species decrease virulence by disrupting Campylobacter jejuni phosphotyrosine signaling. , 2012, Cell host & microbe.

[137]  L. Comstock,et al.  Bacteroides thetaiotaomicron: a dynamic, niche-adapted human symbiont. , 2003, Bioessays.

[138]  C. Hauser,et al.  Visceral surface oxygen tension in experimental colitis in the rabbit. , 1988, The Journal of laboratory and clinical medicine.

[139]  M. Tomikawa,et al.  Decreased endothelial nitric oxide synthase in gastric mucosa of rats with chronic renal failure. , 1998, The American journal of physiology.

[140]  M. Geiszt,et al.  Dual oxidases represent novel hydrogen peroxide sources supporting mucosal surface host defense , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[141]  E. Purdom,et al.  Diversity of the Human Intestinal Microbial Flora , 2005, Science.

[142]  I. Lawrance,et al.  Ulcerative colitis and Crohn's disease: distinctive gene expression profiles and novel susceptibility candidate genes. , 2001, Human molecular genetics.

[143]  B. Roe,et al.  A core gut microbiome in obese and lean twins , 2008, Nature.

[144]  John E Tomaszewski,et al.  Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. , 2004, The Journal of clinical investigation.

[145]  D. Granger,et al.  Role of exchange vessels in the regulation of intestinal oxygenation. , 1982, The American journal of physiology.

[146]  D. Granger,et al.  Regulation of Murine Intestinal Inflammation by Reactive Metabolites of Oxygen and Nitrogen , 2001, The Journal of experimental medicine.

[147]  Paul S. Cohen,et al.  Respiration of Escherichia coli in the Mouse Intestine , 2007, Infection and Immunity.

[148]  Dean P. Jones,et al.  Commensal bacteria modulate cullin‐dependent signaling via generation of reactive oxygen species , 2007, The EMBO journal.

[149]  J. R. Lancaster A tutorial on the diffusibility and reactivity of free nitric oxide. , 1997, Nitric oxide : biology and chemistry.

[150]  A. Perner,et al.  Extremely low oxygen tension in the rectal lumen of human subjects. , 2003, Acta anaesthesiologica Scandinavica.

[151]  W. Martin,et al.  Single eubacterial origin of eukaryotic sulfide:quinone oxidoreductase, a mitochondrial enzyme conserved from the early evolution of eukaryotes during anoxic and sulfidic times. , 2003, Molecular biology and evolution.

[152]  J. Lancaster,et al.  Nitrite inhibition of Clostridium botulinum: electron spin resonance detection of iron-nitric oxide complexes. , 1983, Science.

[153]  N. Matsuki,et al.  The possible role of hydrogen sulfide as an endogenous smooth muscle relaxant in synergy with nitric oxide. , 1997, Biochemical and biophysical research communications.

[154]  E. Mittge,et al.  Epithelial cell proliferation in the developing zebrafish intestine is regulated by the Wnt pathway and microbial signaling via Myd88 , 2010, Proceedings of the National Academy of Sciences.

[155]  R. Jaenisch,et al.  HIF-1α Is Essential for Myeloid Cell-Mediated Inflammation , 2003, Cell.

[156]  Xiaoping Liu,et al.  The biological lifetime of nitric oxide: implications for the perivascular dynamics of NO and O2. , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[157]  N. Docherty,et al.  Sulphate‐reducing bacteria and hydrogen sulphide in the aetiology of ulcerative colitis , 2009, The British journal of surgery.

[158]  John Crank,et al.  A moving boundary problem arising from the diffusion of oxygen in absorbing tissue , 1972 .

[159]  Julian Lewis,et al.  Organizing cell renewal in the intestine: stem cells, signals and combinatorial control , 2006, Nature Reviews Genetics.

[160]  R. Rao,et al.  Probiotics ameliorate the hydrogen peroxide-induced epithelial barrier disruption by a PKC- and MAP kinase-dependent mechanism. , 2008, American journal of physiology. Gastrointestinal and liver physiology.

[161]  James B. Mitchell,et al.  Electron Paramagnetic Resonance Imaging of Tumor pO2 , 2012, Radiation research.